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DR. KYLE GILLETT: TOOLS FOR HORMONE OPTIMIZATION IN MALES | HUBERMAN LAB PODCAST
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Dr. Andrew Huberman is a neuroscientist and tenured professor in the department
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DR. KYLE GILLETT: TOOLS FOR HORMONE OPTIMIZATION IN MALES | HUBERMAN LAB PODCAST
102
DISCLAIMER: THE CONTENT BELOW IS FROM THE HUBERMAN LAB PODCAST. AND ALL
AFFILIATE LINKS GO TO HIM. IF YOU WISH TO SUPPORT DR. HUBERMAN YOU CAN CHECK OUT
THE SPONSORS BELOW.
Dec 14, 2022
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DISCLAIMER:
The content here is a transcription from Andrew Huberman’s podcast with Dr. Kyle
Gillett. All sponsored links go to Huberman’s account.
CONTENTS
1. Introduction
2. Sponsors
3. Puberty: Height, Resistance Training, Childhood Obesity
4. First” vs. “Second” Puberty
5. Hormone Optimization & Blood Work
6. Diet, Exercise, Sleep & Hormones
7. Hormones, Stress, Social Connection & Purpose
8. Hormones, Supplementation & Medication
9. Determining Individual Hormone Levels, ADAM Questionnaire
10. Libido, Masturbation, Pornography & the Dopamine “Wave Pool”
11. AG1 (Athletic Greens)
12. Sustainable Exercise Regimen for Hormone Health
13. Testosterone Replacement Therapy (TRT)
14. Supplementation: Creatine & Hair Loss, Betaine, L-Carnitine & Allicin
(Garlic)
15. Vitamin D, Boron; SHBG & Free Testosterone
16. InsideTracker
17. Tongkat Ali (Eurycoma longifolia; Longjack) & Steroid Pathways
18. Fadogia Agrestis & Testosterone
19. Optimize Growth Hormone & IGF-1: Diet, Fasting, Supplements & Exercise
20. Optimize Thyroid Hormone: Iodine & Goitrogens
21. Peptides: Growth Hormone, Tesamorelin, Ibutamoren & Gut Microbiome
22. Testosterone Therapy
23. Prescriptions & Hormones: Human Choriogonadotropin (HCG), Clomiphene
24. Testosterone Therapy + HCG, Fertility & Temperature
25. Hormone Health Q&A: Marijuana, Nicotine, Cycling, Pelvic Floor, Alcohol,
Fat
26. Prostate Health & Tadalafil, Prostate Specific Antigen (PSA)
27. Hair Loss & DHT; Turmeric & Curcuminoids
28. BPAs, Phthalates & Hormone Health
29. Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors,
Social Media, Momentous, Neural Network Newsletter
30. Introduction
HUBERMAN
Welcome to the Huberman Lab Podcast, where we discuss science and science-based
tools for everyday life.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at
Stanford School of Medicine. Today, my guest is Dr. Kyle Gillette.
Dr. Kyle Gillette is a dual board certified physician in family medicine and
obesity medicine and an expert in hormone optimization. He is an MD, that is a
medical doctor, and he treats patients with a variety of backgrounds, ages, and
goals.
Today, we discuss male hormone optimization. We discuss behavioral tools,
nutrition-based tools, supplement-based tools, prescription drug-based tools,
and their interactions in determining overall levels of testosterone, free
testosterone, dihydrotestosterone, estrogen growth hormone, thyroid hormone, and
many other hormones that impact mood, libido, well-being, strength, cognition,
and various psychological factors.
We've covered hormone optimization in both men and women in previous episodes of
the Huberman Lab Podcast, but today's discussion is different. Dr. Kyle Gillette
offers very specific recommendations for people with different goals and of
different ages, and we get deep into the weeds of, for instance, how does one
know whether or not their testosterone is optimized or not? How often to test
for specific hormones, such as testosterone and other hormones, and really how
to gauge how good one should feel.
This is something that's often overlooked in discussions about hormone
optimization or health optimization of any kind for that matter.
For instance, people will talk about reduced libido and discuss whether or not
testosterone levels are to blame, but how does one calibrate their libido in the
first place? That is, how does one know whether or not their libido is normal,
too low, or too high?
We also discuss, for instance, whether or not hormone optimization should be
pursued continually throughout the year. For instance, whether or not you should
cycle on and off supplements and or prescription drugs geared towards hormone
optimization. And we discuss the behavioral foundations of optimal hormone
function.
These are things that every male should be doing and various things they should
actively avoid if their goal is to have healthy hormones and to quote unquote
optimize their levels of every hormone from growth hormone to testosterone at
any stage of life.
And while today's discussion is about male hormone optimization, I want to
emphasize that we discuss all the various ages for male hormone optimization. So
for those of you that are parents, for those of you that are young, those of you
that are middle-aged or old or teenagers, we explore adolescent, puberty, teen,
and late teens, early adulthood, adulthood, and into the late geriatric ages.
So regardless of your age and whether or not you are male or female, today's
episode ought to be of interest to you.
I should also point out that we will soon also be hosting an expert guest on
female hormone optimization.
One thing that I'm certain people of all ages and biological sex will enjoy
about today's conversation is that we also get into descriptions of how
psychology and life events impact hormones and how hormones impact our
psychology and the way that we show up to various life events.
So today is really a broad overview that goes all the way down to fine details
about male hormone optimization. And I'm certain that by the end of today's
episode, you'll have an immense amount of new information about how this
endocrine, that is hormone system in your body works and how it interacts with
your brain and other tissues and many, many actionable tools that you can pursue
regardless of stage of life.
Before we begin, I'd like 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.
SPONSORS
Our first sponsor is Thesis. Thesis makes custom nootropics. And as I've said
many times before on this podcast, I am not a fan of the word nootropics because
it means smart drugs. And frankly, there are no specific neural circuits in the
brain or body for being quote unquote smart. Thesis understands this and they've
developed custom nootropics that are designed to bring your brain and body into
the state that's ideal for what you need to accomplish.
They use the highest quality ingredients, things like phosphatidylserine,
alpha-GPC, many ingredients I've talked about before on this podcast and that I
happen to use myself.
I've been using Thesis for over a year now and I can confidently say that their
nootropics have been a game changer. For me, I like their nootropic for clarity.
I use that before cognitive work often and I like their nootropic for energy and
I often use that before workouts, in particular workouts that are especially
intense.
To get your own personalized nootropic starter kit, go online to takethesis.com
slash Huberman, take their three-minute quiz and Thesis will send you four
different formulas to try in your first month. Again, that's takethesis.com
slash Huberman and use the code Huberman at checkout to get 10% off your first
box.
Today's episode is also brought to us by Roka. Roka makes eyeglasses and
sunglasses that are the absolute highest quality. The company was founded by two
all-American swimmers from Stanford and everything about Roka eyeglasses and
sunglasses were designed with performance in mind.
I've spent a lifetime working on the biology, the visual system and I can tell
you that your visual system has to contend with an enormous number of challenges
in order for you to see clearly.
For instance, when you move from a sunny area to a shady area and back again,
whether or not you're looking at something up close or off into the distance,
Roka understands the biology of the visual system and has designed their
eyeglasses and sunglasses accordingly so that you always see with perfect
clarity.
Roka eyeglasses and sunglasses were initially designed for activities such as
running and cycling and indeed they are very lightweight. Most of the time I
can't even remember that they're on my face, they're so lightweight. But the
important thing to know about Roka eyeglasses and sunglasses is that while they
can be used during sports activities, they also have a terrific aesthetic and
they can be used just as well for wearing to work or out to dinner, et cetera.
If you'd like to try Roka eyeglasses and sunglasses, you can go to Roka, that's
R-O-K-A.com and enter the code Huberman to save 20% off on your first order.
Again, that's Roka, R-O-K-A.com and enter the code Huberman at checkout.
Today's episode is also brought to us by Helix Sleep. Helix makes mattresses and
pillows that are of the absolute highest quality.
I started sleeping on a Helix mattress well over a year ago and it's been the
best sleep that I've ever had.
One of the things that makes Helix mattresses so unique is that they match the
design of the mattress to your unique sleep needs. So for instance, if you go
onto their website, you can take a brief quiz, it's only takes about two or
three minutes and you'll answer questions like do you tend to run hot or cold
throughout the night or whether or not you sleep on your back, your side of your
stomach, or maybe you don't know.
Regardless, they will match you to the custom mattress that's ideal for your
sleep needs. For me, that was the Dusk D-U-S-K mattress, which for me was not
too firm, not too soft and was ideal for my sleep patterns.
You take the quiz and you'll find out what mattress is ideal for your sleep
patterns. So if you're interested in upgrading your mattress, go to
helixsleep.com slash Huberman, take their brief sleep quiz and they'll match you
to a customized mattress and you'll get up to $200 off any mattress order and
two free pillows.
They have a 10 year warranty and you get to try out the mattress for a hundred
nights risk-free. Again, if you're interested, you can go to helixsleep.com
slash Huberman for up to $200 off and two free pillows.
The Huberman Lab Podcast is now partnered with Momentus Supplements. To find the
supplements we discuss on the Huberman Lab Podcast, you can go to Live Momentus,
spelled O-U-S, livemomentus.com slash Huberman. And I should just mention that
the library of those supplements is constantly expanding. Again, that's
livemomentus.com slash Huberman.
And now for my discussion with Dr. Kyle Gillette. Dr. Gillette, great to have
you back. Great to be back, thank you.
PUBERTY: HEIGHT, RESISTANCE TRAINING, CHILDHOOD OBESITY
GILLETT
You
HUBERMAN
I'd like to begin with a question about one of the most mysterious and important
phases of life, which is puberty. I've long wondered whether or not how quickly
somebody goes into puberty, so at what age and how long puberty takes. So how
brief or protracted that puberty is for them to acquire the so-called secondary
sexual characteristics, things like hair growth on the face for males or changes
in bone and muscle density and growth, et cetera. You know, when I was in middle
school and high school, I noticed that some people transitioned into all that
very fast, and some people took a long time to acquire those characteristics.
Can we learn anything about ourselves, our hormones, and maybe even how long
we're going to live based on the time in which we enter puberty and how long it
takes us to progress through puberty? I guess that also raises the question,
does puberty ever truly end?
GILLETT
There are many takeaways from puberty. Some of the actionable items from it is,
yes, it can and does affect your adult height and also stature and also body
composition. So puberty is a time, and if we're talking specifically about
males, think of it as a time where if you have obesity as a child, you could
potentially use that time to change your lifestyle and habits and reset things,
and it is a bit easier. It's almost like a free injection of testosterone and
metabolism and drive and effort into your life. There's a wide variation in how
quickly puberty goes through. So there's stages called tanner stages, which we
don't necessarily need to get into, but if you enter puberty very early, then it
can decrease your adult height or stature.
HUBERMAN
So for a given male that enters puberty at 13 versus a male that enters puberty
at 15, can we say that the guy that entered puberty at 13 is going to be shorter
than the guy that entered puberty at 15, or it's not quite that straightforward?
GILLETT
If they are identical twins, and the individual who entered puberty at age 13
also finished puberty, went all the way through the Tanner stages, and if you do
a bone scan, which I believe is usually done on the left wrist, and it says,
yes, your growth plates are mostly closed, you're not gonna grow more than a
couple inches of height after that.
HUBERMAN
Okay, just a related question. When I was growing up, it was thought, or at
least people would say, that resistance training in particular, lifting heavy
weights could stunt one's growth. Is that true or false?
GILLETT
It is false when you're talking about just lifting heavyweights. Dirty bulking
certainly has the potential to stunt one's growth for two main mechanisms. Could
you define dirty bulking? Dirty bulking is eating an excess of calories, not
just to acquire lean metabolically active body mass or get stronger, but
purposely acquiring body fat.
HUBERMAN
So purposely acquiring muscle and fat by overeating. Yes. And lifting weights
can stunt one's growth. Do I have that correct?
GILLETT
Correct. So it does two things. If you're doing it as a very young child, it
can, that fat can become leptin resistant and it can produce more leptin. And
that leptin can activate the hypothalamus, which activates the pituitary, which
releases gonadotropins, which basically just increase testosterone and estrogen
earlier than it otherwise would have. It's the same mechanism behind why
childhood obesity causes early puberty.
HUBERMAN
Interesting. I do remember a paper published in Science Magazine, I believe it
was focused mainly on females, but showing that when enough body fat
accumulates, the hormone leptin is secreted and that triggers the onset of
puberty. Correct. Given the increase in childhood obesity that we're observing
now, are we seeing an earlier onset of puberty in males and females? Yes.
GILLETT
Yes, in both males and females. Not to get too technical, but there's a
G-protein-coupled receptor on the hypothalamus and leptin directly binds it, so
it does appear directly causatory and not just correlation.
HUBERMAN
Okay. So, and if I understand correctly, what you're saying is for a young guy,
let's say 13, 14, who wants to really bulk up and deliberately, deliberately,
excuse me, overeats and is doing their squats and deadlifts and bench presses
and really trying to get big, they will get big, but only in the lateral
dimension. They are effectively limiting their total height and it can shut down
the long bone growth of their limbs. Is that correct?
GILLETT
Correct. The growth of the long bones is mostly related to the estradiol-alpha
receptor, so basically one of the receptors for estrogen which can be secondary
to early puberty and also is related to body fat because you have that
conversion of testosterone to estrogen.
HUBERMAN
So can we assume that if a young male wants to get into resistance training,
that body weight exercises are probably okay, and maybe even some weight
training, kettlebells, et cetera, but that they should avoid doing so-called
dirty bulking, trying to deliberately gain weight up until what age? Until
puberty is over?
GILLETT
I would say an individual should limit the amount of abnormal body fat
accumulation or dirty bulking indefinitely throughout their entire life.
HUBERMAN
So again, if I understand correctly, that recommendation to avoid deliberate
weight gain or rapid weight gain is not just to allow an individual to reach
their maximum height, but also to avoid laying down a lot of body fat cells.
Correct.
GILLETT
Correct. The balance between that is when you are going through puberty, you are
able to add a lot of lean body mass, not just muscle mass, but bone mass and
other mass as well.
HUBERMAN
I started lifting weights when I was 16 and I confess I trained pretty heavy at
times. I don't know whether or not I would have been taller than I am now. But
when I started that training, I had already reached what was at least close to
my predicted height. I can't say that I deliberately waited until I'd grown. It
just so happened that I stumbled into the weight room and found that I liked it
at age 16, at which point I was already the height that I am now. So in any
case, what I'm hearing is that laying down a lot of excess body fat is not a
good idea. What if somebody grows up chubby or fat? For whatever reason, reasons
related to the eating patterns in their family, maybe even some genetic reasons,
is it safe and or wise for a young person? So let's say somebody who's around
the age of puberty or even younger or in their late teens to be dieting and
actively trying to lose body fat. Is that safe?
GILLETT
Under the supervision of a physician, it is certainly safe to change your body
composition. In pediatric obesity medicine, you're often talking about a
recomposition or a renormalization of the growth curve compared to peers.
“FIRST” VS. “SECOND” PUBERTY
HUBERMAN
Great, thank you. So as you may have sensed, we started chronologically with
puberty. And I know that there's another puberty that even precedes the puberty
that we're all familiar with. Maybe if you want to just briefly mention that,
because I was talking with you about this before we started. The puberty that
I'm most familiar with, and I think most people are most familiar with, the
acquisition of deepening of the voice, growth of muscle and bone, body hair,
acquisition of libido and things like that. That's actually the second puberty
that we all go through. Maybe just mention for us and educate us on the first
puberty. I think most people will be hearing this for the very first time.
GILLETT
The first puberty of everyone's life is the first three months of their life.
You may notice that your baby has more acne the first three months and that they
also have in general just more changes related to androgens and estrogens,
perhaps oilier skin, even more genital growth during the first three months. And
this is mostly due to DHEA, which is an adrenal hormone. The second puberty or
the puberty that most people know of actually starts that same way as well. It's
called adrenarche and it's when the adrenals kick in, I guess, for the second
time.
HUBERMAN
Is there a standard age or age range in which the testicles descend in males?
GILLETT
usually before birth. It is not uncommon to have one or even two undescended
testes, but there is a risk of testicular cancer, especially if they're not
fixed early, and also heat damage to the testes.
HUBERMAN
Well, thank you for that coverage of the two puberties. So early in life, I
imagine some of our listeners are probably still in one or the other puberty.
The ones that are in the first puberty, obviously aren't aware that they're
listening to this podcast, but maybe it'll be embedded in their subconscious.
But some listeners probably are still in puberty, but I think everyone can
remember back to their puberty and roughly when they first entered puberty and
how quickly they aggregated the secondary sex characteristics.
HORMONE OPTIMIZATION & BLOOD WORK
HUBERMAN
I'd like to turn now to a general question about what all males ought to do in
order to optimize their hormones. So if you could just list off the things that
all males should do on a daily basis, weekly basis, I mean, should guys in their
teens and 20s be getting their blood work done? Should they be taking
supplements? We already talked about weight training. What should they be doing?
What should they avoid doing if the goal is to have a long arc of healthy
hormone optimization throughout the lifespan?
GILLETT
There's many things that you should do. An analogy that I often make is when
there's a brand new car that comes off the assembly line, you do a full scope of
diagnostic workup, hook it up to the computer. I think we should do the same
thing with humans as well. During puberty, obviously you're a functioning human,
but I would say there's still development. I think that the human always
develops. I don't think development ever ends. It's a person's lifespan.
HUBERMAN
Oh, sorry, so for blood work, I mean, what would be the earliest, let me put it
this way. If blood work didn't cost anything and everyone could get it, when
would you want to see everybody get their blood work done for the first time?
GILLETT
Obviously individuals under the age of 18 should talk with their parents about
this. And as long as the parents and the child kind of agree and the parents are
on board with this as well, you can start getting blood work. Often a child will
come in with complaints of either precocious puberty or delayed puberty, and
this individual might be 9 or this individual might be 15. For a healthy child,
when they're going through kind of their later tanner stages, 4 and 5, so
they've developed several secondary sexual characteristics, they might have hair
growth or starting to notice more beard growth, that's a good time to do it. If
you're concerned with stature or height or if you're not tracking along where
most members of your family have, not just their height and stature but also the
timing of their puberty, then that's time to get labs.
HUBERMAN
Right, so if I could travel back in time, I would have gotten my blood work done
for hormones and lipids and everything else at 18. I unfortunately didn't know
where and how to get that. And I didn't have any pressing clinical issues. And
so I think the first time that I got my blood work done, I was in my late
twenties, maybe even my early thirties. And I'm still dying to know what my
blood work was when, for instance, I was 17 and I felt a certain way. And I
confess that in many dimensions, I actually feel better now at, I'll be 47 soon,
at 47 than I did in my teens and twenties. And I think it was more on the
psychological side. I think that, but in terms of just understanding why we felt
great or why we felt or feel terrible or not so great, I think blood work is
extremely informative. What do you think are the key things to look for in blood
work? I mean, testosterone is always the topic that comes up in the context of
male hormone optimization, but certainly there are a lot of other hormones that
are important as well.
GILLETT
And with testosterone, you want to get either testosterone and a SHBG or a free
testosterone.
HUBERMAN
Could you define SHBG for our listeners, please?
GILLETT
It is sex hormone-binding globulin. It is the protein that binds up all
androgens and estrogen in the body. So the stronger the androgen, the stronger
it binds. During puberty, strong androgens, especially DHT, which is the
strongest bioidentical androgen, has a huge role, a prominent role in secondary
sexual characteristics. And if your SHBG is very high, then your DHT can run
higher because it's not metabolized, but there's not quite as much free DHT. So
you want to balance between a high enough free DHT and a high enough total DHT.
HUBERMAN
And obviously these blood tests are going to have to be read and interpreted by
a qualified physician. Most people aren't going to be in a position to evaluate
them properly, or at least not with the full depth that they could if they had
an MD like yourself looking at them. Okay, so everyone should get blood work as
early as possible, depending on their budget and availability. What should
everybody do in terms of monitoring those markers? So assuming that there's no
major intervention, how often do you recommend that people get their blood work
done?
GILLETT
Let's say, let's take an individual who just turned 18, they just got their
first set of blood work. They'll probably find something in it that they may
want to optimize using shared decision-making with their physician. Usually a
good follow-up is about six months.
HUBERMAN
months. Okay. So twice a year, getting blood work done and having a physician
evaluate it. That sounds reasonable to me. And for those that didn't initiate
this at 18, such as myself, it's the best time to start then would be as soon as
possible. Yeah. Right.
DIET, EXERCISE, SLEEP & HORMONES
HUBERMAN
In terms of the other things that all males should do, meaning all males of all
ages, puberty and beyond should do, what, what are some of those things? So on a
daily basis, maybe you could just take us through the arc of a day and and push
out some of the protocols that you use or the things that you'd like to see your
male patients use in order to try and optimize their hormone status.
GILLETT
I'll briefly touch on some of the lifestyle pillars to start. Diet and exercise
are the first two. In puberty, sleep is particularly important, of course. But
with diet and exercise, throughout a lifespan you want to not exclude things
that are helping you. For example, during puberty, if you're consuming dairy and
then all of a sudden you cut out all dairy, you're going to lose a lot of
weight.
HUBERMAN
And just again for our audience, maybe you just mentioned what having enough
IGF-1 can do for us that's beneficial is.
GILLETT
We hit a trap.
GILLETT
It helps you grow. It helps with genital development, secondary sexual
characteristics, and long bone growth, skin growth, hair growth, a host of
things.
HUBERMAN
So getting an array of nutrients that include dairy, what other sorts of
nutrients are important during development?
GILLETT
You want to have adequate vitamin D. Vitamin D helps with testosterone
production, it helps again with bone mineralization and stature. After an age of
about 25, and there's not a strict cut-off, but up to about an age of 25,
optimizing your growth hormone and IGF-1 helps with bone density and bone
growth. So from the dietary standpoint, you want to have enough free estrogen,
not too much when you're growing, but you want to help basically stockpile bone
to prevent a risk of osteoporosis or thin bones fractures when you're older.
HUBERMAN
I was someone who broke his left foot five times while in high school. I can say
that whatever young people can do to optimize their bone density would be great.
That problem seems to have resolved itself over time, but I don't know, back
then I was, I did a short run as a vegetarian, but I've always been an omnivore.
I realized that some of this relates to ethics and food allergies and things of
that sort. But would you say that on balance that most people would benefit from
eating a combination of quality proteins from animal sources and non-animal
sources, fruits, vegetables, and starches? I mean, what do you think, for
instance, about people following a pure carnivore or a very pure vegan diet in
their 20s and 30s?
GILLETT
In their late 20s, it might be a reasonable option. In early 20s and certainly
teens, it is a horrible idea because it is likely to significantly decrease your
free androgens so you will have less testosterone acting on receptors through
the body.
HUBERMAN
Are there any other micronutrients or macronutrients that people in their 20s
and 30s should emphasize?
GILLETT
We haven't really touched on fatty acids or fiber too much. Fiber is going to be
paramount in kind of like setting your set point of your gut microbiome the rest
of your life. There is prebiotic fiber, which you could think of as fish food
for your good gut microbiome. It's kind of like an aquarium or a fish tank.
HUBERMAN
goldfish swimming around and that the goldfish eating people don't eat goldfish
people. I hope this video helped you
GILLETT
live or dead. Yeah, but any fiber or food that you're putting in your gut, it's
going to skew your gut microbiome towards something that is more beneficial
HUBERMAN
And would you say that the prebiotic fiber and getting essential fatty acids,
that would be important to do throughout the lifespan or just for people in
their 20s and 30s?
GILLETT
Throughout the lifespan, particularly important in the teenage, 20s, 30s,
because it helps with brain development. You're certainly more of an expert than
me when it comes to brain development, but it does continue to develop really
throughout the lifespan, but certainly through the 20s and 30s as well.
HUBERMAN
What about taking a multivitamin while you're growing up? So many people do
that. Is it necessary? Is it useful? And if it's not necessary, is it safe to do
anyway?
GILLETT
It's generally safe to do anyway. I do not think everybody needs a multivitamin.
The more exclusionary your diet is, for example, if you have celiac disease or
if you're planning on fertility soon, then perhaps it's more reasonable to take
a multivitamin.
HUBERMAN
In a previous discussion of ours, I asked you about caloric restriction and
testosterone. And if I recall correctly, the idea was that if somebody is
overweight, they have excess fat adipose tissue, then getting rid of some of
that adipose tissue through caloric restriction and exercise, provided it's done
not too fast in a healthy way, is going to be beneficial for testosterone in the
long run. But that for individuals who are not carrying an excess of body fat,
caloric restriction is actually going to lower testosterone. First of all, do I
have that correct? And second, are there any addendums to that that you'd like
to give us now?
GILLETT
That's correct. If you look at an individual in a caloric deficit, several
changes will happen. One is that they'll have less building blocks for hormones.
Another is that they will be in a catabolic state more often, so that balance of
anabolism and catabolism will be different. They'll likely have less signaling
from growth hormone and IGF-1, and they'll also have the high SHBG that we
defined earlier as the binding protein, so their free androgens and free
estrogens will go down.
HUBERMAN
Okay. So we touched on sleep being critical. I would say throughout the
lifespan, try and get enough quality sleep, at least 80% of the nights of your
life. And the other 20% are just what happens when there's noise outside or
you're stressed. It just, you have an exam or you're having a great time for
whatever reason. There are a lot of good reasons to lose some sleep now and
again as well. But so we have sleep, we've got nutrition. And we touched on
that. We'll get back into supplementation. Now, what are some of the other
pillars of creating the proper environment for hormone optimization?
GILLETT
Stress is probably the next one. During both puberty but also the 20s and 30s,
individuals are figuring out how they want to cope with stress and also figuring
out what they want to choose to put their effort into. So if someone is
overstressed, then it can put all the other lifestyle pillars and then they stop
dieting well, they stop exercising, and everything else can go askew. There is
also some degree of social component to this, so perhaps I need to add a seventh
pillar of social. During your 20s and 30s, you may be forming a family as well,
perhaps you have children, and the health of the family unit is going to be
vitally important, not necessarily directly for hormone optimization, but it's
going to throw everything else off if it's off.
HUBERMAN
And for people that are not starting their own families in their 20s and 30s,
can that social connection be extended to friendships and work relationships as
well?
GILLETT
have.
GILLETT
Absolutely. In fact, if someone's not starting a family, it is just as
concerning, but for other reasons. Each individual is going to have their close
group of family and friends, and if someone does not have one of those
connections, that's when things can potentially get bad, not just for them
individually, but also society.
HUBERMAN
So when you say stress, you mean learn to manage your stress. What does that
look like? I mean, if a patient has high blood pressure, or even if they don't,
you just sense that there's stress, they have a lot of pressured speech, or
they're not feeling well, or communicating that they're not doing well, what are
some of the things that you recommend in order to try and ameliorate that
stress?
GILLETT
There's different mindfulness or relaxation techniques. Going outside can often
help with this as well. Dietary changes and exercise can help with this too.
Some people like prayer or meditation and a lot of people like counseling or
therapy or even just talking openly with a family member or a friend.
HUBERMAN
what would be some of the other pillars for hormone optimization? Here, I feel
like we're not just talking about people in their 20s and 30s, but again, we're
wrapping our arms around basically puberty onward. I mean, gosh, looking back, I
started meditating pretty early. I started weight training and running early. I
gave some thought to my diet in high school, but really it was in college that I
started thinking more about what I was ingesting and why and trying to do better
there. But people are coming to the table at different stages of life and trying
to optimize for hormones. So what would be some of the additional things that
everybody should do?
GILLETT
Everyone should get outside and find a movement pastime to last a lifetime.
You're gonna get sunlight, you're gonna get some degree of heat and cold
exposure, and you're also just gonna move more. Being in an artificial
environment where there's artificial lights, artificial air conditioning is
going to have many effects on your body. So that's vital. Another one is finding
what your purpose is in life. So I call this spirit, but it's really just the
self-actualization component of Maslow's hierarchy of needs, which is basically
your physical needs, your mental needs, and then your purpose in life, what you
really like to do.
HUBERMAN
picking some goal or target. And I always say that you don't have to stick to
the same goal over time. Certainly I haven't, although I got started early in
the science game and I'm still in it. The idea is not to pick the end goal, is
to pick a goal. And then once you reach that goal to assess and then pick
another goal and so on. I think sometimes when people hear about picking a
purpose, they're like, oh my goodness, I have to define, sort of like naming
oneself, that you actually can change your goals and purpose over time. This is
terrific. Do you suggest that people actively use or avoid supplementation prior
to doing all these other things? I'm somebody that likes to throw the kitchen
sink at things, but I also like to do things pretty systematically. So I always
say behaviors first, then nutrition, then supplementation, and then maybe, and
if and only if there's a real need, and of course, working with a doctor,
prescription drugs. But, you know, there are probably people in their 20s or
30s, maybe even in their 50s that aren't feeling great and they want to do
something in order to be able to train more or to feel more confident to seek
out social connection. They try and go about the whole business from the other
side as well. But what are your thoughts on that?
GILLETT
I see supplements and medications as very similar. One's prescribed and one's
not. In general, medications have more side effects or potentially stronger
therapeutic with more efficacy. But they're just tools to reach an end goal. So
depending on the goal, if there's an individual that's an athlete, then
certainly they should consider supplementation. Or if someone desires optimal or
a very high level of cognitive performance, they should also consider
supplementation. At the same time, food is medicine and a lot of the benefits
you can get in supplements, you can get in food as well. I guess it depends on
the person.
HUBERMAN
and how much time and energy you're willing to spend, and also finances. You
know, I know that when I was in college, I could afford just a few supplements
and they were basically whey protein and some fish oil. I was fortunate that I
was pointing the direction of those things and some creatine. I couldn't afford
much else. Over time, of course, I could afford more, but it really does often
depend on finances. Before we get into some specific recommendations to optimize
testosterone, estrogen, thyroid, growth hormone, et cetera, I want to ask you a
question I've been wondering about for a long time. You know, so often in the
discussion about male hormone optimization, people will say, well, you know, if
your libido is suffering, you know, you might want to be concerned about
testosterone or even estrogen, right? Because we know that estrogen can impact
libido as well. Sometimes having estrogen too low is detrimental for libido. Or
people will say, you're not recovering from workouts or you're just, or you're
feeling kind of depressed. The problem is it's all subjective. So how does one
know whether or not their recovery from workouts, their energy, their
confidence, their libido is within a healthy range? I mean, obviously for people
in the relationship, they can know whether or not their libido matches the sort
of cadence of the relationship in their partner, but how should people think
about this and maybe even start to talk about it? Because one of the big
differences I think between males and females is that because females have a
monthly cycle, they are familiar with the changes that occur in their hormones
over time, because every 28 days, those hormones are changing dramatically in
ways that impact their physiology and psychology. But for males, I feel like
there's sort of a dearth of language to get into the more subtle aspects of
this. It also has to do with privacy issues and people feeling like they don't
want to overshare too much, not knowing what's appropriate to share. But when
you talk to a patient who's in their thirties or maybe even their seventies or
sixties, it doesn't matter, a male patient, what are you listening for? And I
know you're not a psychiatrist, but what are your ears tuned to in order to try
and figure out whether or not this person could really use some help with
hormone optimization or whether or not something else, or maybe they're just
doing great and they don't realize it because they're placing demands on
themselves that are excessive.
GILLETT
You want to use a lot of open-ended questions. This process is called
motivational interviewing. And your goal is to listen to the patient and not
plant an idea in their mind that they can follow. Because everybody is going to
have a different goal. Some people are better at reading their biofeedback or
telling how they feel on a daily basis. There is screening questionnaires
designed, for example, on Adam Questionnaire to look at men's health and
hormone-related health.
HUBERMAN
League.
HUBERMAN
It's called an Adam Questionnaire? Adam Questionnaire. A-D-A-M? Correct. Is it
available online that people could administer it to themselves? Although we
don't want people making clinical diagnoses of themselves or anyone else. Is it
that sort of exam?
GILLETT
It is. Interesting. I don't believe it is a clinically validated tool like an
ASCVD, which is like a risk of heart attack and stroke tool or many other tools.
There's one for depression, there's one for anxiety. They're called PHQ-9 and
GAD-7, respectively. But anyway, there's often an in the Adam questionnaire and
what you hear from the patient, it's a little bit different.
HUBERMAN
Can you give me an example of some of the questions on this Adam questionnaire
or the sorts of motivational interviewing that you might do? So say I'm your
patient, we sit down, what sorts of questions would you ask to probe these kinds
of dimensions of hormones?
GILLETT
Questions about libido, questions about athletic performance, questions about
motivation, and often the patient will answer one thing, but what you hear from
them subjectively is far different.
HUBERMAN
Interesting, can you give me an example of a question? I'm happy to be the
guinea pig here.
GILLETT
A classic one is a guy comes in and a lot of times they say, oh no, the wife
made me go to the doctor. I go, once a year, that's it. I don't want anything. I
don't want any medications. Their screening questionnaires might be zeros across
the board. So nothing, no issues. They're apparently in perfect health. They
talk to you for a while. They get some rapport. They like you. And then right as
you're finishing up the visit and about to go out the room, they mentioned that
their libido isn't quite there and they're having a little bit of ED as well.
And perhaps they're even having some chest pressure tightness. I see.
HUBERMAN
So right as you're leaving the room, a patient will tell you that they're having
some sexual side effects, or not side effects, they're having some sexual
challenges, and then they'll mention chest pressure. Is the chest pressure a
sort of general decoy for it's got to be my heart, or is it related to the other
things they're reporting?
GILLETT
It can be related. In fact, erectile dysfunction is known as the canary in the
coal mine. So coal miners would take the canary down and the canary would die
before the coal miners would have, I believe, carbon monoxide poisoning. And
often one of the causes of ED is plaque buildup, which can happen in the
coronaries as well, but sometimes they notice the symptom in the genitals in the
coronaries.
HUBERMAN
So for such a patient, um, let's say that patient was a young person where
plaque buildup in the arteries and veins is not all that likely if they're,
let's say in their twenties or thirties. Uh, what would be your next step of the
interview at that point? And what, what would you consider? Would you
immediately order labs for that person to try and rule out any kind of, um, uh,
actual hormone level deficiency?
GILLETT
I certainly would order labs. There are some individuals that are very similar
and they come in and they have the same symptoms and one individual might have a
very, very high testosterone and one individual might be severely hypogonadal.
So there's a big difference between the subjective and what the labs look like.
So I certainly order labs. You also ask them about if it's situational or not.
You ask them about their habits. You even ask about porn and masturbation and
all these issues. And of course that's between the doctor and the patient. And
depending on what they tell you, you can often determine if there is a
situational component. Some people call it psychogenic ED, but I don't love the
term psychogenic ED because it kind of puts some blame on the patient's mind.
But a lot of the time that is the case. This is very rarely ordered, it's called
penile tumescence.
HUBERMAN
is it true that there are periodic erections during sleep?
GILLETT
Correct. Yeah. So you basically put a cuff to see if you're having a normal
sized erection during sleep. And I believe about 90% of the time they do that
test they are indeed having erections.
HUBERMAN
which would point to this psychogenic origin of whatever challenges they're
having in terms of sexual interactions. You mentioned porn and masturbation.
This topic has come up a bunch of times on this podcast and on other podcasts
I've gone on because of the relationship between dopamine, sexual motivation and
sexual behavior. And I've been of the pretty strong stance that, while I'm not
judging porn or masturbation, it can create a brain wiring situation where males
in particular essentially teach their brain to be aroused by watching other
people have sex as opposed to being the first person actor in sexual
interactions. So in that sense, that's more about the brain wiring and
neuroplasticity and dopamine, but what are your thoughts on porn and
masturbation as they relate to hormones? I mean, this is a big debate on the
internet. In fact, one of the most common debates is whether or not masturbation
increases or decreases testosterone in males. Certainly it will decrease
motivation to go find sexual partners. We know this and there are more and more
data on this all the time. In terms of the effects of pornography and
masturbation, and here I suppose we need to be somewhat specific and
operationally define what we're talking about. We're talking about porn and
masturbation to the point of ejaculation. Because my understanding is that the
ejaculation and orgasm associated with it causes an increase in prolactin, which
blunts libido for some period of time. The duration of that will vary from
person to person and circumstance to circumstance. But basically all of this
points to the fact that porn and masturbation can really limit libido in the
real world. And to me, pornography and the screen is not the real world. Screens
exist in the real world, the real world doesn't exist in the screen.
GILLETT
That's an accurate statement and prolactin does have a significant acute
increase after ejaculation. It does to some degree after orgasm as well, but
prolactin acts on the pituitary to inhibit the release of the hormones LH and
FSH of which LH can increase testosterone. So this may be one of the cases where
the dose makes the poison and if it is a very frequent habit, certainly daily or
more than once a day would be very detrimental from a hormonal component not
even taking into account the neural wiring.
HUBERMAN
Listen, I think it's terrific that you've actually defined frequency because
this is the problem on the internet or even in the doctor's office. You'll see
descriptions about pornography being dangerous for certain things or detrimental
to hormones. People say frequent, but what's frequent? So you were saying daily
or multiple times per day would be potentially detrimental to the hormone
profile of a male of essentially any age.
GILLETT
And that's just for masturbation. With pornography, with porn use as well, it
would likely be worse.
HUBERMAN
And why is that? Just the sort of dopaminergic drive of the stimulus, just a
really intense visual stimulus.
GILLETT
Dopamine sensitivity, I think that using the analogy of a dopamine wave pool, it
would deepen the pool but not increase your supply of dopamine.
HUBERMAN
Maybe you could describe the dopamine wave pool because I think it's such a
powerful way of thinking about dopamine and what dopamine does. In fact, I've
always credited you when I've done it, but I've generally stolen your analogy of
the dopamine wave pool because it's so astute.
GILLETT
Dopamine wave pool describes the natural variation of ups and downs in your
dopamine or your motivation. And in the wave pool, depending on how high the
peak is, you often have a deeper trough. So you do not want too high of a peak.
In addition, if your peak is very, very high, for example, when you're using
many substances like cocaine or like amphetamines, your dopamine can go so high,
you lose almost all the water from the wave pool. And then when you crash from
that, not only is the trough low, you have less dopamine in the pool to begin
with. The dopamine receptor is extremely sensitive, as is the GABA receptor,
which is an inhibitory receptor. Whereas dopamine is technically a stimulant
more related to adrenaline and noradrenaline. The depth of the pool can change
very quick. So you wanna have that happy medium where you're fairly near the
top, but you're not so near the top that the depth of the pool is gonna go down.
HUBERMAN
So if I interpret that in the context of this discussion about libido, sex,
porn, and masturbation, if somebody has a very intense sexual experience, and
here we're not necessarily talking about an intense orgasm, we're talking about
just a lot of intense visual, so a lot of intense imagery or auditory input or
both, that is going to lead to a situation where dopamine is going to be
depleted afterwards. A guest on this podcast before, my colleague at Stanford,
Dr. Ana Lemke, who's an expert in addiction, talked a bit about this as sort of
a seesawing. Here we're talking about a wave and a crashing out of the water
from the wave pool there. It was a seesawing from pleasure and pain. There's
gonna be a longer and deeper period of lack of pleasure following that. And I
think a lot of people think, oh, well, that's great. You know, they want the
intense experience. But if that intense experience is coming from pornography
and masturbation, or I suppose coming from high-adrenaline activities like
life-risking parkour, hanging off the side of a building, it inevitably is going
to lead to depressive episodes, low-libido episodes that follow. Is that right?
GILLETT
Correct, in a similar physiologic way to withdrawal from stimulants like
amphetamines.
HUBERMAN
Now is sex with a partner different? Because there are many people who are
chasing more and more intense experiences with a partner as opposed to through
pornography and masturbation. Again, here we're talking about all ages and I
should always say, anytime we're talking about sex with a partner, we're
talking, you know, the four conditions that I always lay out on the Human Lab
podcast are that we're talking about consensual, age appropriate, context
appropriate, species appropriate interactions.
GILLETT
Yeah, and this is also a case where the dose makes the poison. So if there's,
you know, obviously meeting all those criteria, if they have one preference,
that for both of them is a positive experience, then that is likely okay. You're
not gonna be able to maintain dopamine over a certain threshold for a long
period of time. So there very well may be a crash from that experience as well.
And the crash may be different in one partner than the other.
HUBERMAN
Interesting. Oh, I'll draw an analogy to food. It'd be like, you know, you don't
have to serve the banquet meal seven nights of the week, maybe just two. Is that
right? And there are other delicious foods out there. Can we use that analogy?
That is very reasonable. Okay, not trying to be PG-13, just trying to parsimony,
Occam's razor, the ability to describe a lot of things in a few words. I'd like
to return to the key things that people should do, or I should say the key
things that men should do to optimize their hormones. So we talked about getting
some movement, getting some sunlight, getting quality social connection one way
or the other, avoid excessively frequent masturbation and viewing pornography.
And for some people, zero might be the optimal number. And I keep coming back to
this- For most people. For most people, interesting. I feel so fortunate to have
grown up prior to the availability of internet pornography. I've never been a
big consumer of pornography. It just not been my thing, but I hear so often from
males of all ages about their addiction to it, their affliction by it. It's
really a serious issue. And that's one of the reasons why I'm grateful that
you're willing to talk about this and your clinical experience with these
patients. I'd like to take a quick break and acknowledge one of our sponsors,
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athleticgreens.com slash Huberman to get the five free travel packs and the
year's supply of vitamin D3K2. In terms of exercise, you know, here's, again,
it's a double-edged sword. On the one hand, it's great to get exercise, but I'm
familiar with, you know, if I train an hour a day, you know, 10 minutes of
warmup and 50 minutes to an hour of weight training or 50 minutes to an hour of
cardio, I feel great, especially if once a week I take a complete day off.
That's sort of my general schedule. I'm also familiar with when I go out for
runs that are excessively long, two-hour runs, or I spend 90 minutes in the gym
too frequently, I start to feel like garbage. Everything suffers. My sleep
starts to suffer. It doesn't matter how much I eat. I don't seem to recover. I
don't feel well. So I realized that recovery ability varies between individuals,
but what do you think is a healthy, sustainable exercise regimen that anyone can
follow that will also support their hormone status?
GILLETT
Yes. We use that analogy.
GILLETT
Keep coming back to this.
GILLETT
For really vigorous exercise, around three to four times a week is very
sustainable over a long period of time. On top of that, you could add in three
or four more instances of less vigorous exercise.
HUBERMAN
Okay. So for less vigorous, what do you mean that, you know, zone two cardio
where you can hold a conversation, but beyond which you, you can't. And for more
vigorous, you're, you're thinking weight training or hit a high intensity
interval type training?
GILLETT
Is that right? Correct. You can also weight train and have some benefit even at
a low to moderate intensity. If you think about weight training where you have,
and it's not necessarily related to the incidence of DOMS, which is delayed
onset muscle soreness, but if you weight train lazy or easy from time to time,
obviously you wanna weight train very heavy from time to time as well because of
more lean body mass growth. But if you weight train lighter, you're going to be
able to do it more often. And it can still help with the hypertrophy of
collagen, for example, in tendons and ligaments. 00.06.51
HUBERMAN
So here again, like to perhaps drill into this notion of intensity and
lightweights, because for me, some of the most brutal workouts I've ever done
were in what I would consider a high repetition range, 15 to 50. Actually, I
went up to Oregon to watch the International Track and Field Championships. We
went by Cameron Haynes' place, right? The Cameron Haynes. And he and his trainer
put us through a workout that was 25 to 50 repetitions per set, and it was done
in circuit, and it was brutal. So it was light. I mean, those weights were
nothing. In some cases, it was body weight, but the number of repetitions was
brutal. So when you say limiting intensity, are you talking about limiting the
number of sets to failure? Are you talking about really being kind of a lazy
bear in the gym? I like to do that every once in a long rest, that sort of
thing. What are your thoughts on that as it relates to hormone optimization? So
I'll just mention, and then I'll let you answer. I feel best overall when I'm
training for 10-minute warmups and about 45 or 50 minutes of weight training,
where I'm pretty lazy between sets. Two to three-minute rest, training somewhere
in the six to 10 rep range, going to failure every once in a while, but mostly
getting that sort of last rep before what I would think is failure. No forced
reps, that kind of thing. And then jogging on the other days, nice and easy.
When I do that, I feel fantastic in all other dimensions of life. When I train
more intensely than that, even with lightweight, so faster cadence and lower
rest, I feel like garbage. I get a headache, I'm kind of ornery, everything
suffers. So what are your thoughts on kind of defining a optimal exercise
strategy for hormones? I've never measured my hormones in those two different
contexts, but I have to imagine that it's cortisol-related.
GILLETT
When they study the effect of exercise, specifically vigorous exercise, one area
that's been studied is vigorous exercise episodes lasting longer than an hour.
They usually track it by a rating of perceived exertion, which isn't perfect and
it's not extremely actionable, but it's helpful for clinical science. But the
takeaway from that is basically it is not hormonally helpful to train,
especially regularly train, vigorously for longer than an hour.
HUBERMAN
Great, so I'm happy to hear that because it sounds like for most people that
hours of work is really the threshold. I think this is important for people to
hear, especially males, because I think with all of the incredible examples out
there of people like Cam, like David Goggins, people who are training for very
long periods of time, you know, and leaving aside all issues of what people are
doing in order to optimize their recovery, I think an hour a day of exercise is
just a great program, that most anyone can follow. And beyond an hour, you start
running into challenges. And I, you know, the occasional 90 minute or two hour
workout is no big deal. But if you start doing that more than once every two
months, I think you're headed for trouble. Have you seen that in people's blood
work and in their hormones? Do you ever see people that are just badly
over-trained because they're just training too hard and too often?
GILLETT
Yes, when the blood work is particularly bad, they're often in a large caloric
deficit as well. There's a synergistic effect between a caloric deficit, even if
you're maintaining adequate protein intake, you might not be maintaining
adequate iron intake or adequate vitamin D, and you're also just literally in a
caloric deficit, perhaps low carbs as well, very low free testosterone, and
they're simultaneously doing a lot of vigorous exercise.
HUBERMAN
Interesting. I often hear, and I'm starting to wonder whether or not some of the
quicker-to-results nutrition tactics, things like dropping all carbohydrates or
the quicker-to-results exercise habits, like starting to do six-day-a-week
really intense workouts, whether or not in the short run they work because they
cause the cosmetic changes that people are seeking, but that they really
undermine the overall goal, which is, at least to me, to have your hormones
maybe not optimized to the 100%, but to always be aiming for 100% and be close
to it at every stage of life.
GILLETT
Consistency is key here. If you are not consistent, then the Law of Diminishing
Returns certainly applies. So 80 or 90% of the benefit over many, many months is
far better than 100%, but only half the time.
HUBERMAN
Yeah, one thing that I've found to be tremendously useful is to finish the
workout while I still have energy to not take myself to exhaustion. And then I'm
able to kind of talk about the dopamine wave pool. I'm able to sort of ride that
into the rest of the day, feeling great. I sort of save or bank some of the
vigor from the training to bring it into my work. But then again, I'm not an
athlete. I get paid to think and to speak, not to lift weights or to run.
GILLETT
Another component of that is the balance between your sympathetic, which is your
fight-or-flight nervous system, and your parasympathetic, which is your
rest-or-digest nervous system. There is an anecdote which is likely true that
many elite bodybuilders are very parasympathetic besides while they're lifting
weights.
HUBERMAN
and they like to eat a lot. The lazy bear in the gym, kind of.
GILLETT
It's a phenomenal phenomenon. Absolutely. But that being said, after a very,
very vigorous workout, for example, one where you're trained to failure, which
bodybuilders and powerlifters do all the time, you feel the tiredness or you
feel the strain from that heavy sympathetic activity when you are lifting a
heavy weight. And it can potentially affect how you feel the rest of the day. So
people who are highly cognitive do not like to have an extremely vigorous
workout in the morning,
HUBERMAN
When I exercise early in the morning, that is before 9 a.m., I have more energy
all day long. If I do it mid-morning, I have experienced more of an afternoon
crash. There's probably some circadian biology in there. I also noticed, and
I've actually seen in my blood work, that if I don't get out for a 45-minute jog
at least once a week, all of my blood profiles suffer in the direction that I
don't want them to go. In particular, testosterone and estrogen move in
directions that are not conducive to my goals. So I'd like to talk about some of
the approaches that people can use in order to optimize hormones. And these
days, for better or for worse, I think for worse, younger guys are asking about
and using testosterone replacement therapy, so-called TRT. And I just want to
frame this up by saying there is no strict cutoff for what is TRT. There are
plenty of people whose blood levels of testosterone and estrogen are within the
normal reference range and decide to start doing these things. Of course, they
can limit fertility. There are a bunch of issues, even at non-quote-unquote
steroidal performance-enhancing dosages. I'd love to frame this up by first
defining our terms, because one of the challenges on the internet is people talk
about TRT, then they'll talk about performance-enhancing drugs, they'll talk
about steroids. They're all steroids, right? I mean, testosterone, estrogen are
both steroid hormones. But what one considered replacement therapy versus what
one considers performance-enhancing is going to depend, right? So here's my
question. Why in the world, why in the world would any male in his teens or 20s
or even 30s whose blood levels of testosterone and estrogen are at the
appropriate levels, meaning within the normal reference range, why would they
take exogenous testosterone given all the negative effects on fertility, some of
the challenges that it can present if the dosages aren't quite right, et cetera,
why would they do that? Certainly if they are not being paid for a particular
endeavor, like they're not making money. If they are playing a sport, chances
are they're not allowed to do that anyway. It's on the banned substances list.
So to me, it just seems like a crazy idea. But then again, I'm of a generation
that really hasn't thought about doing that stuff until people were in their 40s
and 50s or even never. So is there ever a case for somebody in their 20s or 30s
to take testosterone if their blood levels are within the 300 to 900 nanograms
per deciliter reference range?
GILLETT
Not many cases, the reason for any performance-enhancing drug, whether or not it
is a steroid, synthetic, bioidentical or otherwise, it varies a lot. Some
individuals do it only for cosmetic reasons, even if it can have deleterious
effects on the cosmetic appearance, for example, of your skin in the long run.
Everyone has their different reason as far as like when does the benefit
outweigh the detriment. Not very often if you're in your 20s and certainly
almost hardly never. There's always rare cases like Kalman syndrome and whatnot,
but almost never if you're very young.
HUBERMAN
Okay, so for people in their 20s, 30s and beyond, 40s, et cetera, whose
testosterone and estrogen levels are at the appropriate ratios and within the
normal reference range and they feel pretty good, right? We talked about the
Adam's exam or this sort of like feel pretty good is sort of code for libido
energy recovery, et cetera, are feeling at least workable for their lifestyle.
For those people, what can they do besides get great sleep, train but not too
hard or too often, et cetera, et cetera? What are some of the things in the
realm of supplementation that can help them optimize their testosterone and
estrogen without suppressing their own endogenous production of testosterone and
estrogen?
GILLETT
Let's mention creatine as the first one. Creatine is interesting because it has
multiple different effects. It helps with amino acid synthesis. It also helps
with oxidative stress. It can also serve as the backup fuel tank for your
mitochondria. So kind of holding backup ATP. And it does slightly increase total
testosterone. And it also increases the conversion of testosterone to
dihydrotestosterone. So potentially it's especially useful in men in even their
teenage years and their 20s.
HUBERMAN
You mentioned the conversion of testosterone to dihydrotestosterone, and there
is mythology out there that creatine can increase hair loss. I'm guessing
because there's at least one study showing that creatine can increase DHT,
dihydrotestosterone and DHT is one of the primary hormones that can promote male
pattern baldness. So the question therefore is, does creatine supplementation
increase the rate of hair loss?
GILLETT
Theoretically, it can, but in each individual, preventing hair loss is a very
poor reason to take creatine because it's not going to take you to a
supra-physiologic level. It's not going to, you know, increase your androgens to
an unnormal level of binding. So I feel like this, if that was a reason to not
take creatine for hair loss, then that's.
HUBERMAN
then that's- Sorry, you mean hair loss is not a reason to avoid taking care of
your hair?
GILLETT
Correct. Hair loss is not a reason to avoid taking creatine. Think of it as just
bringing you to what you are naturally inclined to have. If your conversion of
testosterone to DHT is already high, then often creatine does not affect this.
It just kind of resets your balance between testosterone being aromatized to
estrogen or being 5-alpha reduced DHT. It's not going to speed up hair loss more
than just naturally being a male does. In some individuals, it will have no
effect. In some individuals, for whatever reason, they have almost no 5-alpha
reductase activity. It will return them to natural or normal.
HUBERMAN
I see. Well, I take five grams a day of creatine monohydrate. I do it for the
tissue voluminizing effects for exercise benefits, but also for the cognitive
effects. I don't know if it's increasing my hair loss. I mean, I've got a little
bit of a sort of a widow's peak type hair loss. That's where it is for me. I
suppose beard growth is associated with DHT too. Most, is that right? I, my,
what I learned, but then again, I haven't been into this literature in a long
time. Is that because of chain differences in receptors that DHT causes hair
growth on the face and hair loss on the head. Is that right?
GILLETT
Right? Yes, and the amount and the sensitivity and density of those receptors is
genetically determined.
HUBERMAN
And is it true that if your mother's father was bald, that you will be bald in
the same pattern and if that he wasn't, you won't?
GILLETT
That is a decent correlation. Part of the proposed mechanism of this, well,
there's several genes and you can actually test your genes for hair loss. You do
get a decent amount of them from your mother. The unique thing you get from your
mother that she may have gotten from her father, that she got one of the copies
from her father, is your X chromosome. And the androgen receptor gene is on your
X chromosome. So all men got their androgen receptor gene from their mother.
HUBERMAN
It's on their X chromosome, not on the Y chromosome. Correct. Interesting. Even
though all of the sort of, quote unquote, male promoting genes are on the Y
chromosome, like mullerian inhibiting, et cetera. Interesting. Okay, so five
grams a day of creatine for most people should be fine. Beneficial for tissue
voluminizing, so strength, bringing water into the muscles, and for the
cognitive effects and the clinical support for creatine, I think is quite strong
at the five gram per day dosage. What other sorts of supplements can people
benefit from? We already talked about the omegas and making sure that people are
getting enough prebiotic fiber to support the gut microbiome and vitamin D. So
what other supplement-based tools can people consider?
GILLETT
Another one we can loop in with creatine is betaine. Some people are
non-responders to creatine, so you can increase that to 10 grams or you can use
its cousin betaine to help with amino acid synthesis and shunting of energy.
Along with that I would put L-carnitine, which is actually the smallest peptide
hormone. It's just two amino acids that are put together. It's a hormone.
Interesting. I'm not challenging it. Yeah, I would call it a peptide more than a
hormone. I would not call L-carnitine a hormone, but I would call dopamine a
hormone.
HUBERMAN
I'm not challenging it. Peptides. Yeah. I'm not challenging it.
HUBERMAN
Uh-huh.
HUBERMAN
Yo.
HUBERMAN
a neuro-hormone, it's so hard to define things as transmitters or hormones at
some level. I agree. So L-carnitine, actually I should backtrack, betaine, do
you recall what dosage people typically would take, if they're a creatine
non-responder?
GILLETT
It's so hard to.
GILLETT
One to three grams. In fact, several versions of creatine have beta-ene mixed in
because it helps with the processing of methionine and homocysteine.
HUBERMAN
In fact, so.
HUBERMAN
So if somebody is already taking creatine and likes it and responds to it, I'll
raise my hand such as myself, would adding betaine help or is it redundant with
creatine?
GILLETT
Only if their homocysteine is persistently elevated and homocysteine is kind of
like an inflammatory marker that can build up if you're not converting enough of
it downstream. How would I know? Just a blood test. Okay. Or if you knew your
MTHFR polymorphism, which is basically how you add methyl groups to codon, what
would that be?
HUBERMAN
you
HUBERMAN
many things in the body. Great. Any side effects of beta-ene that people should
be aware of? Not that I know of. Okay. People can look it up on examine.com is a
great site for that. They'll surely list it. They just revamped their site, by
the way, and it was awesome before and it's platinum now. So L-carnitine, what
are the ways to take L-carnitine? I know that there's an oral form, so capsules
and there's injectables. Injectables, I think you need a prescription. Is that
right? Correct.
GILLETT
You need a prescription for the injectables or you should really get a
prescription for the injectables. For when you inject it, of course, at the
supervision of your doctor, it's usually done intramuscularly. It's an aqueous
solution. So it does not have like an oil or a carrier oil in it like
testosterone esters do. However, if you inject it too superficially, it's not
gonna make or break anything. Often it just burns if you inject it
subcutaneously. And it does not disseminate throughout the body as well.
L-carnitine potentially has localized effects if you inject it. If you ingest it
orally, then it has a very low bioavailability, maybe only 10%.
HUBERMAN
Well, I think most people are going to be able to get L-carnitine only or, you
know, in its capsule form. So what are the dosages of L-carnitine that one needs
to ingest then if they want to get a benefit? Because if only 10% is being
absorbed, it's probably a lot of L-carnitine. How much should people take per
day?
GILLETT
Usually I recommend for oral L-carnitine between 1,000 mg and up to 4,000 or
5,000 mg.
HUBERMAN
or one to four, maybe even five grams, correct?
GILLETT
Up to five grams a day. If you're on that much, especially if you have a
dysregulated gut microbiome, you should be concerned with TMAO, which is a
potential carcinogen that both carnitine and choline can convert into. Your gut
microbiota determine how much that happens.
HUBERMAN
Is it true that I can offset any negative effects of alpha-GPC choline, that is
NL-carnitine, that I take by ingesting garlic? Is that right?
GILLETT
There's a compound in garlic called allicin. I believe it's A-L-L-I-C-I-N. It's
also part of the scientific name, the genus of types of garlic. And this can
help decrease the conversion to TMAO. Berberine actually slightly decreases the
conversion to TMAO as well, probably through alteration of the gut microbiome
and then just optimizing your gut microbiome can decrease conversion. So not
everyone needs allicin, but it's something that you should certainly consider if
you were on a high dose.
HUBERMAN
I'm going to continue to take the 600 milligrams of garlic every time I take my
l-carnitine but I'm going to skip the berberine because berberine gives me
brutal headaches and it makes me crave carbohydrates because it drops my blood
sugar.
GILLETT
It has many other effects including the dawn phenomenon where it drops your
blood sugar when you're sleeping and you can't even realize it.
HUBERMAN
I am not a fan of berberine, and I'm sorry for those of you that are. I'm not
trying to offend anyone, although frankly, if you're being offended by my stance
on berberine, then maybe we should have another discussion. In any case,
injectable L-carnitine, if one can get that through a doctor, how much is
absorbed and how much should one take.
GILLETT
Almost all of it's absorbed in general you're taking between 500 milligrams up
to you can take a pretty high dose up to 2,000 milligrams.
HUBERMAN
And what we did not talk about is what L-carnitine does. So why should someone
go through all of this? Is it to optimize testosterone? Is it working on the
receptor side? What's L-carnitine doing?
GILLETT
It's a shuttle. So I think it's named carnitine palmitoyl coenzyme A. Basically,
it just takes nutrients from outside your mitochondria and puts them in. It also
has a unique effect. Well, not too unique, because tidalafil actually has this
effect as well, is that it increases the density of the androgen receptor in the
cytoplasm of your cells. So even if your androgen receptor sensitivity doesn't
change and even if your testosterone does not change, you will have more
testosterone binding to that increased number of receptors.
HUBERMAN
Does one need to cycle L-carnitine, creatine, betaine? No.
GILLETT
No reason to cycle any of those.
HUBERMAN
okay, what other supplements can one use to try and improve hormone profiles?
And here I realize we're using a very broad brush because when we say improve
hormone profiles, what are we really talking about? And for me, at least I think
about the subjective stuff. You know, do people feel like they are going to have
more energy as a consequence of doing these things? Are they going to have the
more optimized libido? Are they going to have more optimized recovery from
exercise, right? Because, I mean, it's not clear to me that taking one's
testosterone from 600 to 800 is always going to be a good thing, especially if
estrogen is increasing in parallel. That could cause issues. It could certainly
make things better. It could certainly make things worse, right? So with that
backdrop, what are some of the other things people can take? And then we'll go
back to this issue of what really is optimization.
GILLETT
Let's briefly mention vitamin D, which is also a hormone. It's actually a sterol
hormone. And if you have deficient vitamin D and you replace it, then you will
optimize your testosterone. Let's also mention boron. So if you have a very high
SHBG, boron can acutely help lower it, usually in a dose of five to 12
milligrams per day. It's not really a sustained effect, but boron is depleted in
soils. In many countries, I believe it's very high in soils, in Greece and
Turkey, so eating dates or raisins that are from those areas potentially have
more boron. Boron also might be one of the reasons why the reference range for
testosterone is much higher in those countries than other countries.
HUBERMAN
And just to remind people that SHBG, sex hormone binding globulin, is attaching
to the testosterone molecule and limiting the amount of so-called free
testosterone that's available to have its impact on cells. When Dr. Peter Atiyah
was on this podcast, in fact, sitting in that very chair, he said that the ideal
level of free testosterone in males should be about 2% of one's total
testosterone. Would you agree with that number or disagree? I'm sure Peter would
be fine if you said either.
GILLETT
2% is a good rule of thumb. Usually the reference range is between about 1% and
4%. Some people do have genetic polymorphisms in SHBG, a specific gene mutation
where they have very low SHBGs. Also men that have varicose veins in their
testes, also known as varicoceles, tend to have very high SHBGs. So that
percentage would likely be less than 2%. So just because your percentage of free
T to total T is a little bit above or below 2%, that's okay. We just need to
figure out the reason why it is.
HUBERMAN
How would somebody know if they have varicose veins in their testicles,
especially if their testicles are still attached to their body?
GILLETT
Sometimes it's hard to tell, there is several grades. If you have a grade three
or a grade four varicoseal, it has what's called a bag of worms appearance. So
think about if you've just resistance trained or it's a really hot day or you're
wearing very tight fitting clothing, then if you feel it and it almost feels
like there's worms in the scrotum. The other way is to do- It's a scary visual.
Yeah, bag of worms.
HUBERMAN
Worms. Yeah. Well, it was just that, yeah, anyway, I think parasites when I hear
that, but that's not what you're referring to. You're talking about just the
texture.
GILLETT
Sure. The best way for most people to check is to valsalva for a long period of
time. When you valsalva, venous return will decrease. Can you explain valsalva
for people? It's bearing down, like you're lifting a weight or having a bowel
movement where you swallow. And a lot of times you can almost see buildup of
blood in your jugular veins as well. So you have decreased blood return to the
heart and increased blood in the veins themselves.
HUBERMAN
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off. Okay, so vitamin D3, I'm guessing you're talking about vitamin D3
specifically when you say vitamin D, and then boron, five to 12 milligrams per
day, right? And then what are some of the other things to optimize testosterone
that are in supplement form?
GILLETT
We could talk about things that affect the steroidogenesis cascade, so we could
touch on Tongkat Ali. We talked about that a little bit before.
HUBERMAN
Yeah, but I'm guessing a number of people probably haven't heard that
conversation.
GILLETT
also known as long jack and that up-regulates several different enzymes in this
steroidogenesis cascade. And by that, what you mean is, and this is another good
thing to Google, I think anybody interested in hormone optimization should
understand where sterol hormones come from. They come usually from cholesterol
and they can be shunted off to vitamin D very easily. They can be shunted off to
testosterone or estrogens or progestogens quite easily as well. But Toncat helps
with the conversion of multiple key steps where you synthesize testosterone.
Another, think of it as like a co-enzyme or a co-factor, an up-regulator of
these steps is insulin and IGF-1. So a good rule of thumb is, if you are not
expecting as much growth hormone, insulin and IGF-1, for example, lower carb
diets, caloric deficits, you're trying to cut body fat or body weight, then
Toncat is going to be theoretically especially powerful.
HUBERMAN
What sorts of dosages of Tonga do you recommend to your patients?
GILLETT
Anywhere from 300 to 1,200 milligrams a day with Toncat, you need to be careful
with the standardization because if you're thinking about a general Toncat
supplement, which is by far the most well-studied, then you're looking at the
uricomonone content, which is a plant compound that is likely the main active
pharmacologic effect. So that's the compound that's having the effect on the
body. And if you standardize the uricomonone very, very high, then theoretically
you're having more effect at a lower dose.
HUBERMAN
I take 400 milligrams of Tonga Ali per day. I take it early in the day because
it has a bit of a stimulant effect. And if I take it after 2 p.m. it starts to
inhibit my sleep. I've been taking it for years and I rather like the effects.
It seems subtle, but consistent. I've never cycled it. Do you recommend cycling
it?
GILLETT
I don't see any reason to cycle it. There is a reason to cycle some supplements,
but no reason to cycle Tonka.
HUBERMAN
My blood work tells me that it causes an increase in free testosterone for me
and also a slight increase in luteinizing hormone for me. What are some of the
other effects on various hormones that you've observed in the blood work of your
patients taking Tonga Ali?
GILLETT
Tongkat can also slightly increase DHEA, and if you have a very high SHBG, again
that's the protein that binds up your androgens and estrogens, an extremely
important protein. The higher your SHBG, the more it helps decrease it. So
they've studied Tongkat in populations with very normal SHBGs, and it does
nothing for SHBG.
HUBERMAN
Interesting. Does that mean it does nothing for somebody overall? So if somebody
has SHBG that's in the normal range, will taking Tongat benefit them in any
other way?
GILLETT
Yes, it'll increase their total and free testosterone. Got it.
HUBERMAN
But okay, is it known to have effects on anything else like thyroid hormone,
growth hormone, or is it purely in these steroid synthesis pathways? Or steroid,
I should say, synthesis and receptor and modulation pathways?
GILLETT
There's no direct effect on those pathways. However, anytime you alter your free
androgen or free estrogen, particularly one without altering the other, it will
alter the binding protein that binds thyroid hormones. So any change you make,
whether it's natural optimization or hormone replacement, you're going to
slightly skew your thyroid hormone profile. One common actionable example of
this that I see often clinically is someone starts, let's say, estrogen
replacement or testosterone replacement. Maybe they're taking AI with their
testosterone replacement. Aromatase inhibitor. Correct, an aromatase inhibitor,
which blocks the conversion to estrogen. If they're taking testosterone and they
have very little estrogen, then you're going to decrease the binding protein,
also known as thyroxine binding globulin, which binds active thyroid hormones.
So if you start TRT and you either have low aromatase activity or no aromatase
activity, no conversion to estrogen, then your free thyroid hormones will go up.
Even just acutely, usually feedback inhibition, which is how the body talks to
itself and says, we need to make more of this or less of this. But acutely,
there's not always enough time. You're going to have very high thyroid hormones
and you can have tachycardia, which is a fast heart rate, or you can feel kind
of like overly fight or flight due to increased thyroid hormone activity in the
end tissue. Thank you very much for your time, and I'll see you next time.
HUBERMAN
Interesting. Okay, so Tongali, that's a broad range, 300 to 1,200 milligrams per
day, and I realized that the source matters there. What are some of the other
hormones that you prescribe to your patients who do not want to go on
testosterone replacement therapy or take exogenous DHEA or anything like that?
GILLETT
We can talk about Phytogia next. Phytogia is interesting because it's a genus of
plants. Phytogia agrestis is one of them. There's many others that are very
interesting. That species is likely the most well-studied, and it will increase
LH. I would not consider it an LH memetic, so it doesn't really mimic it, but it
increases the release of luteinizing hormone from the pituitary. That's a
hormone that binds to the leydig cell, to the LH receptor, kind of like HCG
does. It will increase the release of testosterone.
HUBERMAN
I see, so I think for people that aren't familiar with HCG, so human chorionic
gonadotropin is basically synthetic luteinizing hormone, and luteinizing hormone
is the hormone released from the pituitary that is going to travel down to the
testes to stimulate the production of sperm and testosterone, but mainly
testosterone, is that correct?
GILLETT
I'm mostly correct. Technically, synthetic LH is also known as little R LH or
recombinant LH. And HCG can be synthetic, but often it is just refined from the
urine of pregnant ladies since the placenta makes it. That's why it's called
chorionic gonadotropin.
HUBERMAN
So where are they getting all this pregnant women's urine? I mean, is, I mean,
is there a location? I mean, not that I want to go there. Donation, yeah.
Really, so they're women- First trimester pregnant ladies, it's very high.
Donating their urine, and then they're purifying it, and then men are injecting
it.
GILLETT
You
GILLETT
Go there. Yeah.
GILLETT
I'm the first tribe.
GILLETT
Yes. Wow. And that's actually the same for menopausal ladies. So first trimester
pregnant ladies, that's how you can make, you know, non-synthetic HCG. And then
for minotropins, which are also known, there's a couple of different names for
it, like Minopure. You have menopausal ladies that have very high LH and FSH,
and then you refine the FSH and LH.
HUBERMAN
Okay, so moving away from the sources and from urine, Fidogia agrestis, what
dosages do you have patients take? I've heard of some potential toxicity to the
testicular cells.
GILLETT
There is one study, and this is a rat study, but you can equate the dose of
toxicity in rats and humans. They did not give these rats any antioxidants, but
it increases a couple different like pro-inflammatory markers. One is GGT or
gamma-glutamyl transferase, comes from both the testes and the liver, and one is
alkaline phosphatase, also known as ALKFOS, again, coming from both areas. There
are several different ways that you can attenuate this increase, and you can
also just check to see if you have increased. In the rat dose that equates with
humans that had no effect, so the safe dose, was an average of 300 milligrams a
day.
HUBERMAN
So that would be 300 milligrams a day in humans is the dosage that did not have
toxicity, correct? Correct.
GILLETT
And often, even if there is toxicity in rats, there is not toxicity in humans,
so it's not directly equitable. But to be safe, another regimen that I have
people take is 600 milligrams every other day or 600 milligrams three times a
week, often Monday, Wednesday, Friday.
HUBERMAN
This is very interesting and relevant because I've been taking Fidogia for some
period of time. All my markers and tests indicate that there's no toxicity, but
I've been taking 600 milligrams per day, but I've been cycling it for about
eight to 12 weeks on, and then a few weeks off. But based on what you're saying,
I'm thinking maybe three times per week or every other day might be better. Is
that right?
GILLETT
based on what you're saying.
GILLETT
If you weren't gonna get any labs, that is certainly the regimen that you want.
If you're gonna check your GGT and ALK-FOS or even take other things to prevent
those from increasing, then you can certainly be more aggressive with your
fiducia dosing. You can increase it quite a bit and it has a dose-dependent
response in both the activities associated with high testosterone and also just
LH and testosterone. So the more aggressive regimen would be 600 milligrams
daily for a month and then take one to two weeks off.
HUBERMAN
Great, I think that's more or less what I've been doing. Okay, terrific. In
terms of other hormones, what are some of the supplements that can support
growth hormone, right? A hormone that's associated with tissue repair and in
some cases, metabolism and fat loss. What are some of the tools, nutritional and
or supplement based, one can do to tap on the growth hormone pathway and let's
lump IGF-1 in there too, since they're essentially working along the same
dimensions.
GILLETT
A quick synopsis, growth hormone is a peptide hormone and it is released by the
pituitary. There's growth hormone releasing hormone and ghrelin that stimulate
the release. So there's also peptides that are very analogous to these two
things. You have that pulsatile secretion of growth hormone in a very fast
half-life of just minutes and then it increases IGF-1. There is both peripheral
IGF-1 and central IGF-1 and IGF-2 but no need to get into the specifics. There
is a happy medium to where your growth hormone is at a adequate level and your
IGF-1 is an adequate level. Usually those two are congruent. So in most cases,
we just check an IGF-1 and occasionally the binding peptides for IGF-1 kind of
like SHBG that we talked about earlier but you're estimating a free IGF-1. It's
kind of confusing because almost all hormones have binding proteins to help
regulate them but often you wanna look at free testosterone, free estradiol,
free IGF-1 or at least estimate it, free cortisol even and free thyroid hormone.
But when you're talking about growth hormone and IGF-1, usually you don't need
to do anything to optimize it. If you are a diabetic, then depending on the type
of diabetes, your IGF-1 and growth hormone can be too high. Specifically in type
1 diabetes, your growth hormone is extremely high but your IGF-1 is low. So if
you're in a dysregulated state or have pathology, I would just talk to your
doctor about IGF-1 or growth hormone. Taking amino acids before you go to bed
could potentially help with growth hormone release just because most growth
hormone is released while you sleep.
HORMONES, STRESS, SOCIAL CONNECTION & PURPOSE
HUBERMAN
I've heard that fasting can increase growth hormone and I know there are certain
patterns of weight training that can increase growth hormone. Some of those
regimens in the weight room that increase growth hormone have been covered by
Dr. Duncan French, who is a guest on this podcast. So maybe we'll refer people
to that episode for the specific protocols, these high volume training.
GILLETT
During those training exercises it usually does it transiently for a period of a
few hours. And a lot of this IGF-1 is released by the muscle itself. So it's not
necessarily released by the liver. IGF-1 that is released directly due to growth
hormone signaling, usually the growth hormone comes from the pituitary and binds
to the liver, where it usually has a half-life of about a week, where the
paracrine or autocrine, think of it as like the peripherally acting or acting in
the muscles itself, which is also helpful, is released and is not as concerning
because it's not related to insulin resistance, but it is related to the
training itself.
HUBERMAN
So fasting and growth hormone, is it true that fasting can increase growth
hormone? And maybe as a little related tangent, I've heard that limiting food
intake for the two hours before going to sleep can increase the pulse of growth
hormone that one experiences during sleep. Of course, everyone gets a pulse of
growth hormone during sleep, but especially carbohydrate laden meals can blunt
that peak that occurs during sleep quite substantially. So two questions. Does
avoiding food intake in the two hours prior to sleep help increase growth
hormone release? Maybe it's being overly neurotic. Maybe people need to avoid
food in the four hours before sleep. But regardless, what is the relationship
between fasting and growth hormone release? I find this really interesting.
GILLETT
Fasting certainly potently increases growth hormone release. However, the end
binding to the receptor is less sensitive. So although fasting does increase
growth hormone, the genes that are downstream to it, both the growth hormone
genes and IGF-1 related gene transcription activity will not be significantly
higher. However, if you are optimizing the growth hormone that is released as
pulsatile secretion, it is helpful to avoid eating for two hours. So the general
rule of thumb is avoid eating about two hours before bed. I think that's
clinically significant and helpful, but fasting otherwise specifically for
growth hormone optimization and someone who already has normal growth hormone
signaling is not helpful. Let's see.
HUBERMAN
extremely useful to hear, because one of the major reasons why people fast is to
get that growth hormone increase. But if they're adjusting things on the back
end that negate that, well then no such luck. Not that I have anything against
fasting. I do a pseudo-intermittent fasting, mostly because I prefer to eat at
fairly regular times of day. Okay, so it doesn't sound like there's a lot that
people can take in supplement form to improve growth hormone. What about thyroid
hormone? What are some of the things that people can take or do in order to make
sure that their thyroid hormone levels are appropriate?
GILLETT
you wanna have a balance of iodine and you wanna have a good source of iodine.
So there's some camps that say you should use a huge high dose of iodine and
there's protocols for it. And there's some that say you should use just barely
enough iodine. I believe it's like 200 micrograms per day, but you wanna
balance. One of the things that I see that many people do not talk about when it
comes to iodine and thyroid is there is compounds known as goitrogens. Or
goitrogens. And these goitrogens are neither good nor evil, but they're actually
kind of a nice check and balance. You need more iodine if you consume more
goitrogens. And some examples of these are some of my favorite foods,
cruciferous vegetables. Boron is also a goitrogen. So higher goitrogens, higher
iodine.
HUBERMAN
So ingesting iodine containing salt is useful, yes or no?
GILLETT
Iodized salt does prevent goiter, but it is not necessarily the ideal form of
iodine. Good forms of iodine often come from the ocean. If you look at a chart
of hypothyroidism, there is a tendency to have more hypothyroidism the more
inland you go.
HUBERMAN
So trying to eat some cruciferous vegetables each day would be the best way to
improve thyroid function.
GILLETT
or a tumor? Along with plenty of iodine. You don't want too much iodine
signaling. Many people are familiar with radioactive iodine tablets, and that's
basically an extremely high amount of iodine to block out the radioactive iodine
that comes from after, you know, like a nuclear meltdown or whatnot.
HUBERMAN
So we've got creatine, betaine, l-carnitine with allicin, garlic to offset the
TMAO, vitamin D3, boron, tonga, ale, fedogia, some fasting. Love to talk to you
about peptides. So I can imagine a hierarchy. The hierarchy starts with
behaviors and nutrition. Behaviors, of course, includes training and limiting
stress and all the things we talked about before, sunshine, et cetera, and
optimized nutrition. Then we talked about supplements, all the things we just
listed off to optimize testosterone. And we can get into this, but estrogen as
well, which is important for libido and brain function and tissue function and
joints feeling good, et cetera. But then we get into the realm where one might
or could consider exogenous hormones, taking a small dose of testosterone or
taking a small dose of GH even, if that were appropriate, and certainly only
working with a doctor. But in between, there's a step of so-called peptides. And
of course, there are many peptides. We've already talked about some of them, but
when people talk about taking peptides, the ones that I hear most often about is
a category that increases GH and IGF-1. And those, to my knowledge, go by the
things like sermorelin, ipramorelin, tesamorelin, sort of a kit of things that
taken separately or in combination to increase GH and IGF-1. But then other
people, for instance, are taking peptides like BPC-157 to try and improve tissue
healing and recovery. There's a lot of interest in peptides. Please, if you
would, tell us about what you know about the safety of peptides in terms of
their sourcing and the utility of peptides. Is this something that people should
consider before thinking about hormone replacement? Should people be wary of
these things? I am very wary of particular sources that are sold online that are
not clean. They contain contaminants and it could be dangerous. I really would
love your thoughts on peptides. I'm just going to sit back and let you riff on
peptides. But if you could touch on some of the ones that I mentioned, I'd be
most grateful.
GILLETT
A peptide is just a chain of amino acids between two and a couple hundred in
length. So I think of peptides as several different categories and the GHRPs
that you mentioned, I would consider those and that stands for growth
hormone-releasing peptide. You have two main types. The ghrelin agonist or they
hit the ghrelin receptor and it helps release growth hormone because of that and
then also the GHRH-like peptides. So they're very similar to growth
hormone-releasing hormone. Often they just change a couple amino acids and it
acts like that. Tessamoralin is one of them. Cermoralin is another one and CJC
is another common one. I believe those are all in the class of GHRH-like
peptides, whereas ipomorelin or ibutamorin, which is also known as MK-677, those
two are in the class of ghrelin agonist. So they're more like they hit the
receptor that ghrelin does, whereas the other ones hit the GHRH receptor. I
think of GHRH-like peptides as being more like GHRH-like peptides, whereas the
GHRH-like
HUBERMAN
I think of ghrelin as making me hungry. Hungry and angry. Why would I want to
take something that would increase ghrelin or signal?
GILLETT
Some people are trying to gain weight. It also does increase your growth
hormone. So if your growth hormone is very low, you can consider it. Ibutamorin
is a long-acting, so it has a long half-life, also known as MK-677. It was
studied mostly in growth hormone deficiency. And do these.
HUBERMAN
Do people get angry also?
GILLETT
They can, many people report a side effect of anxiety or significant hunger.
Most people take it in the evening so they don't notice that hunger as much. It
can also greatly increase your blood glucose. So if you're insulin resistant or
pre-diabetic it gets especially concerning.
HUBERMAN
this is one of those rare moments where I hear something and I think, okay, even
though there's this kit of compounds that can increase GH and IGF-1, based on
everything you're telling me, maybe just taking GH is the better option for
those people because growth hormone, at least it's synthetic growth hormone is
mimicking an endogenous hormone. I mean, certainly not taking anything might be
the ideal, but for those that want to increase growth hormone and they want to
use pharmacology to do that, it sounds like these peptides are pretty
precarious.
GILLETT
Yeah, it kind of depends on the situation. If there's an individual that
struggles with hunger and not eating enough, for example, someone who has a very
small stomach or they just have a very low hunger drive, sometimes you want more
of that orexigenic signaling. The hypothalamus, you have anorexigenic signaling,
which is kind of like anorexia, and orexigenic signaling, the center of the
hypothalamus or the hangry center. And if there's an imbalance between those
two, then perhaps it'd be helpful, potentially theoretically helpful in
anorexics, of which the incidence of anorexia in men is increasing
significantly.
HUBERMAN
as you're telling me this, I'm remembering being 14 or 15 years old and I would
go into the kitchen sometimes and I was so hungry, I would just obliterate all
the food. And I do remember being, I've always been a pretty high energy guy,
but having an immense amount of energy. I don't, I can't recall if it was a
hangry feeling or not, but I'm guessing that was growth hormone. I grew one foot
in a single academic year. So I imagine that was at least in part due to growth
hormone. In any case, sermorelin is the peptide that I hear the most often
about. I admittedly tried a run of it. I was researching a book and decided to
take it before sleep on an empty stomach. It gave me a tremendous depth of
sleep, but that sleep was really truncated, which is just nerd speak for saying
deep, but short sleep. I would wake up after very intense dreams. I can't say
that it helped me recover from exercise that much. I didn't notice any
additional fat loss or anything. Sort of abandoned it, except for occasional
use. Again, this was prescribed by a doctor. You know, I was trying to get the
sense that these peptides and their effects are somewhat vague and distributed
and highly individual. Is that a fair way to describe them?
GILLETT
Part of the problem with the effective peptides is many people take them in
levels that are far above the physiologic range. Even individuals who are
checking their IGF-1 while they take these different GHRPs, most of them do not
check the binding peptides. For example, IGF binding peptide one, two, or three,
and their free IGF-1 level might be significantly different. So the common doses
that people will take these off-label for as a supplement are often much greater
than the therapeutic or physiologic range.
HUBERMAN
which for me just underscores the fact that it's pretty precarious. I mean, I'm
not coming in here as the referee of what anyone should or shouldn't do. I'm
just trying to gather and distribute information, but it, I've heard for
instance, that some companies where people can acquire these things without
prescription, they, those companies are not good at cleaning out the L the lipid
polysaccharide, the LPS, which can cause an inflammatory response. In other
words, these are dirty compounds. And that just sounds risky. It just sounds,
frankly, it just sounds really dangerous to me.
GILLETT
LPS is a common additive in many companies that are not pharmacies, but they're
selling things that people often use as human consumption. One interesting note
about lipopolysaccharide is your gut microbiome actually makes a lot of it as
well, especially Prevotella, which is a specific species that can have to do
with your baseline body temperature. So your baseline body temperature might
also change depending on if you're on a peptide that has LPS in it. Yikes.
HUBERMAN
yikes and yikes, but I tend to be pretty conservative when it comes to taking
anything exogenous, but I do rely on many of the supplements that we talked
about earlier. And I do try and optimize the behavioral things and nutritional
things for a long time. Okay, so then leaving peptides behind, we are now, I
suppose, in the territory of exogenous hormone. So let's say that somebody
decides they're not concerned with fertility or they're gonna bank sperm or they
already have kids or they're going to defer on this issue of wanting to have
kids. My understanding is that nowadays, a lot of people are using testosterone.
Let's not even call it replacement therapy because some of these people have
600, 700, or even 800 nanogram per deciliter reads. So they're not replacing
anything that is diminished. They're just trying to augment what's already
there, increase what's already there. My understanding is that taking a low dose
more frequently is going to be more beneficial than the kind of old school way
of giving, you know, a hundred or even 200 milligrams in a single injection once
every two weeks. Is that right? And what do you do with your patients? So let me
give you a hypothetical. Somebody comes into your office, their blood work and
they have blood levels of, let's say 600 nanograms per deciliter testosterone.
Their estrogen is also in normal range. Everything else checks out, but they're
complaining of, you know, slightly diminished libido, slightly poor recovery
from workouts, maybe, you know, reduced motivation and drive, although no major
depression. And you come to the conclusion that testosterone therapy, not
replacement, but testosterone therapy might be a good option to explore. What's
a typical dosage range and frequency of administration range that you might
consider exploring?
GILLETT
And some of this depends on the SHBG and free testosterone as well. So if that
same individual had a very high SHBG, which again is the binding protein that
binds up the testosterone and all androgens and estrogens, if it is extremely
high and they have a free testosterone of 2, then they might need a different
dose because they need enough testosterone in order to have a normal eughenadal
free testosterone. But a general normal dosing range, especially for someone
starting, is around 100-120 mg divided over the course of a week, usually either
every other day or three times a week, occasionally twice a week. Many people
with SHBG a bit higher can get away pretty easily with twice a week. This is
assuming that the ester is sipionate or enanthate.
HUBERMAN
So 260 milligram injections of testosterone cypionate per week. Yeah, very
common dosing. To hit that 120 milligrams per week as kind of the typical
average.
GILLETT
Average, correct. And I would consider this like a physiologic, you can add a
dose. For many people, even 200 milligrams a week is far above the reference
range. All of this is said with the caveat that testosterone is normally
released in a pulsatile manner. So it's high in the morning, low in the evening.
Whereas if you're on a testosterone therapy, then you're going to have a steady
state. So your testosterone level is gonna be pretty much the same even in the
evening.
HUBERMAN
And in your experience, when patients do that, I'm guessing they report the
normal constellation of positive effects, you know, improved mood, improved
energy, improved sleep, recovery, et cetera. What are some of the hazards or
things that can crop up in blood work or just subjectively that can be warning
signs that even a dosage of 120 milligrams divided into these two or three
dosages per week is too high?
GILLETT
Every organ system in the body. So this is when you really have to be at least
well-versed in every organ system, not just the genital system. You need to have
dermatology prowess, acne is a very common change, lots of different skin
pathologies or even bruising can be related to hormone replacement. Hair loss is
very common to see as well. Mental status changes. Occasionally it even induces
a manic or a bipolar episode because testosterone is also dopaminergic. And then
cardiovascularly, not just in the heart, but also concerns for like
microvascular ischemic disease, ferritin buildup because the estrogen also
increases, and then fertility concerns as well and lipid concerns too. So you
really have to be a hematologist, dermatologist, cardiologist, lipidologist, the
whole nine yards.
HUBERMAN
so
HUBERMAN
another reason or set of reasons rather to if one is considering using
testosterone therapy to really do this in close communication with a really good
physician because that's a lot to monitor. Knowing whether or not you have acne
or not is one thing, but knowing whether or not your LDL is going up, your ApoB
is going up, that's a whole other biz and that needs to be done through blood
work is what I'm interested in.
GILLETT
I'm hearing. Correct, and if your physician that is managing or prescribing your
testosterone therapy or your HRT is not well-versed in these systems, you would
want him or her to be part of an interdisciplinary team where they have other
experts that can monitor those systems.
HUBERMAN
I skipped over a sort of still intermediate set of things, prescription drugs,
but maybe talking about testosterone first was a bit of a mistake on my part,
because I'm aware that there are actually, I think there are companies, but
certainly groups out there that say, no wait, don't go straight from nothing to
supplements to testosterone. Once you're doing behaviors and optimizing
nutrition supplements, let's forget peptides, but instead of going straight to
testosterone therapy, one idea that many people are pursuing is to take the
prescription drugs that trigger luteinizing hormones, so taking HCG, human
chorionic gonadotropin, which my understanding is will increase testosterone,
but also estrogen, or they'll take things like clomiphene. In fact, I think
there are a bunch of companies out there now that are saying, don't take
testosterone, it shuts down spermatogenesis, shuts down testosterone production,
clomiphene is the way to go. Maybe you could educate us about the HCG
monotherapy, I think it's called where you're just mono, one, just taking HCG,
and clomiphene as a, and or clomiphene as a tool to ratchet up hormones.
GILLETT
So quick points on HCG, human chorionic endotropin, made during especially the
first trimester of pregnancy. It has effects other than binding to the LH
receptor. It also binds to the TSH receptor in the thyroid. So
thyroid-stimulating hormone. Yes. In fact, if you look at a molecule of HCG and
thyroid-stimulating hormone, they are extremely similar. However, you need a
relatively high dose of HCG to bind to the TSH receptor. This is a normal
mechanism in pregnancy that accounts for the increased need of thyroid hormone,
usually about 30% to 40%. So that's why if someone has hypothyroidism, you need
to increase their dose of thyroid because the HCG is not going to be doing it
for you. The clomid or clomiphene, there's two main, I believe it's
diastereoisomers, and one of them is N-clomiphene and one of them is
ZOO-clomiphene. These two work slightly differently. N-clomiphene, I believe,
has a faster half-life and it is potentially slightly better tolerated. However,
they were studying it... Clomid is a very commonly prescribed drug and obviously
there's plenty of N-clomiphene in clomid. However, the drug which was Andrazol,
A-N-D-R-O-X-A-L, did not go all the way through the FDA approval process with
clomid being FDA approved.
HUBERMAN
Okay, so there's Clomid, which contains clomiphene, but they're also, because
we're talking about male hormone optimization this episode, there are males out
there who want to increase their testosterone and other hormones, maybe growth
hormone, et cetera, who opt to not take exogenous testosterone. So no cream, no
pellet, no pill, no injectable, sipionate, but decide to take clomiphene a
couple of times a week. My understanding, I've never done this, I would say if I
had, my understanding is that taking clomiphene, maybe two 50 milligram tablets
a week is what I hear people are doing, will increase what? Luteinizing hormone,
the various estrogen receptor subunits. Could you explain how clomiphene would
benefit anyone? And is this a good strategy? I'm hearing that it's being done
quite a lot now.
GILLETT
It will increase testosterone in a dose-dependent manner, but it has many other
pharmacodynamic effects, which is the effect of the drug on the body, other than
its effect on the hypothalamus and the pituitary. So in the hypothalamus and the
pituitary, it does what's called negative feedback inhibition, or it blocks the
oxygen of estrogen. So it crowds out estrogen from the estrogen receptor on the
hypothalamus and the pituitary.
HUBERMAN
And what's the subjective effect that that would cause? So my understanding and
experience of estrogen is that if I ever took, and I did take a very low dose of
an aromatase inhibitor once, and I felt terrible. Actually, reduced libido,
joints felt achy. That's when I discovered that, wow, estrogen is actually
really important for your brain function, for joint function, and for libido.
And suppressing estrogen, for me, just turned out to be the wrong idea. But my
levels indicate that it's within reference range. Okay, so why would I want to
take something that would increase the activity of an estrogen receptor? I just
can't find the rationale for that.
GILLETT
The main rationale behind taking a CIRM is as a very temporary measure that is
not going to suppress pituitary or hypothalamic function. If your testosterone
is just so drastically low that it is unlikely to recover anyway. So most of the
time it is not clinically useful and CIRM should not be prescribed very often,
certainly not as long-term testosterone replacement or testosterone optimization
in most individuals. There's always exceptions to everything, but there's five
different estrogen and estrogen-related receptors. There's two main estrogen
receptors and Clomid and every CIRM has a very unique profile because they
selectively inhibit some receptors in some tissues, but not other receptors in
other tissues. For example, Clomid can inhibit receptors that are in the eye and
it can cause visual changes, blurry vision, especially at higher doses. And it
also acts in every other tissue of the body. So side effects from Clomid and
other selective estrogen receptor modifiers are very common.
HUBERMAN
So I'm, at least by my mind, I'm going to pool them with peptides and say, it
sounds precarious and probably not ideal for most people. Going back to
testosterone therapy, then again, notice folks I've deleted the replacement part
because I think so many people are using testosterone therapy without the need
to, the sort of reference range need to, to replace anything, but rather
building on what they already have for purposes of increasing vitality, et
cetera. Going back to that, my understanding is that taking HCG several times
per week can help maintain spermatogenesis and fertility, even while people are
on testosterone, but, and you and I were talking about this earlier, that
there's tremendous variation. Some people will take a small amount of
testosterone and just crush their sperm count. They just won't make any viable
sperm. Other people can maintain viable sperm production while on testosterone,
especially if they're taking HCG. Is that right?
GILLETT
Correct. And there's many reasons for this. Some of this has to do with heat
damage to the testes. So, potentially cold therapy could be helpful for that.
Ice baths, cold showers.
HUBERMAN
showers or just avoid, and certainly avoiding sauna and hot tub. Yeah.
GILLETT
Sauna and hot tub. Yeah. Yeah. Stopping the daily hot tub can restore fertility
in many people.
HUBERMAN
I know a number of people that are trying to conceive children that go into the
sauna and they'll just put a cold pack in their shorts or between their legs,
depending on whether or not they're wearing shorts or not when they go in. Or
they'll alternate ice and heat in a way that maintains coolness of the milieu in
which the sperm live. In other words, they're cooling their scrotum deliberately
in order to avoid killing the sperm. Actually, I saw an interesting paper that
said that for every two degree increase in temperature of the scrotum, there's a
20% decrease in spermatogenesis and viability of sperm. And that actually, if
you look at the difference between people who stand a lot, sit a lot, and drive
a lot, what you see is a progressive decrease in sperm count because when people
are sitting, there's an increase in temperature. And then when they're sitting
on the hot seat of the car, or using the heated seats, actually it kills sperm.
I think there are good data on that.
GILLETT
Yeah, excellent data and anecdotally you see it as well. I've had several
patients come in for fertility consultations and all we do is like, you know, no
medications, no supplements. We change their like several lifestyle things. Very
tight-fitting clothing is another one. And soon they have fertility and they're
no longer... they have sperm whereas before they did not. Interesting.
HUBERMAN
I'd like to talk about some of the do's and don'ts, but we have talked about a
lot of do's, things that one can do to optimize hormones. Maybe we could just do
sort of more rapid fire Q&A on some of the don'ts and maybe throw in some
science where you feel it's appropriate. Cannabis, marijuana, THC, yes or no, it
diminishes testosterone levels.
GILLETT
Smoked cannabis, I would say diminishes testosterone, increases prolactin,
that's a no. Other cannabinoids, not particularly harmful. So CBD, CBD, not
particularly harmful. Smoked CBD, I'm not sure.
HUBERMAN
What about edible cannabis and THC?
GILLETT
As far as I know, edible cannabis and THC does not significantly increase
prolactin to a point where it would be disruptive of hormones.
HUBERMAN
Can marijuana, THC, cannabis, whatever you want to call it, increase
gynecomastia, the growth of male breast tissue?
GILLETT
Yes, it certainly can and there's a pretty good association between smoked THC
and gynecomastia.
HUBERMAN
What about nicotine and testosterone and estrogen and other hormones? Smoked
nicotine.
GILLETT
Nicotine is particularly concerning not only for testosterone, but also for
estrogen. Part of it is, if you're talking about nicotine from tobacco, there's
many other carcinogens in it, especially if it's smoked. But nicotine, even if
it is chewed, in a dose-dependent manner, so if you can use an extremely small
amount of nicotine, then it's not as concerning in the long run. But it's a
vasoconstrictor and one of the main concerns with it could be cardiovascular
disease or even microvascular ischemic disease that can lead to
neurodegenerative disease. So like a type of dementia that can be partly due to
nicotine. If you use nicotine for a very long period of time, especially at a
higher dose, it's a dose-dependent effect on your hormone profile.
HUBERMAN
Is that also true for Nicorette and nicotine, other nicotine gums?
GILLETT
At high doses, if you can use an extremely low dose of a nicotine gum, then
theoretically that would be maintainable. It's not going to overload the
nicotinic receptor. You have acetylcholine and the cholinergic system as one of
your main nervous systems, of course. And you have muscarinic receptors and
nicotine receptors. And there's just better ways to optimize your nicotinic
receptor activity. For example, acetylcholine precursors like alpha-GPC,
phosphatidylserine, phosphatidylcholine. Acetylcholinesterase inhibitors,
especially natural ones, potentially have a part as well. And then other
alkaloids. So nicotine is an alkaloid from the tobacco plant. There's other
plants like cytosine and that genus of plants, and that alkaloid is also a
nicotine receptor agonist.
HUBERMAN
Is it true that cycling for too long, literally bicycling, sitting on a bike
seat too long can damage the prostate?
GILLETT
Yes, it can be very concerning, especially if you're seated while cycling,
especially if you're putting a lot of pressure on the perineum. Your core is
kind of like a box where your diaphragm sort of makes the top and your abs and
serratus make the front and the sides, your back muscles make the back, and then
your pelvic floor makes the bottom of the box, which is arguably the most
important part of your core. And that pressure can weaken and even lead to
incontinence and impotence.
HUBERMAN
So we were talking earlier today in the gym about how heavy leg work, hack
squats, deadlifts, those kinds of things that a lot of guys are doing to
increase their testosterone done correctly can actually augment and build up the
strength of the pelvic floor done incorrectly can actually weaken the pelvic
floor and lead to all sorts of issues, including sexual effects, negative sexual
effects. So how does one go about learning whether or not their movements are
being done properly to support pelvic floor or to destruct pelvic floor?
GILLETT
The pelvic floor is a constellation of muscles just like any other kind of like
system in the body. And, you know, form is important if you're doing the
Valsalva maneuver, which again is that kind of like bearing down or deep breath
where you feel all of your abs are tight. You can also notice that your pelvic
floor is tight as well. If you have a history of an inguinal hernia, which is a
hole kind of like connecting the abdominal cavity down through the pelvic floor
or even the scrotum in some cases, and that can be a sign that there is weakness
in that area and you might have to concentrate on it most or even have a
physiotherapist or a physical therapist specifically target the pelvic floor.
Many exercises in which you Valsalva or use your glutes or legs, you can learn
to squeeze them and have that mind muscle connection in order to help build up
the pelvic floor. And there's other things, many people are familiar with
Kegels, that is just one of the many different exercises that can help your
pelvic floor.
HUBERMAN
My understanding is that while strengthening the pelvic floor is good, excessive
contraction of the pelvic floor can actually limit blood flow to the pelvic
area, the penis and so forth. So this is, again, it's a double-edged sword,
right? I mean, you don't want guys out there to just start doing endless number
of Kegels every day because they're actually gonna constrict blood flow to that
area, right? There's a, and in fact, the erection response is parasympathetic.
It's a relaxed induced response, right? Correct. So, you know, for the reason I
chuckle is that, you know, because we're talking about things, we don't have
visuals or charts, and certainly it's hard to know whether or not a given
exercise like Kegels are gonna be good or not good. If it's excessive, what, you
know, how many sets and reps does it take before it goes from good to bad? Is
there a kind of general rule of thumb for people to think about this? I mean,
clearly blood flow to that area is key, right, for sexual performance, and yet
when one trains the legs or even walks, you're getting blood flow. So my
understanding is this, that a combination of weight training to stimulate the
positive hormonal and muscular and connective tissue growth is key, provides not
overtraining, but so is casual exercise like walking and stretching and the
sorts of things that will then return blood flow to that area. Is that an overly
basic way to think about it, or will that suffice?
GILLETT
I think that's a good way to think about it. I think the main point with Kegels
is they're just one of many different things. So if you're having some pelvic
floor pathology certainly or even just concerned about your pelvic floor, don't
just take the advice, do Kegels and you'll be okay. That is not near enough.
It's just one of the many aspects.
HUBERMAN
Okay, so going back to the rapid Q&A and then we'll come back to this issue of
blood flow because there's some interesting science and protocols there.
Question I have is alcohol, does it increase aromatase, the enzyme that converts
testosterone into estrogen or not? And is there a dose dependence there?
GILLETT
It significantly does. There is a dose dependence in general. I would not
recommend more than three to four, you know, standard drinks. One huge glass of
wine is probably five standard drinks, but I would say everyone should try it.
HUBERMAN
every two weeks. Yeah, that's consistent with what I discovered researching
alcohol in an episode we did on alcohol, that no alcohol is definitely better
for all aspects of health than any alcohol. And anyone that says that, well, red
wine contains these various things, well, it doesn't contain enough of those
positive things to have a positive effect. But that if people do opt to drink
alcohol, that two drinks per week, and meaning 20 grams of alcohol, so that's
probably two 12 ounce beers or two four ounce glasses of wine is going to be the
upper limit beyond which you're going to start seeing all sorts of negative
effects.
GILLETT
The other thing to keep in mind with alcohol is it has a lot of calories, seven
kilocalories per gram, almost as much as fat, which is nine. And then it's also
very GABAergic, so it can activate inhibitory neurotransmission. And that can
also affect how much LH and FSH is released, so that can also decrease
testosterone, almost kind of similar to how opiates can decrease testosterone.
HUBERMAN
I feel very lucky that I don't enjoy alcohol, never really did, can kind of take
it or leave it. Certainly don't like sedatives like Valium or anything like
that, which as you just mentioned can suppress testosterone. You said the word
fat, so I'm going to pick up on that and say, in order to optimize hormone
production, is it important to have some saturated fat in one's diet? And what
happens on very low fat diets to testosterone, estrogen, and other steroid
hormones?
GILLETT
Fat's interesting because there's so many different beneficial fats, omega-3s.
Almost every American gets plenty of omega-6s in any developed country, really.
When it comes to saturated fat, there is more of a correlation with hormone
optimization. If you're eating things with saturated fat, you tend to have,
those are things with more, you know, fat-soluble vitamins and things that are
very nutrient-dense otherwise, but it is not vital. In general, you want to
eliminate any trans fat unless it's trans fat from the ruminants. There's always
an exception to everything, right? So there is healthy trans omega-3 fats, which
are formed in the stomach of like grass-fed and finished ruminants.
HUBERMAN
But ingesting mostly olive oils, maybe nut butters in limited amounts because
they're very calorie dense, but unless people are trying to increase their
calories, in which case they're a great source of calories. Small amounts of
butter or ghee, probably okay, but not excessive amounts. Is that the idea?
Okay.
GILLETT
Is that the idea? Correct, yes. Fat is perfectly fine. Cholesterol has an
interesting, so cholesterol and in general phospholipids make the bilayer that's
around the cell. But cholesterol is also a hormone in and of itself because it
binds to the estrogen-related receptor alpha. So I consider that like in the
estrogen receptor category and that can help with metabolism, but also
potentially have concerns for cancer and tumor risk.
HUBERMAN
you
HUBERMAN
I want to go back to the prostate and talk to you about something that's kind of
a newer emerging trend. I know that you've talked to a little bit about this in
previous podcasts, that a number of men, or I should say a number of physicians
are prescribing low dose Tadalafil, also known as Cialis, to their male
patients. So in dosage ranges of like 2.5 milligrams to five milligrams per day,
but not for erectile dysfunction, but rather for improving prostate health. And
presumably they get sort of a boost in terms of blood flow to the genitalia as
well. But again, not specifically a deal with erectile dysfunction, but to deal
with prostate health and blood flow to the prostate. Is that something that you
sometimes often prescribe to your patients and of what age?
GILLETT
Tadalafil is a very underrated medication. The age would kind of depend on the
indication. So Tadalafil is also a blood pressure medication. It can very
slightly decrease blood pressure, especially at higher doses. At higher doses, a
high dose would be 20 milligrams, not 2.5 milligrams. But consistently, it can
somewhat affect with the cones in the eye that have to do with red and green
sight. Although if you remove it, that effect is reversed. So basically, if you
don't need really, really good red-green discrimination, you can take higher
doses. But in general, I recommend no higher than 10 milligrams a day, usually
just two or five milligrams. One other benefit or other use of Tadalafil is that
it increases the density of the androgen receptor, similarly to L-carnitine. So
that's an interesting benefit. Another benefit is that if you give it to people
with nocturia, which is urinating at night in general, it will cut the episodes
in half. So it could go from two to one, which can make a big difference for
your sleep, which will secondarily make a big difference for your growth hormone
and testosterone optimization.
HUBERMAN
Interesting. So you said 2.5 to 5 milligrams per day is typical for these
prostate enhancing effects. Yes. And you mentioned the potential side effects on
adjusting visual perception. As a vision scientist, that rings in my mind. But
in terms of red-green color discrimination, I'm guessing unless you're going to
be a subject in one of the experiments in my lab or you want to be a fighter
pilot, chances are you can probably get away with a little less red-green color
discrimination.
GILLETT
Correct. It's not considered clinically significant unless someone is a
commercial pilot. Right. So if someone's getting their like pilot exam, that's
one of the things we look for.
HUBERMAN
Great.
HUBERMAN
Okay, so commercial pilots aside, you might want to ask your doctor about low
dose to Dalafil for sake of enhancing prostate health. Certainly monitoring PSA,
prostate-specific antigen is important. I can give an anecdote there. When I
tried Cermoralin, one of the surprising side effects that was not welcome was a
dramatic spike in my prostate-specific antigen. No one could explain to me why
that would happen. But when I stopped taking Cermoralin, it went back to normal.
So it's one reason I avoid Cermoralin. At least frequent use of Cermoralin. PSA
should be kept, what, below levels of, you know, somewhere between one and four
is considered healthy, is that right?
GILLETT
It depends on the age, if there's a 20-year-old, likely between 0 and 1. If
there's a 40-year-old, likely between 1 and 3. And then if there's an
80-year-old, it would not be abnormal to have a PSA of 5 and have that be well
within the reference range. Another thing we should mention about PSAs, if you
do take a 5-alpha reductase inhibitor like finasteride or dutasteride, often
these will cut your PSA in half. For example, if you have a PSA of 6 and you
start finasteride or dutasteride and then you recheck it in 6 months and it's
6.5, that is a huge concern because that's actually doubled.
HUBERMAN
I'm glad you brought this up because I almost overlooked the fact that I get a
lot of questions about drugs to offset hair loss. Most of those drugs are going
to operate through the DHT system, the dihydrotestosterone system for the
reasons we talked about before, DHT receptors being on the scalp and causing
beard growth on the face. Is it the case that a number of people taking things
like Propecia and other things to block the DHT or disrupt the DHT pathway are
going to experience diminished sex drive, diminished kind of motivation and
general vigor? And if so, are there alternatives like topical DHT antagonists
that they might use if they want to keep their hair but not have those negative
effects?
GILLETT
The way that I think about hair loss is you have your fertilizers, also known as
a growth agonist, and then you have your anti-androgens. Whether they're
systemic or topical, there's both, but that's the general layman's way to think
about hair loss. If you're only putting fertilizer in your hair, but you have
androgenic alopecia or male pattern baldness, then those hairs will still
miniaturize and eventually you'll still have loss. Such a great way.
HUBERMAN
word, miniaturize. It's enough to send anybody off to find a therapeutic, right?
GILLETT
And by the way, it's difficult to tell if miniaturization is happening unless
you have a magnifying glass. You can use a- Yeah, yeah. For a second.
HUBERMAN
For a second there, I didn't know whether or not you were making a joke. You're
talking about miniaturization of the hair follicle. Correct. So what can reverse
that miniaturization? That's just a fun word to say. I'm going to just keep
saying it.
GILLETT
Correct. Yeah.
GILLETT
Each individual has, again, we mentioned the androgen receptor. Males only have
one androgen receptor gene. It's on their X chromosome. So depending on how
sensitive that androgen receptor is and depending on the density of the
receptors in the hair follicle, you can have an arbitrary threshold and you
don't know what this threshold is until you start to have miniaturization and
loss of hair. But over the threshold, the follicle will die and eventually the
stem cell will leave. But under the threshold, you're okay. Every androgen binds
to the same androgen receptor. So there is nothing special about DHT. DHT is
just a stronger androgen. So the higher your SHBG, things that increase SHBG,
are beneficial for hair loss prevention because you have less binding of that
receptor. So if you think about hair loss, specifically androgenic or male
pattern baldness in the terms of that androgen receptor and everything in
general binding to it, not just DHT but also testosterone, it's helpful. It's
just that DHT is a huge battering ram whereas the other androgens are just light
presses on the door.
HUBERMAN
Got it. So are some of the topical DHT receptor antagonists going to be a better
choice for people that want to maintain their hair or grow more hair if they
want to avoid side effects?
GILLETT
Likely so, some individuals benefit from systemic, a systemic decrease in DHT
for a couple of reasons. One could be prostate, and then one could actually be
hypertrophy of the myocardium. So DHT also disproportionately thickens the
ventricle. So for someone on TRT, that might be a benefit that is prone to
thickening of the ventricle at baseline. However, many people that have just a
bit of predisposition, they can use things that are topical anti-androgens.
Ketoconazole is one of them. Caffeine is actually another one. Wait, drinking
caffeine?
HUBERMAN
topical caffeine. Oh, I was going to say, my hair tends to grow pretty fast. So
it might be that, but I drink a lot of caffeine. So topical caffeine, really
rubbing coffee on their head or taking caffeine tablets. And how does it wait?
You have to explain how this works. How do people get caffeine into the hair
follicle?
GILLETT
Topically, the caffeine enters the scalp and crowds out, like somewhat crowds
out the androgen. It is a weak effect. It's likely just strong enough to be
clinically significant. Usually caffeine is put into formulations with other
things like ketoconazole that are also weak anti-androgens. Of note,
spironolactone can be prescribed topically, but it is absorbed systemically
because the size of the molecule. So unless your doctor specifically prescribes
that for you, especially as a male, do not use topical spironolactone. Topical
finasteride is also a smaller molecule. So it is also systemically absorbed, but
it is not extremely well systemically absorbed. If you take topical finasteride,
then usually your systemic DHT will decrease by about 30%. Topical dutasteride
is likely a tiny bit systemically absorbed, but it's unique because it's
half-life is much faster at a lower dose. So topical dutasteride will not affect
your systemic DHT at all. And I've seen this anecdotally on many people on
topical dutasteride therapy.
HUBERMAN
We're going to have to get you back on here and do an episode all about DHT and
hair loss and hair growth is, you know, again, not a topic that I focus on a lot
for myself, but that I get a lot of questions about for men and women.
GILLETT
One thing that we could mention I got a ton of questions about turmeric and
curcuminoids after last episode
HUBERMAN
Oh yeah, but I had reported my own anecdotal experience that taking turmeric
really crushed my DHT levels and I did not feel good. I mean, it crushed all
sorts of positive feelings of vitality. The moment I stopped taking turmeric,
felt great again.
GILLETT
Many people report this and the interesting thing about tumeric is most of its
beneficial action, not all of it, some people benefit from systemic tumeric and
some people that can tolerate it well, it's actually great for the prostate. But
most of the action, it does not need to be bioavailable. It acts on the gut
microbiome. So you can take tumeric and if it is not absorbed, some tumerics is
put in special formulations like micellar, liposomal or complexed, but a lot of
it is put with black pepper fruit extract, which is also known as bio-purine,
which is actually also a 5-alpha reductase inhibitor and it affects liver
cytochromes. And so many supplement companies put this black pepper fruit
extract, bio-purine in almost everything. So some people are on really high
doses and that could also be making most of the effect of people who do not
tolerate tumeric well.
HUBERMAN
Yeah, I avoid turmeric like the plague based on that one previous experience
because it was clearly turmeric that caused the negative effect coming off it,
everything reversed rapidly. And the bio-purine, the black pepper extract, I
also avoid that like the plague based on everything you just said. I want my
five alpha reductase, I want my DHT to be optimized simply because my
understanding is DHT is the more powerful androgen and it's the one that, yes,
it causes a little bit of hair loss, and I've got a few patches here and there,
but I'm willing to live with that based on all the other wonderful things that
DHT optimization does.
GILLETT
I'll quickly mention a few other things. One, salpalmetto is also a
5-alpha-dexase inhibitor, but only a couple of the isoenzymes. There's three
main isoenzymes, and a lot of the problem is that you're inhibiting a couple of
the isoenzymes, but not the other one. Finasteride inhibits one and two.
Dutasteride actually inhibits all three. And finasteride inhibits the isoenzyme
that is in genital skin, but not in the skin throughout the rest of your body.
So a lot of the side effects of finasteride, which is loss of sensation and loss
of erectile function, have to do with the disconcordance between the sensitivity
of the genital skin and the skin.
HUBERMAN
And again, another reason to not disrupt 5-alpha reductase. And we'll definitely
get you back on here to talk about D, I think we should just do a whole episode
about DHT, because so often when people are thinking about optimizing hormones,
especially males trying to optimize their hormones, they're thinking
testosterone, testosterone. Maybe nowadays they think a little bit more about
free testosterone, and maybe they think about estrogen as also being important
not to crush estrogen, but DHT is, you know, at least to my mind, the linchpin
of so many of the things that subjectively people are really focused on, libido,
motivation, drive, et cetera. I have one final question, it's just a brief one,
but many of us have heard that the BPAs that are present in, you know, plastic
bottles and even in certain aluminum cans, and phthalates, a difficult word to
pronounce, but a fun one nonetheless, phthalates and work by Dr. Shana Swan has
shown that phthalate exposure to the fetus, to pregnant mothers and the fetuses,
very likely is negatively impacting sperm counts, testosterone levels, and even
changing genitalia size for the worse in males nowadays. I saw a beautiful
lecture that Dr. Shana Swan did on this when I was in Copenhagen, and it's very
clear that it's negatively impacting the male fetus. She was also on Joe Rogan's
podcast. I hope to get her on this podcast. However, what she couldn't answer
for me was whether or not phthalates and BPAs and these things present in
plastics, and some people would claim in tap water, are bad for males after
they're born and after puberty. What are your thoughts on, or I should just ask
you, do you drink water out of plastic bottles? Do you avoid drinking out of
cans that are not specifically non-BPA containing cans? And do you actively
avoid phthalates? My understanding is that phthalates are most enriched in
pesticides, and that's why you're seeing dramatic drops in sperm and
testosterone levels, mainly in rural areas where they're dust cropping.
GILLETT
Yeah, so I do avoid drinking out of cans that are plastics that may have BPA or
bisphenol A in them. Bisphenol A is known to bind to what I would consider the
fifth estrogen receptor, estrogen-related receptor gamma. So I would consider it
a xenoestrogen. So phytoestrogens are estrogens from plants and in general,
they're not concerning or clinically significant and xenoestrogens are just
other estrogens. So I do avoid BPA and I also test my water. I use a water
testing service and I test it both after it's through my water filter and the
tap water that my two boys drink almost every day. And it was very interesting.
I only found one microplastic just a bit over the reference range. So it wasn't
a terrible tap score, but even in developed countries, these are widely
variable. As far as pethylates, again, very difficult and interesting to
pronounce, but I remember learning about these because there was, I believe, a
lawsuit that had to do with mac and cheese. And this was probably five years ago
and I was coming up with my list of, each provider that does obstetrics has a
list what to avoid for the pregnant lady, sketchy deli meats or high mercury
fish like swordfish and salmon. And I actually added processed mac and cheese to
that list. And it was very interesting.
HUBERMAN
Well, thank you for that. I'm going to extract your statement that you avoid
drinking out of plastic bottles when possible. I'm guessing you're not
neurotically attached to that. If you were dying of thirst, you might crack a
plastic bottle of water to survive. But listen, Kyle, Dr. Gillette, thank you so
much. You gave us an enormous wealth of knowledge, everything from behaviors to
psychology, to supplementation, to prescription drugs. We will make sure to
point out where people can get ahold of you on Instagram and on Twitter and on
other websites in our show note captions. But really just on behalf of the
audience and just for myself, thank you so much. You have an immense amount of
knowledge and you're exquisitely good at sharing it with people in an actionable
way. So thank you. My pleasure.
GILLETT
Yup.
GILLETT
My pleasure.
HUBERMAN
Thank you for joining me today for my discussion with Dr. Kyle Gillette, all
about male hormone optimization. And I just want to remind everybody that we
will soon have an episode all about female hormone optimization. If you're
learning from and are enjoying this podcast, please subscribe to our YouTube
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Huberman Lab on all social media platforms. During today's episode and on many
previous episodes of the Huberman Lab podcast, we discuss supplements. While
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Dr. Andrew Huberman is a neuroscientist and tenured professor in the department
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