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. Sarah Gottfried.
Dr. Sarah Gottfried is an obstetrician gynecologist
who did her undergraduate training in bioengineering
at the University of Washington in Seattle.
She then completed her medical training
at Harvard Medical School,
and she currently is a clinical professor
of integrative medicine and nutritional sciences
at Thomas Jefferson University.
She has also been a clinician treating men and women
in various aspects of hormone health and longevity
for more than 20 years.
She is an expert in not just traditional medicine
as it relates to hormones and fertility,
but also nutritional practices,
supplementation, and behavioral practices,
and combining all of that expertise
in order to help women navigate every aspect
and dimension of their hormones, longevity, and vitality,
ranging from puberty to young adulthood,
adulthood, perimenopause, and menopause.
And nowadays, she’s also treating men across the lifespan
in terms of longevity, vitality, and hormone health.
During today’s discussion,
Dr. Gottfried shares an enormous amount of information
and tools that women can apply toward their hormone health,
fertility, vitality, and longevity.
We discussed the gut microbiome,
which many people have heard about,
but Dr. Gottfried points out the specific needs
that women have in terms of managing their gut microbiome
and the ways that that influences things
like estrogen levels and metabolism,
testosterone, thyroid, and growth hormone, and much more.
We also discussed nutrition and exercise.
We touch on how the omega-3 fatty acids
play a particularly important role
in managing female hormone health.
Dr. Gottfried points out why women have particular needs
when it comes to essential fatty acids
and how best to obtain those essential fatty acids
for hormone health.
We also discuss exercise,
and she offers some surprising information
about the types and ratios of resistance training
to cardiovascular training that women ought to use
in order to maximize their hormone health.
We also talk a lot about the digestive system.
This was a surprising aspect of the conversation
I did not anticipate.
Dr. Gottfried shared with us, for instance,
that women suffer from digestive issues
at more than 10 times the frequency that do men.
And fortunately, that there are tools specific to women
that they can use in order to overcome
those digestive issues,
and that in overcoming those digestive issues,
they can overcome many of the related hormone issues
that so many women face.
Dr. Gottfried also shares with you tremendous knowledge
about the specific types of tests, not just blood tests,
but also urine and microbiome tests that women can use
in order to really get a clear understanding
of their hormone status, not just of present,
but also where the trajectory of their hormones
is taking them.
So we have an avid discussion about puberty,
about young adulthood, adulthood, perimenopause,
and how best to manage and navigate perimenopause
and menopause, including a discussion
about hormone replacement therapy.
In addition to her academic and clinical expertise,
Dr. Gottfried has authored many important books
on nutrition, hormones, and supplementation
as it relates to women and to people generally.
The two books that I’d like to highlight
and that we provided links to in the show note captions
are Women, Food, and Hormones, and The Hormone Cure.
I read The Hormone Cure and found it
to be tremendously interesting and informative,
not just in terms of teaching me about female hormone health
and various treatments for female hormone health,
but also as a man trying to understand
how the endocrine system interacts with mindset,
nutrition, and supplementation more generally.
So I highly recommend The Hormone Cure
for anybody interested in hormones and hormone health
and Women, Food, and Hormones in particular for women.
Although again, both books are going to be
strongly informative for women wishing to optimize
their hormone health, vitality, and longevity.
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.
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And now for my discussion with Dr. Sarah Gottfried.
Dr. Gottfried, Sarah, welcome.
Thank you, so happy to be here.
Yeah, I’m delighted and very excited to ask you
about an enormous number of topics.
You are expert in so many things.
So the challenge for me is going to be
to constrain this walk as it were,
but I’m hoping that we can touch on
a great number of things today.
The first of which is really about hormones
and female hormones in particular.
And I have a question which is,
is it ever informative for a woman regardless of age
to know something about her mother’s,
perhaps even her grandmother’s experience
Not just pregnancy challenges with,
or ease with pregnancy and child,
rearing childbirth, this sort of thing,
but what sorts of conversations
should women be having with themselves
and with family members to get a window
into what their specific needs might be?
Love this question.
So my work is really at the interface
between genetics and empowerment.
So your question gets to both.
And I think it’s essential that you understand
what your grandmother went through.
I’d even say your great-grandmother,
depending on longevity in your family.
So I grew up with my great-grandmother, I get that.
And especially your mother.
So I would probably start first with trauma
and intergenerational trauma,
because I think that affects the endocrine system so hugely,
especially cortisol signaling,
but the broader pine system,
And then there’s, if I think about the stages,
the life cycle that a woman goes through,
if you think about puberty,
I think, I don’t know how genetically determined
the age of puberty is.
Certainly there’s a lot of environmental influences,
like toxins can affect it.
But pregnancy, the age at which you start
to go through perimenopause menopause,
many of those have a genetic component.
So with pregnancy, I mean, you can certainly think
the shape of the pelvis,
your ability to have a vaginal birth.
Some of that is genetically determined.
I mean, you do have the sperm donor affecting some of that.
But in my family, for instance,
we have no cesarean sections.
So everyone goes through this process
of a relatively easy vaginal birth.
I was a forceps baby, but for the most part,
you can find out about that.
And then there’s certain female conditions
that have a very strong component genetically,
most of which run in my family.
So that includes endometriosis, fibroids.
I just had a hysterectomy.
I had 50 plus fibroids and polycystic ovarian syndrome.
And of those three, how frequent are those?
And maybe I can constrain the question a little bit
by saying today’s discussion I imagine is gonna be heard
by men and women of all sorts of ages.
So maybe I’ll direct the question a little bit
toward at what age should these discussions start?
We always imagine that women in their 30s and 40s
and 50s and onward should be getting certain tests
and addressing things like ovarian reserve
and other sorts of things.
But maybe we could march through and just say
for a woman in her teens who’s already hit puberty,
what sorts of biomarkers,
whether or not they’re blood-based or phenotyping,
the outward appearance of,
should those young women be paying attention to?
Likewise for women in their 20s, 30s,
maybe we could take it more or less by decade
starting at puberty.
Assuming that woman hits puberty sometime,
what between what is it now?
The average in the US is somewhere
between 12 and 16 years old.
Do I have that right?
No, you do not.
I love to be wrong, so.
So it used to be 12 to 16.
I would say 50 years ago.
It’s been moving younger.
And we think some of that is related to toxin exposure
as I mentioned, but I was 10 when I went through puberty.
So, well, I should say menarche
and I started growing breasts much before that.
So I think now I’m gonna step away
from the science for a moment.
I’m gonna do that pretty fluidly
and I’ll try to call it out.
I think there’s also a huge influence from stress
and like the development of the adrenal glands.
So going back to the science,
the issue in teenage years
is that the hypothalamic pituitary adrenal axis,
and I like to think of it broader.
So stay with me.
Hypothalamic pituitary adrenal,
gonadal of recent women, testes of men,
thyroid, gut axis.
So that to me is the control system.
So I’m kind of expressing my bioengineering side here.
Well, I think it’s great to include the other organs
and tissue systems of the body,
because as we both know that the narrow definition
of just hypothalamic pituitary adrenal,
it can’t be just that, right?
No. It can’t, right?
It doesn’t tell the whole story.
So if you look at the main sex hormones
in a young woman who’s in her teenage years,
the hypothalamic pituitary adrenal gonadal part of that
is not fully mature.
So they’re more likely to skip periods,
especially under stress.
They have a lot of influences.
It really doesn’t get well-established
until you’re done with adolescence.
And I’m told that adolescence now
is till like age 25 to 26.
I heard that and I was like, I’ve got two daughters.
And I was thinking, that’s a really long time.
Not just psychologically defined or biopsychosocial?
Mostly psychologically defined.
I heard that from a psychologist.
So biomarkers you asked about.
In your teenage years, what I think is really interesting
is to look at cortisol.
To look at the dance between estrogen and progesterone
in those years is less helpful,
because I think there’s a lot of variability
due to the immaturity of the system.
If you’ve got someone who’s got really regular periods,
it’s probably better to do some benchmarking at that age.
But generally I find that benchmarking
is best performed in your 20s or 30s.
Are periods not that regular in terms of duration
of the menstrual cycle
when the menstrual cycle first sets in?
So I was like clockwork every 28 days
until I had my hysterectomy in August.
Same thing with my daughters.
I’ve got two daughters.
One’s 17, the other’s 23.
For a lot of women, they’re not regular.
And then there’s the whole piece of oral contraceptives
and other forms of contraception
where you have no idea what the normal cycle is.
And I hope we’ll have some time
to talk a little bit about oral contraceptives,
because I think it is,
this is now opinion again and not science,
I think it is the number one endocrinopathy
that is iatrogenic for women.
I get a lot of questions about oral contraceptives
in the social media space
and also questions about IUDs quite a lot.
In particular, copper IUDs, non-hormonal IUDs.
So we will definitely touch on that.
I’m an IUD crusader,
so I just want to give you that warning.
You’re a fan, do I have that right?
Or you’re anti-IUD?
I am a huge fan.
Which IUDs in particular?
So I like copper because it’s non-hormonal.
It’s as effective as getting your tubes tied.
Who would have thought?
I mean, it’s that toxic to the sperm mobility,
is that how it works?
That’s my understanding of it,
is that it basically,
it’s like more or less an electric fence to the sperm cap
and just, that’s it.
Electric fence is a bit of a harsh analogy,
but I’ll work with that.
But it’s, you know,
to have something that can last for 10 years
so that you really have complete autonomy
and sovereignty over your sexual life,
And to not get all those downstream risks
that are associated with the birth control pill.
The other thing that’s important to know about it,
I know this is a sidebar,
women who use the copper IUD
have the highest satisfaction rate
of anyone on contraceptives.
The highest satisfaction rate.
And yet, it is the least used
of all forms of contraception.
Now, my favorite is vasectomy,
but short of vasectomy,
I think the IUD is a really great choice.
There are some risks associated with it,
I’m not saying it’s risk-free,
but I love the IUD.
And I love it for younger women too,
because it used to be that
when I went through my training,
which was 30 years ago,
we were told, you know,
don’t put it in someone who hasn’t had a baby.
And that is patriarchal messaging.
But getting back to your original question,
which is about biomarkers per decade,
in your 20s,
that’s when you want to do some base casing
with estrogen, progesterone, and testosterone.
So I think it’s really helpful
to know about this tango.
You’re from Argentina, or your father is.
I have Argentine lineage.
My grandparents did tango into their late 80s.
I’m in my late 40s and I still haven’t started.
So I suppose there’s time.
It might be time for you to look at that.
And it might be a factor in their longevity.
Did they have good healthspan?
Not just lifespan?
And my grandfather smoked cigarettes daily,
remained mentally sharp until he died in his late 90s,
but almost burned down their apartment several times
falling asleep with a cigarette in his mouth.
So I don’t recommend anyone smoke, by the way.
But it was coffee, mate, red meat, and cigarettes,
and they lived into their 90s.
That side of my family has the genetic advantage.
The other side, less so.
But in any event, tango is a 2023 goal.
It has been every year.
I’m gonna hold you accountable to that.
Okay, will do.
And there will be no YouTube video of me doing tango.
At least not initially.
Tim Ferriss, actually, a phenomenal podcaster, as we know.
He’s a bad-ass tango.
He’s a bad-ass tango dancer.
I know this through various sources.
Yes, I’ve seen.
Yeah, so this tango between estrogen and progesterone
is incredibly important.
You wanna have the right lead,
you wanna have the right follow between the two hormones.
Again, I’m stepping away from my science hat.
But what happens a lot of the time
is that estrogen dominates in that tango.
And when that happens, it sets you up
for greater risk of fibroids, endometriosis, breast pain,
probably in association with the microbiome
and the oestrobilome.
Can you familiarize me with the oestrobilome?
I’m delighted to know that I don’t recognize the term.
Yeah, so the oestrobilome is the set of microbes
in, and their DNA, their DNA mostly,
in the gut microbiome, that set of microbes in their DNA.
So it’s in the, if you look at the totality,
the subset of particular bacteria modulate estrogen levels.
So a lot of this work was spearheaded by Martin Glaser.
And what we know is that there are some women
who have an oestrobilome that makes them have a greater risk
of certain estrogen-mediated conditions
like breast cancer, endometrial cancer,
and in men, prostate cancer.
So the oestrobilome is incredibly important.
There’s not a lot of attention paid to it,
but I always think in terms of my patients,
could this be someone who’s got a faulty oestrobilome
and we need to adjust it with some of the microbiome
modulating nutrients, nutraceuticals that we have
so that they’re less likely to have that tango
that’s not working with estrogen and progesterone.
So getting back to the biomarkers,
if you gave me an unlimited budget,
which I kind of have with some of my clients
that I work with now, what I would wanna know
is estrogen, progesterone, testosterone,
and I want the timing right for that.
I’d wanna know about DHEA
and sort of the whole androgen pathway.
I’d wanna know about the metabolites of estrogen
because some of them are protective and very helpful.
Others are a bit like Homer Simpson.
I mean, they are just like causing all kinds of problems
in your body, increasing the risk of quinones,
like DNA damage,
and potentially an increased risk of breast cancer,
although that data I think is mixed.
I’d also like to know about their stool.
So I wanna know about the microbiome.
So the best that we have right now is to look
when we do stool testing, and I do a lot of stool testing.
We can look at things like beta-glucuronidase.
Are you familiar with BG?
I’m familiar with it as a term.
And so for those listening, very often,
not always when you hear an ACE, A-S-E,
you’re dealing with an enzyme.
So we can take a stab there.
And it sounds like it’s somehow involved
in glucose metabolism of some sort, or is it?
Glucuronidase, so it’s involved in,
when you produce estrogen in the body,
this is like the simplified version,
but when you produce estrogen, you are meant to use it,
like send it to the receptors where it’s meant to go,
and then lose it.
Like you don’t wanna keep recirculating estrogen
like bad karma, and that’s what happens
with people who have high beta-glucuronidase.
So it’s this enzyme that’s produced by three bacteria
in particular in the gut.
And I see a lot of men and women
who have elevated beta-glucuronidase,
and then they have some estrogen dominance related to that.
Is that the total reason?
We don’t really know, but it’s one of the drivers.
It’s one of the levers.
And it can be detected from a microbiome,
aka stool sample.
And in terms of blood testing or various tests
for these other biomarkers,
getting estrogen, testosterone, and other ratios,
I realized people have different means, financial means,
but in general, people wanting to do a blood test,
it sounds like they’re going to need to do it.
Women will need to do it
at different stages of their menstrual cycle.
If they had to pick one,
either in the follicular phase or in the luteal stage
of their ovarian menstrual cycle,
excuse me, ovulatory menstrual cycle,
when would you suggest they do that,
if they had to pick one?
So if you forced me to pick one,
I would say probably day 21 to 22 for someone in her 20s.
So we’re focused right now on that decade.
So for most women, they’ve got a menstrual cycle date
that averages out at 28 days.
So this is about a week before they start their period.
For women who are more regular, it’s harder to do that.
As women get older, and we’ll talk about this in a moment,
usually the cycle gets a little shorter.
So as they start to decline in their progesterone production,
their period gets a little closer together.
Like mine before August was about every 26 days.
So at that point, you want to test sooner, like day 19, 20.
And I’m not talking about blood tests.
So a blood test is the cheapest thing.
It’s usually what’s covered by insurance.
But my preference would be to do dried urine.
I like to use saliva for cortisol.
I like to use dried urine so that I get metabolomics
in addition to the levels of these hormones.
And if I’m forced to, I’ll use blood testing.
And that’s certainly the gold standard
for all of these hormones that we’re talking about.
But it’s not as comprehensive.
And as you know, it’s a quick little snapshot
while the needle’s in your vein for 30 seconds.
Yeah, the salivary cortisol makes sense to me
because my understanding is that you get free cortisol,
which is the active cortisol.
You said with urine, you’re also getting the metabolites.
And then for blood testing,
you’re getting sort of a crude window into the averages.
A static total level.
So let me go back and say one other thing about biomarkers.
A big part of the testing that I do
in phenotyping my patients, I practice precision medicine.
So I like to almost start with nutritional testing.
I don’t think I’ve ever had a teenager.
I’ve got some NBA players that are 19, 20, 21.
So maybe those count, but those are men, obviously.
But for nutritional testing,
that would be potentially a helpful thing to do
in your 20s.
Becomes less important as you get older
and you develop more micronutrient deficiencies.
But micronutrients play a huge role
in terms of hormone production.
Magnesium is hugely involved
in the way that you get rid of estrogen.
That’s an example.
So micronutrient testing,
what I usually do is a combination of blood and urine.
And so I’m looking at all of the micronutrients
that we can measure
that have some clinical scientific basis behind them.
If I could do that for a teenager,
I think it might be helpful
because I recently gave a lecture
on breast cancer risk reduction.
Another quick sidebar.
And I was sad to find that intake of vegetables,
polyphenols, is such an important predictor
of future risk of breast cancer,
like when you’re 50, 60 plus.
And the most important time is when you’re a teenager.
Now I have one daughter that eats vegetables.
She loves them.
And I have another daughter who eats food that’s beige.
And it’s very hard to get her to eat
the volume of vegetables,
five colors a day, which is what I do.
And if you have evidence
that you could show a 17-year-old
that they’ve got micronutrient gaps,
I think that would be a motivator
for them to eat differently
at a time when it’s so critical.
Even though it’s 25 years in the future
that it’s gonna potentially change this arc that they’re on.
What do you do for a young woman
who doesn’t like vegetables
or is not somehow able or willing
to get those five colors a day of vegetable
to help support the microbiome?
Are supplements a useful tool in that case?
What other sorts of tools,
behavioral or otherwise, are useful?
Such a good question.
So here I’m gonna invoke Rob Knight at UCSD.
So I think his gut project
has really been helpful
in terms of understanding
what kind of modulators are gonna be important.
So what I try to get that person to do,
and I don’t see many teens anymore
other than MBA players,
what I try to get them to do is to have a smoothie.
Very hard to get them to have a smoothie every day.
But if I could get them to have a smoothie
three times a week
and to throw some of these vegetables in,
that makes a huge difference.
I mean, we know that makes a difference
in terms of microbiome change.
So you’d be blending up broccoli or kale.
So cauliflower is great.
Even they’re putting things into the smoothie.
Yeah, I don’t know if you can get a teenager to do that,
but they often will use,
like I have them do steamed broccoli that’s in the freezer
because it’s got very little taste.
So that they could do that in a chocolate smoothie.
They could add some greens.
I like greens.
Powders are super convenient.
So that with kind of a taste that they like,
whether that’s chocolate,
which is what most of my clients want,
or vanilla with berries and that sort of thing.
So that can go a long way if you don’t like vegetables.
And short of that, I would say some supplements,
but I would say that’s a distant second to making a smoothie.
I’ve got one patient that I have to mention
because he took this to the extreme.
So he is a retired physicist professor at UCSD.
He found out that his microbiome was a hot mess
and developed autoimmune disease.
And so he became hell bent like only a physicist could
on changing his microbiome.
And he dramatically shifted it
by having a smoothie every day
with 57 vegetables and fruits in it.
So, I mean, this just warms my heart,
the way that he did this.
But he would go to the farmer’s market,
he would just get a bunch of this, a bunch of that,
and he would go home, make the smoothie,
and then stick it in the freezer
so he’d have a serving every day.
And he became a completely different person
based on this microbiome change.
His autoimmune disease is in remission.
He dropped a huge amount of weight.
He went from being kind of this phenotype
that I know you know well
of a professor, high-performing, traveling around the world
on so many boards, so much innovation,
so many great ideas, supercomputer guy,
to being someone who gets up in the morning,
gets in his hot tub, exercises for like one
to two hours a day, and then does a little work.
Like he completely shifted the way that he lives
and his microbiome shift.
Who knows what’s the chicken and what’s the egg there?
But he had a huge change in his physiology.
Glucose went from being quite high,
and he tracks all of this, of course.
It’s like on a Jupiter.
And retired, I suppose, might have had.
And he’s retired, but he’s got the longest time series
of anyone I know.
And he’s tracked his glucose and insulin
going back 20 years.
So he can show you, okay,
here’s where I started having my smoothie,
and here’s how my glucose and insulin changed
as a result of that.
I’d like to take a quick break
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In addition, Athletic Greens contains
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And it tastes great.
If you’d like to try Athletic Greens,
you can go to athleticgreens.com slash Huberman,
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And they’ll give you a year’s supply of vitamin D3K2.
Again, that’s athleticgreens.com slash Huberman
to get the five free travel packs
and the year’s supply of vitamin D3K2.
Is there a case for, I’ll say young women,
but young women and men using over-the-counter probiotics
as a way to enhance the microbiome?
This is something I hear about a lot.
I’ve heard that excessive doses of capsule probiotics
can give a brain fog-like condition.
I personally don’t use capsule probiotics
unless I feel like my system’s
under a significant amount of stress,
in which case I might add that in for brief periods of time,
or if I’ve just taken antibiotics for a period of time.
Do you ever recommend that the college student
or the high school student
that she or he take capsule probiotics,
assuming that they’re getting,
let’s say three to five servings of vegetables per day,
either in smoothie form or some other form?
What are your thoughts on supplementing probiotics?
It sounds like such a simple question.
It is such a complex answer,
and I don’t think we really have the answer.
So I’ll tell you the way that I approach it.
I look for randomized trials to support my use of probiotics.
And frankly, I’m underwhelmed.
So I’ve seen some data,
if I invoke my MBA players for a moment,
almost every player I’ve tested
has increased intestinal permeability.
They just have such a high training load,
probably mediated by cortisol,
very high glucoses when they drain,
that they have increased intestinal permeability.
So those tight junctions in their intestine become loose.
They develop a lot of inflammation as a result of that.
And when you’re a professional MBA player
and you’re making 20 million a year,
like you don’t want a lot of inflammation.
You want a little bit to like help your muscles recover,
but you don’t want it to be adding to problems
when you develop an injury.
So this is leaky gut.
I don’t love that term, but yeah, we’ll use it here.
So there’s a particular probiotic
that is helpful in athletes with leaky gut.
So that’s the kind of specificity and randomized trial
that I’m looking for.
The rest of it, I think there’s support
if you find help from it.
As you described, if you take a course of antibiotics,
I mean, first of all,
I would question whether you need them,
but there’s a time and a place.
There’ve been instances where they’ve been prescribed
and I took them, mostly in the past.
I was in college.
They seemed like they kind of gave them out.
You had a sinus infection, they give you antibiotics.
Yeah, the worst treatment ever.
Yeah, so if you’re coming off of antibiotics,
I think that’s a good time to do
what we call replacement dose probiotics.
I think what’s far more interesting is prebiotics.
I think the data is much better for prebiotics
and the selective use of polyphenols.
How would a person in their teens and 20s
or any age for that matter,
know whether or not they have nutritional deficiencies?
What is the best way to analyze
if one is getting enough magnesium?
And for that matter,
what is going to be the best way to test the microbiome?
You said stool sample,
and I’ll come right back with the same question I asked
about a blood test.
What time of day?
When during the month?
To establish a baseline.
So this would be prior to embarking on 97 vegetables
or how many per day.
I was only 57.
Well, I love the idea that you’re telling us,
if I’m gathering correctly,
is that yes, there’s a case for probiotics,
but for the typical person, regardless of age,
eating more vegetables or drinking more vegetables
as the case may be,
is going to be beneficial for the gut microbiome,
perhaps without the need to go test
whether or not one is making a certain number
of estrogen related metabolites or not.
Just that that’s a great starting place,
eat or consume more vegetables.
But if one wants to analyze their gut microbiome,
are there good tests available to the general public?
This has been, I’m not going to name companies,
but I’ve been tracking this over the years
and it’s never been clear to me that we know
what constituents of the gut microbiome are best.
We know that dysbiosis is bad
and we know that diversity of the microbiome is good.
We hear this, but no one’s ever told me
that you want a particular ratio
of one microbiota to another
in a way that has made any sense to me, at least.
I’m not a microbiologist,
but whereas with testosterone in men,
we hear, okay, you want your free testosterone
to be about 2% of your total, perhaps.
With women, women are going to have more testosterone
than estrogen on average,
but still less than men when you look at testosterone,
et cetera, et cetera.
But you can get some crude measures.
But for the microbiome,
it just seems like long lists of microbiota
for which I just get dizzy.
If you just wrote out a bunch of I’s and L’s and S’s,
you’d kind of halfway,
you’re getting a bit the same information.
I’m not trying to poke at that field.
It’s a beautiful field,
but they haven’t told me what my microbiota
ought to look like.
What’s a healthy microbiome chart?
Well, that’s because we don’t know.
I mean, the best we have is Rob Knight’s work,
but even that is limited in terms of,
can I tell you that a woman in her 20s
should have this particular pattern with her microbiome?
No, I can’t.
So let me go to your first question
because I think you just asked about sex.
Your first question is about nutritional testing.
What I like to do with nutritional testing
is run a panel that’s looking at antioxidants,
so like vitamin A, vitamin C, alpha-lipoic acid,
because you can measure that in the blood.
I like to look at some of the key vitamins,
especially the B vitamin range,
because as you probably know,
if you’ve got particular genetic polymorphisms,
you might be less likely to be absorbing
the right level of vitamin B9, folate, vitamin B12, et cetera.
I’m also looking, going back to the antioxidants,
because I think that’s such an important lever
when it comes to detoxification,
which we haven’t talked about yet.
And then I’m looking at some of the minerals.
Magnesium is really the most important,
and we know that somewhere around 70 to 80% of Americans
are deficient in magnesium.
That’s like the lowest hanging fruit.
I would be curious, for instance, like with magnesium,
if that number of people are deficient,
does that mean that that number of people
should be targeting their nutrition
towards foods that contain magnesium
and or supplementing with magnesium?
And if so, what forms of magnesium?
We’ve talked about Mag 3 and 8 for sleep.
There’s Mag Citrate.
There’s so many forms.
It can be a little bit of overwhelming to people.
So any detail and sourcing, I would appreciate it.
Great, so first, in terms of testing,
what I prefer to do is to mention more than one lab
and more than one brand.
And I’m speaking mostly from experience.
So for testing, I do a lot of Genova neutrovalves.
During the pandemic, they developed an at-home test.
Normally with a neutrovalve, you have to get your blood drawn
and you have to do a urine sample.
So a lot of people can’t do that.
The great thing about this test is your insurance
usually pays for most of it.
And so the copay is about $150.
So during the pandemic,
they developed another test called metabolomics,
which does much of the same testing,
but it’s a finger prick.
So most of my patients prefer that.
In fact, they haven’t gone back to the neutrovalve.
Second lab is SpectraCell.
I use SpectraCell occasionally.
I find it not quite as easy
in terms of fitting into my practice,
but I’ve got friends and mentors like Mark Houston,
who does a lot of kind of precision
He thinks SpectraCell is the best test out there.
So you asked about magnesium.
You have to measure red blood cell magnesium,
like whole blood.
And with deficiency, it’s interesting with supplementation.
For my patients who tend toward constipation,
and that’s frankly about 80% of the women
that I take care of.
I’d be curious as to why that is.
I can guess, diet, stress.
That they may not know about.
So pine, the-
The pine system.
neural and endocrine factors combined, is that?
And then I would say there’s another factor
which is being female is a health hazard.
So we have twice the rate of depression, insomnia.
We’ve got three to four X increased risk
of multiple sclerosis.
We’ve got five to eight times
the risk of thyroid dysfunction.
So if you just look at that,
and you look at subtle preclinical thyroid dysfunction,
a huge number of the women that I take care of,
well, let me back off.
A large number of the women that I take care of
have thyroid dysfunction
that’s contributing to constipation.
And if we go back to that control system,
the hypothalamic, pituitary, adrenal,
thyroid, genital, gut axis,
and they have a lot of perceived stress
together with this borderline thyroid function
that no mainstream medicine doctor
has told her is a problem.
And then she’s got a problem with the tango
between estrogen and progesterone.
She’s going to tend toward constipation.
Women have a lot more constipation than men.
The gut is about 10 feet longer in women compared to men.
We should talk about some sex and gender differences
and define those.
And they are much more likely to have a torturous colon.
And the way you know that is you get a colonoscopy
and they tell you,
yeah, it was really hard to get in there
and do what we need to do.
As a brief tangent,
but I think this is the time to ask,
at what age now do physicians insist
their female patients get colonoscopies?
For men, I think the age used to be 50.
Now it’s getting ratcheted back to 45 or 40.
Again, these are recommendations, not requirements,
but they’re pretty strong recommendations
depending on where you live, et cetera.
For women, how early do you think
they should get a colonoscopy to explore
for possible polyps and or colon cancer?
Yeah, it’s a really good question.
I don’t know the answer.
So what I’ve always operated with is 50.
The way that I answer that
is to go to the U.S. Preventative Task Force rating
to determine based on their synthesis of the data
what age is the most appropriate.
Has it changed as you just described for men
from 50 to younger?
I don’t know.
So we should fact check that.
All these additional health hazards for women,
you mentioned some of the,
you broadly mentioned psychological impact, right?
And of course these things are all related,
And one of the, I think, wonderful things
about neuroscience and science in general and medicine
is that there’s now an understanding
that all the organs are connected to one another.
It’s a network.
It’s a network.
And that the microbiome sits at a key node
within that network.
And I think most people accept that now.
That seems to be a theme that,
at least in the last 10 years, is really wonderful
because certainly for neuroscience,
it was thought that unless it’s in the cranial vault,
it’s not neural, which is ridiculous
because there’s lots of nervous system outside the skull.
But in any case-
Can I interrupt for a second?
So I think you’re right that there’s an understanding
about the network effect.
But I think that as much as I love mainstream medicine
and I trained in it and I’m so grateful for my education,
I still think it is a silo-based way
of taking care of patients.
So even if there’s an understanding of the network effect
more at the science level,
or as you described in neuroscience,
there’s still, if you are a woman
who has constipation, fatigue,
maybe an autoimmune condition,
feel stressed out all the time,
feel like your hormones are out of whack,
you get sent to the gastroenterologist
for the constipation,
you get sent to the rheumatologist
for your autoimmune issues,
you maybe get sent to an endocrinologist
if you’ve got thyroid problems,
and there’s very little collaboration between these groups.
So even though there’s an understanding
of the network effect in real life, it’s not happening.
Let’s go deeper down that path
because you point out something really important.
And you’ve mentioned constipation a few times.
Can we view constipation as a serious enough symptom
that it warrants an immediate intervention?
That is, does it flag or signal problems
that are severe enough that that should be the issue
that’s dealt with for anybody that’s experiencing it?
And I mean, it’s sort of an odd topic for many people
because they think, oh, bowel movements,
and there’s that kind of pre-adolescent humor around this,
but I think it’s so important.
What I’m hearing you say is that constipation
is far more common in women,
and it signals a general set of many problems occurring.
Does that mean that women should address constipation?
And if so, what’s the best way to address constipation?
Yeah, I love this question because you’re doing,
can we have a quick little meta conversation?
So you’re doing something that I knew you would do,
which is you’re teaching me something,
and you’re changing,
like there’s a social genomics thing happening
where you’re changing my thought about this.
So I just wanted to acknowledge that.
I think for me, when I hear that there’s a kind of,
you’re talking about a phenotype,
constipation is a phenotype.
It’s one that people generally don’t wear a T-shirt
explaining it to people,
but that I’m guessing anything to do with sexual health,
bowel health, urology, people just don’t talk about
for all sorts of reasons.
And those reasons are probably so obvious
that they’re not even worth discussing,
also because we won’t change them
except by talking about them.
So if you say women are far more constipated
and that’s signaling a larger set of problems,
then my immediate thought is,
well, will relieving constipation,
pun intended retroactively,
will that assist in a great number of issues
and or will it get them down the road
of thinking about those other issues more specifically?
Like, do I need more magnesium
or should I be putting vegetables in my smoothie?
So I’m curious about constipation as a target
for intervention that then opens up
a bunch of other discussions,
because there are these certain nodes
in the mental health, physical health space
that when someone, like we talk a lot,
deliberate cold exposure, do I think it’s magic?
No, but I think that if someone’s getting themselves
into a cold shower once a day,
it opens up a number of questions about themselves
and reveals a number of things to themselves.
I’m like, how do I buffer stress?
What sorts of levels of control do I actually have?
And on and on.
So perhaps not the best example, but-
Some of us hate cold exposure.
Right, which is probably-
And we have like a gene that makes us stress out
like you wouldn’t believe with cold exposure.
Which I would argue makes it very likely
that even 10 seconds of cold exposure
gets you the effect that you want.
As opposed to someone who adores cold exposure
like a penguin, needs a lot more cold exposure
for it to have the adaptive response.
Anyway, that’s my way of gumbing through that quite,
you’re quite correct.
So let’s answer this question.
The constipation issue.
Yeah, so this is how you’re changing
the way I think about this.
So you’re asking, okay,
instead of looking at constipation
as a constellation of symptoms,
what about if you just used it on its own
as sort of a key indicator or signal
of dysfunction with the pine network
or maybe something broader?
And I think that’s right.
So it makes me think of a few things.
It makes me, you’re also changing this book
that I’m writing on autoimmunity and trauma.
So thank you for that.
So women experience more trauma than men.
This is well-established.
If you look at the ACE studies that were done
by the CDC and Kaiser in 1998,
we know that men for the most part,
middle-aged men have about 50% of them
experience significant trauma
as defined by the ACE questionnaire.
Women are at 60%.
And that’s pretty durable since 1998.
So women have more.
They have different forms of abuse,
much more likely to have sexual abuse.
They have a different HPA response than men.
Their perceived stress tends to be higher,
and I’m generalizing for a population.
Side note, in precision medicine, we don’t do that.
We do medicine for the individual,
not the population, not medicine for the average.
And so if you look at the physiology of a female,
I think that constipation and that need to like control
and restrain and hold things in,
you know, tighten the anal sphincter,
I think that’s part of the physiology.
So I’m veering away from the science,
but I do think that it is a really important signal
to pay a lot of attention to.
Now, you also asked about microbiome testing.
Should we do that or do you have one?
I have a couple more questions about constipation.
I never thought I’d ask this many questions
about constipation, but now I’m fascinated.
By the way, also this morning,
I taught medical students at Stanford
about the fact that we are basically a series of tubes.
So you talked about the anal sphincter.
We are a set of sphincters from one end to the other.
I mean, we are a set of tubes,
a nervous system being one of those tubes.
And I think in Eastern medicine,
they talk about the various locks
between those tubes and chambers.
And it’s not without coincidence.
There’s some real wisdom there, of course.
Wait, did you just talk about energetic anatomy?
More or less.
I didn’t say the word chakras, but I might in passing.
Well, it’s the bondas that you are questioning.
The bondas, right, are the sphincters, right?
Yes, that’s right.
Thank you for that.
So what defines constipation?
I mean, in other words, let’s think about the healthy,
rather than think about the unhealthy,
how many bowel movements should a woman
or a man have per day, assuming,
and this is where it gets tricky
because some people are doing time-restricted feeding.
Some people are eating more.
Some people are eating more fiber, more bulk,
larger meal at the end of the day,
a larger meal at the beginning of the day.
We will never be able to sort out all those variables,
but on average, how many bowel movements
and is timing during the day
for bowel movements at all informative?
What works for you?
Well, when I’m asleep,
generally I don’t want a bowel movement.
So I’m going to be like most people, right?
Well, sleep is primary for you.
I always assumed that morning time
was a healthy time for bowel movements.
And I think almost everybody, babies included,
recognize the feeling of being lighter and more energetic
when they’ve evacuated their colon.
In fact, so much so that I’m obsessed
with Jungian and Freudian psychology
that the first thing we learn
when we come into this world, right,
is that we want something,
we feel some sort of autonomic arousal stress,
whether or not it’s food or warmth
or the need to have a bowel movement.
And one of the first things that parents learn
is how to recognize that,
not by the odor coming from the diaper,
but by the look on the baby’s face or their agitation.
Agitation signals the need for some sort of relief, right?
Temperature relief, food relief,
evacuating the bowel relief.
So my understanding is that as autonomic arousal
increases in the early part of the day,
ideally after a good night’s sleep,
that bowel movements become more likely,
unless that arousal becomes so great
that then people feel so quote-unquote locked up
because of the balance of the autonomic features.
So early day, I’m guessing,
and again in the second half of the day,
and here I’m totally guessing,
and certainly not having to wake
in the middle of the night.
Yeah, those are my best guesses.
So I would agree with that.
When I was at Harvard Medical School
and UCSF for residency,
I was taught that constipation
is having a bowel movement less frequently
than once every three days.
So I don’t think I’ve ever laughed out loud
on this podcast as a consequence
of textbook medical knowledge.
Are you kidding me?
Is that ridiculous?
Well, that sounds like, and here pun intended,
that sounds like the conclusion of some very-
Constipated person. Emotionally
and in other ways, constipated individuals.
And again, this might seem like an odd conversation,
but the discussion around constipation
is present in psychological literature
because of this relationship to the autonomic system.
Well, it’s a metaphor in literature.
So you spoke to a number of different threads
that I think are important here.
So that’s the definition that I learned.
And I heard that and I was like,
hell no, that doesn’t work for me.
Doesn’t work for anyone I know.
And I spent a lot of time,
especially in medical school and in my internship,
where you rotate on medicine,
disimpacting women, like older women who come in
who haven’t had a bowel movement in a month.
And let me tell you, that is not nice for anybody.
Believe me, I became a scientist and a physician
for a number of reasons, both positive and negative.
That’s one of them.
So my definition of constipation
as a Western, mostly white girl,
is that if you’re not having a bowel movement
every single morning
and you have a feeling of complete evacuation,
anything less than that is constipation.
So that’s how I define it.
If you’re in India and you’re eating food
that’s got a fair amount of microbes in it,
it’s less sanitary, I’m using that word
as carefully as I can.
Generally, they have a bowel movement after every meal,
but they’ve got a different microbiome.
They’re exposed to different microbes.
Here in the US, I would say once a day.
You also spoke to something very important,
which is the balance
between the parasympathetic nervous system,
rest and digest and poop,
versus the sympathetic nervous system,
kind of the on button, you know,
fight, flight, freeze, spawn.
So I think for those of us
who’ve got issues with autonomic balance,
it can lead to constipation.
And I like that constipation could be pulled out
and kind of writ larger as an important signal.
What sorts of tools do you recommend people use
to relieve constipation?
In eating more fiber,
it sounds like reducing stress is going to be a huge one.
What are your favorite stress reduction tools?
I like to divide these into real time tools.
So big proponent of like physiological sighing,
real time, you know, these sorts of things,
but things that can really lower the baseline
on stress overall to facilitate constipation
and other broad indicators of health.
So I’m not a fan of lowering stress.
I’m a fan of lowering perceived stress.
And I think the distinction is really important.
I learned when I was in my 30s
that I was a massive stress case and I didn’t know it.
It was just sort of, I think I, through residency,
through working 120 hours a week,
I just was so accustomed and sort of-
That was 120, not under 20 folks.
Yeah, not unusual in medicine.
Well, they’ve changed training
so that you work no more than 80 hours a week now,
but that was before my time.
So I became accustomed
to a massive amount of cortisol, massive.
And I would say I’ve spent the past 20 years
really working on perceived stress to find,
I think all of us need an a la carte menu
of what is most effective.
So what works for me now at my age is different
than the TM I did as a college student,
It’s different than the,
I became a certified yoga teacher when I was in my 30s.
That is very effective for a lot of people.
It wasn’t enough for my matrix.
I do holotropic breath work.
I didn’t read it,
but I saw that you just had a paper in cell on your sign.
And it made me think like,
teach me how to sigh, teach me how to sigh.
Can you say a little bit about that?
Like, how do you do it?
Yeah, very briefly,
that study was we wanted to find
a minimal effective dose intervention.
Yeah, five minutes.
So I just wanted, yeah, so five minutes a day.
We needed to figure out what people do every day.
And we were monitoring subjective mood, et cetera,
but also biometrics remotely.
So it’s kind of a nice study.
HRV, nighttime sleep.
So this was done during the pandemic,
more than a hundred subjects.
The advantage was that we got data 24 hours a day
because they’re pinging us in their data.
So that was nice.
Resting heart rate,
subjective mood, we would get in touch with them daily.
So when people were swapped between groups,
like any good study,
but five minutes a day of sort of standard, if you will,
forgive me, meditations or just sitting,
no instructions about how to breathe,
just focusing on closing their eyes
and focusing on focusing.
Another group did box breathing.
Inhale, hold, exhale, hold for equal durations.
The duration of each of those inhales and holds
was set by their carbon dioxide tolerance.
So somewhere between three and eight seconds,
depending on how well they regulate to carbon dioxide.
Another group did cyclic sighing.
So this would be double inhale through the nose.
So big inhale through the nose,
followed by a, to lungs, empty exhale.
That second inhale after the first big long inhale
through the nose is really important
because it makes sure that all the collapsed avioli lungs
And then the exhale, you offload a lot of carbon dioxide.
That’s very similar to holotropic breath work.
Yes, not unlike holotropic breath work,
little bit pranayama-ish,
but the exhale is rather passive as opposed to active.
And then the fourth category was cyclic hyperventilation,
which is a lot like tummo, aka Wim Hof-ish breathing,
different than Wim Hof breathing.
So this would be, so very active inhales and exhales.
Every 25 cycles of inhale, exhale, that would be one cycle.
Long exhale, hold lungs empty, 15 to 30 seconds,
then repeat for about five minutes.
Everyone did that for five minutes.
And what we found was that the cyclic sighing
led to the greatest improvements in mood around the clock,
not just around the practice or during the practice,
as well as lowered resting heart rate,
improvements in sleep, et cetera.
And you got it published in Cell, that’s so amazing.
Yeah, we were very fortunate.
I think that thankfully the reviewers and editors
understood that these minimal intervention things
hopefully are gonna be of use to people.
So useful to people.
I mean, how often do you read a paper like that
that could offer a behavior change
that is so easy to implement?
I mean, I love that question.
So what about, did you tell them not to drink
because alcohol has such a huge effect on HRV?
Yeah, so in this case,
we didn’t tell them to alter anything else
about their behavior.
Just hoping it was background
kind of across the same allegory.
Yes, and some were Stanford students,
others were from the general population.
Any frat boys that were drinking heavily?
Well, during the pandemic,
I think alcohol intake went way up across the board.
I mean, if I had a magic wand,
I would ask that people either not drink
or drink two drinks per week maximum.
At least that’s my understanding of the literature.
Are you familiar with the WHOOP data with alcohol?
No, but we have a collaboration with WHOOP
through that paper.
And it certainly disrupts patterns of nighttime sleep.
In particular, from my understanding,
that first phase of sleep,
that’s related to the massive growth hormone release
that we all really need and want in that person.
And you didn’t measure growth hormone?
We did not.
No, the second iteration of this study
will certainly include free cortisol by saliva.
A hormone panel?
Yeah, a hormone panel.
Well, I’m beginning to think that we should also
be asking people how often they’re going to the bathroom
and what time of day.
I mean, this thing around constipation is super interesting.
And I think that plus blood markers,
and then I’m very excited to learn
that urine contains additional markers
that could be informative.
So yeah, it was a fun study,
not easy study to do with that number of subjects.
Takes a lot of training for your research assistants.
Yeah, it was a big group.
It was nine people in our group and three clinicians
and a lot of phone calls and a lot of back and forth.
And thank you to the subjects
who served as the real life guinea pigs.
So yeah, I think that stress,
I think people are starting to appreciate
that there are ways that they can relieve their stress
that don’t only fall under the categories
of vacation and meditation.
But I want to say that meditation
is obviously a wonderful tool.
It’s just, it’s a tool not unlike any other tool
that is great for some people and less great for others.
Well, certainly it’s a great tool
and it’s got such a scientific basis behind it.
But there’s so many things on this a la carte menu.
Sex, orgasm, connection, feeling heard and seen and loved.
Yeah, let’s talk about that.
You mentioned earlier that all these stress factors,
you said patriarchy, right?
But I think what, if I may,
at risk of just strengthening that statement,
I mean, that to me is signaling a bunch of other factors
around, as you said, like keeping things in
what do you think explains, let’s talk about that.
Because I think that that’s likely to have raised
a certain flag in people’s minds.
Like, what exactly is she talking about?
Are you talking about less opportunity?
Are you talking about less opportunity to vocalize?
Are you talking about less opportunity
to vocalize and be heard?
I mean, I realize that there are an infinite number
of variables, but given that it sounds like
a really strong input to the system,
what I mean by that is that psychology
is influencing biology.
And you’re saying that these power dynamics,
structures and dynamics are impacting it.
I’d love to, let’s hear your thoughts on that
because I hate to let a flag like that go by
without fleshing it out.
Never waste a good flag.
Well, and let’s preface it by just saying that
like people will have different opinions on this
and I think that’s healthy.
And like with the discussion about constipation,
let’s talk about what people aren’t willing to talk about
when it comes to health.
So we might need to talk about patriarchy on part two,
but I’ll give you some material that I’ve been working with.
I started, I did not even understand the existence
of patriarchy until I was a bioengineering undergraduate.
At MIT, I should mention.
Which has always had a bit of a male,
a skewed male in terms of faculty numbers.
Well, that’s true at most universities.
True, well, my postdoc advisor was the late Ben Barris,
who was a female to male transition, transgender.
First transgender member
of the National Academy of Sciences,
one of my closest friends.
Unfortunately, he died of pancreatic cancer.
We were very, very close.
They’re actually making a documentary about Ben.
But Ben, this is interesting,
Ben went to MIT because he wanted to be around a lot of men.
That’s a lesser known fact.
But then he was a very strong advocate for women.
He went as Barbara when he was Barbara.
And by the way, he’s given me permission to share all this.
Prior to his death,
I recorded a lot of conversations with Ben.
I only ever knew him as Ben, by the way.
But when he was at MIT, he was identified female.
And he later talked about the intense suppression,
oppression, literally is how he described it.
Especially given that he was performing so well.
Yes, so you just defined patriarchy.
You did it yourself.
When I was in bioengineering,
I took a women’s studies class.
And it was all about teaching undergraduates
about the existence of patriarchy.
Which I would define maybe at its simplest as power over.
I’m not saying men are patriarchy.
I’m saying something very different, which is power over.
Let me correct one thing that she said.
I didn’t go to MIT as an undergraduate.
So I’m from, I was in Alaska
and I went to the University of Washington
I dropped out of a graduate program in bioengineering
to go to the Harvard-MIT program
for health sciences and technology in Boston.
Thanks for that clarification.
University of Washington, also wonderful place.
I have many, many, many, many, many,
wonderful close colleagues there.
It’s an incredible place, especially for vision science.
It’s especially good for engineering, bioengineering.
But yeah, so my MD is jointly between MIT and Harvard.
And it’s the oldest, maybe largest,
although Harvard says this a lot,
program for biomedical engineers
and MD-PhDs, Physician Scientist Training Program.
Great, thanks for that clarification.
I’m gonna blame the internet for this one.
We need to send our Wikipedia editors out.
I think LinkedIn is correct.
Well, Wikipedia editors, note,
get out there and make the correction.
Now you heard it.
So stress that is,
what you’re really talking about is systemic stress
in the body as a consequence, excuse me,
of systemic stress of environment.
But there’s particular forms of it.
I would say this also relates to white privilege.
It relates to racism.
And when you look at kind of the way that systems,
including my beloved MIT,
the way that they’re set up is that might makes right.
And generally the people that are the strongest,
big men, strong men,
they’re the ones who tend to be the most successful.
So for people who are BIPOC,
for people who don’t have white privilege,
for women, it’s a different experience.
And so I’m using patriarchy as kind of a umbrella here,
but it connects to many other things.
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I want to use this as an opportunity
to A, keep this in mind as we turn to a question
that I didn’t close the hatch on earlier
and it’s my fault,
which is I’m now clear on the fact
that a woman in her late teens, early 20s
ought to know something about her testosterone,
estrogen, thyroid, cortisol levels.
Should start at least thinking about her microbiome.
Should be thinking about how many bowel movements
and the timing of those bowel movements per day, really.
And I’m assuming that what I just described
is also true for women in their 20s, 30s, 40s, 50s,
on up to hundreds.
Is that correct?
That’s correct, but I would say
that there are differential opportunities by decade.
So I’m glad she’s circled it back
to teenagers and testosterone
because I think if you know, for instance,
in your teenage years that you have high androgens
and that you’ve got this potential phenotype
way into the future that you may not even notice.
I mean, maybe you notice you’ve got a few extra hairs
on your chin or something.
If you know that your testosterone is elevated
or some other androgen, it might change the arc
of how you take care of yourself.
So I think that could be very helpful in your teenage years.
In your 20s, for people who are a stress case like me,
so age 27 on the wards at UCSF,
if I had known that I was such a high cortisol person,
I think I would have done things differently.
I would have changed my behavior.
And I don’t know because I didn’t base case these,
but your testosterone can decline starting in your 20s,
kind of depending on how much stress your matrix is under.
So for women that can start as early as 28,
usually your testosterone declines by about 1% per year.
What level of testosterone do you like to see in a woman
once she’s post, let’s say after age 25,
what kind of range is healthy?
I know what the reference range is only
because I know one could look it up.
I don’t know it off the top of my head admittedly.
But what’s a kind of a nice reference point there?
So the way I tend to describe this on podcasts
is the top half of the normal range.
So that I think is a good benchmark.
You know, for PCOS, generally it’s much higher than that.
You know, I’ve seen patients with PCOS
where their total testosterone is 100 to 200.
Do they always have peripheral manifestations of that?
A little bit of hair, the skin plaques I’ve heard about,
you know, so darkened skin plaques.
Is that, you know, I get a lot of questions about PCOS.
And you’re the first person we’ve had on this podcast
that’s really qualified to talk about PCOS in a real way.
So here we’re talking about too many androgens,
cysts on the ovary, irregular ovarian, excuse me,
I keep saying that, ovulatory slash menstrual cycle.
What are some other indicators?
And do you recommend that women
start taking androgen blockers or, I mean,
how does, it seems to be a lot of PCOS out there.
I’m hearing about it a lot.
So glad you asked about this.
So PCOS is one of those really poorly understood conditions
that gets, it kind of flies below the radar
until a woman wants to get pregnant
or she’s got some other issue
that drives her to a physician.
The problem is that it is a syndrome, right?
So polycystic ovary syndrome,
sometimes polycystic ovarian syndrome,
and syndromes don’t necessarily fit together
into a really clear diagnostic criteria.
So in this instance,
there are three different criteria that we look for.
So cysts on the ovaries,
having clinical manifestations of hyperandrogenism.
So that could be hirsutism, acne, other things,
and then usually irregular periods.
And the way that that’s defined,
at least by the latest criteria,
is having a period every 35 days or less.
So typical cycle length, 28 days, 35 days,
you know, you’re skipping a period here and there.
So those are the criteria that we use to diagnose PCOS.
There are about four different systems out there
in the literature for diagnosing PCOS,
which is where it starts to get confusing.
So there’s some women who have no cysts on their ovaries,
but they’ve got hirsutism,
and they’ve got irregular periods.
Could you define hirsutism?
Hirsutism is increased hair growth,
usually in places that you don’t want it.
So for women, it can be, you know, kind of male pattern.
They might notice it on their breasts, on their chest.
And then there’s, of course, a familial quality to that.
Like I was just looking at a paper last night,
looking at Israelis and how much hirsutism they have,
and whether this is related to CAG repeats
on the androgen receptor.
Do they get, not Israelis,
but do women who might have PCOS experience
androgenic alopecia, so hair loss,
that’s sort of the quote unquote male pattern baldness.
Of course, it’s androgen pattern baldness
as opposed to male,
that we’re talking about testosterone, DHT related.
Sometimes, you know, this is where
I’m gonna invoke clinical experience
rather than what I’ve seen in the literature.
Women definitely can have some androgenic alopecia.
I tend to see it later in life.
But this is an important point,
because we think of PCOS as, you know,
I was just talking about it in teenage years.
Like, wouldn’t it be nice to know
that you have this phenotype and you’re at risk
for all the things that people are at risk for?
And we haven’t talked about glucose and insulin yet.
What we know is that PCOS is not just a problem
in terms of irregular periods
and then difficulty getting pregnant.
So those are mostly problems in your 20s, 30s, early 40s,
but it is a massive risk factor
for cardiometabolic disease as you get older.
So many people tend to pigeonhole PCOS
as a problem of reproductive age.
We have to be thinking of it
over the entire female life cycle.
And I would say it’s even more important
to consider it over the age of 50,
you know, average age of menopause is 51 to 52,
because we know that that elevated testosterone,
the high androgens, are probably the greatest
cardiometabolic driver of disease for women with PCOS.
Now, one other thing I wanna mention,
and I still have my notes
that we’re gonna talk about microbiome testing,
because that’s such a fun subject.
What I was taught to do,
again, saying this with so much love
for the people who have taught me how to do medicine.
What I was taught to do is that
if you have a woman with PCOS,
you make the diagnosis, you measure her testosterone,
you see if she has acne, blah, blah, blah.
You ask that woman one question.
Do you wanna get pregnant or not?
So then you have these women with PCOS
who get started on a birth control pill
if they don’t wanna get pregnant.
If they wanna get pregnant,
then you help them get pregnant
by addressing some of these PCOS issues,
like maybe you give them Clomid,
or you do something to make them ovulate more frequently.
That is the way that most conventional medicine
approaches this, and it does women a gigantic disservice.
So one of the things I’m speaking into
is the gender gap that exists.
So my feeling is that the research money
that goes into women’s health is abysmal
compared to what goes into men’s health.
And I think that’s changing,
but there’s also a huge lack of awareness
of sex and gender differences
when it comes to the way that we construct
clinical trials and other experiments.
Well, that’s absolutely true.
I mean, I’ve sat on NIH review panels
for more than a decade now.
I’m a regular standing member,
which is only to say that I see the research
as it’s being proposed.
And now it’s required, no grant will get funded
without sex as a biological variable.
And here I’m, by the way, folks,
this is sex, biological sex, the noun, not sex, the verb.
Both are super interesting, obviously.
But when we say sex as a biological variable,
meaning even if it’s a study on mice-
Where did that start, though?
That didn’t start that long ago.
It must’ve been, I think we can thank,
I don’t want to misattribute here.
I think we can thank Francis Collins
for insisting on this.
And Bernadine Healy.
Bernadine Healy has done so much to help us,
but she made the Women’s Health Initiative,
which I hope we’ll get to, which is a hot mess.
So confusing, the data that came out of that.
Yes, and these trials are long,
and so the data are only now starting to emerge.
So just to be clear, I mean, I have a question
that I don’t think is going to take us off track,
but I’m going to pose this question as a hypothesis
because I think it’s likely to be a little bit of a,
not a barbed wire question,
but maybe like a prickly question when people first hear it,
but it’s posed as a hypothesis.
You mentioned some of the psychosocial stress issues
based on, at the organizational level,
institutional level, societal level,
maybe right down to the family and just life,
that are biasing health outcomes for the worse
in female populations, okay?
You refer to it as the patriarchy.
I’m just trying to make sure
that we’re both talking about the same thing,
and that’s non-exhaustive, I realize.
That’s just a subset of the issues.
I’m also hearing there’s a lot more PCOS,
which is hyperandrogenization of the ovary.
We’re talking about, you mentioned it,
excess testosterone, which females naturally
have more testosterone than they do estrogen anyway,
but we’re talking about elevated levels.
Here’s a hypothesis.
One hypothesis would be that the increased androgens
and the PCOS are a consequence
of the psychosocial conditions that are,
I don’t want to say forcing,
but are biasing the need for females
to think, behave, react, act in certain ways
to survive, let alone thrive.
Is that a, I don’t say this
for any kind of political correctness hypothesis.
This is a, in my, this would be a fun, interesting,
and I think important study to run, right?
Depending on stress and the conditions,
the specific type of stress,
do females underproduce or overproduce androgens,
or is it a neutral effect?
Does that make sense?
I love this question.
So let me just paraphrase the last part of it
to make sure I got it.
It sounds like what you’re asking is,
could PCOS or at least some phenotypes of PCOS
be a response to what I’m calling patriarchy?
And then you add a second part to it,
which is, do healthy women,
like what is their production of testosterone like?
Is that right?
Yes, and with the acknowledgement,
I mean, you’re the expert here.
You’re the physician, clinician, and expert in hormones,
and I’m not, but with the understanding
that absolute levels of hormones are interesting,
but perhaps not as interesting
as the ratios of testosterone to estrogen.
So when we’re talking about excess testosterone,
we’re really not talking about,
oh, women making a lot of testosterone
because frankly, they already make a lot.
Then most people weren’t aware of that.
I wasn’t aware that women make more testosterone
And we need it.
Right, and so it’s not saying
that testosterone in women is bad
or is always a reaction to the environment,
but when it becomes super physiological or hyper elevated
is I could imagine all sorts of social conditions
that would create that, so in males and females,
but here we’re talking about PCOS
and females in particular.
So I’d love for you to speculate.
Should we run the study?
We should totally run the study
because I don’t know the answer.
I suspect that you’re onto something.
It may not explain all of the women with PCOS
because as I mentioned, there’s a lot of different phenotypes
but I think it could explain a significant portion.
And you’re almost, you’re saying,
if we look at the gene environment interface,
this environmental influence of having,
being someone who’s got power over you,
if PCOS was a response to that,
the way that we treat it would be completely different.
So on the one hand, I wanna be careful
not to dismiss the suffering and experience
of women with PCOS.
I’ve got a lot of women with PCOS in my family
and it is, there’s so much pain and suffering,
especially if you wanna have a baby
and you try for years and you just can’t ovulate.
On the other hand, I read a paper recently
and maybe we could cite this,
that compares the phenotype of a woman with PCOS
to a man who is hypoandrogenic.
And I think that’s a really interesting way to look at this
because the thread we haven’t talked about with PCOS
is the role of insulin and glucose.
So for some of the phenotypes of PCOS,
the problem is hyperinsulinemia,
high insulin in the blood,
is driving those theca cells in the ovaries
to overproduce testosterone.
These women are insulin insensitive,
so more insulin’s being cranked out
and the cells in the ovary are therefore
making more androgen.
You don’t like to say insulin resistant?
Oh, I can, I don’t have a problem saying insulin resistant.
I’m just a little bit outside the lane lines
of my expertise, so I was trying to use that.
What is the correct nomenclature
so that we can make sure we’re on course?
Well, what I like about insulin insensitive,
the way that she just said it,
is that I think that offers people a way in
and I love to do that in terms of messaging.
Insulin resistance starts to lose people
because they don’t really get what that means
at a receptor level.
I think I say insulin insensitive
because when people hear insulin sensitive,
it almost sounds like a bad thing,
but that’s actually what you want.
So I think that’s how I defaulted to insulin insensitive.
What’s your insulin?
I don’t know.
I’m due for a blood test.
Yes, you are.
I’m due for a blood test.
I had blood work done about eight months.
Can I interpret it?
Sure, that’d be great.
I’m always experimenting with different supplements
and different behavioral regimens
and I’ve kept charts since I was 19.
Oh, you’re like my patient.
I’ve been sort of obsessed by this
and I would say everybody, if you can afford it,
and at the time, actually, I had to save up,
insurance wouldn’t cover it,
get some basic blood work done
so that you have a reference point.
Do it as soon as possible
because even, we’ve been talking about these women
over the life cycle.
I wish I knew what my insulin was when I was a teenager.
I wish I knew what my fasting insulin was.
I really wish I knew my postprandial insulin
like in my teenage years, in my 20s, in my 30s.
Well, I knew it at my 30s, starting at 35.
Are you a fan of continuous glucose monitors?
The hugest, most gigantic fan of CGMs.
I’ve never seen any tool that I’ve ever used in medicine
change behavior the way that CGMs do.
Wow, why do you think they are so effective
at changing behavior?
I’ve tried one and I really liked it.
I learned that in the sauna, my insulin,
my blood glucose goes up probably by a bit of dehydration.
I learned what kind of foods work for me, which don’t.
I thought it was fascinating.
I learned how every behavior you could possibly imagine,
use your imagination, impacts blood glucose.
It was totally fascinating to me,
including how two wake-ups during the middle of the night
versus one versus none impacted blood glucose
the next morning.
For a data junkie like me, it was like, I was in heaven.
Why do you think they are so effective
in changing behavior?
Is it because of that, that people can see
that real-time control, like scan in and like,
oh, that’s the sandwich glucose?
I think it’s many things.
I think it’s generally the enchantment
of learning about your own chemistry and biology.
I love that.
And I think for me, what I’ve seen,
I feel like doctors are basically marketers,
like a sacred marketing.
Our job as a physician is to convince people
to do something that we think is good for them
based on the best science, but we can’t just say,
here, why don’t you fill this prescription for OCGM?
You have to market it.
You have to say, I think this completely changes
the way that you approach your prediabetes.
I think this could dramatically affect
your risk of Alzheimer’s disease
that you’re so worried about that your mother has.
So our job as physicians is to be that sacred marketer.
So CGMs are one of my tools that I think are so crucial.
So enchantment, number two, yeah, it’s the real-time effect.
So if you go get your glucose and insulin measured,
or maybe you do like a two-hour glucose challenge test
where you look at glucose and insulin
at the fasting point one hour later,
two hours later, or more frequently,
that does not have the same kind of behavior effect
as having continuous data where you can say,
okay, I drove to see you, Andrew, from my place in Berkeley,
and it was stressful, it was torrentially raining,
and I know my glucose was elevated.
I think really understanding what the mediators are
of your glucose control is essential.
Now, that said, it’s also kind of a later effect.
I mean, I’d rather know your insulin,
and we know from the Whitehall study
that insulin, especially postprandial insulin,
fasting insulin too, can change years and years
before you get a change in glucose.
So that’s more for prediabetes and diabetes.
So I think those are the main reasons
why I think it’s such an important tool.
Third thing is it democratizes data, which you do too.
I mean, incredible how you do that with your podcast.
But I think one of the most hopeful and exciting things
that I’m seeing right now in the health space
is that we’re going from this patriarchal relationship
where doctors hold the power
and are the gatekeepers of data
to patients and clients having much more access
to that enchantment about their own chemistry
and their own biology.
So to me, that is so exciting.
Like for me to be able to, I’ve got probably 100 patients
that are in a data stream with me
where we’re looking at their glucose,
and I can, I mean, I’m on sabbatical,
so I’m not doing this so much anymore,
but I can call a patient, be like,
why is your glucose so high?
Like, what did you do?
Oh, it was my birthday.
I had a piece of birthday cake.
Like that kind of collaboration
that also is teaching the patient
to be their own clinician.
To me, that is a loop of benevolence and integrity
that I think is essential to creating health.
We’ve got a disease care system.
We need the democratization of data
to become a health-based system.
Amen to that a million times over.
We share that sentiment.
I can tell it at a deep level.
I think the pandemic actually assisted in,
well, it harmed many things,
but it assisted in people’s understanding
that no magic fairy, nor the government,
nor anyone was gonna arrive at their door
with a kit of things to make them healthy
that provide sunlight, movement, sleep,
and all the various aspects of nutrition.
No, nothing, nothing that everyone has to have access to
first and foremost,
and then implement those things as best they can.
Speaking of which,
and kind of circling back to this idea
of people in their late teens, 20s, 30s, and onward,
if you had a magic wand
and you could give two or three don’ts,
or to make it personal,
if you could go back in time and erase certain behaviors,
what would the don’ts category be?
You can tell us more than two or three,
but if the goal is to maximize vitality and longevity,
and those are not always parallel to one another,
certainly not the same thing, sometimes orthogonal,
but let’s just say fertility being a proxy
for vitality and longevity.
I think people will sometimes forget this,
that fertility isn’t just about people
who wanna conceive children.
It can serve as a proxy for vitality and longevity.
So what would you like to see patients,
let’s focus first on female patients,
but if it extends to male patients as well,
what would you like to see them not do or do far less of?
I really like that.
So I would say a few things.
I’ll just headline them and then we can go into detail.
Number one, sleep.
I do wanna diverge from you a little bit on some things,
but sleep is probably not one of them.
No, well, feel free.
I mean, you’re the one that worked 120 hours a week.
I’m just not sleeping much then.
I can’t imagine unless you lived in a different reality
than I do.
And there are times in my career
where I was pulling all-nighters and sleep deprived.
I don’t recommend it, but I did it.
I hope you don’t do that anymore.
No longer, if I can avoid it,
but there were years, many years where it was like,
all right, here we go.
And I’m quite adept at it for one cycle,
but two nights I kind of start to fall apart.
So I would say sleep, alcohol, high perceived stress.
And I’d love to talk about maybe the data on telomeres
and what we know.
So you’d like to see people get enough sleep.
So don’t just-
Yeah, not all of these are concordant.
So not enough sleep, too much alcohol,
too much perceived stress, eating the wrong foods,
toxic relationships and isolation.
And then number six,
not moving enough or not moving and exercising
in a way that really fits with your body.
Can we start with that one actually?
Just cause it’s such a, and then work backwards.
I think nowadays people appreciate the need
for quote unquote cardio.
I know that the exercise physiologists cringe
and dissolve into a puddle of tears when I say that,
but getting the heart rate up over some period of time
longer than 10 minutes
in order to generate cardiovascular health circulation.
So, and resistance training of some kind, maybe flexibility.
What do you mean by body phenotype and exercise?
I’ll speak from personal experience.
So what I did through,
I mean, I gave up my twenties to medicine.
And during that time, I occasionally got to the gym,
you know, at UCSF on Parnassus, you could go to the gym.
And then as soon as your beeper went off,
you’re back into the hospital.
But I didn’t exercise much.
I had, do you remember Nordic tracks?
I had a Nordic track in my house and that was like it.
What I believe, because for me,
the primary outcome that I’m interested in
is cardiometabolic health.
So when it comes to exercise,
what I really feel,
if we’re gonna be at a population level,
I feel that about a third cardio,
two thirds resistance training
is based on my synthesis of the literature,
the best combination.
And I think there’s, you know,
as you described with your sign study,
I think there’s a minimal effective dose,
which for a population is about 150 minutes.
I think most of us need a lot more than that per week,
but I think, you know, for me,
because I have a phenotype that produces a lot of insulin,
kind of depending on how I’m on my game,
I have a lot of glucose.
So I have to exercise a lot more to dispose that glucose.
So I think you then have to move from medicine
for the population or prescriptions for the population
to what works for the individual.
I think that recommendation is fantastic.
I think resistance training, well, let me put it this way.
I’m neither a trainer nor a physician,
but I’ve seen in family members that were doing,
I wouldn’t say a lot of cardio, but just cardio,
that when they add resistance training,
everything in terms, including their biomarkers,
have improved dramatically.
This is in particular for female members of my family.
Well, one of the mediators that I think is important,
especially for people who do what I call chronic cardio,
which is what I did, is cortisol.
So we know that runners, especially marathon runners,
people who do a lot of cardio
and don’t do much resistance training,
they tend to have much high cortisol levels.
And you can buffer that with vitamin C.
Vitamin C can decrease the effect,
but chronic cardio doesn’t always serve people.
So quick personal example.
When I first started measuring hormone panels in myself,
I went to my physician and I said,
I’m 35, I’ve had one kid, I wanna have another kid.
I’ve never been so exhausted in my life.
I just feel like I’m pushing a rock up the hill.
I’ve got this belly fat that I don’t like,
and I don’t wanna have sex with my husband.
So what do you think?
What can we do about this?
And he offered a birth control pill and an antidepressant.
So I left him and I went to the lab
and I ran a hormone panel,
and my cortisol was three times what it should have been.
My insulin was in the 20s, I was fasting.
My glucose was 105.
My thyroid was mildly abnormal.
My progesterone was low.
And that set me on this course of realizing
that what I was doing as a physician,
taking care especially of women,
was not getting to some of these root causes
that are so essential.
And I would say, I had to start first with cortisol.
At that time, I was running four miles,
three times a week, four times a week.
That was just racing my cortisol further.
So that was not the right exercise for me.
I needed more adaptive exercise.
I started doing Pilates, more yoga.
That helped to lower my cortisol.
I mean, it started me on changing the way
I was managing perceived stress
and it also changed my supplement regimen.
Can we talk about that?
With the moment you said lowering cortisol,
thought of the two supplements that come to mind
are ashwagandha, which I think can potently reduce cortisol,
but I’ve heard some recommendations about cycling it.
And I’ve always wondered about time of day
for ashwagandha intake because sort of,
quote unquote, want cortisol elevated
in the early part of the day.
We know this.
We know you do not want cortisol peaking later in the day.
No, you do not.
Interferes with sleep.
Interferes with sleep.
And then the other supplement is rhodiola rosacea.
Do I, am I pronouncing that correctly?
Yeah, so rhodiola is very effective.
It’s been shown in multiple randomized trials
to lower cortisol.
So that could be very effective.
What’s your dose?
I’ve started taking it recently, by the way,
and I made a huge mistake.
I like to make the mistakes first
so then my audiences don’t make them.
As I was taking it, I heard it was an adaptogen.
So I thought, oh, I’ll take it before resistance training.
But of course you want the cortisol peak
during resistance training
because that’s going to set in motion the adaptive response.
So I started taking it later in the day
and it’s really improved.
I would say my late day, second half of the day cognition,
this is subjective, to be fair.
I just feel like I’m in a more even plane of attention
in the second half of the day.
So you’re describing an NF1 experiment, which is-
Well, it is not anecdotal.
So I was taught at Harvard Medical School
that the hierarchy of evidence starts at the lowest
with expert opinion, case studies,
then you’ve got cohort studies,
then you’ve got observational data that’s prospective,
then you have randomized trial.
But the highest quality evidence of all
is the NF1 experiment, where you serve as your own control.
So what you’re describing with rhodiola,
I would frame that as an NF1 experiment
where you have a washout period
and you compare before and after.
And I’d like to measure some other metrics
to see if there’s an effect, including your cortisol.
So rhodiola has been shown in multiple randomized trials
to reduce cortisol.
The other thing that I think is super effective
is phosphatidylserine, PS for short.
Fish oil also more modestly reduces cortisol.
Ashwagandha is interesting.
So in my first book, The Hormone Cure,
which I read, by the way.
You did? I did.
I was hoping that was the one you read.
I did, I read it and it’s spectacular.
And I thought going into it, I had this like,
you know, let’s just call it what it was.
It’s kind of male bias.
Like, is there gonna be anything in here for me?
Because I don’t have ovaries and you know,
is this gonna be, and it was immensely informative.
So thank you.
Yeah, I have very fond recollections
of the walks I took listening to it.
And then I own the print version too.
So I like to switch back and forth.
So thank you for that.
It’s a superb book for anyone to read.
I so appreciate that.
So in chapter four, you may or may not remember
that Ashwagandha, at least the time that I wrote that book,
Ashwagandha’s data is not great,
but lack of proof is not proof against.
So with Ashwagandha, most of the data comes
from thousands of years of using it in Ayurvedic medicine.
And it’s considered, again, not my science hat.
It’s considered a double adaptogen
so that it’s potentially helpful
when you are a high cortisol phenotype,
like I was, like I sometimes still am, or low cortisol.
I haven’t found that in my patients,
although I’ll give you one exception.
So Ashwagandha is mostly based on animal studies.
There’s not as much human data,
but it is used a ton in integrative medicine.
There’s one supplement that I’ve found
to be incredibly helpful for people
who tend to have high cortisol at night,
and that’s called a Cortisol Manager.
It’s by Integrative Therapeutics.
I don’t have a second supplement manufacturer
that makes something similar.
It’s their number one selling supplement
because it’s so effective.
Is it a cocktail of several things?
It’s a combination of phosphatidylserine and Ashwagandha.
Tell me more about phosphatidylserine.
I am familiar with it for,
it’s been mentioned by some guests
that were on the Tim Ferriss podcast long ago
for other reasons, I think related to sleep.
And maybe that’s another reason why you like it.
But before we move on from rhodiola,
is there a dosage of rhodiola rosacea that you-
So I would refer people to my book
because the randomized trials
and the doses that were used are in there.
So I can’t remember with rhodiola,
although I took it this morning to prepare it
to be with you.
We can look it up and put a show note caption
so people can link it.
I can remember the dose with phosphatidylserine
because I take that regularly.
So 400 to 800 milligrams is the typical dose for PS.
And what’s interesting is that
in the randomized trials that were done,
400 milligrams was more effective than 800 milligrams.
I’ve found that for several supplements
that the lower dose was more effective.
Yeah, it doesn’t matter what those were.
And so when you say PS,
you were referring to, by the way, folks, not PCOS,
just because scientists and clinicians are familiar with,
and military, very familiar with acronyms,
phosphatidylserine, PS, so 400 to 800 milligrams,
400 being more effective,
taken later in the day or early day?
Does it matter?
It depends on when your cortisol is high.
So for me, I tend to, you know,
what’s the pattern for cortisol?
Typically it rises to its peak
30 to 60 minutes after you get up.
Then it has this gradual kind of asymptotic decline
until you go to bed.
So if you’re someone like me who peaks like way crazy high,
I don’t do that anymore, but that’s what I used to do.
I needed phosphatidylserine in the morning.
For people who are high at night,
who have what’s known as a flat cortisol pattern
or a inverted pattern, you wanna take it at night.
And the flat pattern, just quick sidebar,
is that that’s associated with a number of conditions
that most mainstream physicians don’t know about.
So a flat pattern where it’s low in the morning
and it’s high at night is associated with anxiety,
depression, decreased survival from breast cancer.
That was studied at Stanford by David Spiegel.
He was my close, even collaborator,
even on the breathwork study that we just did.
Yeah, he’s our associate chair of psychiatry now.
So a wonderful human being has been a guest on this podcast
and I’m now fantasizing about a conversation
that includes a panel of incredible minds
like you and David from the clinical side.
So in any case, yeah, the late shifted cortisol, not good.
And it seems to have the worst immune downstream issues
of any of the cortisol patterns.
So that’s really important to know about
because it then maps to things like,
it’s related to PTSD.
So that’s the pattern we see like in vets
who’ve got PTSD as well as others.
It maps to auto-immunity.
It maps to fibromyalgia.
I was told that one in 12 people have our heterozygous,
so one mutant copy or hypomorphic for some mutation
in adrenal related genes,
so congenital adrenal hyperplasia.
Is that true?
And if so, that means that one in 12 people walking around
are cranking out far too much cortisol
or not enough cortisol or the cortisol system
is already skewed in a direction
that makes life more challenging
at the levels we’re talking about.
Did I hear that correctly?
Because that one in 12 is not a small number.
It’s not a small number.
It fits with what I see clinically.
I mean, I wanna see that data just to see
what does that mean?
And could you modulate it with environmental influences?
But it certainly fits with what I see.
I was taught once again in mainstream medicine
that in terms of adrenal function,
it’s very binary how most clinicians think about it.
You either have Addison’s disease
and you don’t make enough cortisol
or you’ve got Cushing’s or Cushingoid pattern
and you make too much cortisol
and anything in the middle is normal.
And my experience is that, hell no,
like there are those of us like me
who make a lot of cortisol.
I don’t have Cushing’s.
Maybe I’ve got one of these.
I wouldn’t call it a mutant gene.
I would call it more of a vulnerable gene.
So maybe I have one of those.
Maybe that’s part of the reason why
I make two to three times what I should be.
I’m aware of certain groups of individuals
from within the military sector
that there’s a more frequent occurrence
of some mutation in CH, congenital adrenal hyperplasia.
Not necessarily two copies,
which if people look that up, they’re gonna go,
oh, wow, there’s all these phenotypes.
But sort of hypomorphic type things,
less than or too much cortisol.
And they are very good at staying up
multiple days per night, multiple nights in the series.
So they can pull all-nighters very easily.
They can push harder when most people would quit.
And everyone thinks, well, that’s a great phenotype to have,
but guess what?
It’s because they hyperproduce cortisol.
And so that’s interesting.
And I think if we were to panel medical students
and graduate students,
and you were to look at who’s pulling excessively long hours,
who’s stressed out a lot,
even outside of academia and medicine,
and pushing, pushing, pushing really hard.
I think the ability to push and not crash,
we think of it as adaptive,
but in some sense it’s maladaptive over a series of years,
which is sort of what you described earlier.
Yeah, it’s such a good point because,
in some ways you wanna select for that
in certain professions,
like in the military, like in medicine.
But I would wonder for those folks
about the downstream consequences
of producing so much cortisol.
No, it’s gotta be detrimental for their health
in the long run.
And you see that.
But even the data shows that if you’re someone like me
who makes a lot of cortisol, higher rates of depression,
like 50% of people with major depression
have high cortisol levels, higher rates of suicide.
Much more metabolic dysfunction.
We know that trauma, as an example,
maps to an increased risk of glucose metabolism issues.
And certainly high cortisol does that,
because it’s one of the jobs of cortisol
is to manage a glucose.
And it kind of sets you up for this one number five,
which is toxic relationships.
Someone who hyperproduces cortisol,
it’s hard to live with someone like that.
I would say people that have this,
let’s just call it biological resilience.
It’s not always adaptive
because you can stay in bad circumstances longer.
The ability to crash,
provided it’s not suicide or life destroying
or long arc of pause and the requirement
to take two years off from work or school or something.
The ability to keep pressing on is a double-edged sword.
Let’s put it that way.
I want to make sure in staying within this conversation,
because you mentioned phosphatidylserine,
we talked about rhodiola rosacea.
We talked a bit about ashwagandha.
You’ve also talked about omega-3s and fish oil in particular.
I’d love to know your favorite sources of these.
I think nowadays there’s more general acceptance
that getting these essential fatty acids is important.
Do you have a threshold level of sort of grams?
I’ve encouraged podcast listeners
to consider, depending on what they’re eating,
to try and get a gram of EPA or more per day.
Does that seem excessive?
And what are the real data on EPAs?
Because then the cardiovascular experts
always hit back and say,
oh, no, it’s not good for cardiovascular health.
And then you go,
oh, it’s better than antidepressants and other studies.
And they go, no.
So I feel like if you really want to make your life difficult,
if you want to raise your cortisol,
you go on Twitter and you say something positive
about omega-3s and fish oil.
And you learn a lot.
What are your thoughts on omega-3s?
I take a lot of them.
I’ve always been a big fan.
So this is where I personalize.
I think some people need more than others.
And what I do is I measure your level.
So this gets back to nutritional testing.
So for you, I would suggest an OmegaQuant
or one of my favorite cardiometabolic panels
is to do a Cleveland Heart Lab.
So I think they give me the most reliable information,
not just for lipids and subclasses and NMR fractionation,
but it also gives me an insulin resistance score.
It gives me levels of omega-3s.
We’ll provide links to these different sites
so that people-
But one quick thing about that,
the whole story is not omega-3s and taking fish oil.
So the work of Charlie Serhan at the Brigham
is showing that the way that we resolve inflammation,
our understanding of it is really,
I think, in the learning to crawl stage.
And so if you look at the omega-3-6 pathway in the body,
fish oils can help kind of push the reactions
in a particular direction,
but typically they’re not enough
for the resolution of inflammation.
Now, what most people do, including my MBA players,
is they pop an ibuprofen or something like that
when they’ve got inflammation
that’s got lots of other side effects
that are not so good for you.
And we know in terms of the resolution of inflammation
that taking something like ibuprofen
reduces the amplitude of inflammation by about 50%,
but then it potentially blocks
the complete resolution of inflammation.
So there’s these new supplements
called specialized pro-resolving mediators.
There’s a lot of different supplement companies
that make them.
And that combined with fish oil
seems to be the best combination.
And what I do for athletes who’ve got
kind of the normal aches and pains
of the training load they have
is I’ll combine a little aspirin,
small dose, just like 81 milligrams
or two of those, baby aspirin,
together with fish oil
plus specialized pro-resolving mediators.
And there’s some that are NSF,
they’re certified for sports.
But the dose, I would say with my patients,
some of them only need 1,000 milligrams,
your gram that you mentioned for the population.
Some of them need six grams together with SPMs.
So I think it has to be personalized.
How young is it okay for people
to start taking omega-3s?
For instance, young women in their teens,
in their 20s and their 30s,
young guys in their 20s and 30s,
should they take fish oil?
Assuming they’re not going to get anything tested.
I’m thinking about the college student
who is really into biomarkers
and that sort of thing will go do some of this.
But many people won’t,
but they want to do the right thing.
So they’ll try and drink a little less.
Hopefully they won’t smoke or vape.
Please don’t smoke or vape.
The idea that vaping is, okay,
it’s like we had this whole episode.
It’s so bad.
So bad for everything we’re talking about.
Let’s end that chapter.
So just, you know,
hopefully they’ll try and avoid those things.
Hopefully they’ll avoid hard drugs.
Hopefully they’ll avoid getting any STIs.
If they do, they’ll resolve them quickly, hopefully.
So, but they might say, oh, well, okay,
I’m willing to, you know, take some magnesium
or take some phosphatidylserine,
buffer my cortisol, eat some vegetables.
Should they consider taking fish oil
as a kind of across the board inoculatory thing?
So I’d like to rank order these.
I would say fish oil, yes.
I think a thousand milligrams
as a general recommendation is good,
but I also have a food first philosophy.
So my preference would be that they’re having salmon
or some kind of smash fish,
and they’re getting that as the primary source
of their omega-3s.
And then the days that they don’t have fish,
I recommend it probably twice a week
that they take fish oil.
Then I would put magnesium next,
since so many people are deficient.
Then I’d probably put vitamin D.
How many IU of vitamin D per day?
Well, you keep asking me this, like for the population.
Well, let me put it this way.
For the lazy person or, and this is an or, not an and,
or the person who just doesn’t have the finances
to go get levels measured.
Because, you know, our audience is a huge range.
We’ve got people who can have tons of disposable income
that listen to this podcast.
We have people that have no disposable income.
So 1,000 to 2,000 international units.
But my, you know, what I do is I dose to a serum level
that’s between about 50 and 90.
And so I have a vitamin D receptor snip.
And so I need to take about 5,000 a day
to get to what I need.
A lot of people don’t need that.
And, you know, there’s some supplements that
I don’t know if they need.
So you mentioned phosphatidylserine.
For someone who’s a college student
and their cortisol is completely normal,
they’re wasting their money on PS.
They might need it later, but they don’t need it now.
I’d like to make sure that we circle back to birth control.
In particular, oral contraceptive birth control.
And we should touch on IUDs perhaps a little bit more.
But what are your thoughts on sort of
pure estrogen birth control?
This is what I learned when I was in college
is that birth control is basically tonic estrogen.
So constantly taking estrogen, estrogen.
Women are taking estrogen
so that they don’t get the estrogen priming of progesterone.
You’re not getting any ovulation.
And I’ve known women that have been taking oral,
or that took oral contraception as like estrogen pills
basically for five, 10, 15 years.
Are there long-term consequences of this
as it relates to pregnancy, PCOS, menopause?
If so, what are some of those consequences?
What are your concerns?
What do you like about oral contraceptives?
What do you dislike about them?
I like how balanced you ask that question.
So women who take oral contraceptives,
as long as you’re describing like 10 years or longer,
we call those Olympic oral contraceptive users.
In terms of benefit, I think that,
especially when they first came out and even now,
it gives women reproductive choice and that’s essential.
As you may know,
our reproductive choice has been declining recently.
So I’m a big fan in that regard,
and we’ve got a lot of data to show both the risks
and also the benefits of it.
So I’ll speak first into the benefits
because I’m gonna get on a soapbox a little bit
about the risks.
So we know that it reduces the risk of ovarian cancer.
So there’s something about this idea of incessant ovulation
that is not good for the female body.
So if you look at, for instance,
women who are nuns,
who don’t take oral contraceptives
and they have a period every single month
of their reproductive lives,
they have a greater risk of ovarian cancer.
So if you look then at women who have several babies
and they’ve got a period of time when they’re pregnant
that they’re not ovulating
and then they breastfeed for some period of time,
they have a lower risk of ovarian cancer.
So oral contraceptives help with reducing ovulation
and reducing risk.
We know that if you take the oral contraceptive
for about five years,
it reduces your risk of ovarian cancer by 50%.
And that’s significant because we’re so poor
at diagnosing ovarian cancer early.
There’s really no method that’s really effective.
We use CA-125 and ultrasound screening,
especially in women who are at greater genetic risk.
But even that, often we diagnose it in a later stage.
Maybe just because that statement is gonna highlight
for a number of people,
the question of what are some of the earliest symptoms
that people can recognize without a blood test?
So is ovarian cancer, is it gonna be pain?
So the problem is the symptoms are so vague
and they’re so nonspecific.
One of the most common symptoms is bloating.
And we’ve already talked about constipation.
We’ve talked about how women have this longer GI track.
And so bloating is a really common experience
for most women.
You can have bulk symptoms,
feeling like your lower belly is kind of pressed out.
So the way that we inform women
in terms of watching for this
is to get regular gynecologic exams
for women who are at high risk
or they have, for instance, an ultrasound for some reason
and it shows a mass that we’re concerned about.
There’s a way to triage that
in terms of what kind of evaluation that they need.
And that’s a situation where you might get a blood test
called the CA-125.
Yeah, the problem is the symptoms are so vague.
It could be, it depends on how big the tumor is,
how much bulk you have, what it’s pressing on.
So if taking estrogen
and thereby reducing the frequency of ovulation
lowers the risk of ovarian cancer,
should women that are,
even women who are not sexually active,
so they’re not actively trying to get pregnant
or avoid getting pregnant,
but if they’re not sexually active,
then the probability of conceiving
unless they go through some IUI or some other route
is very low, as far as I know.
That’s what I was taught in high school anyway.
Would they be wise to suppress ovulation
for periodically using hormone-based contraception
just so that they can offset the risk of ovarian cancer?
That’s a very rational question.
And I would say that’s what mainstream medicine
has had at its back to recommend oral contraceptives,
not just for women who are seeking contraception,
but for acne, for painful periods,
for really kind of the drop of a hat,
they’re prescribing oral contraceptives.
That’s what I was taught to do.
But there are so many consequences.
And I think the issue here is more about consent
because in OB-GYN,
and I started out as a board-certified OB-GYN,
and I now mostly see men,
but I was taught as an OB-GYN
to convince women to go on the oral contraceptive.
And I think a lot of that is pharmaceutical influence.
So maybe we could talk about the risks
and why the answer is no to your question.
As we do that, could I just ask,
is the so-called ring,
it used to be called the NuvaRing,
maybe that’s a brand name,
but when I was in college,
there was all this discussion about the ring
by both men and women for reasons
that don’t belong on the podcast.
Use your imagination, folks.
So the ring, obviously, it’s not oral hormone contraception,
but it’s hormone-based, right?
The ring is releasing estrogen locally
as opposed to taking it orally.
But would you slot it under what you’re about to tell us
in terms of the concerns?
So we have less data about the ring.
So the oral contraceptive is two hormones.
It’s ethanol estradiol,
and it’s a progestin.
So it’s not the normal progesterone that your body makes,
that your ovaries make and your adrenals make.
It is a synthetic form of progesterone.
And it is the same progestin, similar,
same class that was shown to be dangerous and provocative
in the Women’s Health Initiative.
So I’m not a fan of progestins.
I do not recommend them for any woman
unless the consequence of not taking them
is surgery or some other,
unless it gives them some freedom in some way.
So I don’t like progestins.
The NuvaRing is estrogen plus progestin,
but it’s released transdermally through the vagina.
So given the way that it’s delivered to the vagina,
the doses are lower than what’s taken orally.
But in terms of some of the risks
that I’m about to talk about,
we don’t know about much of the data.
We think that it’s similar.
There’s probably a spectrum of risk,
and the NuvaRing is a little more towards the middle
than what I’m talking about with oral contraceptives.
Are you ready for that?
Yeah, I’m ready for the risks.
Okay, so like with almost any pharmaceutical,
the oral contraceptive depletes certain micronutrients.
So magnesium, there’s certain vitamin Bs that are depleted.
It also affects the microbiome.
That data is not as strong,
but there seems to be some effect,
and there’s also an increased risk
of inflammatory bowel disease in autoimmune condition.
It increases inflammatory tone.
So the studies that I’ve seen increase
one of the markers of inflammatory tone,
high-sensitivity CRP, by about two to three X.
It seems to make the hypothalamic-pituitary-adrenal axis
more rigid so that you can’t kind of roll with the punches
and wax and wane in terms of cortisol production
the way that you can off the birth control pill.
It can affect thyroid function.
I’m thinking of the slide that I have
that has like 10 problems associated
with the oral contraceptive,
but that’s what I can remember right now.
That’s very helpful, and it makes me wonder whether or not,
if on the one hand, oral contraceptives are protective
in women against ovarian cancer,
but then they have these other issues.
Yeah, there’s one other I want to mention.
Anytime you take oral estrogen,
it raises sex hormone-binding globulin,
and you’ve talked to other podcast guests about this.
Kyle, I think.
Sex hormone-binding globulin, I think of as a sponge
that soaks up free estrogen and free testosterone.
So when you go on the birth control pill,
you raise your sex hormone-binding globulin.
It soaks up especially free testosterone,
and for some women, it’s not a big deal.
They don’t notice much of a difference,
but then there’s a phenotype,
maybe related to CAG repeats on the androgen receptor,
who are exquisitely sensitive
to that decline in free testosterone.
So this then opens the portal of talking a little bit
about testosterone in women.
So we’ve mentioned already that it’s the most abundant,
biologically, the most abundant hormone
in the female system.
Even though men make almost 10 times as much
or even more than 10 times, it is so important for women.
It is essential to so many things,
not just sex drive and muscle mass
and seeing a response to resistance training,
but also confidence and agency.
And so those women who are so sensitive
to their testosterone level,
they’ve got this high sex hormone-binding globulin,
their testosterone declines,
what they describe is vaginal dryness,
maybe a decline in sex drive,
but there’s also this bigger issue
related to confidence and agency,
even risk-taking from studies
that we’ve done with MBA students
that I think is a serious problem.
Maybe the most important out of all of these things
is that it can shrink the clitoris by up to 20%, 20%.
And that includes a regression of the nerves
that innervate the clitoris?
Is that, I mean-
That’s a very good question as a neuroscientist.
Yeah, I would think,
used to teach the neural side of reproductive health.
We need to do a series on sexual health.
Maybe you would co-host that with me.
We could certainly use your expertise.
I think, yeah, that’s a dramatic number.
Yeah, but then let’s go back to the sacred marketing.
If I’ve got a woman
that I think should not be on the birth control pill,
maybe she’s taking it for acne
or she’s taking it
because her periods were a little painful.
What I’m gonna do is say,
let’s leverage these other ways
of making your period less painful.
Let’s take the message of your painful periods
and figure out, okay, is it your inflammatory tone?
And we give you some fish oil and SPMs,
maybe a little aspirin when you’ve got your period.
Like, let’s find some other ways to deal with it
than to take the oral contraceptive,
which you have not received informed consent about,
because it can shrink your clit by up to 20%.
Now, that usually convinces most people to come off of it.
Is that reversible?
The elevation in sex hormone binding globulin
does not seem to go away
when you come off the birth control pill.
To me, that is the biggest problem
with prescribing oral contraceptives.
Now, the data that we have is limited.
There’s one woman who, Claudia something something,
who looked at sex hormone binding globulin
a year out from stopping the birth control pill,
and it was still elevated.
It wasn’t as high as it was when they were on the pill,
but it was still elevated.
So your question about reversibility,
I don’t know if we know the answer to that.
That’s, yeah, that’s a significant statement
and something that for consideration.
Related to this, although this might seem not related,
it is, how early do you recommend
that women go get their follicle number assessed?
In other words, to get a sense of the size
of the ovarian reserve and their AMH levels measured?
I’m an amateur outsider as I say this,
but we have an episode on the fertility
where I just described the ovulatory menstrual cycle.
I’m not the best person to answer that.
Yeah, well, we can-
I’m too far out from it.
Okay, well, I suppose then from taking the perspective
of somebody who thinks about fertility
in terms of at least congruent with vitality and longevity,
given that it’s fairly non-invasive,
it’s an ultrasound or a blood draw for AMH or both,
is there any reason why a woman
would not want to get her follicle number assessed
or her AMH levels assessed?
Is there any reason why?
Because I was shocked to learn
that most women don’t do this
until they’re hitting their late 30s or early 40s
and they either haven’t conceived
or they suddenly decide that they want to conceive.
And I thought, why doesn’t every doctor insist
that their female patients have their AMH level addressed
so that if they need to-
Freeze eggs, they can.
Yeah, so I think if you’ve got
the disposable income to do it, go for it.
It’s not included in a standard blood panel?
The only women in my practice who’ve had AMHs done
and have looked at their follicle count
are women who want to freeze their eggs
or, and that requires disposable income,
or they are having trouble getting pregnant.
So they are in the reproductive endocrinology system
and they’re getting an evaluation.
And then there are also the women
who have symptoms of early menopause.
So premature ovarian insufficiency, which is before age 40.
Those are the women that I see getting attested.
And I think you’re right
that it should be offered more broadly.
It speaks to the democratization of data again.
And I think most women don’t know that.
So you’re doing a huge service,
I think, to be speaking into this.
One other point related to that
is that what I see in conventional medicine
is that when a woman asks for a hormone panel
and she’s not trying to get pregnant,
she usually gets told that hormones vary too much.
It’s a waste of money.
You don’t need it.
Or if you’re feeling hormonal,
why don’t you go on a birth control pill?
Unless she’s trying to get pregnant.
If she’s trying to get pregnant,
suddenly those same tests are very reliable
and they get their testosterone,
their free testosterone, their thyroid panel,
they get their estrogen and progesterone,
maybe they get their cortisol, they get their AMH.
So there’s a double standard
between those who wanna get pregnant and those who don’t,
and that needs to end.
Yeah, I totally agree.
As I’ve learned more about ovulatory cycle and AMH
and the enteral population of follicles,
it’s fascinating, it just seems to me,
wow, a relatively straightforward test.
One, definitely invasive ultrasound, but-
I didn’t consider that.
Yeah, not terribly invasive, but invasive,
but the other one, just pure blood test,
just seems like, why wouldn’t this be offered
or covered by insurance or that anyone that wanted?
But now I understand why.
You mentioned menopause, huge topic, enormous topic.
We had a guest on the podcast who’s not a clinician
who said something in passing,
so I’m likely to get this wrong,
but what they said was that the results
of the large-scale trials on hormone replacement therapy
for women for menopause said something to the effect of,
if the hormone therapy was started early enough,
it was very beneficial for vitality and health outcomes.
Whereas if women went through menopause
and then initiated the hormone therapy,
hormone replacement therapy,
that it could be detrimental to their health.
So first of all, do I recall that statement correctly?
And then second of all,
what sorts of hormones are being replaced?
Is it just estrogen and how is that done?
Is it done through birth control?
So oral contraceptives, NuvaRings,
what are your thoughts on menopause?
When should people start thinking about it?
And what is the palette of things available
so that we can do an entire episode with you
on this topic in the future?
But just to, I get a lot of questions about this,
and I’m guessing, based on everything you’ve told me today,
that there are women in their 30s
that while they may be 20 years out from menopause,
probably should be doing things now
in anticipation of that.
Yes, so we haven’t talked about the 30-something,
but I totally agree with you.
The more you know about your phenotype,
your hormonal phenotype when you’re in your 30s,
you’re set up in terms of what to do in the future,
especially things like your thyroid,
your estrogen and progesterone levels,
because you can replace to a state of euthyroid,
whatever that is for you.
You can replace, I don’t usually go exactly back
to where the estrogen and progesterone levels were,
but we can get pretty close.
So in your 30s, having a base case,
I think is really essential.
So you spoke to the Women’s Health Initiative,
which was published in 2002,
and we went from a huge number of women
taking hormone therapy to a very small percentage,
like in the range of 5%.
And that means we’ve got millions and millions of women
who are suffering needlessly with things like insomnia,
difficulty with their mood, difficulty with sex drive,
feeling like they are closing the store in terms of sex,
because they’re not on hormone therapy.
I would agree with the statement that you made
that hormone therapy, particular forms
that are similar to what your body always made,
when it’s given judiciously at the right time,
typically within five to 10 years of menopause,
which is 51 to 52, that it is incredibly safe.
So it’s a complicated study, the Women’s Health Initiative,
but it was the wrong study and the wrong patients
with the wrong medications
and with some of the wrong outcomes.
So it was powered to look at cardiovascular outcomes.
It was not powered to look at breast cancer.
It was stopped because of breast cancer risk.
But what happened in the control arm of the study
was that they had an incredibly low rate of breast cancer.
And so as a result,
they ended up having this increased risk of breast cancer
at five years, and they stopped the study.
Now, the study was done with synthetics.
It was done with conjugated equine estrogen,
known as Premarin, and medroxyprogesterone acetate.
Those were the so-called estrogen and progesterone.
Those are synthetic hormones.
We think especially the progestin is associated
with the greater risk of breast cancer.
Although the subsequent re-evaluations of the data,
now 18 years out, have shown that this problem
with the control group and no increased risk
of breast cancer.
And for the women who got estrogen only,
those who had a hysterectomy, the Premarin,
they actually had a decreased breast cancer risk
and decreased breast cancer mortality.
So there’s a lot to be said about this.
I’m trying to keep it really brief.
But if you look at the women 50 to 60,
so within 10 years of menopause,
they’re the ones who seem to have the greatest benefit.
So they had a decreased subclinical atherosclerosis,
so less cardiovascular disease.
They had an improvement in terms of bone health,
less progression to diabetes.
And then over the age of 60,
they started to have greater risk of certain outcomes,
such as cardiovascular disease,
myocardial infarction, and so on.
You asked about, what do I do?
And to me, this problem is not just menopause.
What’s more interesting is to talk about perimenopause.
So perimenopause is the period of time
before your final menstrual cycle.
And for most women,
depending on how attuned you are to the symptoms,
it can last for 10 years.
So I’m still in perimenopause.
It’s been like 20 years
because I’ve been tracking it so carefully.
It usually gets kicked off
by having your cycle get closer together.
So that can happen in your 30s or your 40s.
You go from 20 days to 25 days, that sort of thing.
You may notice that you start sleeping more poorly
because progesterone is so important.
You talked about that with Kyle.
You may notice it as more anxiety, difficulty sleeping,
and that probably is related to the estrogen receptor.
So ER alpha is, estrogen receptor alpha is angio.
It increases anxiety.
ER beta is associated with an anxiolytic activity.
And then there’s a total of about six estrogen receptors.
Now there’s the G-protein coupled estrogen receptors,
and those are mixed, anxiolytic, anxiogenic.
So there’s this whole period of perimenopause.
And what’s most fascinating to me,
and we’ve got to talk about this
either today or another time,
is that there is this massive, massive change
that happens in the female brain
that people are not talking about enough.
And so looking at the work of Lisa Moscone at Cornell,
from starting around age 40,
there is this massive change in cerebral metabolism.
So you can do FDG PET scans, you can look at glucose uptake,
and there’s about, on average, a 20% decline
from premenopause, you know, up to like age 35,
to perimenopause, to postmenopause.
The women who are having the most symptoms
in perimenopause to menopause,
the hot flashes, the night sweats,
the difficulty sleeping,
those are the ones who have the most significant
So it’s almost like a,
I don’t want to scare people with this language,
but it’s a low level,
or let’s call it pseudo dementia of sorts.
Yes, it seems to be a phenotype
that you can then map to Alzheimer’s disease,
because that’s Lisa Moscone’s work.
She’s looking at, okay,
Alzheimer’s disease is not a disease of old age,
it is disease of middle age.
What are some of the biomarkers that we can define
that can tell you what your risk is?
I’ve got a mother and a grandmother
with Alzheimer’s disease,
you can believe I am all over this data.
And insulin resistance,
insulin insensitivity, as we talked about it before,
seems to be somewhere in there,
which I think when that first,
when that idea first surfaced,
a few people were like, really?
But then of course, right?
I mean, the brain is this incredibly
metabolically demanding organ.
You deprive neurons of fuel sources,
or you make them less sensitive to fuel sources.
They start dying, they certainly start firing less.
It makes perfect sense.
And I think now it’s,
thanks to Lisa’s work,
work that you’ve done and talked about quite a lot
is in your books and elsewhere,
I think has really highlighted for people
that metabolism and metabolomics
is going to be as important as genes and genomics
when it comes to dementia,
perhaps, especially in women.
Is it safe to say that?
I think so, because
we believe that the system is regulated by estrogen.
So the decline in estrogen starting around age 40,
43 is kind of the average,
seems to be the driver behind cerebral hypometabolism.
The way I describe it to my patients is,
it’s like slow brain energy.
So you walk into a room, you can’t remember why,
like you just notice that you can’t manage all the tasks
the way that you once could.
Like things are just a little slower.
And I say that to women,
and they’re like, I have that, like, help me.
So this is then circling back to WHI,
where women are scared to death of taking hormone therapy.
And we’ve got all of these women
that are marching toward potentially
a greater risk of Alzheimer’s disease.
And they have this opportunity in their 40s and their 50s
to take hormone therapy, and they may not be offered it.
Because the typical conventional approach based on WHI
is to say, unless you’re having hot flashes
and night sweats that are severe,
I’m not gonna give you hormone therapy.
And I just wanna call that out.
I would say, no, that is not the way to approach it.
the concept right now in conventional medicine
is that hot flashes and night sweats
are these nuisance symptoms
that we will take care of temporarily,
maybe with a little bit of estrogen and progesterone,
or a birth control pill, because it’s given a lot.
Or that they pass.
Or that you just suck it up, suck it up.
It doesn’t matter that you’re not sleeping anymore.
Turn down the temperature in your room.
And that’s not right,
because hot flashes and night sweats
hot flashes and night sweats
are a biomarker of cardiometabolic disease.
They are a biomarker of increased bone loss.
They are a biomarker of changes in the brain.
So many of these symptoms that occur in perimenopause
are not driven by the ovaries.
They are driven by the brain.
Yeah, it’s the bidirectional crosstalk
between the body and the brain keeps,
I think is the resounding theme.
We had Chris Palmer on here, a psychiatrist
who’s talking about ketogenic diet
for treatment of mental health.
I know we could have a whole other discussion,
and we will, I hope, if you’ll agree to it,
about nutrition and, as it relates to hormones,
specific diets and so forth.
And that’s a question too,
whether this problem of cerebral hypometabolism,
could we solve it with estrogen
and or increased metabolic flexibility?
So I just wanted to footnote that.
Sorry to interrupt you.
I know you’re, as long as we’re there,
I know you are a fan in some instances
of intermittent fasting, time-restricted feeding,
and or ketogenic diet to get cells sensitive to insulin,
which is not to say, if I understand correctly,
which is not to say that women need to stay
on the ketogenic diet for long periods of time
or intermittent fast by only time-restricted feeding
for eight hours or six hours a day,
but that by increasing,
you said metabolic flexibility, excuse me,
but by increasing cells’ sensitivity to insulin
and then maybe returning to a more typical eating pattern
and periodically switching back and forth,
that might actually be beneficial.
Do I have that right?
Yeah, I love the pulse.
So I feel like it’s much more physiologic
than, say, going on a ketogenic diet
and staying there for years.
All of the data that we have on the ketogenic diet,
it’s pretty limited in terms of duration.
The longest players that we have in terms of the data
are the folks with epilepsy,
and that’s just a different phenotype.
So I think in terms of microbiome effects,
diversity, dysbiosis, some of those issues,
we really don’t know in terms of long-term effects.
So I prefer with a ketogenic diet
that it’s used as an end-of-one experiment
and that you do it for four weeks.
Maybe you measure biomarkers before and afterwards.
Maybe you look at your stool before and afterwards,
and we still haven’t talked about stool tests yet,
but you could measure your fasting insulin and your glucose.
You could just start there, do four weeks of keto,
clean keto, including vegetables.
It doesn’t have to be 57 a day,
and then measure it again afterwards.
Since you mentioned stool testing,
what is your recommendation about stool testing?
So my recommendation, this is, again,
in the field of if you have the disposable income.
So I usually start with Genova
because they’ve got a good copay system with insurance.
That’s what I typically use.
So I usually do their one-day stool test
where you have to go digging through your stool
and send it off to this lab that’s in North Carolina.
I usually do the one-day
unless I’m concerned about parasites.
In that case, I tend to do three days.
I do that for people who travel a fair amount
and go to places where there’s greater risk
or they just have gut symptoms.
Another test that I do a lot is,
because I always like to mention two labs,
is a test by Wengevity.
And this is much more of a data wonk type of test
because it’s powered by AI.
It was designed by a guy who’s got inflammatory bowel disease
and he’s a PhD deep phenotyping bioinformatics guy
who wanted to make this really easy.
So the test is under the umbrella of THORN
and they used to call it GutBio.
They might have another name for it.
And they just improved it so that it’s a wipe
instead of digging through your stool.
And so my athletes will do it now.
They were not so into digging through their stool before.
Really, no one is.
I don’t want the answer to that.
I know the answer.
I prefer to that question.
But that’s a super interesting test
because you get much more dense data.
The issue is, with apologies to my friends at THORN,
the issue is that their recommendations
end up being THORN supplements.
So that can be very easy for people
who want to connect the dots.
But that’s not always the way that I like to do it.
First of all, three things.
You’ve shared with us an immense amount of knowledge.
And in that first statement, I also want to apologize
because I threw at you the entire lifespan
of a female lifespan, reproductive health,
contraception, diet, microbiome, so many things.
But I first, I just want to say
you’ve taught me a tremendous amount,
including, I think, something that most people,
including myself, have not thought about enough,
which is the psychosocial impact
on things that we’re all familiar with.
Constipation, bowel movements, what we eat, what we avoid.
I have to say, really, a huge thank you for that
because it’s not something that’s been discussed
on this podcast before.
Sort of know that brain communicates with body,
psychology and biology are linked.
But I think this is the first time
that anyone’s ever directly linked circumstances
and biology and psychology in such a concrete way.
So that’s the first thing.
And I speak for many people on that.
Second of all, we barely scratched the surface
of your knowledge, which is both frustrating for me
because I always want to learn more
and I know many other people do as well,
but also very, very exciting
because hopefully without much persuasion,
we can have you back on to talk about things.
Like men’s, I know you’re working with men now,
men’s health, some particulars around,
I think there’s more for us to explore
in terms of PCOS, menopause, contraception
and all of the above.
But then something that you and I were talking about
off camera before we started,
which I think is a really important factor
that ties back to this issue of trauma and stress
and the bi-directional relationship
between biology and psychology.
Hopefully someday we won’t even separate those two,
which is the use of specific medicines,
including plant medicines
and how that can influence overall health,
which no doubt will include hormone health.
So I say all of that for two reasons.
First of all, to cue up the,
we won’t even call it a part two,
but a sequel to this,
I’m gratified to hear that you’ll join us for that.
And then also to just really extend a huge thank you,
the amount of knowledge that you shared is immense
and is going to be very, very useful and actionable
for men in terms of their thinking and their actions
and for women in particular,
today’s discussion in particular for women
in terms of how to think about their health and biology,
how to think about their psychology
and the environment that all of that is embedded in.
I just want to say an enormous thank you.
Thank you, Andrew.
I so appreciate that.
And I so appreciate what you offer to the world
in terms of a way in, a way to understand physiology
and how to craft a architect, a better life.
Can I just add one last thing?
Because I didn’t talk about it
since we didn’t get to the forties and the fifties
in this list of biomarkers.
So I feel like if people,
if women went away with one thing today,
it would be to do a coronary artery calcium score
by age 45 and sooner if you’ve got premature heart disease.
How is that taken?
So it’s a CT scan of the chest.
You can self-order it.
Like I think at Stanford Hospital, you can self-order it.
Last time a patient checked, it was $250.
So again, disposable income, but it tells you,
it almost gives you this fork in the road
in terms of how much you need to pay attention
to cardiometabolic health as a woman.
And it’s a 45 for men too.
So if you haven’t had one, have you had one?
You need one.
Insulin, cortisol, CAC.
Great, I’ll run all that by you.
It’s really essential.
And it’s, yeah, it’s so fascinating
because there’s some women who have a zero.
So my score is zero and that’s great.
So often you can just keep doing what you’re doing.
But if you’re 45 and you’re starting to be elevated
or you’ve got, you know, maybe you’ve got PCOS
or you’ve got some other biomarkers
tending you in this direction toward the number one killer,
really eight to nine out of the top 10 killers in the US,
that allows you to really start to make changes.
And I think it’s essential to know that data.
It’s not, it’s probably not going to be offered
by your doctor.
Certainly Peter Atiyah is going to offer it,
but most conventional doctors are not going to do it.
And then the last thing I want to say.
So if I were to go to my doctor and I just say,
I want a cardiac calcium score,
that’s what people should ask.
Coronary artery calcium score, CAC.
So everyone hear that and know that if you’re 40 or older
and maybe if you’re-
45 or older, get it.
So the last thing is, and this is for men and women,
is your ACE score.
So adverse childhood experiences.
Knowing your ACE score is so essential
in terms of a baseline for how much trauma your system,
your pine system endured when you were a kid.
And we know that childhood trauma,
whether it’s abuse or neglect
or having an alcoholic parent,
that maps to disease in middle age.
And it can give you so much insight.
I’ll give you an example.
I’ve got a patient who had
an elevated coronary artery calcium score
who does everything right with her food.
I think it was her trauma that elevated her CAC
when she was 45.
So I think an ACE score, knowing your ACE score,
starting as a teenager, like knowing it
and knowing how to work with that is really essential.
There are certain people, they are exceedingly rare,
but you are one such person that when they speak,
knowledge just comes out of them
and it’s incredibly useful and helpful knowledge.
So thank you.
I’m gonna get both of those things.
And I highly recommend that everyone else pursue ways
that they can get those,
or if they can’t get them,
that they earmark those as things to get
at the point where they can obtain
sufficient disposable income.
Sounds like that the health,
the detriments to health that those can offset
would be well worth the cost.
Thank you for joining me for today’s discussion
all about female hormone health,
vitality and longevity with Dr. Sarah Gottfried.
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of Dr. Gottfried’s excellent books that she’s written
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notably Women, Food and Hormones,
and her book, The Hormone Cure in our show note captions.
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