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

vis-a-vis hormones?

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,

psychoimmunoneuroendocrine 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.

Oh, great.

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?

No. Yeah.

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?

It depends.

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.

Totally.

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?

Right.

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,

that’s profound.

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.

Yes.

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.

Okay.

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?

Yeah.

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.

That’s right.

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.

That’s right.

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.

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.

Cauliflower.

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.

57 independent.

57 independent.

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.

Right.

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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The reason I started taking Athletic Greens

and the reason I still take Athletic Greens,

once or usually twice a day,

is that it gets me the probiotics

that I need for gut health.

Our gut is very important.

It’s populated by gut microbiota

that communicate with the brain, the immune system,

and basically all the biological systems of our body

to strongly impact our immediate and long-term health.

And those probiotics in Athletic Greens

are optimal and vital for microbiotic health.

In addition, Athletic Greens contains

a number of adaptogens, vitamins, and minerals

that make sure that all of my foundational

nutritional needs are met.

And it tastes great.

If you’d like to try Athletic Greens,

you can go to athleticgreens.com slash Huberman,

and they’ll give you five free travel packs

that make it really easy to mix up Athletic Greens

while you’re on the road, in the car, on the plane, et cetera.

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.

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.

Totally.

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.

Totally.

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,

plant-based antioxidants,

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,

at glutathione,

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

cardiometabolic health.

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.

Really?

Yes.

Wow.

I’d be curious as to why that is.

I can guess, diet, stress.

Patriarchy, rage.

So psycho-

That they may not know about.

So pine, the-

The pine system.

Right.

Psychology, immunology,

neural and endocrine factors combined, is that?

Yes.

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,

psychology, immunology.

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.

Yes.

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?

Yes, please.

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.

Thank you.

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-

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.

Right, exactly.

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.

That’s great.

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.

It’s crucial.

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.

Whoa.

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.

Yeah.

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.

Yes.

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,

transcendental meditation.

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.

Which biometrics?

HRV, nighttime sleep.

Cortisol?

I wish.

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.

Wearing-

HRV 24?

Yeah.

Nice.

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.

Yep.

Another group did box breathing.

Yep.

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

snap open.

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.

Thank you.

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?

Probably not.

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.

Yes.

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.

And let’s-

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.

Love it.

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, my-

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.

Interesting.

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.

Amazing.

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.

Couple things.

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

for bioengineering.

In Seattle.

In Seattle.

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.

I am.

We need to send our Wikipedia editors out.

I think LinkedIn is correct.

Okay, great.

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.

That’s right.

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.

Great.

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.

Irregular periods.

Irregular periods.

Is that, you know, I get a lot of questions about PCOS.

Yeah.

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.

We should.

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.

Wow.

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.

Amen, Francis.

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

than estrogen.

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.

What?

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.

Fascinating.

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.

Totally.

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?

Sure.

Just cause it’s such a, and then work backwards.

That’s interesting.

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.

Yes.

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-

Anecdata.

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.

Thank you.

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.

Interesting.

I’ve found that for several supplements

that the lower dose was more effective.

Yes.

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.

Oh, interesting.

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.

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.

Yeah.

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.

Great.

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.

Exactly.

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.

Great.

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.

Please.

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.

Wow, okay.

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.

And-

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-

It’s cost.

Freeze eggs, they can.

It’s cost.

It’s cost.

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?

No.

Wow.

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

cerebral hypometabolism.

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.

Further,

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.

Please interrupt.

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.

Is anybody?

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?

No.

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.

Okay.

So everyone hear that and know that if you’re 40 or older

and maybe if you’re-

45.

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.

Good.

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.

Totally.

Thank you.

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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and her book, The Hormone Cure in our show note captions.

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