Huberman Lab - Dr. Peter Attia Improve Vitality, Emotional & Physical Health & Lifespan

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. Peter Atiyah,

his second time on the podcast.

Dr. Peter Atiyah is a medical doctor

who did his training at Stanford School of Medicine,

Johns Hopkins School of Medicine,

and the National Institutes of Health.

He is a world expert in all things related to healthspan,

vitality, and longevity.

In this episode, we focused on many topics,

focusing mainly, however,

on healthspan and longevity and mental health.

Healthspan and longevity, of course,

relate to how long one lives,

and Dr. Atiyah goes systematically

through the seven major causes of death worldwide,

beginning with cardiovascular disease

and cerebrovascular disease,

also cancer, also accident-related deaths,

dementia, deaths of despair,

and in every case, explains the three or four major levers

that one can employ in order to offset,

that is to prevent those major causes of death.

What follows is an incredibly informative

and actionable set of tools for anyone,

male, female, young, or old.

He explains the behavioral, nutritional,

supplementation-based, and prescription drug-based approaches

that one can use in order to extend healthspan

and longevity.

Dr. Atiyah explains the key tests and markers

that we should all pay attention to

if our goal is to extend our healthspan

and how to do so while maximizing our vitality.

This is something that not a lot of people think about

when they think about healthspan and longevity,

but as Dr. Atiyah illustrates for us,

emotional health has everything to do

with our physical health and vice versa,

and he shares quite openly about his own experiences

in pursuing ways to improve emotional health

and thereby healthspan, lifespan, and vitality.

Dr. Atiyah is quite open about his own experiences,

exploring different practices to improve emotional health

as ways not just to improve healthspan, longevity,

and vitality, but of course,

also to derive the most meaning and satisfaction from life.

Throughout today’s discussion,

we also discussed Dr. Atiyah’s newly released book,

which is entitled,

“‘Outlive, the Science and Art of Longevity.”

This is a phenomenal book.

I’ve read it cover to cover now three times.

I have extensive notes written throughout,

and the book of course focuses on longevity and healthspan,

and also has an extensive section on emotional health.

It gets quite detailed into Dr. Atiyah’s personal experiences

with emotional health and tools to improve emotional health

that are very actionable for anybody to use.

I think the best way for me to summarize my feelings

about the book would simply be to read the back jacket quote

which I provided.

So I read, quote,

Finally, there is a modern, thorough, clear,

and actionable manual for how to maximize our immediate

and long-term health.

Firmly grounded in data and real life conditions,

this is the most accurate

and comprehensive health guide published to date.

“‘Outlive’ is not just informative, it is important.”

And indeed, “‘Outlive’ is an important book,

as is the discussion that Dr. Atiyah

so graciously provided us in today’s episode.

“‘Outlive’ is released on March 28th, 2023,

and is available for pre-order prior to that date.

You can find a link to where it’s sold

in the show note captions.”

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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As I’ve talked about before on the Huberman Lab podcast,

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And now for my discussion with Dr. Peter Atiyah.

Dr. Atiyah, Peter, welcome back.

Thanks, man.

Good to be back and sounding better this time.

Looking forward to talking about a number

of important topics with you that you cover in your book.

Maybe we could start off by trying to set the frame

for what people should be thinking about

in terms of vitality and especially longevity.

So, I mean, I think you have to be mindful

of how you define these terms.

And I’m not gonna suggest that the way I define them

is the only way or necessarily the best way,

but I think from a clinical perspective,

it’s the way that makes the most sense to me,

having thought about this for the better part of a decade.

So it involves some bifurcation

between lifespan and healthspan.

Lifespan is very easy for people to understand.

It is binary.

You are alive or you are not alive.

And clearly part of longevity is about how long you live.

Now, I think for a lot of people,

that tends to be where the discussion ends.

That tends to be the focus of it, right?

It’s sort of like, you know,

longevity somehow implies living for 100 years,

120 years, something like to that extent.

We talk a lot about maximum lifespan.

Even in laboratory experiments with mice,

that’s sort of one of the metrics that’s discussed

is what’s maximal lifespan of the animals.

But there’s an equally, if not slightly,

I think potentially more important part of longevity,

which is healthspan.

And healthspan is squishier,

and I think it requires some definition.

Now, the medical definition of healthspan

is the period of time by which you are free

from disability and disease.

I find that to be a not particularly helpful definition.

Because by that definition,

you and I have the same healthspan today

that we did 30 years ago.

But I know you pretty well, you know me pretty well.

30 years ago, we were twice the men we are now

based on what we believe our healthspan is, right?

In terms of our cognitive function,

our physical performance and things like that.

So, you know, I’ve clearly experienced the deterioration

of my physical function, as I’m sure you have,

going back to when you were a teenager,

late teenager, early 20s.

And I think that needs to be captured somehow

in healthspan.

So, the way I think of healthspan

really is along these three dimensions,

physical, cognitive and emotional.

Again, not necessarily suggesting

that that’s the only way to do it,

but I do think that clinically it makes the most sense.

And so therefore, anything that really becomes a question

of longevity has to address all of these issues.

Lifespan, physical health beyond that

of just straight up disability and disease,

cognitive health, independent of

and separate from pathology such as dementia

and emotional health, which of course is by far

the most complicated of all of these

because we have no biomarkers for it.

We have no, you know, it’s not like you can get a scan

on somebody and determine the state of this,

but nevertheless, it’s important, right?

And it dramatically factors into quality of life.

So, with all of that in mind,

what are the major exit points

for people along the lifespan route?

So, start with the binary one, dead or alive, right?

I think most everyone who’s healthy

would like to be alive rather than dead.

So, what are the typical ways that people exit

from alive to dead and how can people stay

on the freeway of life, so to speak?

So, this is again, a great analysis.

We internally in our practice

call this the death bar analysis

and it’s a surprisingly trivial analysis

that I’m just surprised the death bars

aren’t plastered front and center on every doctor’s office.

So, if you simply just look at actuarial data,

which are readily available through the CDC

and do a little bit of data, you know,

manipulation and analysis,

you can pretty quickly realize

what the horsemen of death are

because there’s largely speaking

kind of four horsemen of death.

The first and most consequential in terms of the numbers

is the diseases of atherosclerosis.

So, that’s cardiovascular disease

being the lion’s share of that,

but also cerebrovascular disease.

So, anything that has to do with atherosclerosis

rises to the top.

Now, that’s true in the United States,

but it’s even more true outside of the United States.

It’s even more true globally.

So, in other words, when you look at the relative difference

between the number one cause of death in the U.S.

and number two, which is cancer,

the gap is actually smaller in the U.S. than globally.

Globally, it’s enormous.

We’re talking about 18 to 19 million people a year

that are dying of atherosclerotic cardiovascular disease

in the world,

whereas number two is cancer at about 11 million.

How does the number change

when you include cerebrovascular disease?

Yeah, it adds a bit to it.

Cerebrovascular disease has, largely speaking,

you can die sort of through embolic events,

which are the majority of them.

Can you explain for people what embolic events are?

Yeah, so taking a step back,

what does the brain need more than anything?

It needs blood flow.

Anything that interrupts blood flow to the brain

that results in ischemia is devastating,

and it’s devastating in a more readily apparent fashion

than virtually any other organ.

So, one way that that can happen

is if a clot or disruption of blood flow

occurs through obstruction of blood flow.

So, that can occur through a clot.

So, for example, if a person has atrial fibrillation

and a blood clot gets festering in the right atrium

and they happen to have a hole

between the atria of their hearts,

called a patent foramen ovale,

and a clot goes from right to left,

it can make its way up into the arterial circulation

and happen that way, where you include blood flow.

The much more common way it occurs

is the same way it occurs in the heart,

which is you have plaque buildup,

and that plaque becomes unstable, that plaque ruptures,

and the rupture of that plaque

results in an immediate attempt by the body

to fix the problem.

But in doing so, it walls off the artery,

meaning the blood flow distal to that point,

so that now blood is acutely being robbed of that.

However, there are other ways

that people can have this problem.

So you have the whole hemorrhagic side of this.

So you can have blood vessels,

small blood vessels in the brain

that will rupture as a result of high blood pressure,

for example.

So hypertension factors into both sides of this equation,

both in the heart and in the brain.

The majority of these are embolic, however.

So don’t quote me on this exactly,

but call it four or five to one strokes

result from an embolic phenomenon

as opposed to a hemorrhagic phenomenon,

a bleeding phenomenon.

I don’t want to take us too far off on a tangent,

but as long as we’re here

talking about bleeds versus clots,

what are some of the major risks for bleeds?

I mean, I know some people out there

have genetic predispositions for being bleeders,

as they’re sometimes called, or clotters.

So things like factor V Leiden mutations,

which can be exacerbated in women, for instance,

by taking certain oral contraceptives.

I mean, and there’s a huge list.

If people are interested in them, they can look up,

what are the factors controlling bleeding

and predispose people to being clotter.

But for the typical person out there who feels healthy,

but might do well to know whether or not

they are predisposed to be a bleeder or a clotter,

what sorts of things rise to the top of that list

and that people might want to check into?

Well, I mean, there might be sort of two different things

going on in that question.

But I think if your question is,

when we look at the subset of people

who are at highest risk for hemorrhagic strokes,

the far more germane question

is not underlying coagulopathy.

The far more germane question

really comes down to blood pressure.

Blood pressure would be the first, second,

and third driver of that.

So hypertension is hands down the leading driver

of hemorrhagic stroke phenomenon.

Okay, so I’ll just briefly interrupt and ask,

since sometimes your recommendations deviate

from the standards that one would find online

or in the typical doctor’s office,

at what point do you get concerned?

Well, I actually find myself quite in line

with the most recent available data on blood pressure.

And this has been, obviously,

there’s a topic that’s of high concern

to any doctor who’s taking care of patients

who even pays a fraction of attention

to the available literature,

which is that basically

with each subsequent blood pressure trial,

the data are becoming clearer and clearer

that the more aggressively you manage blood pressure

to be within the 120 over 80 range, the better.

So, you know, there’s a recent study

that even looked at going

from what used to be considered acceptable,

which was 130 to 135 over 80 to 85.

We used to basically say,

that’s kind of the first level of hypertension.

And we would say, well,

do you really need to be better than that?

And the answer turns out to be, yes, you do.

If you want to reduce heart attacks and strokes,

it’s better to be 120 over 80 than 135 over 85.

Now, this is a whole other rabbit hole

that we don’t need to go down,

but it’s a total obsession of mine,

which is how do you measure a person’s blood pressure?

I think this is potentially,

I’d have to give it thought,

but honestly, I could say top three

under-diagnosed fixable problems

in the United States today, and probably globally.

In other words, there are too many people walking around

with high blood pressure who don’t know it.

And I think part of the problem is,

it’s something that is mostly done in the doctor’s office,

and the readings that you get in the doctor’s office

can be often misleading.

You’ve heard of this phenomenon of white coat hypertension.

So you go to the doctor,

your blood pressure is virtually never measured correctly

in the doctor’s office.

That cuff they put on and that squeeze bulb,

that’s not accurate.

Yeah, if you look at the rigor

with which you need to measure a person’s blood pressure,

the right way to do it

is the person has to be sitting like this

for five minutes doing nothing.

Okay, folks, so when you go to the doctors now,

you don’t let them take your blood pressure

until you’ve been sitting for five minutes.

And that doesn’t include in the waiting room,

because if you walk from the waiting room.

Right, because then you get up and walk over, right.

Okay, so make them stand there.

Right, so you wanna be sitting there like this.

A manual cuff is better than an automated cuff,

but not enough people use manual blood pressure.

So a manual blood pressure means they put a cuff on you

and they actually put a stethoscope on the brachial artery

and they’re using the human ear to listen,

which believe it or not,

you would think a machine is better, but it’s not.

The machine can be misled by different sounds.

Now, I don’t wanna suggest that automated cuffs are useless.

They’re not.

But when an automated cuff gives you an answer

that is potentially suspect,

always back it up with a manual.

I’m pretty relentless about checking my blood pressure.

And so I’ll do side to side manual

versus automated every day.

And there’s easily a 10 to 15 point difference between them.

Maybe this is a silly question,

but can people check their own blood pressure?

Meaning manually?

Yeah, just could I get a cuff and a bulb

and learn how to do it?

Yeah, I think so.

I mean, I can do it, but honestly,

I usually have my wife do it.

She’s a nurse, but it’s not rocket science

to check blood pressure.

I guarantee you there’s a great video on YouTube

that explains the physiology of it.

And if you’re willing to splurge

on a good enough stethoscope and cuff,

like the cuff I have is really easy to use.

Once you put it on, it’s in a single thing.

I’m squeezing the bulb and looking at the pressure gauge

while I’ve got the stethoscope on my artery.

I mean, given the importance of blood pressure

and this arteriosclerosis being at the top of the list

of risks for dying,

it seems to me it might be worth the expense.

What’s a typical range of costs for the quality?

I don’t, it’s not inordinate.

I feel like my blood pressure cuff is 40 bucks.

And the stethoscope is a couple hundred bucks

if you’re getting a good one.

And, you know, a good automated cuff,

there’s, I have no affiliation with any of these companies.

I use two automated cuffs.

One’s called Withings.

The other one’s made by a company called Omron, O-M-R-O-N.

And they’re both decent, but again, they tend to run high.

And I have yet to find a credible explanation

from cardiologists as to why.

Everybody acknowledges that the manual one,

when done correctly, is the answer.

But I’ve heard wonky answers

about why automated ones are sometimes incorrect.

And again, it’s just made me realize

we’re not checking blood pressure often enough on people.

We’re overly relying on blood pressures

in the doctor’s office, which are not being done correctly.

So we basically have our patients do this relentlessly.

So how often, let’s say someone buys this,

because I think for $240,

I mean, I realize that’s prohibitive for some people,

but given the cost of some of the other things

that are discussed on this and many other podcasts.

First of all, I would just have people start

with an automated cuff to begin with

and just start with there.

We generally have people do it for two weeks.

You know, we give our patients a little spreadsheet

that automatically calculates averages

and stuff like that, tells them what to record and where.

And we just say, look, for two weeks,

we want to see two recordings a day.

And, you know, do a morning and an afternoon

slash PM recording twice a day for two weeks

and let us see those numbers

and we’ll scrutinize them further.

And if those numbers come in fine, let’s revisit in a year.

Will a day ever come when a watch

or a wristband can do this really well?

So I hope so.

And I’m investigating it.

I’m actually going to be trying one out

in a couple of weeks with a company

that I tried two years ago.

Two years ago when I tried it, I was not impressed.

So I kind of punted on it.

The company, which I guess I’ll not share

the name of the company just yet,

but they claim that it’s significantly better.

So I’m going to put it to the test again.

And it’s basically a continuous monitor.

So it’s a wrist device that about every 15 minutes

throughout the course of the day

will check your blood pressure.

To me, this would be, honestly, probably more important.

You know, you know how much emphasis I place on CGM

as a great thing to be able to test.

Right, I would argue this would be more important.

When the day comes that we can continuously

assess people’s blood pressure,

it would be an integral part of a person’s, you know,

health checkup once a year is do two weeks

of continuous blood pressure monitoring.

Right now to do that, which I’ve done as well,

is so cumbersome that it borders on absurd.

You actually have to wear a blood pressure cuff

that is attached to a clumsy device

that goes through the whole insufflation exercise

every 15 minutes, including while you’re sleeping.

You know, it provides some insight,

but it’s so disruptive that it’s not what we really want.

What we, the dream would be like a patch

that you could put, I don’t know, over your chest

that can somehow impute changes in blood flow

or something like that and regulate.

But we’ll see, you know, between optical sensors

and things like that,

I hope that we’re getting closer to having something.

So I don’t want a stroke.

I don’t want to bleed in the brain.

I don’t want to clot.

As long as we’re at this number one on the list,

arteriosclerosis being the number one killer,

what are the major ways to prevent it?

Yeah, so there’s three big ones that stand out,

you know, top and center.

And then there’s kind of a fourth one

that I think is the foundational piece.

So the three big ones, we’ve talked about one,

blood pressure.

So if your blood pressure is 120 over 80 or better,

that’s important.

The second is not smoking.

So it turns out that smoking and blood pressure

are both devastating for arteries,

but for different reasons, right?

So smoking is devastating from a chemical perspective.

So it’s completely irritating to the endothelium.

So the endothelium, as you know,

is the single cell lining that is the innermost part

of the arterial and arterial wall.

So this is a pretty special organ.

Again, it’s a bit naive,

but understandable that people just think

of arteries as tubes.

They’re much more complicated than that.

They have many layers to them,

but this particular layer is unusually important.

It has an outsized importance

because it is the one that’s in contact

with the luminal side, right?

Where the blood is flowing in the tube

and anything that injures that

has significant consequences.

So smoking is irritating to that in a chemical way

and blood pressure is irritating to that

in a mechanical way.

So those two things basically,

you just wanna,

that’s the low hanging fruit in my world, right?

You just don’t wanna have those things

causing irritation to the endothelium

because that renders you now susceptible

to the third factor,

which is ApoB bearing lipoproteins.

I wanna talk about ApoB in depth,

but as long as don’t smoke

is the second recommendation on the list,

can we better define smoking and what’s being smoked?

So assume nicotine for,

what about cannabis and what about vaping

of nicotine and cannabis?

Because vaping has become so much more common.

Yeah, it’s a great question

and it’s sadly something we don’t have a great answer for.

So I can certainly tell you

that there’s no reason to believe

that smoking cannabis is somehow better

than smoking cigarettes,

but the dose seems to be significantly lower.

In other words,

let’s consider a person who smokes a pack a day for 20 years.

We call that a 20 pack year smoker.

Someone who smokes two packs a day for 15 years

is a 30 pack year smoker.

That’s a person who’s dramatically increased

their risk of many cancers, including lung cancer,

and also their risk of cardiovascular

and cerebrovascular disease.

Again, I’m not a THC guy,

so I can’t necessarily speak for the habits

of people that are smoking marijuana.

I can’t imagine they’re smoking that much.

Probably not.

Yeah, so while on a joint to cigarette basis,

they’re probably equivalent in terms of harm.

I don’t know.

Let’s say a person smokes a joint a day,

that would be like smoking a cigarette a day.

You know, that’s a 20th of a pack.

Again, I don’t wanna say that there’s no downside to that,

but it’s probably significantly less.

So I don’t think the risk fully tracks.

I think the same is probably true for vaping,

and I wanna be clear, like,

I don’t think vaping’s a good idea.

The last time I looked at the data on this,

it was surprisingly sparse,

but to me, the only advantage I could see to vaping

was if it was the only way a person would stop smoking.

So there was, you know, I sort of looked at it as,

it was definitely the lesser of two evils,

but by far the better scenario

was not to do any of these things.

If nicotine is what you’re after,

there are better ways to get nicotine, for example,

through lozenges and gum and things like that.

So you shouldn’t be turning to those things to do it,

but if it was like, if gum is here and cigarettes are here,

you know, vaping was probably here, but boy, I don’t know.

For those listening, Peter spaced his hands

far apart for gum and smoking

and put vaping about a third of the way

from gum toward smoking.

In other words, vaping isn’t good for you,

but it’s not as bad as smoking.

That would be my, I mean, do you have a,

you’ve probably looked into this as well.

What are your views on this? Yeah, we did an episode

on nicotine, I did an episode on cannabis,

and, you know, the discussion around cannabis

gets a little contentious for reasons that aren’t important.

It’s kind of funny, people, the moment someone starts

to confront cannabis as a potential health harm,

people say it’s not nearly as bad as alcohol,

which is a crazy argument, right?

Getting hit by a bus isn’t nearly as bad

as getting hit by a motorcycle in most cases,

but sometimes, you know, so that’s just kind of silly.

And clearly cannabis has medical applications, clearly.

And then it becomes an issue of the ratio of THC to CBD,

pure CBD forms actually being quite effective

for the treatment of certain forms of epilepsy,

so-called Charlotte’s Web, that’s actually what it’s called.

Very high THC-containing cannabis clearly predisposes,

especially young males, to later-onset psychosis.

Those data are starting to become clear,

clear enough to me anyway that people ought to be aware

of them at least, and maybe make decisions

on the basis of those.

When it comes to the smoking versus vaping,

it’s just very, very apparent

that the chemical constituents of the vape

and what people are inhaling are terrible for people

and are loaded with carcinogens and a bunch of other stuff,

many of which cross the blood-brain barrier.

So that’s what worries me the most.

Now, obviously I’m not a clinician,

but anytime I hear about small molecules, you know,

these small inorganic molecules getting

across the blood-brain barrier

and then being maintained in neurons for many, many years,

I worry because the experiment is ongoing

mostly in young people.

So anyway, without going too far down that track,

I think if people can avoid smoking and vaping, they should.

And as you mentioned, there are other delivery devices

for nicotine and cannabis, tinctures and patches

and gums and things that, edibles that,

if people choose to use those substances, they can offset.

I think sometimes people would benefit to imagine

what the surface area of the lung is, right?

If you took the alveolar air sacs of the lungs

and spread them out, you would easily cover a tennis court.


So just think about anytime you inhale something,

you are exposing, your body is so adept at absorbing it.

I mean, we have this unbelievable system for gas exchange

that was designed for gas exchange.

And anytime you’re putting something else in that wake,

you’re doing a really good job of getting it into your body.

So be mindful of what that is.

And that, look, that applies to pollution too.

I mean, the PM 2.5 data is pretty good.

I think once you,

so particulates that are less than 2.5 microns

are getting straight into the body,

which is like a great argument for avoiding air pollution.


I mean, I always find it funny,

not to get off on this tangent,

but to me, the most compelling arguments

around cleaner energy

have nothing to do with greenhouse gases.

They have to do with air pollution.

I promise you more people are dying

from the particulate matters in air

that result from burning coal

than are ever going to die

from the CO2 emissions that result from that.

It’s not, and I would argue

that’s gonna be two orders of magnitude.

It’s not even in the same zip code.

That makes sense.

During the fires, which seemed to follow me,

because when I was in Northern California,

there were a bunch of fires

and we were constantly looking.

I mean, you’d wake up in the morning,

everything was covered with ash.

My dog was having trouble breathing.

I was having trouble breathing.

Everyone was suffering.

But there are websites that one can go.

You can just look at air pollution.

And we tend to only do this during fires.

And then when I’m in Southern California,

there tend to be fires here.

So it’s correlation, not causation,

but for sure, I didn’t set those fires, folks.

But it’s clear that it disrupts your breathing

for a very long period of time.

But it’s the long tail of that

that we’re really talking about here.

The very small particulate that,

we know firefighters, for instance,

and certain industrial workers

can end up with that stuff embedded

in their brain tissue for extremely long periods.

It’s just not good.

You make a really interesting point

about the call for cleaner energy.

Can we run that one up to Washington

or settle some of the debates about climate change

just by getting straight to that?

Right, right, I feel like-

To help me just bypass all the garbage

that’s being spewed back and forth

and basically get to the issue at hand, right?

Yeah, just make it better for people

to not die from the direct consequence.

I’d like to take a quick break

and acknowledge one of our sponsors, Athletic Greens.

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So trying to avoid, such a difficult word to say,

especially for a neuroscientist, arteriosclerosis.

Did I get it right?

Well, it’s athero, which is easier, because yeah.


Oh, there.

I’ve been making life more complicated for myself.

Typical of me.

Okay, so blood pressure, keeping it 120 over 80 or better.

Don’t smoke.

Let’s just throw in don’t vape.

I’m going to just plant my flag on it.

Just don’t vape.

There are other ways to get those things in your system

if you really want to get nicotine or cannabis

into your system.

ApoB, what’s the story with ApoB?

Okay, so to explain this,

you have to tolerate a little bit of chemistry.

So everybody’s heard of cholesterol.

And I certainly devote quite a bit of time in the book

to explaining this because it is so important.

And it’s definitely one of those areas

where I initially received a lot of pushback from the editor

and there was a thought that,

hey, this is a bit more technical than it needs to be.

But I think that sometimes you do need to resort

to longer dissertations to dispel mythology.

So cholesterol is a lipid.

It is a molecule that the body synthesizes.

It is a molecule that is essential for life.

So if you cannot synthesize cholesterol, you can’t live.

You’ll die in utero.

So there are rare genetic conditions

that prevent the successful synthesis of cholesterol.

Embryos that have those mutations do not survive.

Okay, so why do we need this stuff?

So we need this stuff primarily for two reasons.

First, it makes up a very important structural component

of cell membranes.

So as you know, a cell is a sphere.

We look at them and think they’re circles,

but they’re spheres and they’re fluid, right?

They aren’t just like little perfect,

big bowling balls or balloons.

They actually morph and shape and move in these paths.

And this is what allows cells to be next to each other

and all sorts of things.

They also have channels across all of them.

And those channels are held in place by,

among other things, cholesterol and phospholipids.

The second thing that makes cholesterol so important,

it is the precursor

to some of the most important hormones in our body.

So our sex hormones, testosterone, estrogen, progesterone,

in addition to glucocorticoids.

If you look at them, it’s really funny.

People, if you’re looking at, if you Google,

like give me the structure of these things,

you’re kind of like, wow, they’re all basically the same.

They all look really similar.

And they’re all pretty much just templates of cholesterol.

So understandably, when it’s something

that’s that important,

the body would leave nothing to chance.

We make all of our own cholesterol.

The cholesterol that you eat in food, largely irrelevant.

It’s esterified cholesterol.

So it means it has an ester side chain.

It’s too bulky to absorb in the gut.

So most cholesterol that you eat in food

just goes out your GI tract.

Okay, so we have this super important molecule

that every cell in the body makes,

but there’s a bit of a problem.

There’s actually two problems.

The first problem is,

not every cell can make as much as it needs all the time.

So you have this demand problem.

So for example, if you’re sick,

you’re gonna need to make far more glucocorticoids.

Your body’s response is going to be

to ramp up cortisol production,

to mobilize fuel and do a whole bunch of other things.

And certain cells like the adrenal glands

are gonna be called on to rise

to a higher level of performance.

And they’re not gonna be able to make enough cortisol.

So they’re going to have to borrow

or take cholesterol from other cells in the body.

In fact, one of the things we used to notice in the ICU,

I never knew why it was happening.

I now know is the few times I would accidentally

order the wrong set of labs on a patient in the ICU

and also order like a lipid test or something,

you would always notice their cholesterol levels

were dropping, serum cholesterol levels.

And I now realize why,

because they were basically just funneling cholesterol

to the adrenals to make more of the cortisol

that they needed to combat whatever

they were in the ICU for,

which is usually the most severe form of stress

the body is under.

So you have to be able to transport this stuff.

And then the second problem is, as you know,

cholesterol being a lipid is not water soluble.

So the most dominant highway in the body

is the circulatory system.

We can use the lymphatic system and things like that.

But for the most part, we use our circulatory system

as the highway to move stuff around.

And the highway is made up of water.

Plasma, which is the liquid component of your blood,

is water.

And therefore things that are water soluble move easily.

So glucose, sodium, electrolytes,

all of those things are dissolvable in water.

And therefore they don’t need a carrier.

You just dissolve them in the water and they can go.

So that’s why your liver can make glucose

that your brain can easily get.

And there doesn’t need to be a carrier or an intermediary

or anything like that.

But unfortunately with cholesterol being a lipid,

we can’t do that.

Just as water and oil don’t mix,

cholesterol and plasma don’t mix.

So the body had to come up with a trick.

And the trick was designing a vehicle

that was water soluble on the outside

and fat soluble on the inside,

that you could bury the cholesterol inside

along with triglycerides.

And on the outside, it was covered in protein,

which is water soluble.

And that’s the thing that moves around.

And that thing is called a lipoprotein.

And as its name suggests, it’s part lipid, part protein.

Lipid on the inside, protein on the outside.

And those lipoproteins come largely

in two different families.

So one family comes from a lineage called ApoB.

So the ApoB family,

which is short for apolipoprotein B100,

is a family that is derived from the liver.

And each of those lipoproteins

has one and only one apolipoprotein B100 on it.

We shorten it and just call it ApoB

because we don’t really worry about apolipoprotein B48,

which is attached to chylomicrons

that are responsible for fat absorption in the gut.

They’re very short-lived.

They don’t really factor into atherosclerosis.

So we’re gonna just, for the purists out there,

there’s an ApoB48, we’re not gonna talk about it.

So when I say ApoB, what I’m talking about

is a protein that wraps around

a subset of these lipoproteins.

There’s another family of lipoproteins called ApoA

or apolipoprotein A.

This is a much more complicated family.

And I’m not gonna talk about it here

because we would take an hour to just explain

how the apolipoprotein A family works.

But again, the punchline is

there are many apolipoprotein A’s.

There’s variable numbers of ApoA’s on those proteins,

and they are all part of a family

called high-density lipoproteins.

Back to the ApoB guys,

they are of the low-density lipoprotein lineage.

So you’ve heard the term LDL and HDL.

What is it referring to?

It’s basically referring to the relative concentrations

of protein and lipids in the lipoproteins.

And not surprisingly, based on their names,

the HDLs are higher density, more protein, less lipid.

The LDLs, low-density lipoproteins,

and VLDLs, very low-density lipoproteins,

and IDLs, intermediate-density lipoproteins,

are all lower density, which means more lipid to protein.

There are different sizes.

There’s a whole bunch of other things going on.

Most important fact in all of this

is that the ApoB’s are atherogenic.

So what we’re about to talk about next

is perpetuated by lipoproteins that have an ApoB on them.

So everything in the story right now

is just about how do you get cholesterol around the body.

And these proteins that have lipid in the middle,

so let’s just take ApoB, for example,

many, many billions of them floating around in our body,

even in the healthiest of people.

And they’re being shuttled to tissues that need them,

like the adrenals, muscle, heart, et cetera.

What sets the demand for these things?

So for instance, could somebody have relatively high LDL,

maybe even higher than sort of high end of chart

or even above high end ApoB,

but there’s some sort of demand, metabolic demand,

or they’re weight training a lot,

or they’re running marathons,

and so they need a lot of LDL.

The reason I ask this is because it’s so easy

for the uninformed person,

which I include myself in that group,

to just hear, oh, LDL, bad, cholesterol, bad, ApoB, bad,

when in fact, you very graciously spelled out the fact

that these things actually perform a functional role

in the healthy body.

So before we get into why they are or can be bad,

why would you want a low-density lipoprotein?

What is that doing for somebody?

And is there any circumstance

where the way people are exercising or thinking

or not sleeping or sleeping too much,

it’s that a higher level actually reflects

a healthy metabolic need?

We don’t have any evidence of that to date.

All of the functions that I described

can be done by the HDL.

So the high-density lipoproteins, the ApoAs,

can do all of it.

So ApoB and low-density lipoproteins

are just the necessary, the waste?

No, we don’t understand why we have them, Andrew.

This is the part that’s really interesting to me.

Most species do not even have ApoB.

And as a result of that,

most species are chemically incapable of atherosclerosis.

So if someone could zero out their ApoB and their LDL,

we assume they would function just fine.

We know they would because we have certain people

who walk around with genetic mutations

that render them that way.


Furthermore, we also know that

there’s a bit of a myth out there that cholesterol,

the cholesterol you measure in your blood

is essential for brain health, for example.

It’s an understandable thing, right?

You can speak to this very eloquently,

the role of cholesterol in the brain.

Yeah, I wrote down when I was a postdoc at Stanford.

So I always point out, I was born at Stanford,

trained at Stanford, worried I’d probably die at Stanford

hopefully a long time from now.

You’ll tell me how long from now by the end of the episode.

We’re gonna do the Charlie Munger thing

and make sure that you never go back to Stanford

so that you can’t die there.

There, exactly.

We cured already.

When I was a postdoc, I worked with a guy named Ben Barris,

who I know you know probably as a different person then

for reasons that people can look up Ben’s name.

Anyway, incredible scientist.

But there was someone in his lab that discovered

that cholesterol is a critical component

of the synaptogenesis process,

the formation of connections between neurons

in the developing brain.

And then that went on to lead to the discovery

of things like thrombospondins being important

for synaptogenesis, et cetera.

But cholesterol sits central

in the brain development mechanisms.

Like you want cholesterol around for brain development.

In fact, I think very low fat diets

and very low cholesterol diets during early development

can really impair brain development as I understand.

Yeah, it’s not entirely clear why,

but here’s what we know.

When you’re born,

your serum cholesterol levels are very low.

So children, infants and children,

have very low levels of cholesterol.

They would have,

and I should explain one thing that’s important.

They’re not myelinated yet, right?

I mean, sorry to interrupt,

but myelin of course,

the sheathing around neuronal axons,

which accelerates the propagation of nerve signals

and which is deficient in things like multiple sclerosis

is essentially fat made up of phospholipids

and requires cholesterol for synthesis.

But young children are not very well myelinated.

I mean, the spinal cord is myelinated.

Right, so this is what’s interesting, right?

We would all agree that cholesterol is more important

to infants and children than to anybody else, right?

It would be the most important substrate

for CNS development.

And yet infants and children

have virtually unmeasurable levels of cholesterol.

It really starts to take off in your teenage years, right?

So cholesterol basically,

serum cholesterol levels rise

basically monotonically throughout life.

Women get a big bump at menopause.

So it really goes up for them.

But what’s interesting is how is it,

how do we reconcile the fact that infants and children

have really low levels of serum cholesterol

yet clearly undergo CNS maturation without any problems?

And it basically comes down to the following.

What you measure in the serum

is but a fraction of the total body pool of cholesterol.

So we get a little bit of the light under the,

what’s the street lamp under the-

The drunk under a lamppost, yeah, yeah, right.

Just because we’re looking there,

we tend to think that that’s what we’re seeing.

But if you took the entire circulatory pool of cholesterol,

it’s about 10% of your total body cholesterol.

It’s a tiny fraction of it.

So it’s what we measure,

because that’s all we have access to,

but it really represents virtually none of it.

I do wanna say something,

because you mentioned LDL.

I wanna tie this back to the reader, right?

Or the listener, rather.

ApoB refers to the lipoprotein,

the singular lipoprotein wrapped around an LDL particle.

So if you happen to be lucky enough

that your doctor measures an ApoB level,

it’s a blood test.

It says ApoB, X number of milligrams per deciliter.

That’s measuring the concentration of that protein.

It is a direct measurement of the concentration

of LDL and VLDL particles.

When you have a blood test that says LDL,

it usually doesn’t say LDL.

It usually says LDL-C or LDL-cholesterol,

because LDL is not a laboratory measurement.

LDL-cholesterol is a laboratory measurement,

and it’s just taking the total number of LDL particles,

breaking them apart,

and measuring how much cholesterol is in them.

So LDL-C measures the total concentration

of cholesterol in the LDLs.

ApoB measures the number of them.

And they’re different,

but one of them is far superior at predicting risk,

and it’s ApoB.

The number of particles is much more predictive of risk

than the amount of cholesterol contained within them.


First time I’ve understood HCL, LDL,

and these lipoproteins in a way that makes sense.

So thank you.

I’m sure others feel the same way.

What ApoB level is your red flag cutoff, right?

I actually had my ApoB measured recently,

and I’m definitely above the high end.

We’ll be discussing this over dinner on Saturday night.

And just to tie this back,

I hope that’s a steak dinner,

and that should be fine,

given the fact that dietary cholesterol

has no direct link to ApoB and LDL.

That’s true, but dietary saturated fat does.

Okay, so-

Which is not to say we’re not gonna have a steak, we will,


Not necessarily one of the fattier cuts,

although probably will be for me.

So what’s the high end that you, high end flag?

Yeah, what point do you start saying,

we need to do something,

and then we’ll talk about what people can do.

Yeah, so this is a complicated question

because it depends on so many factors.

The first factor it depends on is what is your objective?

And I do pose this question directly to a patient, right?

So I say, look, we’ve got this disease

that’s the number one cause of death.

Now, you can die with it, or you can die from it.

Those are your choices.

Statistically speaking, more people will die from it

than anything else.

But if you live long enough,

we will all die with it to some extent.

So if you’re me, and I come from a family history,

as you know, I write about this in the book,

where basically every man in my family except one

has died of atherosclerosis,

and they have all done so very prematurely.

My dad lost brothers in their 40s and 50s.

By some miracle, my dad is still alive at 86,

but I think that’s in large part

because he at least had the good sense

to listen to doctors and take medication

to lower his cholesterol and blood pressure.

If your objective is to not die from heart disease

and only to die with it,

then you want ApoB as low as possible.

Now, how low you go depends on when you start,

because one way to think about this

is it’s an area under the curve problem.

The longer you wait to start doing something about this,

the more aggressively you need to do something about it.

I think a better way to think about this, though,

is to go back to what we talked about with smoking.

So would you agree that smoking

is causally related to lung cancer?


So just to be clear, Andrew,

you do not think that it’s just an association

that smokers get more lung cancer?

No, I do not.

In other words, you believe

that smoking causes lung cancer, then?



I mean, there are a number of mechanistic steps in between.

I mean, if somebody was really wanting to get to,

you know, drill into the logic,

they could say, okay, it’s not actually the smoking,

it’s a, you know, some disruption

of the endothelial cell lining that, you know,

But smoking triggers that, that triggers that.

I assume so.

And I agree with you, by the way.

I think the data are very clear.

I’m very relieved to hear that.

Yeah, yeah, yeah.

But I’m going someplace very important here

because if there’s one topic

that doesn’t get enough attention in medicine,

it’s causality.

And causality is an obsession of mine.

Like most of the day on some level,

I sit around thinking about causality.

And I think the hardest part about studying medicine

with respect to human beings

is how difficult it is to infer causality

for most things that we do.

So if you believe that smoking

is causally related to lung cancer,

then smoking cessation reduces

the probability of lung cancer.

That is a logical equivalency.

There can be no debate about that.

What if I said to you, Andrew,

this is going to be our new philosophy

around smoking cessation.

I’m gonna anoint you the czar of smoking cessation.

So if people pick up smoking, no problem.

We’re gonna let them smoke.

But we’re going to assess their risk for lung cancer

using a model that predicts

when their 10 year risk of lung cancer

gets above a certain level,

we’re gonna recommend that they stop smoking.

So we’re gonna look at their age,

their sex, their family history,

some biomarkers that might help us.

We’re gonna even do scans of their lungs.

And once we think they cross a threshold

where their risk of lung cancer is high enough,

let’s just say it’s 25%, boom.

You make them stop.

You tell them it’s time to stop.

Is that a logical approach

to treating smoking and lung cancer?

Or would it be better to say,

given that we know cigarettes are causally related to this,

how about you never start smoking

and the minute you do,

we pull the cigarette out of your mouth

and explain to you that you’re doing something

that is causally related.

Of course it would be the latter, not the former.

It would be idiotic to suggest that we endorse smoking

until you cross a certain threshold.

Well, this now becomes the germane question.

There is no ambiguity that ApoB

is causally related to atherosclerosis.

You know, how can I tell you that?

I can tell you that looking at

all of the clinical trial literature,

all of the epidemiologic literature,

and perhaps even most importantly,

the Mendelian randomizations.

All of these things tell us, because by the way-

Mendelian randomizations, meaning genetic mutants,

humans out there that make very little ApoB

or excessive ApoB. And very much, exactly.

So we have the whole gradient.

So you can say, if you make very little,

you aren’t gonna die as quickly in your life

as if you make too much.

That’s right.

So Mendelian randomization is such an elegant tool

where you basically let genes do the randomization.

And as you said, there is a gradation of LDL concentration

or ApoB concentration that occurs from insanely low

to insanely high.

And this is a wildly polygenic polymorphic

set of conditions.

And we can look at the outcomes of those people

based on the random sorting of those genes.

And there’s no ambiguity.

LDL is causally related.

LDL cholesterol or ApoB,

causally related to atherosclerosis.

Well, if that’s true,

and I haven’t seen a credible argument that it’s not,

there are people who argue that it’s not by the way,

but they just don’t have credibility in their arguments.

Then you have to say that what we’re doing in medicine today

is very backwards.

Because what we’re doing in medicine today is the following.

We’re saying, I’m coming at this

in a long way, but your question is so important

that I want to answer it this way.

We’re answering your question today as follows.

We’re saying, Andrew, let’s do a 10 year risk calculation

of your risk of MACE.

MACE stands for Major Adverse Cardiac Event.

It is the metric we use in medicine.

So a Major Adverse Cardiac Event is a heart attack,

stroke, or death basically resulting from these things.

So, and we have calculators that are pretty good

at predicting your 10 year event risk.

They’ll look at your cholesterol levels,

your blood pressure, they’ll ask if you smoke,

they’ll ask some family history questions,

and they’ll spit out a number.

Now we should do yours after the fact.

And I don’t know, if we did it for a person who’s is,

you know, you’re in your mid forties,

like it would probably spit out less than 5% risk

for a Major Adverse Cardiac Event in the next 10 years.

In fact, the models don’t even work if age is below 40.

So the first time I went to do one of these tests

when I was in my mid thirties, I couldn’t do it.

Like the algorithm breaks.

So it’s sort of like, you know, just doesn’t work.

So the implication there is if you’re,

if your MACE risk is less than 5%,

the thinking is you do not need to treat LDL or ApoB.

I argue that that makes absolutely no sense.

It’s just as idiotic as the analogy I used around smoking.

If a risk is causal and it is modifiable,

it should be modified regardless of the risk tail in duration.

So then the question becomes to what level?

And again, the earlier you start,

the less aggressive you need to be,

the less damage that’s there already.

So for example, we do CT angiograms on our patients.

If the CT angiogram shows no evidence of calcification,

no evidence of soft plaque,

that means grossly their coronary arteries are still normal.

Histologically, they’re probably not

because nobody probably makes it to our age

with histologically perfect coronary arteries.

You know, we might be satisfied with a person’s ApoB

being at the fifth percentile of the population,

which would be about 60 milligrams per deciliter.

But if we have any other factors,

meaning we’re starting later in life,

or a person already has gross evidence of disease,

calcification, soft plaque, family history is significant,

any other risk factors are present,

I mean, we’ll treat ApoB to 30 to 40 milligrams

per deciliter, which is probably the first percentile.

And if somebody’s sitting up in the, say, low 130s,

where does that, what kind of flag does that raise for you?

And I realize it’s highly contextual, age, et cetera.

No, no, it’s a huge red flag.

Again, just because something is causal

doesn’t mean you’re guaranteed to get it.

There are smokers who don’t get lung cancer.

So, you know, there’s gonna be somebody listening to this

who says, my grandmother’s 95 years old,

she’s, her cholesterol is sky high,

and she’s alive and well.

And I will say, absolutely.

There are a lot of people walking around that way,

just as there are a lot of smokers walking around

who don’t get lung cancer.

You can’t, you can’t impute these things

on an individual basis.

You basically have to ask the question,

how do I make the best judgment about an individual

from heterogeneous population data,

and based on what are causal

and non-causal inferences around risk?

So, you know, to me,

if a person has very high ApoB

and they do not want to be treated for it,

then the best we would do is say,

let’s at least establish

that there are no other risk factors present,

and let’s at least do the most investigation we can

around the existing damage.

And if that person has a perfect CT angiogram,

I’m gonna push less hard

than if they have a devastating angiogram.

And by the way, devastating in my book

is just any amount of calcification or soft plaque.

Anything that shows up grossly that you can see on a CT scan

means that you’ve got a decade plus

of really bad histology building up to it.

This issue of causality,

I think now becomes very clear as to why that is so crucial,

and really appreciate the way you spelled that out.

So let’s say somebody’s ApoB is, you know, 80, 100,

let’s say 130, for example,

what sorts of things can they do to reduce that number?

Is this always gonna be prescription medication?

And if so, what are the more common forms

of prescription medication that work best?

What are their side effect profiles and so on?

So, yeah, usually once you wanna start getting down

into the 30 to 60 range,

you’re gonna require pharmacotherapy.

But, you know, usually we wanna see

how far we can get with nutrition.

So fixing insulin resistance in an insulin resistant person

will bring this down, right?

So one of the hallmarks of insulin resistance

is elevated triglycerides.

They haven’t, we haven’t talked about triglycerides,

but they warrant some attention

because I mentioned it earlier,

but one of the other things that the lipoproteins carry

is triglycerides.

So you’re carrying fat and cholesterol.

And if you recall, ApoB represents the number of particles.

So the purpose of them is to be carrying around

mostly cholesterol,

but if you have a high amount of triglyceride,

you’re basically using up cargo space on the ships.

And so you need more ships.

So if a person has elevated triglycerides,

and I consider anything over 100 to be elevated,

even though most laboratory tests would consider normal

to be up to 150 milligrams per deciliter,

we would want to fix their insulin resistance,

bring the trigs way down.

I would wanna see trigs no more than two times

the HDL cholesterol.

So if their HDL cholesterol is, you know,

60 milligrams per deciliter,

I consider 120 to be through the roof high.

And ideally we want trigs at or below HDL cholesterol.

Trigs being triglycerides.

Does that mean lowering dietary fat?

No, actually it’s most easily accomplished

through carbohydrate restriction.

Triglycerides in some ways are kind of an integral

of carbohydrate consumption.

Any energy restriction will get it for you,

but it’s most sensitive to restriction of,

even under eukaloric conditions,

carbohydrate restriction will lower triglycerides.

So again, energy restriction would be

kind of first order of business,

but within that carbohydrate restriction

will probably get you there quicker.

So, you know, you sort of take the low hanging fruit

off the table.

And where does exercise come play a role?

Minimal role.

For improving insulin sensitivity?

No, no, no, I’m sorry.

For improving lipids in general.


But it can improve insulin sensitivity.

Absolutely, yeah.

Especially combinations of resistance training

and cardiovascular exercise, correct?


So once it comes down to pharmacotherapy,

you basically have several classes of drugs.

So the most obvious and the one that most people

are aware of are called statins.

So statins work both directly and indirectly

on the problem.

So directly they work by targeting an enzyme

very high in the synthetic pathway

of cholesterol production.

Enzyme is called HMG-CoA reductase.

And I think it’s the second committed step.

I might, I could be wrong on that.

I don’t think it’s the first committed step,

but that enzyme gets targeted kind of ubiquitously

throughout the body.

And in response to that, the liver senses a reduction

in the body’s pool of cholesterol.

And the liver really tries to regulate this.

So the liver in response to that increases its expression

of LDL receptors.

So the liver itself has LDL receptors on its surface.

And as the body’s pool of cholesterol goes down,

the liver senses this reduction and says,

I want to bring more cholesterol in.

More LDL receptors go up and more ApoB particles

are coming out of circulation.

So that’s really the dominant way that they work.

And in fact, that’s kind of the dominant way

that all of these drugs work.

So another class of drug is called ezetimibe.

It works by blocking,

we could get as technical as you want on this.

It’s called the Niemann-Pixie one-like-one transporter

in the enterocyte.

I like to explain this.

I borrow this explanation from Tom Dayspring,

but the enterocyte is obviously the luminal gut side cell

that is responsible for absorption of cholesterol.

Remember I said earlier,

most of the cholesterol you eat, you don’t absorb.

The reason you can’t absorb it

is an esterified cholesterol molecule

cannot come in the Niemann-Pixie one-like-one transporter.

It’s physically too large.

But the cholesterol that you synthesize,

which once it makes its way back to the liver,

gets secreted in bile down the intestine

that is unesterified and readily fits into that transporter.

So I kind of described that guy

as the ticket taker at the bar.

He lets everybody in as long as they fit through the door.

There’s a checkpoint inside the bar

that basically says, do we have too much cholesterol?

If so, spit it out.

And there’s another door that acts more like the bouncer

and he’s called the ATP binding cassette G5, G8,

and he spits excess cholesterol out.

And if that system’s working fine,

everything is great.

But in a lot of people,

that ATP binding cassette doesn’t work very well

and it can’t properly regulate

the total body pool of cholesterol.

So there’s a drug called ezetimibe

that simply blocks the ticket taker.

Are there side effects to statins and ezetimibe?

Ezetimibe has virtually no side effects.

You can think of it as a drug

that’s acting outside the body, right?

It’s sort of acting on a turnstile door in your gut.

I have seen one patient get sort of loose stools from it

that became enough of an issue that we discontinued it.

I would say that when ezetimibe is combined with a statin,

which is very commonly done,

it’s not unheard of, I can’t give you a number,

but it could be as high as 10%

that you see an elevation in transaminases,

which are enzymes that are made by the liver

in response to some irritation.

So this is where I think it’s unclear

what the clinical significance of that is.

We tend to abort the strategy

in the presence of elevated transaminases.

Even though the literature says you don’t need to,

our view is we have other options.

Why would we tolerate any inflammation

if you don’t need to?

Statins do have side effects.

So 5% of people genuinely and legitimately

get a muscle soreness that can be debilitating.

It could feel like kind of the worst workout

you’ve ever had that, you know,

like the day after you’ve,

like imagine you hadn’t lifted weights in six months

and then you came over

and I made you do the most brutal workout of your life.

You know how you would feel the next day?

That happens every time I come over to you.

Well, I work out often,

but every time I come over to your house,

you put me through the most brutal workout

I’ve ever been through.

I think you and Cam Haines are the two people

who’ve managed to put me through workouts

that kept me sore for at least two weeks after each visit.

So that soreness,

that imagine you would have that persisting,

5% of people get that response from a statin.

And obviously that’s just non,

you know, it’s a non do.

There’s a narrower subset of people

that do get brain fog

and do experience brain fog from statins.

And we don’t really understand the why there.

We have some theories as to why,

you know, maybe they’re getting too much

of a reduction in central cholesterol.

Maybe they’re getting too much of a reduction

in blood synthesis.

Again, it’s a subjective finding,

but given that we have so many tools in the toolkit,

like we don’t have to tolerate side effects

with these drugs anymore.

There was a day when, you know,

you had somebody who just had a heart attack

and they’re basically looking down the barrel

of being on a statin for the rest of their life.

And there were like two of them

and they, you know, had tons of side effects

and it didn’t matter.

Today, while there were probably nine statins out there,

there were really only four that we even use.

And at least two of them have such a low

side effect profile.

They’re not as potent, but they have a,

I mean, potent’s a bit of the,

potent’s the wrong word.

They don’t have the same effect,

but they’re very potent because you’re,

at least one of them you’re taking at such a low dose,

that we’ve got lots of statin options.

The third side effect of statins,

which again, not common,

but can’t be ignored is insulin resistance.

So it really, and this is one of the,

I think one of the benefits of at least having

periodic CGM tracking is, we’ll see this, you know,

we had a patient who happened to be wearing CGM in general.

And then we started him on, you know,

10 milligrams of Resuvastatin,

which is probably the workhorse statin right now.

It’s a, that’s a generic name for Crestor.

And he pings us like a couple of weeks later

and he’s like, man, my glucose is like 10 points up

consistently from where it has normally been.

Kind of hummed and hawed.

We troubleshooted a few things.

After two months, we’re like,

let’s just stop the Crestor and see if that fixes it.

And it immediately fixed it.

So there was, you know,

we reintroduced the Crestor and it happened again.

So there was no doubt in my mind that, you know,

or low doubt in my mind that Crestor

was responsible for that.

And again, you could say,

well, maybe that’s not that clinically significant,

but I would argue, why bother?

I have other choices.

So those are your two big ones.

The next one that is really the big one

are PCSK9 inhibitors.

So, you know, gosh,

we’re coming up to about 20 years ago,

maybe a woman named Helen Hobbs

made a discovery of a group of people

that had a disease called familial hypercholesterolemia.

So FH or familial hypercholesterolemia

is a very genetic heterogeneous condition.

Going back to that Mendelian randomization study,

these are the people on the far end

that show us how high lipid levels cause atherosclerosis.

So these people have very high cholesterol levels,

typically north of 300 milligrams per deciliter.

Their LDL cholesterol alone is by definition

at least 190 milligrams per deciliter.

Very high incidence of atherosclerosis in these people,

along with other sort of injuries.

Like they have so much cholesterol,

they accumulate it in their tendons, in their eyes.

It’s a really devastating condition

if not managed correctly.

And she discovered this mutation in a gene for PCSK9.

A gene that codes for a protein that degrades LDL receptors.

So these people had hyperfunctioning PCSK9 genes.

So their genes were just chopping down

all the LDL receptors in the liver.

So these people weren’t clearing LDL.

About five years later, another subset of the population

were discovered that were the exact opposite.

These people had hypofunctioning PCSK9.

They had virtually unmeasurable…

These people had LDL cholesterol levels

up to 20 milligrams per deciliter.

And not surprisingly, they had no heart disease.

So that led to the development of a couple of amazing drugs

that are now used.

So I take one of these drugs.

I’ve been taking one of these drugs for,

I don’t know, I probably started in 2015.

So it’s an injectable drug.

I take it every two weeks

and it’s called a PCSK9 inhibitor.

So the drug blocks the protein

and therefore gives me more LDL receptors,

yanks more apobiotic circulation.


When we were talking about side effects,

I was thinking, are there any short-term benefits?

So I guess we’d call this positive side effects,

but let’s think of it more directly in line

with the underlying biology.

Let’s say my apob is high, mid-range to high,

you know, let’s say 100, you know, 80 to 100.

And I improve my insulin resistance through nutrition,

but we decide, you know, it doesn’t go down so much.

So we’re gonna continue to try and knock this number down.

And I take any number of different drugs to reduce it.

Do I immediately start to feel better?


So there’s no-

You feel nothing.


And I think that’s an important point

because of the causality issue

that we were talking about earlier.

Because a lot of people are walking around out there,

feeling fine, their apob might be a bit high.

They either know it or don’t know it,

but they think, well, I’m feeling fine.

And you gave a very rational argument earlier

as to why, because of the causality involved,

it makes far more sense to intervene.

Yeah, we don’t wanna rely on feeling

when it comes to atherosclerosis,

just to put some perspective on this.

When I was in medical school,

we had a, and I think I even write about this in the book,

we had a pathology lecture

where the professor stands up there and he says,

what is the most common presentation of a heart attack?

And us keener first-year med students,

hands shoot straight up.

Chest pain.

No, that’s not the most common.

Oh, shoulder pain.

Arm radiating down the left arm.



Shortness of breath.

No, no, no.

We rattled this off for a few minutes.

And he goes, death.

The single most common presentation

for a myocardial infarction is death.

More people, now, I would say today,

that was 25 years ago.

Today, it’s probably not the most common

because advanced cardiac life support is so much better,

but it’s still strikingly common.

Well, you could say that the best predictor

of a heart attack is still a heart attack.

I mean, not saying that the best underlying predictor,

and actually, this hits home.

When I was a postdoc, I was living in San Francisco,

and I’ll never forget this,

taking my coffee out on my porch in the morning.

This was right near the UCSF Parnassus campus.

And this guy’s walking down the street.

He was probably about my age.

And I said, hello.

And he said, hello.

He walked a few more steps, and boom,

he just hit the concrete and died right in front of me.

It took a minute or two to know that he was truly dead.

I’ll never forget it because that’s a,

for a non-surgeon, it’s an event, right?

And I followed up on this,

because his family, you know, the whole thing,

because they wanted a report and no cocaine in his system,

no prior history of any kind of health issues.

And, but he was just strolling along and just boom,

as if he’d been hit by a bus.

It’s crazy.

So it’s, I mean, again,

this is just one of those things where we’re gonna,

he’s spent a lot of time talking about things

that feel good and feel bad when you change them, right?

Like if you take a person who’s not sleeping well,

but who thinks they’re sleeping well,

and you ask them for a leap of faith,

which is, hey, give me a month

to help you sleep really well.

Yeah, you’re gonna feel better.

You might not know it now

because you don’t know how bad you’re sleeping now.

You’ve become acclimated to this,

but this is not one of those domains.

You know, exercise, nutrition, sleep, all those things.

When you do those things better, you feel better.

But, you know, I don’t wanna over-promise on this.

You’re not gonna feel better in the moment

when you fix your lipids,

but you’ll feel better when you don’t have a heart attack.

So by all this logic,

everybody should get their ApoB measured.

How early in life should people do that,

starting in their 20s, in their 30s?

Certainly, if you have a family history

that is of any concern,

like if I could live my life over again,

knowing, if I knew everything, you know,

then that I know today,

yeah, I would have had mine measured in my 20s.

You know, I didn’t get my ApoB measured for the first time,

probably till I was in my 40s because, you know, that’s,

well, yeah, maybe late 30s, early 40s, right?

I had my first calcium scan when I was 35

and I had to beg, borrow, steal to get it done

because everyone was like,

why does a 35-year-old wanna do this?

But I, something,

I just felt something was wrong given my family history.

And I’m glad I did.

I’m glad I did that because I learned something

that completely changed the direction of my life.

Okay, I know my ApoB numbers

and that I might be that guy who’s up in the,

you know, above a hundred,

so I’m gonna get this treated.

That’s a promise to myself.

I’d like to just take a brief moment

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We covered the three major risk factors,

which were blood pressure, keeping that in check,

don’t smoke, and ApoB.

And we’ve now talked about the things to adjust ApoB levels.

We did not really talk about things to adjust blood pressure.

I’m assuming exercise sits as one of the foremost.

Exercise and nutrition, yeah.

Weight management is a huge one here.

So, you know, you take a person who’s blood,

and this is one of those things where we don’t immediately jump

on the pharmacotherapy train with blood pressure

because here there are side effects sometimes.

And you do have to worry about overshooting.

You don’t really have to worry

about overshooting a person’s lipids.

We do back off if we overshoot,

but it doesn’t cause a symptom.

There’s not a short-term immediate risk from doing that.

If you overshoot somebody’s blood pressure medication,

you trade one problem for another problem.

They become lightheaded when they get up to pee at night.

They fall and bang their head.

That’s a devastating consequence, totally unacceptable.

So our goal is to see how much we can lower blood pressure

without medication before we turn to medication.

And let’s be clear,

the meds today are so much better than they used to be.

Again, there was a day when the side effects

of these medicines were miserable.

That’s simply not the case today.

I mean, ACE inhibitors, angiotensin receptor blockers,

I mean, these things are very well tolerated,

especially the ARBs.

So again, almost anybody can be on these things,

but if we could get a person to lose 10 pounds

and exercise every day,

we see great effects with zone two stuff, right?

So kind of the low intensity cardio.

What’s your recommendation there?

I know you talk about this in the book,

but I’ve thrown out numbers about 150 to 180 minutes

per week, you go a bit higher.

Yeah, we go 180 to 250, 240.

Yeah, I’d like to see three to four hours a week of zone two.

So that’s an important piece and sleep is an important piece.

So get the sleep right, get the exercise right.

If you’re overnourished, let’s correct that problem.

And if all of that doesn’t work,

and by the way, that works a lot of the time,

that works most of the time.

If that doesn’t work, then we’ve got pharmacotherapy.

There is still a true phenomenon of essential hypertension,

which is in individuals for whom

all the fixable stuff has been fixed

and they still have high blood pressure,

we still have to medicate those folks.

By the way, there’s something that I wanna mention here

that doesn’t get much attention, but it’s so important,

which is the effect of high blood pressure on the kidney

and also the brain itself.

We’ve talked about the brain, we’ve talked about the heart,

but the kidney doesn’t get enough attention.

The kidney is a remarkable organ.

And I think if you’re really in this game

of trying to live longer, right?

If you think, hey, maybe we’ll live 80, 85 years,

but if we kind of start doing all of these other things

and really optimizing our behaviors, that could be 95.

Well, you have to start thinking

about the capacity of the kidney.

And once the glomerular filtration rate

falls below a certain level,

you have to be very careful with how you live your life.

And unfortunately, this is one of those things

that is another sort of mistake

that’s made in kind of modern medicine,

which is we don’t pay enough attention

to how to measure kidney function correctly.

We rely very heavily on something called creatinine,

as opposed to looking at another biomarker

called cystatin C, which is far more accurate.

And we also tolerate too low of a kidney function

for a person’s age.

So we might look at someone who’s 50,

whose kidney function is at 65% and say, you’re totally fine.

Because it’s true that at 65%, there is no problem.

But you’re not thinking,

well, if this person has to live another 40 years

and this continues to go down,

they’re going to potentially be staring down the barrel

of needing dialysis the last five years of their life.

Again, you want to die with compromised kidney function,

but never from compromised kidney function.

In fact, the hazard ratio of all-cause mortality

associated with compromised kidney function

is even greater than that of heart disease.

Once you cross that threshold, I mean, lights out.

Once you are needing dialysis,

I mean, your risk of death is higher

than that of someone with high blood pressure, smoking,

even someone who has cancer.

You have a higher risk of death

having end-stage renal disease than you do having cancer.

So the kidney is so sensitive to blood pressure.

This is a tiny organ that on every pump of your heart

is getting 20 to 25% of your blood.


So just imagine how sensitive and susceptible it is

to elevated blood pressure.

We’ve covered quite a few corners

of avoiding the major killer, arthrosclerosis.

Let’s talk about cancer.

Nobody wants cancer.

Everybody seems to know somebody who has had

or has died of cancer and probably no surprise

given that it’s number two on the list.

What are the numbers and what can people do to offset cancer?

And of course, there are a huge number

of different types of cancer.

And inside of this conversation, I just want to earmark

that it might be good to have a conversation about alcohol,

which we didn’t talk about in the last discussion.

But if alcohol is involved or is a risk factor rather

for cardiovascular disease or cerebrovascular disease,

now would probably be the time to mention it.

Yeah, this has been looked at in a number of ways.

And so if you look at sort of top-line epidemiology

and you’ve heard of these things called the French paradox,

which is, oh, come on, like they eat all of this fatty stuff

and drink all this wine and they have a slightly lower risk

of cardiovascular disease.

You just have to kind of throw that stuff out the window

because there’s so many confounders there

that it’s kind of useless epidemiology.

If you really look at the data clearly,

and there was actually a really elegant analysis

that included some genetic studies

that came out in JAMA about a year ago,

it’s actually pretty clear that there is no dose

of ethanol that is healthy.

Okay, so there’s no J curve.

So it used to be kind of this literature that said

there’s a J curve associated with ethanol.

So meaning at total abstinence,

there’s a slightly higher risk of death

than if you’re drinking one drink a day.

And then if you go beyond one drink a day,

the rate of death starts to climb.

The problem with that analysis,

so there’s just been a lot of consternation around that.

But the problem with those analyses are multiple,

but the most important of these are that the abstainers

have a reason for abstaining typically.

And those reasons can’t be extracted statistically

from these analyses.

So I’ll leave it at that without,

I mean, I’ve written many blog posts about this.

If people are really interested,

they can go and talk about that.

I also do talk about this a little bit in the book,

by the way.

But the short answer is there is no dose of ethanol

that is healthy.

I would argue that it’s not a straight line of risk,

but it probably goes,

I think from zero to one,

there’s probably no measurable harm for most people.

One per day or one per week?

Probably one per day, up to one per day.

It’s probably very difficult to discern the harm,

but I’m gonna put a caveat on that that I’ll come back to.

And then I think the risk starts to climb

pretty steeply after that.

And I think it climbs non-linearly after that.

That is my reading of the literature.

Okay, so then how do you decide

if you’re gonna have up to one drink a day?

And by the way, that’s not the same as seven a week,

because that doesn’t mean seven in a day.

Right, which we know is really detrimental.


Especially for the brain,

but also the cascades that result from disrupted sleep,

not just for that one night, but multiple nights.

Yeah, the literature I’ve seen on alcohol,

that the most, now again, this is an emerging literature

because what you’re describing is exactly right.

But people are now, some more conservative folks

are starting to place it at two drinks per week total,

beyond which you start running into issues,

especially for women in terms of breast cancer risk,

which is something maybe we can circle back.

Yeah, I mean, look, my view is if you can not drink at all,

you’re better off not drinking at all.

And people always say to me,

well, Peter, what’s your view on this?

And my view is I do drink.

I’ll go weeks at a time without having a drink.

I haven’t had a drink, you know,

I’ve had one drink since I saw you last a couple of weeks ago

because I’ve been sick.

So I’m thinking, well, gosh,

like the deck is stacked against me right now.

Why would I do anything to stack in more?

But my philosophy, which is half tongue in cheek,

but is true is like, I just don’t drink bad alcohol.

You know, I sort of, my wife saw me do this the other day.

We opened up a bottle of wine

and it was a very expensive bottle of wine.

And I took a sip and I was like, yeah,

I just dumped my glass.

I was like, I don’t know, just doesn’t taste right to me.

And it tasted fine to her.

So I don’t think it was that the wine had spoiled.

It was just, I didn’t like the taste of it enough

to justify drinking it.

I was like, I don’t feel like drinking it.


I’m fortunate.

There were times in life, you know,

certainly college and portions of graduate school

when I drank, but I’ve never really enjoyed

the taste or experience of alcohol.

So all the alcohol in the planet could disappear.

I wouldn’t even notice,

but I’ll have one every once in a while.

I’m sort of of that mindset,

but great to hear that zero is better than any.

Because I think everyone agrees on that.

So it doesn’t appear that alcohol can be directly linked

to cardiovascular disease and cerebrovascular disease.

Although, well, these indirect effects through insulin,

altering insulin sensitivity.

And through sleep.

And through sleep.

I think the impact of sleep on cardiovascular

and cerebrovascular disease is profound.

And I do think that the impact of ethanol

on sleep is underappreciated.


I think we should do a little nod to Matt Walker,

the great Matt Walker.

Because, you know, 10 years ago,

if someone had a conversation about sleep

and how critical it is

and how not getting enough quality sleep is dangerous,

people would have just kind of shake their heads

and say, what’s the evidence for that?

I think Matt really deserves most of the credit

for alerting people to these issues

around not getting enough sleep.

It’s just remarkable what’s happened in the last decade.

Thanks to Matt.

And while we’re on that topic,

we have the other next horseman of death,

the neurodegenerative diseases.

I think those are also heavily impacted,

especially on the dementia side by ethanol.

So again, I wanna be careful when I say this stuff, right?

I don’t believe in fear mongering, okay?

I just said a moment ago, I’ll say it again.

I drink alcohol and I’m gonna continue to drink alcohol.

But I think that one has to make the trade-offs,

which is like, if I really do love the taste

of certain Spanish wines,

I really do love the taste of certain tequilas,

certain mezcals, and I really do love the taste

of certain weird esoteric Belgian beers.

And it really does give me pleasure to consume those things

in the same way it gives me pleasure

to consume certain foods that are quite vapid, right?

You know, there’s no upside in consuming a brownie

that my kid just made,

except for the fact that my kid just made it

and it’s fun to eat the brownie with them, right?

So, you know, we come back to this thing about like,

longevity is also about healthspan.

And part of healthspan is quality of life.

And, you know, I write about this in the book

that I think there was a day when my approach to this

was purely an engineering approach,

which was we are going to optimize

every molecule of my being for this.

And if you go so far down that rabbit hole

that the quality of your life deteriorates,

what’s the point?

So that’s why I think for somebody like you,

who says like, you could take all the alcohol

off the face of the earth, I wouldn’t even notice,

then that’s a great reason not to bother drinking.

I wouldn’t put myself at the opposite end of that spectrum,

but I’m probably further to the spectrum, you know,

where, yeah, if you told me

I could never drink alcohol again,

I would be fine with it,

but I’d be giving something up that I enjoy.

But at the same time, I know if I have two drinks

with dinner, my sleep sucks.

And therefore, that’s just a threshold I rarely,

rarely cross.

I certainly have my vices.

Alcohol just doesn’t happen to be one of them.

What about cancer?

Again, nobody wants cancer.

We’ve all known people who’ve died of cancer

or have had cancer.

What can be done to reduce one’s risk of cancer?

Well, you asked earlier about the numbers,

let’s throw some numbers out there, right?

So globally, we’re talking about 11,

12 million deaths per year,

about half the number of ASCVD,

still a staggering number.

At the individual level, put it this way,

somewhere between one in three and one in four chance,

anyone listening to this or watching this

is gonna get cancer in their lifetime.

But what’s the probability they will die from that cancer?

Half of that, about a one in six chance of dying.

Okay, so is it true that every male gets prostate cancer?

In other words, on their deathbed-

Every man will die with prostate cancer

and some will die from it.

You and I have prostate cancer right now.

Thank you for informing.


Hopefully we will not die of it.

We should not die of it.

Prostate cancer, colon cancer are cancers

that no one should ever die from

because they’re so easy to screen for.

They are so easy to treat when they are in their infancy

that it’s totally unacceptable

that people are dying from this.

There are other cancers for which I can’t really say that.

Breast cancer, much more complicated.

Pancreatic cancer, much more complicated.

Glioblastomae multiforme, much more complicated.

So as you said a second ago, cancer is not a disease.

It is a category of diseases.

It’s not just that each organ is different

and breast differs from pancreatic.

It’s that within breast cancer, ERPR positive,

HER2-neu positive is a totally different disease

from the triple negative breast cancers.

Those with BRCA mutations or non-BRCA mutations.

Well, even putting that aside,

just looking at the hormone profile

of the individual breast cancers,

they’re totally different diseases.

So it’s not just that breast cancer

is different from prostate cancer.

It’s that all breast cancers are quite different.

Maybe I should frame the question a little differently

than given the vast number of different types of cancers

and categories within those.

Your question is still a fair one.

I just wanted to throw that caveat out there.

So now to your question.

Okay, so what do we know?

It turns out that we can very comfortably speak

to several things.

One is the role that genes play.

So maybe I’ll just spend one second

on a gene 101 thing for the viewer.

We wanna differentiate between

what are called germline mutations and somatic mutations.

So your germline and my germline are set.

When we were born, our germline mutations,

any mutations we have in germline genes

are inherited from our parents.

They’re non-negotiable.

They’re non-negotiable.

You got those things.

So question one is how much of cancer results

from those types of genetic mutations?

And the answer is very little, less than 5%.

So very, you know, you mentioned one a moment ago, BRCA.

Okay, so mutations in BRCA are germline mutations.

A woman will get a BRCA mutation from one of her parents.

And we will often have a sense of that

just from the family history.

You know, when mom and sister and aunt and grandmother

had breast cancer, you’ve got a breast cancer gene.

Now it might be BRCA.

It might be another gene that’s not BRCA,

but there’s no ambiguity.

And we test for these genes

mostly just for insurance purposes, frankly,

but there’s no ambiguity

that that was a germline transmission of a gene

that is driving cancer.

But 95 plus percent of cancers

are not arising from germline mutations.

They are arising from somatic mutations

or acquired mutations.

So the question then becomes

what is driving somatic mutation?

And the two clearest indications

of drivers of somatic mutation

are smoking and obesity.

Smoking we’ve talked about.

Let’s put that aside for a moment.

I’m so surprised about obesity.

I don’t know why I’m surprised,

but I’ve never heard this.

I’m probably just naive to the literature.

Yeah, so obesity is now the second

most prevalent environmental driver of cancer.

Now, I will argue,

and I think I argue this in the book,

hopefully pretty convincingly,

I don’t think it’s obesity per se.

Obesity is just a masquerading proxy.

What is obesity?

Obesity simply is defined by body mass index.

Well, first of all, I don’t think I’m obese,

but I’m way overweight on BMI.

You probably are too.

So, you know, let’s just ignore it.

I’m clinically diagnosable as obese.

Are you?

Oh, no, well, not, well, clinically, maybe as-

That would be BMI over 30.

I don’t think you’re probably there.

No, but if I measure my weight by height-

Yeah, yeah, yeah.

Like my BMI is probably 27 or 28.

Okay, it’s been a little while since I’ve checked.

I only know body fat percentages and things like that.

So, basically, like BMI is a far from perfect proxy,

but at the population level, it’s what we use.

I wish we would get off it, by the way.

I think it’s really crap.

Because it doesn’t take into account

lean versus non-lean tissue.

I think we could get better data

if we looked at waist to height ratio.

That’s a way better metric.

So, this is just a quick test for everybody.

I’m gonna argue your BMI is less relevant to me

than your eye color.

But if your waist circumference

is more than 50% of your height, you should be concerned.

Okay, well, then I’m okay.

Yeah, you’re fine by that metric, right?

But that’s important.

So, if you’re six feet tall,

your waist better be under 36 inches.

And if it’s over, I would argue

that’s the definition of obesity,

not your BMI being over 30.

So, back to this issue,

because we’re using such a crude measurement,

it basically is catching a whole bunch of stuff.

But the question is, what’s driving it?

And I think if you really look at the physiology of cancer,

I don’t think it’s obesity.

I think it’s two things that come with obesity.

Insulin resistance, which is, you know,

two thirds to three quarters of obese individuals

are insulin resistant, and inflammation.

And I think those two things,

with the inflammation and the immune dysfunction,

with the insulin resistance,

and the hyper, basically,

tonic growth stimulus that’s coming,

that’s what’s driving cancer.

So again, is it because a person is storing extra fat,

you know, and their love handles,

that that’s driving the risk of cancer?

No, those are just two things

that are coming along for the ride.

So, beyond those two things,

and along with certain,

there are also certain environmental toxins

we absolutely know are doing this, right?

So we understand that people who, you know,

have exposure to asbestos have a much higher risk

of certain types of lung cancers and things like that.

But for the most part, those are our big risks.

Beyond that, we talk about alcohol in certain cases,

absolutely, alcohol is a carcinogen.

It’s the dose part still isn’t clear to me.

I don’t know, is one drink a day

moving the needle much on cancer risk per se?

It’s not clear.

And it might depend on those genetic predispositions.


So, yeah, if step one is don’t get cancer,

you have no control over your genes,

you have control over smoking,

you have control over insulin sensitivity,

I wish I could sit here and tell you

that there is a proven anti-cancer diet,

or that if you do X amount of exercise per week,

you’re gonna not get cancer.

We just don’t have a fraction of the control

over cancer that we have with cardiovascular disease.

We don’t understand the disease well enough.

So we don’t understand kind of the initiation process

and the propagation process.

And we have to rely much more on screening.

Are there good whole body screens for cancer?

In other words, can I walk into a tube

and or a cylinder rather,

and get screened for the presence of tumors

any and everywhere in the body outside the brain?

Because the brain is a little harder to get to, right?

Believe it or not,

the brain is actually pretty easy to screen for.

It’s so fatty and floating in water.

Well, and also the head,

when you put the head into an MRI scanner,

there’s no movement.

It’s the least motion artifact is in the brain.

So when you use something called diffusion-weighted imaging

with background subtraction in an MRI,

a technology that was actually pioneered in the brain

for stroke identification,

it’s also really good at looking for tumors as well.

So let me make the argument for why screening matters.

Because this is again,

kind of an area where I go far down a rabbit hole

in a way that I think traditional medicine

would argue against.

So my argument for screening

is an argument at the individual level.

And it goes as follows.

To my knowledge,

there is not a single example of a cancer

that is more effectively treated

when the burden of cancer cells in the body

is higher than when it is lower.

So the two examples I think I talk about in the book

are colon cancer and breast cancer.

So when you take an individual with stage four colon cancer,

that means that the cancer has left the colon

and is now outside of the colon.

So it’s usually in the liver at a minimum,

potentially in the lungs or in the brain.

That person’s five-year survival is very low.

Their 10-year survival is zero.

We will treat them with a very aggressive regimen

of multiple drugs.

And again, you’ll get a five-year survival

of maybe 10 to 20%.

And by 10 years, nobody’s alive.

If you take a person with stage three colon cancer,

so the colon cancer is big

and it’s even in the lymph nodes around the colon,

but at least grossly,

you can’t see colon cancer cell,

you can’t see those cells in the liver.

Microscopically, of course, we know they’re there

because if you don’t treat those patients,

they still die of colon cancer,

but you whack them with the same chemo regimen

that you were gonna give the metastatic patients,

80% of those people are alive in five years.

So night and day difference in survival.

What’s the difference?

In the person with metastatic cancer,

you’re treating a person with hundreds of billions of cells

in the adjuvant setting,

which is what we call it adjuvant

when you treat people who have only microscopic disease,

you’re treating billions of cells.

The same is true with breast cancer.

So we have the clinical trial data to put them side by side.

So rule number one is don’t get cancer.

Rule number two is catch cancer as early as possible

if you’re gonna get it,

which brings us to your question of how do you screen for it?

The first line of screening is imaging,

is a sort of visualization.

So you have cancers that occur outside the body

that you can look at directly.

So skin cancer, you can look directly at the skin.

Esophageal, gastric, colon cancer,

those are outside the body, right?

Mouth to anus embryologically is outside the body.

So you can put a scope in

and you can look directly at the cancer.

But for all other cancers that are inside the body,

yeah, you have to rely on some sort of imaging modality.

Although now we’re starting to look at things,

things called liquid biopsies.

So blood tests that are looking for cell-free DNA.

And the cell-free DNA gives us a sense of,

based on the epigenetic signature

of what you’re looking at,

hey, is there a cancer in the body?

And if so, what tissue is it potentially coming from

based on these epigenetic signatures?

So the problem with relying on any one modality

is a problem of sensitivity and specificity optimization.

Now with MRI scanners,

which are in some ways the best way to do this

because they don’t have radiation.

So you don’t wanna be incurring damage as you do this.

The irony of doing a whole body CT scan

to screen for cancer is your whole body CT scan

would be close to 30 to 50 millisieverts of radiation.

It’s a staggering sum of radiation.


Does that mean that people should,

sorry to pull you off this,

but I was going to ask about this anyway,

avoiding going through the whole body scanner

at the airport.

Noise, so low, so low.

Yeah, going through a whole body scanner at the airport

or even getting a DEXA scan.

I mean, these are trivial amounts of radiation.

What about flying?

You hear that pilots get more cancer.

If you’re a pilot who’s flying over the North Pole

back and forth and back and forth,

you’re probably getting five to 10 millisieverts a year.

The NRC suggests that nobody should get

more than 50 millisieverts a year.

So you and I both travel a fair amount,

but typical travel for the busy person,

let’s say two round trip flights

of more than two hours per month

and an international trip every three months.

Probably still less than a millisievert a year.


Living at sea level, one millisievert a year.

Living at a mile elevation,

if you lived in Denver,

you’re at two millisieverts a year basically.

I have to ask, standing in front of the microwave.

I’m just, we’ve got friends.

They ask.

With or without testes on the counter.

That’s an inside joke that unfortunately,

and fortunately deserves no description.

And Peter’s not referring to me.

But people worry about other sources of radiation.

So it doesn’t sound like the microwave is a concern.

What are the other major sources of radiation?

I mean, outside of sort of nuclear stuff

where things go sadly wrong.

Yeah, if you live near a plant

or there’s been a…

Yeah, there’s been a…

It’s mostly at the hands of medical professionals, right?

It’s the CT scanner and the PET scanner

are hands down the biggest source of radiation.

What about the x-rays at the dentist

when they go…

They’re very low.

When they scurry behind the wall

under the lead blanket.

They’re very low, relatively speaking.

Fluoroscopy is very high.

They tend to try to cover up all of you that…

So for example,

if they were doing a fluoroscopic study of your kidney

because you had a stone

or if you were getting an injection into…

If they were doing a fluoroscopic guided injection

of one of your discs in your neck,

that would be a locally pretty high dose,

but they’re gonna cover the hell out of you elsewhere.

And again, if you get one of these things,

it’s not the end of the world,

but boy, I wouldn’t wanna be getting one a month.

And back to the point about screening,

a chest, abdomen, pelvis CT scan is probably…

I mean, look, there’s probably a scanner out there now

that’s moving fast enough that it’s much lower,

but I’ll give you an example.

Okay, remember how I talked about we do CT angiograms

on all of our patients for coronary artery disease?

An off-the-shelf scanner for this

is 20 millisieverts of radiation.

Okay, so calibrate me because-

That’s 40% of your annual allotment.

Oh wow, so the medical practitioners

really are the major culprits here.

That’s right, so what we say is,

and I think most doctors are now realizing this,

is no, no, it behooves you to pay a little bit more

to go to a really good place

that can do that scan for two millisieverts,

meaning they have a much faster CT scanner,

much better software, and they’re better engineers.

So they have better engineering

that they can do on the scanner to get that done.

So if someone listening to this, here’s my take.

Do not get a CT scan or any imaging study

without asking, how much radiation am I seeing?

And if a person can’t tell you

how many millisieverts of radiation you’re being exposed to,

then just say, I’m gonna wait a minute

until somebody can tell me that.

I realize-

And keep in mind, if 50 is the most

you should ever be exposed to in a year,

there better be a damn good reason

why I’m gonna get 25 in a day.

Now, there are some people who have to do this.

If you’re a cancer patient

and they’re scanning you as a part of your treatment,

I mean, you have to pick and choose

between those two opportunities.

So I also don’t wanna create some fear-mongering

where, oh my God, if you hit 50 in a year, you’re hosed.

No, it’s just, I wouldn’t wanna hit 50 a year

every year for my whole life.

And I certainly wouldn’t wanna be hitting hundreds a year

for any period of time.

I think we’re just trying to raise awareness

and also calibrate people to what the sources are

and so they can make good choices,

not to place them into a chronic state of fear

or even an acute state of fear.

So for that reason, we prefer MRI scanners

because there’s no radiation.

I realize this might sound like a specialized circumstance,

but I’ll just start off with my own,

which is when I was a graduate student,

I worked with fixatives, so paraformaldehyde.

Paraformaldehyde, excuse me.

Glutaraldehyde, we know that these are mutagens.

They mutate cells, not good.

You do some molecular biology in the lab,

you use DNA intercalating dye,

those little bands and gels,

the reason they label is because they get between the DNA,

not good to get into your own DNA.

And that’s a very specialized circumstance.

I also injected tritiate radioactive proline

into the animals and things of that sort.

Again, very specialized.

And yet, most people, I think,

will be exposed to pesticides.

They’ll put stuff on their lawn

or they’ll have paint thinners and things of that sort.

Is there any sense of what the average, if one can,

average risk is incurred in terms of carcinogens

just through this interaction with weed killers,

paint thinner, detergents around the house

that we now know, there’s some major lawsuits

that have been successful

against the manufacturers of these things.

And what is the real cancer risk created

by having those kinds of solvents

and pesticides and things around?

I don’t think I know, truthfully.

I think it’s very complicated to calculate such things

when their ubiquity is so high.

So one argument is, look, it’s kind of baked

into the baseline prevalence of cancer today

because these things are so ubiquitous.

Yeah, asbestos, in California, for whatever reason,

it seems that there’s an asbestos warning

on pretty much every building, if you look carefully enough,

except maybe the ones built in the last five years.

I don’t think I’ve ever worked in a building

where the elevator was updated in terms of the inspection.

It was almost like 10 years back.

You always see it while you’re in the elevator.

No one seems to worry about those.

Or where there was not an asbestos warning

or a lead warning.

It seems like it’s just kind of everywhere

and they’re noting it in these little flags.

I don’t walk around worried about it.

I don’t lose sleep over it.

But it sounds like a real risk

or else they wouldn’t bother, right?

Clearly, they’re just trying to cover their legal backs.

Yeah, it might be more CYA than anything at this point.

I mean, I don’t know how much of a risk asbestos poses

when it’s not being agitated.

In other words, I don’t know that the asbestos

in the ceiling, four layers up, is really a problem.

But if they had to come in here and rip this ceiling apart,

I don’t know that I’d want to be in here either.

Right, it was like post 9-11,

a lot of the workers on the World Trade Center pits,

because that’s what was left, sadly,

were developed cancers, right?

Probably from exposure to those kinds of things.

Well, I mean, I would argue it’s also just the unbelievable

amount of pollution, micropollution,

that was in the air following those things.

I mean, that’s devastating stuff.

So yeah, those are fortunately the outlier events

that are dramatic.

But again, my focus is basically,

look, I could hermetically seal myself

somewhere in the world, maybe,

and maybe that would reduce my risk by 1%.

But I’m gonna focus my energy on what I control,

because that’s really hard for me to control.

I like focusing my things on,

I like focusing my energy on things I can control.

What I can control is the timing

and frequency of my screening.

I can’t control my genes anymore.

They are what they are.

I got whatever predisposing cancer genes I’m gonna get.

I might be lucky in this regard,

in that I seem to get all these horrible heart disease genes,

and maybe not as much.

But you can also argue,

there are cancer bad genes in me

that we don’t really know about,

because everybody was dying of heart disease so young.

But boy, am I gonna control the screening thing.

What source of genetic screening

do you recommend to your patients?

Because there are a lot of them.

There’s 23andMe, there’s whole genome sequencing,

plays, you know, available now in a variety of formats.

This is actually one of the questions

our research team is working on as we speak.

So we’re trying to decide,

so we do genetic screening for certain things,

like ApoE is a gene we wanna know in everybody.

For its role in neurodegenerative disease.

Correct, specifically in Alzheimer’s disease.

We are selectively using cancer screening in some patients,

but in our practice, it’s less important

because we’re generally so aggressive anyway

that it turns out to be a little bit moot.

We don’t learn a lot in the genetic screening

that’s changing our screening practices,

because we’re so thorough in our family history,

and we’re so aggressive in everybody,

regardless of family history.

But I think there’s a place for these things.

For example, if you’re looking for reimbursement

on certain tests, you know, I’ll give you an example, right?

So colon cancer historically was not covered by,

colonoscopy screening for colon cancer

was not covered until you were 50.

That’s been bumped to 45.

We still think everybody should be screened

no later than 40.

No, I haven’t had one, so I suppose I should.

Yeah, I mean, look, I’m 50 and I’ve had three already.

So again, why?

Because colon cancer is not just the third leading cause

of cancer death, it’s 100% preventable.


Because every colon cancer comes from a polyp,

and every polyp can be seen on a colonoscopy.

So there’s simply no reason to not know that.

And that has to be weighed against the cost

of the colonoscopy, both the financial cost and the risks,

which are very low, but not zero.

There’s a risk that comes from electrolyte abnormalities

and hypotension from the bowel prep.

There’s a risk from the sedation,

and there’s obviously a risk of bleeding or perforation

that comes from the colonoscopy itself.

Again, in a generally healthy person,

those risks are so low that they’re almost difficult

to quantify, as evidenced by a recent

New England Journal of Medicine paper

that was a very anti-colonoscopy paper,

which I won’t get into

because it’s probably a little bit of a tangent.

But what’s interesting is,

despite being a very anti-colonoscopy paper,

this paper does a better job demonstrating

the safety of colonoscopy than anything else.

It just was an oddly designed experiment.

So the biggest challenge with aggressive screening posture

is the specificity problem,

which is when you stack more and more modalities

around these things,

you’re gonna start finding things that aren’t cancer.

So MRI has a very high sensitivity.

In English, that just means if a cancer is present,

an MRI is very likely to see it.

But it has a very low specificity,

which means in English, it will see a bunch of things

and think they are cancer when they are not.

And it’s most troubled by glandular tissue.

So glandular tissue is the Achilles heel of MRI.

And therefore, when you use, as we do,

whole body MRI for cancer screening,

we tell our patients going in,

it’s like a 25% chance we’re gonna find something

that is not cancer,

but will require us to do further investigation.

If you’re not cool with that, which is totally fine,

we probably shouldn’t do this.

And again, most people are okay with that,

but it helps to set that expectation going in,

that you’re gonna probably be chasing your tail,

looking at some stupid thyroid nodule

that is absolutely nothing.

I mean, I can’t tell you how many useless thyroid nodules

we’ve had to get ultrasounds on

that proved to be absolutely nothing,

but you have to follow them for a couple of years

to make sure they’re nothing.

What is the typical cost of a whole body MRI?

And so for people who are not your patients,

how would they go about getting those?

Because I think most people’s general practitioner

is not going to script that out for them.


I don’t know the short answer

because I don’t know how many different places are doing it.

I can tell you that we use a couple of different facilities

and I should disclose that I’m a founder of one of them,

but we use a scanner that probably,

we send our patients to anywhere they wanna go,

but within a certain company that we like,

that’s not a company I have an affiliation with,

and I believe they’re charging about $2,500.

Since you don’t have an affiliation, can you mention that?

Because for instance, you are not my physician,

sadly for me, and luckily for you,

but I’d love to get a whole body MRI.

So what is this company?

So the company that makes the MRI

that we’re using right now is called Prenuvo.

I interviewed the chief technology officer

and the head radiologist of that company

on one of my podcasts.

It’s a super interesting technology based out of Vancouver.

And for a long time, that was the only scanner in the world.

So I had my first scan back in 2015.

I went up to Vancouver to get it done.

Probably had my first two up there.

They’ve now opened locations all over the country.

So they’ve got one in the Bay Area.

They’ve probably got one here in LA.

I know they have one in Dallas.

So they’ve got them all over the place.


And then the company that I’m affiliated with

is a different type of company

that does all sorts of diagnostics,

but among them is we have a Prenuvo scanner in that company.

That company is called Biograph, and that’s in the Bay Area.

Biograph. Biograph, yeah.

Spelled as one would expect.


Well, that’s very helpful in terms of understanding

the general risk and ways to offset cancer

to the extent that one can.

And certainly what the consideration should be.

Number three on the list of ways to die.

We should just title this ways to die,

or we should title this how not to die.

Too early.

Neurodegenerative disease.

This is an area I’m somewhat familiar with.

Not because of my own experience, thankfully,

but because of my relationship

to the neuroscience community.

And last time I checked,

I was told that everyone experiences

some age-related cognitive decline.

So we all get less proficient at focus, memory,

complex context-dependent task switching,

all that stuff as we get older.

But it’s the slope of that line

that really can be controlled to some extent.

And that Alzheimer’s dementia represents

just a steep acceleration,

downward acceleration of all of that.

That was what I was told.

I’m guessing that even though I reside in the,

not kind of, but I reside in that community,

that some of that is being revised,

especially with respect to the underlying causes

of Alzheimer’s, because there’s a lot of controversy,

even scandal around this whole APP, APOB,

amyloid, plaque, tangle stuff,

which is the stuff of textbooks for medical students

and neuroscience students.

What is the story with neurodegenerative disease,

Alzheimer’s in particular?

How can we offset it?

And perhaps as importantly,

how can we all slow our own cognitive decline

irrespective of whether or not we get

what is called Alzheimer’s dementia?

So Alzheimer’s disease is both the most prevalent

form of dementia

and the most prevalent neurodegenerative disease.

So it occupies that unique spot.

We’re talking about roughly 6 million people

in the United States have Alzheimer’s disease.

That’s one in, let’s see.

I mean, I haven’t checked it out.

About 2% of the total population.


And that doesn’t include those

with mild cognitive impairment or pre-dementia

or other forms of dementia.

And of course the right metric is not what percent

of the population, which of course includes children,

things like that.

It’s, you know, so-

That’s a function of age.

Yeah, so-

But is age the major risk factor

for getting Alzheimer’s?

Let me say with glaucoma,

a disease I’m much more familiar with

because my lab worked on it for many years.

The biggest risk factor for getting glaucoma is age.

Yeah, the greatest risk factor

for cardiovascular disease is age.

The greatest risk factor for cancer is age.

We tend to not spend a lot of time talking about that

because it’s not a modifiable risk.

So, you know, we tend to focus on modifiable risk factors.

So what else can we tell you

just to give you kind of lay of the land?

So the second most prevalent neurodegenerative disease

would probably be Lewy body dementia

followed by Parkinson’s disease.

Although the rate of growth

of Parkinson’s disease is the highest.

So I think we’d probably be most, you know,

those three diseases

we wanna really be paying a lot of attention to.

As you know,

there are a lot of other neurodegenerative diseases.

Every one of these things is devastating, like-

Multiple sclerosis.

Yeah, multiple sclerosis, ALS, Huntington’s disease.

These are awful, awful diseases.

There are also other kinds of dementia.

Vascular dementia is not Alzheimer’s dementia,

but it produces comparable symptoms.

Each of these things, by the way, are slightly different.

Lewy body is a dementia.

It’s a dementing disease,

but it also has a movement component.

So it sort of sits on a spectrum that’s sort of, you know,

I mean, loosely halfway between Alzheimer’s disease

and Parkinson’s disease.

We talked obviously about age

being the number one risk factor,

kind of not that interesting

because you can’t do anything about it.

So the real goal is as we age,

what are we doing to reduce risk?

Well, let’s start with an important gene.

The gene that everybody’s heard of,

certainly came up a lot on the Limitless special

where Chris Hemsworth was, you know,

made the decision to reveal something

that none of us expected when we started that whole series,

which was that he ended up being homozygous

for the APOE4 isoform.

So maybe folks understand we have two copies of every gene.

So for gene X, you have copy that you got from your mom

and copy that you got from your dad.

And the APOE gene is kind of a unique gene

in that it has three different isoforms

that are all considered normal.

None of them are mutations.

So you have the E2 isoform, the E3 isoform,

and the E4 isoform.

The E4 isoform is the OG isoform.

That’s the one that we have historically had

as far back as we can go.

We actually think the E4 isoform

offered a lot of advantages back in the day.

It’s a bit of a pro-inflammatory isoform

and it certainly offered protection against infections,

especially parasitic infections in the CNS,

which would have been a really important thing

to select for 200,000 years ago.

How do parasites get into the CNS?

I mean, you got a blood-brain barrier, you got a thick skull.

I mean-


I’m not telling you you have a thick skull,

but I mean, it just seems like parasites

in other tissues would be an issue

because what we’re talking about here is brain disease.

Yeah, yeah, yeah.

Anyway, I don’t want to take us off course.

But it also could have protected them.

It probably offered some protection

outside of the brain as well.

Anyway, the E3 isoform, I think, showed up,

God, I think 50,000 years ago,

and the E2 isoform showed up very recently,

about 10,000 years ago.

Now, today, we realize that there’s a clear stratification

of risk when it comes to Alzheimer’s disease

that tracks with those isoforms.

So because you have two copies,

you basically have six combinations

of how you can combine those genes.

You could be 2-2, 2-3, 2-4, 3-3, 3-4, 4-4.

The prevalence of them is basically as follows.

3-3 is now the most common, 3 is the most common.

So double 3 is 55-ish percent of the population.

The next most common is the 3-4,

which is about 25% of the population.

And then after that,

most things are kind of a rounding error.

So 2-3s and 2-4s would be the next most common.

4-4s are very rare.

And 2-2s are the rarest of them all.

2-2s are less than 1%.

4-4s are about one to two percent.

Very important point here

is that the E4 genes are not deterministic.

So they’re highly associated with the risk,

but they’re not deterministic.

There are at least three deterministic genes

in Alzheimer’s disease.

One is called PSEN1, another one is called PSEN2,

and another one is called APP.

Those genes collectively make up about 1% of cases

of people with Alzheimer’s disease.

So they’re fortunately very rare genes,

but sadly they are deterministic.

Meaning if you have those genes,

you do get Alzheimer’s disease.

And what’s perhaps most devastating about those genes

is how early the onset is of the disease.

These are people that are usually getting

Alzheimer’s disease in their 50s.

So we do have a patient in our practice,

actually she’s spoken about this very openly,

whose mom had one of these genes.

And she got Alzheimer’s disease in her early 50s.

I think she might’ve made it into her 60s before she died,

but absolutely devastating consequences here.

Why do people with Alzheimer’s die?

Because I know about the hippocampal degeneration,

hippocampus of course being an area of the brain

important for learning and memory,

but is there brainstem degeneration?

Do they lose breathing centers or cardiovascular control?

Usually what happens is it’s sort of failure to thrive,

aspiration, things like that.

So it’s usually they just stop eating

or they can’t control secretions,

they aspirate, they get a pneumonia

or they really lose the ability to even sense

like pain in their body.

And therefore like they’ll get an ulcer

and they don’t realize it and it’ll become cellulitic

and they’ll develop a horrible infection

in response to it.

I see, so it’s a body vulnerability.

The reason I ask is every once in a while

a news report will come out based on a legitimate

case study where they’ll do a scan on some person

and discover that they’re missing

literally half their cerebral cortex,

like huge chunks of brain

and they’re functioning relatively normally.

And so here we’re talking about a neurodegenerative disease

of relatively, it’s widespread,

but there are a few hotspots, of course,

in the brain that degenerate more profoundly than others

and the people dying.

So that makes sense.

It extends to lack of peripheral awareness or control

and then some acute injury or infection.

Got it.

You mentioned earlier some of the controversy, right?

So what are we talking about here?

Well, it’s, and I do write about this at length

in the chapter on Alzheimer’s disease

because I think this is a very important point, right?

Which is the index case for Alzheimer’s disease,

there’s always an index case, right?

You know, there’s the quote unquote patient zero.

The index case was a woman who, you know,

a hundred years later we realized had an APP mutation.

Obviously these are APP or PSEN1,

but she had one of these deterministic genes

that led to a very early onset of disease,

which by the way,

without which we may not have come up with the diagnosis

because had she just got Alzheimer’s disease in her 70s,

it would have just been referred to as senility,

which is, you know,

was not interesting enough to pay attention to.

But I think it probably set the field on the path

towards an overemphasis on amyloid beta.

And it’s not really clear how important amyloid is,

which is not to say it’s not important.

It is important.

And there’s no ambiguity that amyloid is responsible

for the changes that we see in the brain,

but it’s not crystal clear

because there are lots of autopsies that are done

on people that are completely healthy

and have died with no cognitive impairment

and they’re chock full of amyloid.

So what we don’t fully understand

is exactly what does removing amyloid do.

The other thing that complicates the story

is there has been no shortage of drugs that target amyloid

that have seemed unsuccessful.

And just to clarify, when you say amyloid,

you mean people have died with their brains examined

in autopsy and see that there are tons

of so-called amyloid plaques?


Different than arterial plaques, of course,

but within the brain.

So the two hallmarks of Alzheimer’s histopathologically

would be plaques and tangles.

And even that now is, of course, coming under question,

but it’s what we teach every neuroscience graduate student.

It’s what we teach every undergraduate.

It’s also what we teach every medical student,

and not just at Stanford, but everywhere.

So I have heard that the link between APP

and whether or not one develops genes related to APP

and whether or not it’s cleaved at one site or another,

which is what you were describing,

and risk for Alzheimer’s.

Yeah, so it’s basically a cleavage.

It’s a cleavage question, right?

So people with the APP mutation,

I think have one extra cleavage site.

They result in one extra cleavage of amyloid,

and then it misfolds.

And the misfolding is what the plaque is

that’s being created.

That also then predisposes them

to the neurofibrillary tangles.

And again-

But all this is under question now, right?


I mean, this is what I was told.

And when I look, it sounds like there were some early,

there were some papers early in the chain of discovery,

in the research in Alzheimer’s,

that were either wrong because they were falsified,

intentionally falsified.

There was an intentionally falsified paper

on one particular amyloid variant.

And that clearly set the field back a decade

because a lot of people went down that rabbit hole

based on deliberately falsified data.

So what happened to that guy?

I don’t know why I assume it was a guy,

but what happened to that guy?

Yeah, that’s a good question.

I think I wrote one piece about it

when it happened.

I actually reached out to the person who broke the story

because I wanted to have them on my podcast.

And I forget why he didn’t do it.

I forget why he wouldn’t commit to it

or something like that.

But I thought it was a little odd

because I thought this would be a great way

to talk about this.

I do not know what came of that scandal.

In other words, I haven’t paid attention to it

for probably nine months.

So I don’t know, you know,

obviously the paper has probably been recalled,

but I don’t know what disciplinary action was taken.

The field is,

I don’t know.

I don’t wanna speak like I’m in the field because I’m not.

So I wanna be careful what I say,

but I think the field is probably in a bit of a crisis

because there have been so many bets placed

on anti-amyloid therapies and amyloid biomarkers

and amyloid everything.

And we just haven’t seen efficacy, right?

So contrast that with cardiovascular disease

where, you know, you have this ApoB biomarker.

You understand the pathophysiology of how it works.

You have drugs that target it.

So you have a biomarker.

So you give somebody a drug that lowers ApoB,

you can measure ApoB.

That’s a really important and obvious thing

to be able to do.

And then you have clinical outcomes,

which is, oh, when you take a bunch of people

in primary prevention,

it takes this long before you see an effect.

In secondary prevention,

it only takes this long to see an effect, right?

Different risk stratifications, all these different things.

We don’t have any of that for Alzheimer’s disease.

So we do use,

there are now serum amyloid biomarkers that we use.

And we do track these in our highest risk patients,

but only because we believe,

and I don’t know if we’re right by the way,

that lower is better.

And therefore, if we make these changes to you

and your serum amyloid levels come down,

that that tells us something

about what’s happening in your brain that’s favorable.

But I mean, I would hate to represent

that we are practicing nearly the level

of precision medicine there

that we are in cardiovascular medicine.

When it comes to Alzheimer’s disease,

maybe take a step back.

When it comes to brain health,

I think there are a handful of things

that seem unequivocally true.

And there’s a lot of stuff

that is signal to noise ratio that’s really low.

So the unequivocally true things

for brain health are sleep matters.

Another unequivocally true thing for brain health

is that lower LDL cholesterol and ApoB is better than higher.

Another thing that is unequivocally true

is not having type two diabetes matters.

So having really good…

Being insulin sensitive matters,

sleeping adequately matters,

having lower lipids matters.

Those three things are clear.

And the fourth one that is unequivocally clear

is exercise matters.

More specific form of exercise.

Very, so I tried to answer this question

on a recent AMA that I did,

because the answer is more is always better.

But if you, if I tried to have one of our analysts

look at it through the lens of

if you could only exercise three hours a week,

what would be the highest use case?

And our interpretation of the literature

was if you could only spend three hours a week exercising,

you’d be best off doing one hour of low intensity cardio,

one hour of strength and one hour of interval training.

So if someone who said like,

I only want the minimum effective dose,

you’re going to get a pretty good bang

for your buck doing that.

But I would argue if your brain really matters to you,

do more.

One hour of interval training is no joke.

No, because you’re going to spread that out

over probably at least two workouts.


But Andrew, those four things are basically the only thing

where there’s no ambiguity about the benefit.

What about head hits?

Like don’t get, don’t hit your head.

Seems almost assuredly true

in a susceptible individual for sure.

So I put that, yeah, maybe we could include that as well.

Well, I just mentioned,

one of the things I’ve been learning recently

is I know you boxed for a number of years

when you were younger.

I boxed a little bit,

hit my head a number of times skateboarding,

but we think about sport injuries

as the major cause of head injuries,

but then I’ve got colleagues at Stanford

that say car accidents, bike accidents.

I’ve got so many colleagues and children of colleagues

growing up in and around campus that were hit by cars

on Woodside Road or a mere small object

surrounded by three, was it car weight?

3,000 pounds or something like that?

Yeah, more, yeah.

It’s unbelievable that the number of head injuries

and then construction sites

because those ridiculous little hard hats

which don’t protect against anything,

except, I don’t know, maybe windblown hair,

that they basically predispose,

the whole situation predispose people to head injuries.

Very common on construction sites

and then say nothing of military, et cetera.

So I think that I was told that the best thing to do

if you get a head injury is to not get another one.

In other words, if you can stop doing the activity

that leads to more head injury.

Yeah, the other thing that I think is emerging

and I hope it is studied rigorously

is the use of hyperbaric oxygen

immediately following a TBI, a traumatic brain injury.

I reached out to Dom D’Agostino a little while ago

to kind of, because he knows a lot about this lit,

to say, hey, is there anything out there

that’s really kind of turnkey convincing?

And he said, not yet.

They’re still doing it, right?

So I would do this.

If I was in a car accident tomorrow

and sustained a concussion,

and by the way, I’m not a proponent of hyperbaric oxygen.

So we have an internal white paper

that we wrote inside quite recently

where I examined, when I say I examined,

the analyst team examined and I pushed back and reviewed.

And I came away very kind of bearish on hyperbaric oxygen.

I don’t think it’s harmful,

but I think all of the claims are nonsense.

You know, telomere extension is totally irrelevant.

And if you actually look at the studies,

they’re the worst done studies I’ve ever seen in my life.

I’m sure you’ve seen some of these where it’s like,

you put these people in a hyperbaric chamber

and then watch them do cognitive tasks

act after and they’re so much better.

Well, the fine print is

they don’t even have placebo groups here.

Like, can you imagine doing a study

without a placebo group?

Or your placebo group doesn’t go into a sham chamber.

Yeah, I mean, one of the big problems of the proliferation

of all these pay-to-play journals,

meaning journals that will basically publish a paper

with minimal or poor peer review

because they charge in order to publish

and then offer free access.

You know, free access sounds great,

but when it’s pay-to-play type journals,

there’s been a huge proliferation of papers,

most of which you find on Twitter,

in which the study design is beyond that.

Like a ninth grader who woke up late for school

and was partying all weekend

could design a better study than most of these studies.

And there’s some excellent studies out there as well,

of course, but presumably

and eventually on hyperbaric chamber too.

So I’m not picking on hyperbaric chamber per se,

but the proliferation of truly terrible science

that’s published in peer reviewed journals

is just overwhelming.

Yeah, it’s insane.

And all of that is to say,

I think there are places where hyperbaric oxygen

makes sense, clearly in wound healing, it does.

It’s a miracle treatment for wound healing.

And I would absolutely use hyperbaric oxygen

if I suffered a concussion.

But, you know, beyond that,

I think it’s pretty tough to make the case.

Where do people go for that?

I mean, there are clinics.

Yeah, there are clinics you basically go to.

The protocols have to be very precise.

I mean, this isn’t something to cowboy at home.

No, no, no, no, you have to go into a real chamber.

I think the TBI protocol that’s most commonly used is,

God, I wanna say it’s pretty intense.

It’s like five 60 minute sessions a week

at two atmospheres.

Oh boy.

Like it’s no joke.

So from a cost and time perspective, it’s enormous.

And the time and cost are reasons why I think

when I see people doing hyperbaric oxygen,

just because they think it’s gonna help them live longer,

I’m like, dude, you know what you could do

with five hours a week plus the commuting time

that you put into that, like put that into exercise

and I promise you, you’ll get a bigger benefit

than you’re getting out of hyperbaric oxygen.

But there’s a lot of other stuff

that I just think is maybe helpful.

There’s tons of supplements that I think about

when it comes to brain health.

What about theracumin?

What about magnesium with L3 and eight, the transporter?

What about methylated vitamins that lower homocysteine?

What about EPA and DHA?

And we’ve gone through all of the literature on that stuff.

And many of these things we still are recommending

through a kind of basically like the potential benefits

outweigh the potential costs,

but the evidence is really unimpressive

for most of those other interventions.

So when you think about the big four or big five,

if you include not getting head injury,

everything else is probably a rounding error

compared to those big ones.

Maybe just for sake of thoroughness,

we can just list off those four again, exercise.

Exercise, sleep, insulin sensitivity, and lipid management.

Well, along the lines of head injuries,

we should probably move to the next category

of how not to die as to avoid accidental death.

How common is accidental death

and what are these accidental deaths?

Because we are separating this out from automotive death.

So is this people falling while hiking,

selfies gone bad, what are we talking about here?

I’m not chuckling because I like it.

It’s just, I mean,

it seems like there’s a near infinite ways

to die accidentally.

And when you-

So I think there’s two ways to kind of look at this.

And so here I kind of merge two categories.

So I would call it that overlap

in the way that they’re characterized by the CDC,

but I would sort of,

we’ll talk about them separately and bring them together.

So if you talk about true accidental deaths,

automotive and falls and overdoses are the three.

That’s basically what it comes down to.

So, you know, in our death bar analysis,

we kind of list all this stuff out.

In fact, I think that’s actually one of the figures

in the book is I have the accidental death figure

that we’ve put together where we’ve adjusted by population.

And you’ll see a couple of things.

If you look at it in absolute terms,

it’s basically a pretty constant.

So regardless of what decade of life you’re in,

once you’re above, you know, 20,

accidental deaths are a pretty sizable number of deaths.

Now, car accidents seem to be pretty constant

throughout life.

Little more common if you’re under 60 than over 60,

but they never go away.

I was told that in teenage and boys in their early 20s,

alcohol induced automotive fatalities

would place them at an astronomic risk.

Is that just not true?

It’s not true anymore compared to overdoses.

Is that because young people now

aren’t getting their driver’s licenses?

I’ve also heard that.

Yeah, well, I think it’s also because we’re seeing

such an uptick in the deaths that come from fentanyl.

Got it.

Fentanyl related deaths have basically squashed

all other deaths below 65 on the accidental front.


Oh, it’s not even close.

Because of the number of different substances

that fentanyl is being woven into.

It’s winding its way into everything, right?

So all counterfeit drugs, all illicit drugs.

And look, most of the time you’re not getting a lethal dose.

So it’s, you know, it’s,

but you’re getting lethal doses so often now that,

um, well, you know, I did a little analysis actually

the other day when I looked at how are deaths of despair

increasing over the last five years?

So what did I define as a death of despair?

Suicide, alcohol-related death, or overdose?

Accidental overdose.

So we differentiate that from suicide

where suicide is obviously deliberate and accidental is not.

So if you just looked at those three things,

so accidental overdoses, suicides, and alcohol use,

or alcohol-related death,

not including driving, by the way,

this is like cirrhosis of the liver that comes from,

that number is going up at almost 20% per year since 2019.

So I couldn’t get 2022 numbers yet.

So at the time of the time I did this analysis,

which was last week,


the 2021 numbers was about 210,000 Americans.


Up from 180,000 in 2020,

up from like 150,000 in 2019.

So is this, um.

And that is driven almost entirely by fentanyl use.

So I’m trying to get a sense of how this would happen.

A while back, there was an article in the New York Times

that some photographs of people

that died of fentanyl overdose,

and said they went out to buy cocaine and died of fentanyl.

And I thought to myself,

this is a really kind of odd socio-biological phenomenon,


Because, I mean, here they’re not demonizing

these cocaine users.

I mean, they went out to buy cocaine, right?

This is not a,

I know cocaine has one narrow clinical use

as a prescription drug,

but in general, when people buy cocaine,

they’re, they’re quote, unquote, partying with it,

or using it to work longer hours or something like that.

Um, so the whole nature of the article

was a bit strange to me,

but it clearly pointed to the fact

that people are using cocaine.

Okay, that’s no surprise,

but people are going out and buying cocaine.

They’re presumably buying Valium.

They’re presumably buying.

This is where it’s really killing kids.

I mean, it’s online.

This is in person.

I mean, the reason I’m so,

so baffled by this is,

let me contextualize what I’ve said so far

about this question.

I was surprised that the Times would write a paper

about the tragedy of cocaine users dying of fentanyl.

And I think they did it to highlight this fentanyl problem,

because people have been using cocaine for a long time.

And typically those are not the members of the population

that we’re really focused on,

since the mid eighties,

the so-called cocaine and crack epidemic.

So basically it tells me that people,

like you said, illicit drugs, so cocaine,

but also, you know, what other sorts of drugs

are people buying?

The majority of people are dying from fentanyl poisoning.

And I had a guy on my podcast recently

named Anthony Hippolito.

And if anybody’s interested in this topic,

they really need to go listen to that.

So Anthony-

I watched the YouTube version of this

and your podcasts are excellent.

So people, if you’re interested in this,

and I think everyone should be interested in this.

If you have a child or know somebody who has a child,

you just got to get this podcast into their hands

because it’s the most important public service announcement

I’ll probably ever do

in terms of saving more lives potentially.

Where the majority of this is making its way

into the accidental poisonings

is through illicit counterfeit pills.

So it’s when kids are out there buying,

you know, Oxy, they want Oxy.

Well, they can’t get real Oxy, right?

Cause they’re not going to go to a doctor

and get real Oxy.

So they’re going to buy it through, you know,

Snapchat, right?

They’re going to buy it through some drug dealer

that they’re finding on social media.

They’re buying sleeping pills.

They’re buying all sorts of counterfeit stuff like Adderall.

Any of these things are being laced with fentanyl.



Well, I assumed that fentanyl-

And again, the reasons are it’s insanely cheap

to use synthetic fentanyl.

And secondly, and again-

But the effects of fentanyl are nothing like

the effects of Adderall.

So cocaine doesn’t make sense for that reason either.

Doesn’t make sense either.


And yet it’s still showing up in cocaine.

Again, I don’t think that’s the dominant place

it’s showing up.

I would guess that the dominant place it’s showing up

is in counterfeit opioids.

So any opioid, barbiturate, any sedative, depressant-

Let me tell you what I’m telling my daughter, right?

Cause this is, to me, it’s a frontline problem.

I have a 14 year old daughter.

I’m like, listen, I don’t care which friend of yours it is.

I don’t care how much she’s amazing.

If she tells you to try this sleeping pill

because she took it the night before

and it was really helpful,

or this will help you study better,

or this will help you do anything.

I’m like, just come to us.

We’ve got a better pill for you.


Like in other words, you can’t trust anything

cause you don’t know where she got it.

She has the best of intentions, I’m sure,

when she’s given it to you.

And by the way, she probably took it the night before

and was just fine.

But the people who are making these pills

are not exactly up to GMP standards.

So you just have no idea which pill is getting

what dose of fentanyl.

One thing that Anthony Hippolito told me

that I simply couldn’t believe,

I had to ask him six times,

was that some of these pills

have like one milligram of fentanyl in them.

Now, I made the point on the podcast

that a hundred milligrams of fentanyl

for most people is a hit.

Like I’ve had fentanyl before.

I’ve been in the hospital and I’ve had fentanyl.

A hundred milligrams is like, wow, that is such a trip.

Why are people dying from one milligram intake?

Respiratory inhibition.

You can’t breathe.

That shuts the brainstem off.

Well, I don’t think we can highlight this enough.

Adults are dying, kids are dying.

I met someone earlier this week

who told me her 35 year old son

died of an accidental fentanyl overdose.

And he wasn’t, at least by her description,

a drug addict or anything of that sort.

Yeah, we’re talking about a different game now, right?

So it’s like, these are kids that have anxiety.

These are kids that are sort of addressing another issue

with these pills.

And that’s why I think this whole concept

of deaths of despair is a really important one.

But back to your question,

what do accidental deaths primarily amount to

for the aging population?

Again, it is so clear that it is fall related.

This is where once you hit 60, 65,

the risk of a fall that results

either immediately in death,

you know, you hit your head and die,

going back to like cerebral hemorrhage,

or it is the straw that basically leads you down the path

to death within the next 12 months is astonishingly high.

It’s so high that it’s sort of hard to wrap your head around

but if you’re over 65 and you fall

and break your femur or hip,

so you either crack the femoral neck

or the femur itself,

your 12 month mortality,

the probability you will be dead in 12 months

after that break, if you’re 65 or older,

depending on the study is about 15 to 30%.



So in terms of offsetting the probability of falls,

you talked a little bit about this before,

but you and I have talked a little bit about this before,

but maybe we could go a little bit deeper.

People’s ability to jump and land

seems to be highly correlated with one’s ability to not fall

or at least fall and control the fall

in a way that leads to no or less severe injury.

Yeah, so Andy Galpin talked about this on your podcast,

he talked about it on my podcast.

What is the hallmark of aging on the muscle?

It is atrophy of the type two muscle fiber.

That’s the hallmark.

Fast twitch.

Fast twitch muscle fiber.

So if you wanna understand what looks different

in 50 year old Peter versus 18 year old Peter,

it’s not my type one fibers, it’s my type two fibers,

it’s my fast twitch fibers, it’s my explosive fibers.

I mean, when I was 18 years old,

I could vertical jump over 30 inches.

Today, I’m lucky if I can vertical jump 24 inches.

And when I’m 60, boy, it’s like my goal

is to be able to vertical jump 20 inches when I’m 60,

and I don’t know if I’m gonna be able to do it.

I’ve seen some videos of some 80 year old sprinters

that are pretty impressive,

and certainly 80 year old gymnasts that are impressive.

I’ve not seen very many videos

of 80 year olds dunking basketballs, for instance.

Yeah, it’s-

Who are not taller than six feet, five inches.

Yeah, yeah, yeah.

So when we lose, so again,

if you just think about size, strength, speed,

we lose speed first.

We lose speed, then strength,

and the last thing you lose is size.

So again, size is agnostic to fiber, right?

You could have big type one fibers

and still have lots of size.

They’re not gonna be that strong,

and they’re certainly not gonna be fast.

So what, I mean, we could go through,

we could spend hours on this particular topic,

but I think the most important thing

that people need to understand is you cannot age well

if you are not doing the type of training

that is there to strengthen and delay

or minimize the hypertrophy of your type two fibers.

So everything matters, right?

You have to be doing your zone two.

You have to be doing all of these other things,

but some component of your training

needs to be stressing the type two fibers.

You have to be doing strength training

that taxes those fibers.

You have to be doing reactivity training.

You have to be doing explosive training.

And ideally some training that involves jumping and landing.

Well, jumping is a very big part of it.

And landing is a very big part of another one

of what I kind of think of as my four pillars

of strength training.

So one of the pillars of strength training

is eccentric strength, which is breaks.

So you’re gonna hurt yourself 10 times more likely,

I’m making that number up by the way,

I don’t know if it’s 10 times,

but experientially it seems to be,

you are 10 times more likely to hurt yourself

stepping off something than stepping onto something, right?

Stepping down versus stepping up.

Because when you step up onto something,

you are concentrically controlling muscle.

When you step down, you have to apply the breaks.

And that’s where most people falter.

Much harder to walk downhill than uphill.

Uphill is taxing your cardiovascular system.

But if you slow down enough, you’re fine.

But a lot of people don’t have the ability

to slow themselves down when they’re walking downhill.

And so when an older person steps off a curb

and can’t fully stop themselves, and that results in a fall.

So, you know, I like doing things like a broad jump.

Broad jump’s a fun little test set

I like to do every once in a while.

I always wanna make sure I can broad jump six feet.

That’s kind of my arbitrary number that I’ve chosen.

And the reason is on the takeoff,

that’s a very explosive movement.

But the landing is just as important.

If I can’t stick that landing,

it means I don’t have the breaks.

So those are kind of some of the tests

I wanna be able to do to make sure

that I’m utilizing that system.

Because I do think, you know, look, I’ve watched my mom.

My mom fell, gosh, probably been about four months ago.

Just fell in a typical way that people fall.

By the way, it could have happened to anybody.

It’s not like, you know, my mom walks around

and moves around just fine.

But on this particular day,

she just tripped on a uneven stone and fell

and landed and broke her hand.

And she’s really lucky she didn’t break her hip.

And I told her that because my mom was, you know,

probably in her mid seventies.

And I said, look, you know, if that was your femur,

I’d give you a 30% chance of dying in the next year.

I mean, it’s just an,

those are such difficult to recover from injuries.

Because first of all, you’re dealing with the immobility

of, you know, the hospitalization

and immobility that follows that.

And the amount of muscle loss that occurs

could easily be, you know,

four or five pounds of lean tissue lost

that for most people that age

becomes almost impossible to get back.

And that says nothing about sort of the acute causes of death

like a fat embolism that results from a broken femur,

a blood clot from laying in bed.

Those things are also catastrophic.

But what happens is a lot of these patients

just never get back to the same level of mobility.

And, you know, now I think in many ways

we’re kind of pivoting from what kills you

to what ruins your quality of life.

And we’ve spent so much time talking about what kills you,

but I think you might as well be dead in some ways

if you can’t do the things you wanna do.

And if playing with your grandkids or gardening

or playing golf or going for a walk with your spouse

or think of any of the things that we all do today

and take for granted, if you can’t do those things,

I don’t know, you sort of lose the reason to be around.

And oftentimes the inability to do those things

is associated with pain,

which is psychologically and obviously physiologically

so distressing.

You mentioned the four pillars of health.

Maybe just list those off for people.

Of lifting?

Well, the four pillars of longevity through physical.

Oh, yeah, yeah.

Sort of the exercise pieces of them.

Yeah, so strength, stability, aerobic efficiency

and aerobic peak output.

Okay, so aerobic peak would be, so VO2 max.

And zone two, that’s in my analogy,

that’s your zone two is how wide the base of your pyramid is

and your VO2 max is how tall the peak of the pyramid is.

So the best pyramid has a wide base and a high peak.

So you could have a reasonably wide base and a shallow peak.

If you just did zone two training,

you’re gonna get a reasonable peak,

but it’s not gonna be that high.

You have to do some of that specific training.

If you just focus on high intensity,

you might drive up that VO2 max,

but you’re actually gonna have a relatively wide,

a narrow aerobic base.

So you think about just maximizing the area

of that triangle, widest, tallest.

Stability and strength.

Stability, of course,

encompasses everything we’re talking about

in terms of reactivity.

You know, I dedicate a chapter in the book to this concept

because it is so foreign to most people.

And for understandable reasons,

it’s not sexy, it’s the hardest one to train,

it’s the hardest one to understand,

but it’s so important because it’s the thing

that I think differentiates people who age well

and people who don’t age well.

And I should perhaps throw in there,

please correct me if I’m wrong,

but also most of the machines

that are in typical commercial gyms

that allow people who are not very experienced

to start doing some resistance training

don’t really tap into the stability factor terribly much.

So while there’s value to leg extensions and leg curls

and chest presses and shoulder presses

that are done with machines,

certainly for a number of reasons

and can often be safer than free weights,

especially for people who are approaching it at a later time

or new to the whole thing,

they don’t really lend themselves to real life stability,

walking down, as you mentioned,

walking down stairs in the absence of a handrail

or movements in kind of odd planes,

having to step aside to avoid a bicycle at an angle

as opposed to just moving linearly.

Yeah, and by the way,

a lot of things that don’t involve machines

still don’t give you that, right?

Like, I mean, doing a deadlift,

you have to be stable to lift a heavy weight

like you would a deadlift without hurting yourself.

That requires an unbelievable capacity

to harness intra-abdominal pressure and to be connected.

If you’re gonna lift 500 pounds off the ground,

you’re stable.

But that still doesn’t prepare you

for what you just described.

So stability is multifaceted

and it involves doing a lot of things.

You know, today, for example, I finished my,

today was a cardio zone two day.

So I did my cardio zone two

and I had an extra 10 minutes

before I needed to kind of get moving.

And so all I did was step ups for 10 minutes.

I just did single leg, very slow step up

and insanely slow step downs off a box in a gym.

So two second up, four second down,

two second up, four second down with, you know,

and I would do them with ipsilateral loads,

contralateral loads, all sorts of different things.

And, you know,

basically that’s just a stability game for me.

It’s like, I’m building that concentric strength

in a movement where it’s easy to cheat,

but can I do it without cheating?

That’s terrific.

And it’s terrific that you covered all of that

in the book, in addition to these other topics.

So several times during our conversation today,

you alluded to quality of life.

And one of my favorite segments in your book,

indeed, the segment in your book

that I believe could be its own entire book

of tremendous value is the section on emotional health.

If you could just share with us a bit

of what inspired you to include that section.

Was this, for instance,

based on communication with your patients?

To what extent it was based on your own life experience?

And then maybe we can drill a little bit deeper

into what’s contained in those chapters

and what really constitutes emotional health.

Well, I mean, I think that chapter of the book,

which is a pretty long chapter,

it’s the final chapter as well,

is certainly different from all of the others

in that there’s no confusion about expertise, right?

I think in the other chapters,

I at least try to come across as having some knowledge

on the subject matter.

And I’m writing them most often as,

quote unquote, the doctor, right?

Whereas I think that last chapter

is much more about an experiential side

of my knowledge acquisition.

And therefore really it comes across more as a patient.

And I think you’re right.

I think that that’s a chapter that initially was resisted

by all other parties involved in the book.

So my co-author, my editor,

everybody else sort of felt like this is interesting,

but it’s a separate topic.

If you want to write about this,

you should write another book about it.

But it doesn’t really belong in this book.

I disagreed for two reasons

and ultimately, I guess my opinion prevailed.

The first is I didn’t want to write another book.

So it just that, you know,

not including this in this book

to then write about it in another book

was not something I was interested in doing.

But I think more importantly,

I do think that this book is about much more

than how long you live.

And while we have talked about,

and we’ll talk about in the book that is, you know,

how cognitive and physical health

are just as germane to quality of life

as they are to length of life.

This other piece of emotional health,

you know, it’s potentially the most important of them all.

It’s also the hardest to define,

but without it, none of this other stuff matters, right?

So there’s, you know, infinite lifespan.

If you’re miserable, means nothing.

Maybe worse.

That would be a curse, right?

You could argue, how could you punish somebody the most,

allow them to live forever and be miserable?

Is there a…

Yeah, there’s a Greek god, Tithonus.


Yeah, he was granted immortality.

It’s a bit different.

He was granted immortality,

but without a healthspan, basically.

So he aged forever.



And this would be dreadful too, right?

And I feel like, why did I need to write about this?

Well, I think that, you know,

this is probably my greatest struggle, I think.

You know, way at the outset of the podcast,

you asked me kind of like,

what are the obstacles to longevity?

And that got us down a path

of some very black and white things.

But when I look at a patient,

I create a dashboard.

And the dashboard is,

what are all the things that are a threat

to every component of your longevity,

both lifespan and healthspan?

We talked about a bunch of those things.

So what is your risk for atherosclerosis

and what are we doing about it?

What is your risk for cancer?

What are we doing about it?

What is your risk for neurodegeneration?

What are we doing about it?

What is your risk for accidental death?

What are we doing about it?

What is your risk for physical decline?

What are we doing about it?

And one of those things is,

what is your risk of emotional health

or poor emotional health,

and what are we doing about it?

So when I do that exercise for me,

which I do, right?

I mean, I have that spreadsheet laid out for me

and I know where my factors line up.

And interestingly, despite my family history

being horrible for atherosclerosis,

it’s like sixth on my list.

Because, I mean, basically I intervened early.

I have a clear understanding of the pathophysiology

and I’m doing everything to the maximum.

So I’m actually very confident I will die with

and not from atherosclerosis.

But the top thing on my list is actually emotional health.

That’s the one that is the hardest for me to manage.

And it’s the easiest to get out of balance

and it creates the most pain in my life.

So that’s a long answer to why I felt

this needed to be in here.

Well, in the book, you go into very honest detail

about some of your journeys through

and challenges with emotional health

and paths to overcoming those.

Maybe we’ll get into those a bit,

but before we do, how should we define emotional health?

This to me seems like one of the most difficult areas

to calibrate oneself.

Like even just measuring emotion is tricky.

Language is the dissection tool

for psychologists, psychiatrists, and indeed for all of us.

You know, how are you doing today?

Great, or I’m miserable, or I’m depressed.

I mean, it means such different things to different people.

Obviously, suicide being the far end of, we presume, misery.

There are instances of manic suicide,

but, you know, depressive misery.

But setting that aside, I mean, how should we evaluate,

think about, and communicate emotional health to ourselves

and to the relevant people that could potentially

help us.

Yeah, well, you’re right.

It’s very difficult, right?

And so much of what goes into this book

is about things that are much easier to quantify.

I could sit here and talk for days

about all the ways we quantify from the histologic

to the gross of each of these diseases,

genetically, all of these other things.

With emotional health, it’s far more vague.

And I don’t even attempt to come up with a definition.

I can tell you things that make up components of it.

So, connectivity with others

just seems to be an inescapable part of this.

So the ability to maintain healthy relationships

and attachments to other people, having,

and by the way, these are no particular order,

having a sense of purpose,

being able to regulate your emotions,

experiencing fulfillment, experiencing satisfaction.

All of these things matter.

And I think that for many of us,

if we’re taking an honest appraisal of ourselves,

we’ll notice that we have deficits in these areas.

Being present.

By the way, that’s something that may have been

less of an issue 100 years ago than it is today.

So I think, certainly for me,

being present is very difficult.

It’s not my default state.

I don’t know that it’s the default state

for most people, truthfully,

but I’m very often predisposed

with thoughts about the future,

occasionally thoughts about the past,

but it’s much more often kind of thoughts about the future

and planning and thinking about what I need to do

and what do I wanna do next

and never really being satisfied

with anything that’s happening in the moment.

So I have to work hard to kind of overcome those things.

And I’m sure you can appreciate this,

but when you are present,

you generally are in a much better frame of mind.

Yeah, there’s an interesting study.

I think it was initially published by Dan Gilbert’s lab,

one of these long-term happiness studies

that was published in Science Magazine

that pinged people for their level of happiness,

unhappiness, presence, or lack of presence

multiple times throughout the day.

This was in the early years of smartphones.

So this is around 2010, 2011.

So the technology wasn’t as good as it is now,

but it was good enough to do this

in a very large number of people.

I forget how many, but it’s certainly more than 10,000.

That number is, I’m stating it intentionally low.

And what they found was regardless

of whether or not people were doing something

they enjoyed or not, boring to them or not,

the degree of presence to what they were doing

was a stronger predictor of their happiness

in that moment and overall than was anything else.

And also a pretty fairly rare feature for most people.

So it seems like it’s something that we do need to work at

perhaps nowadays, as you point out,

more than we perhaps had to in our ancestral past.

I’m a little bit surprised that you say

that you find it hard to be present

because you strike me as somebody that is not just willing,

but has a strong, almost reflex toward drilling in,

observing the contour or something,

and then really drilling into it

and really getting to the guts of most everything

that interests you.

So you strike me as somebody who’s very present.

And I guess maybe this gets back to this.

But they’re not mutually exclusive, right?

I mean, I think, so for example,

I’ll notice that sometimes if I’m playing with my kids,

especially my boys, because they’re younger, right?

And playing with them is really being in their world.

Like if I’m with my daughter,

we can be doing things that are kind of mutually,

like we’ll do things together

that I would probably do by myself

or she would do by herself.

But with my boys, it’s generally doing something

I wouldn’t otherwise be doing.

And if I’m paying attention to it,

I’m constantly amazed at how after five minutes

of searching through a bin for just the right Lego piece

that we wanna do to build this one little thing,

like my mind will start thinking about something else.

Like, oh my God, like I gotta go,

oh, I didn’t email that dude back.

And I gotta do this and I gotta do this

and I gotta do this and I gotta do this.

And I just get into the, I gotta do, I gotta do,

I gotta do.

And it’s like, dude, you’ve only been here for five minutes.

Why don’t you just find the Lego piece

that you need to finish building that thing over there

that is this beautiful moment

that you’re not gonna have many of, right?

There’s a very finite number of these moments

you’re going to have.

So you wanna savor every one of them.

So again, I don’t think I’m alone in that.

I think a lot of parents, for example, can relate to that.

And that’s literally just one of many different things.

And by the way, I wouldn’t have said

that that was my greatest challenge either,

but it’s something that requires,

I think, deliberate attention.

What you’re alluding to is a challenge

with holding a single time perception

or perception of time.

One of the most remarkable things to me

about the human brain is our ability to be present

or think about the past or the future

or the present and the future.

And we can occupy different time bins.

And in a recent non-recorded conversation of ours,

you showed me something that I’ve seen before,

but for some reason this time

it had a profound impact on me,

which is that you have a chart of the number of weeks

that you’re going to live

and you mark them off one week at a time.

We were talking about this

in the context of major life decisions.

And it illustrates the fact that we need such a chart

that we can’t really move through our day being present

to the beauty of working on a Lego with our kid

while also paying attention to the fact that,

wow, this is week number, whatever,

600 in the X number of weeks of one’s life.

So that ability to contract and dilate

our time perception is marvelous,

but it’s also a double-edged sword

because it’s what takes us out

of what’s meaningful in the moment.

One sort of has to wonder then

whether or not our challenges in being present,

I guess the psychoanalyst, maybe we need to,

or a psychiatrist, maybe we need to ask Paul Conti,

who you know and I know and respect greatly,

whether or not this is some subconscious refusal

of our own mortality or something, right?

That if we were to really contemplate our mortality

on a regular basis,

not just when we’re marking off the weeks of the poster,

we wouldn’t be able to be present

because it’s kind of overwhelming, right?

I don’t know.

I feel like the literature says

that people who spend more time

contemplating their own mortality

are actually more at peace.

Kind of a little bit of the exposure therapy idea.

And so I’m not sure it’s an unhealthy thing

to be aware of your mortality.

I suspect it’s helpful in as much as you accept it, right?

And you feel like you have some agency

over parts of it, right?

Like I don’t think I have nearly enough agency

over the length of my life.

I think I’ve got five to 10 years of wiggle room

that I can extract.

If I do all of the things

that I’ve written about in that book,

I bet I can stretch my life out 10 to 15 years

at the maximum, call it 10,

over what would have happened if I didn’t do those things.

Maybe it’s more,

but it depends on what we’re comparing it to, right?

From being reasonable

to maybe being a little bit hyper-functioning.

Maybe it’s 10 years.

But where I know I have a much greater agency

is on quality.

And for me now,

a big part of that is in terms of quality of relationships.

I think that’s a big thing.

And I think for most people,

that’s what I hope this chapter does,

is it sort of allows more people

to kind of take an appraisal of that

and ask that question,

which is before it’s too late,

am I living my life more for my resume virtues

or for my eulogy virtues

to borrow from David Brooks’s work,

The Road to Character,

which I talk about as being kind of

one of the many aha moments that I had during this journey.


And there again, thank you.

You recommended The Road to Character to me.

I do an annual solo wilderness trip

and I listened to it during the drive to that trip

and on that trip.

And I would just say it’s a truly important book

for everyone to listen to.

It’s really quite impressive.

What are the things that you do on a regular,

let’s say on a daily basis,

to try and enforce, forgive the word,

but enforce emotional wellbeing and health

in terms of relationships?

Because as you point out,

it’s not reflexive for everybody

and that doesn’t make them bad people.

I think it does have to do with this challenge

in balancing expectations of work and other things.

And for some people, a more inherent selfishness.

And for some people, they aren’t selfish enough, right?

I know plenty of people that are running around

trying to serve everybody

and then their health is crashing

or their mental health is crashing.

So it can cut any which way or all ways.

What sorts of practices do you incorporate

or just even thoughts within your own mind?

Do you use charts and lists?

I mean, you’re very regimented about your workouts,

building grip strength,

eccentric training zone two, et cetera.

Why wouldn’t we also script out the things

to pay attention to each morning and day

as a list of to-dos?

Well, I have done those things, right?

So certainly, and I write about it in the book,

I’ve gone away a couple of times, right?

So in 2017, I spent two weeks at a facility in Kentucky.

In 2020, I spent three weeks at a facility in Arizona.

And on the back end of that facility three years ago

when I got out, I mean,

I had a very clear list of daily things I needed to do.

And so at that point for about six months

following getting out of that stint of rehab,

I mean, I was,

I mean, God, the list of behaviors I was doing

every single day.

I mean, twice a day, standing in front of the mirror,

reading my list of affirmations,

writing in my journal every single day.

I had therapy every single day.

I mean, all of that stuff was highly regimented.

You know, today I would say there’s no one single behavior

that is quote unquote mandated as part of my recovery.

But perhaps the most important thing

that does come up every day is


being mindful of and acting on as quickly as possible

every time I do something damaging to a relationship.

So I would say that like,

if you compare Formula One,

one of my favorites work by far,

if you compare Formula One 40 years ago

to Formula One today,

the difference is not in the number of accidents

that takes place.

The difference is in the fatality of those accidents.

There are just as many if not more accidents

in Formula One today.

The difference is nobody dies in those accidents.

The cars are so much safer.

They’re engineered first for safety, second for performance.

It used to be the reverse.

And that’s why there was a day

when every second or third weekend a driver was killed.

It’s catastrophic to imagine what took place

between the mid 60s and about the mid 80s in Formula One.

And similarly, I would say that the frequency

with which I have an interaction

with a person who matters to me

that is not the best interaction it could be

is only slightly less than what it was five years ago.

The difference is the severity of that is much lower

and more importantly, and most importantly,

the length of time between when I screw up

and when I make amends is infinitely shorter, right?

It went from being, I would never make amends

to if I’m a dick to my wife,

I usually am trying to rectify it within a few minutes

or at most a couple of hours.

And that, and so it’s really, you know,

one thing I learned throughout this journey was

if you hold yourself up to this goal of,

I have to be perfect, I have to be the perfect dad,

I have to be the perfect husband,

I have to be the perfect friend,

you’re gonna set yourself up for failure

because you know, you’re just not gonna be perfect.

But if instead you can say,

what I’m gonna be perfect about

is repairing damage when I cause it,

that’s what matters.

You know, the other day,

I yelled at my son for something.

It was a while ago actually

because it was before I lost my voice.

So, you know, I don’t know,

he was just doing something and he was wrong.

You know, like it was like,

he did something I told him 150 times not to do

and I yelled at him and punished him.

Like, you know, but I was way too harsh.

Like, cause basically I basically,

the first 27 times he did it, I didn’t respond.

And then when I finally did,

it’s like I blew a gasket, right?

But what I realized is, yeah,

you could say, well, maybe it hurts a child to do that,

but I think it hurts them way less

if you can immediately go and repair and say,

hey buddy, daddy was a little harsh in that.

I’m sorry, I didn’t mean to yell at you like that,

but what you did is wrong

and you’re not gonna get to go out and play right now

as a result of it, but I love you very much

and I want us to do better.

I want you to do better and not doing this thing

and I wanna do better and not yelling at you

when you do this thing.

So it’s not rocket science, right?

But I just think I used to live my life in a way

where all I did was break shit and never fix it.

So you’re living in a house where everything is broken.

Whereas now I still break things,

but now I clean up the mess

and oh, like all of a sudden the house is better.

What is your process for when there’s a need for repair,

but you feel that it wasn’t you,

it was somebody else’s error or potential error.

So you very humbly express how you go

about repairing your errors,

but what about situations where a loved one, a coworker,

you feel screwed up or wronged you, right?

As many people do, we all do from time to time

feel this way.

Do you approach them and try and repair the situation

because there’s a little bit less or far less control

when you know, than the situation you described.

And by the way, the situation you described,

I think is a perfect one

because I think we all screw up.

And so the answer to the second question

is sort of the answer to the first,

which is if everyone did what you were doing,

the world would be truly a far better place,

but not everyone’s doing what you’re doing.

So if you feel wronged,

assuming that wrong wasn’t sociopathically motivated,

what is your process for going about repairing

a relationship fracture like that?

Again, this assumes that this is a relationship

that matters, right?

So in every interaction,

you’re only really able to optimize around one thing

and you have to decide,

is this one thing that I’m optimizing around

the relationship or is it the outcome?

I mean, there are other things to optimize around,

but you understand that those are different, right?

Maybe you could elaborate on that a little bit.

I think I get it, but flesh that out a bit.

If I’m at the market and I’m trying to buy a new car

and I’m sitting there talking to the car salesman,

that’s a relationship, that’s an interaction.

Now I want to buy this car for as little as possible

and he wants to sell the car for as much as possible.

Well, in that interaction,

my relationship with him means nothing.

Let’s assume I don’t know this guy

and he’s not like my best friend.

I’m optimizing everything around the outcome.

So everything I do in negotiating

and in interacting with him personally

is based on getting the best outcome for me.

It’s very selfish, right?

Nothing wrong with that, by the way.

He’s doing the same thing.

Well, he’s doing the same, right, exactly.

But now, for example, pretend that you are the car salesman

and you’re one of my closest friends

and it’s your dealership, it’s your money.

You can’t sell this thing to me at a loss.

I don’t want you to do that

because I want you to be able to make money.

And similarly, you care about me

and you don’t want me to overpay for this.

So now we’re negotiating

and we’re both trying to optimize for an outcome,

but our relationship also matters.

It’s a very different negotiation at that point.

And so I think I always try to ask myself this question

when I’m having some interpersonal conflict,

which is what am I optimizing for?

So if I’m having a quarrel with my wife,

I have to remind myself that the outcome is,

the objective or outcome is not necessarily

the top priority.

You know, being right all the time,

which is my default state,

it’s just to be a bull in a China shop.

It’s to be authoritarian instead of authoritative.

And that doesn’t work if the relationship matters.

So to answer your question,

the first thing I’m gonna ask myself if I feel slighted

is what is the nature of the relationship?

Is it even worth trying to do something about this?

And presumably you’re asking the question

because the lens is yes.

This is someone who you care about more

than in just a transactional way.

You know, usually what I’ve realized

is I can’t try to approach the situation

without fully understanding myself.

And that takes a while.

So generally, and this is where, you know,

I still one to two times a week,

I’m still working with a therapist.

I have to kind of try to figure it out on my own

and then usually bounce it off a therapist and say,

well, I think this is why I’m upset about this.

I think that when this person did this or said this,

I felt this.

First of all, am I correcting what I felt?

Because remember, sometimes you might,

at least for me, this was the case.

I would just feel anger in response to every interaction.

But what I didn’t realize was that anger

was really just another emotion

that was superimposed on top of hurt

or superimposed on top of fear

or superimposed on top of shame

or superimposed on top of something else.

But I didn’t know how to articulate

any of those other emotions.

So the only thing I could really articulate was anger.

So if anger is the only thing I know

and anger is the only response I see,

it’s not very helpful.

It’s not very insightful.

So that’s a big part of it

is being able to deconstruct what I’m feeling.

Oh, what I really feel is loss

or what I really feel is abandonment right now.

And that sometimes takes a while to figure out,

at least for me.

Like I’m still, you know,

I’m only a few years into this journey

and maybe other people figured these things out

when they were in their 20s.

And so they’re veterans,

they can do this more naturally.

But that’s step one.

If I don’t really understand what’s going on,

I can’t even begin to try to approach this person

to say, this is how I feel.

This is, you know, how do you feel

and what are we optimizing for in this interaction?

Well, I certainly know you are not alone

in this sense that it’s a process

and it takes a lot of time.

And on a case by case basis

can take a lot of time to figure out,

you know, exactly what one is feeling.

I think it really goes back to the coarseness of language

as a way to sort one’s feelings.

It was actually your other,

like, as we mentioned, Paul Conti,

who was one of your Stanford Medical School classmates,

but another previous guest on this podcast

who was also one of your medical school classmates,

Dr. Karl Deisseroth, right?

Psychiatrist and bioengineer of phenomenal stature

and doing amazing things in the world who said,

most of the time we have no idea how other people feel,

even though we think we do.

And most of the time we don’t even know how we feel.

I mean, our ability to really know

what we’re really feeling is terrible.

And yet we recognize the broad bins.

I’m pissed off, I’m super happy,

I’m relaxed, I’m tired.

I mean, just think about how coarse that language is

for all the nuance and all the underlying things,

conscious and subconscious,

that could be driving an emotional state.

It’s really quite unbelievable.

Yeah, beyond the valence, positive versus negative,

that was about the extent of my emotional language

until somewhat recently.

Well, it strikes me you’ve come a very long way.

Maybe you could share with us a little bit

about what you learned on these,

what you called retreats or,

I mean, in the book chapter you describe

deliberately going off to a treatment center,

multiple treatment centers over time

to really drill into this process

of understanding oneself better

and how one’s current state of emotional processing

and emotional stability are influencing relationships

and the key importance of that.

Was there any kind of overriding theme for you?

For instance, could you trace back to specific events

or themes of childhood that made a lot of it make sense

or is it far more nuanced than that?

Well, the first thing I would say is

I wish I could tell you that this was a very deliberate

and wonderful choice that I just decided

I’m gonna go on a little self-healing journey,

but unfortunately that was not the case.

In both cases, in 2017 and in 2020,

I was as close to having no choice in the matter

as one can have.

So both of these experiences represented

total rock bottom moments in my life.

So these would have been the two lowest points in my life

for different reasons, but they were nevertheless

the two absolute low points in my life.

And I would say, you know, in the first instance,

I guess I could have chosen not to go,

but I would have lost everything that mattered

in my life at that point.

And I had, you know, our good friend, Paul Conti,

basically telling me that I needed to do this,

that I really needed to do this.

And in the second situation,

though completely different circumstances,

you might think how can one person

in just a span of three years find themselves

in a situation where they almost

without having any choice in the matter have to go away

to a place where you’re basically locked up

without a phone for, you know, three weeks

and you’re doing 12 to 13 hours of therapy a day.

So nothing about this was something I wanted to do.

Nothing about this was pleasant.

I would describe these as the most difficult things

I’ve ever done in my life, bar none.

And I’ve done some difficult things in my life,

but they’ve always been physically difficult.

I love doing physically difficult things,

but this was emotionally the equivalent of, for me,

you know, climbing K2

and swimming the English Channel in the same month.

You know, something that just, I could, you couldn’t fathom.

So with that said, yes, I learned a lot.

And I learned that people like me can be overly analytical

and that hyper analytical nature can lead you astray

when you think that your intellect

is giving you a fact-based explanation

for a set of circumstances and you rationalize them away.

Well, this happened to me when I was a kid,

but, you know, like I get it and it’s not really a problem.

And as a result of that, you know, it’s,

these are actually some positive things

that came out of that experience.

And I think the real aha moment in my journey,

which occurred on a day that I remember very well

was the day I finally dropped that.

I dropped that rationalization

and I allowed myself to experience

what a child would experience in that moment

and then understood

what the implications are for a child

going through these things.

And I think that was really the first time in my life

I ever accepted emotionally

something that I had intellectually always said,

yeah, it doesn’t really matter.

I mean, it’s just, you know, that’s just life

and those things happen and lots of worse things happen

to lots of people and that’s okay.

And I think it’s not that once I emotionally accepted this,

I became a victim, it wasn’t at all.

It just finally allowed me to realize,

oh, I can let that go now.

Like I don’t have to, I don’t have to,

I don’t have to be a slave to the adaptations

that came from that.

I can surrender.

That’s beautiful and inspiring to me.

I think that, yeah, there’s this incredible ability

that the human brain has to script a story

and to compare it to other people’s circumstances.

And as you said, you know,

rationalize what are essentially emotional traumas

or physical traumas from the perspective of the adult.

But if I know one thing for sure,

and I’ll make it very clear, I’m not a clinician,

but is that the brain doesn’t discard of any circuitry.

We repurpose the same circuitry

we used as children, as adults.

And so the ability to go back to that and to parse it,

but as you point out,

not from an intellectual standpoint,

but from an emotional standpoint,

seems to be the really hard work.

Do you do that on a regular basis?

No, not at all.

It’s been done a handful of times.

It’s been exhausting.

It’s very difficult.

I don’t know if this is the right word.

I would almost describe it as emotionally violent.

And it’s not something I need to revisit often truthfully.

I think that, yeah,

it’s been done a finite number of times

and I think I’ve captured so much value from it

that there are lots of other things I continue to do.

I mean, I use a system called dialectical behavioral therapy

that is a regular part of the therapy that I do,

but I don’t have to go back to my childhood.

I don’t have to go back to uncovering

and re-exploring a lot of that stuff.

I’ve learned the lessons

and now it’s really about practicing the skills.

I know what I want now.

And I know, you know, you talk about plasticity.

I’ll share one example,

which I know I wrote about in the book,

but just for folks listening that you’ll appreciate.

So I, you know, just one of the,

one of the hallmarks of my existence has always been, you know,

just an insane amount of anger and rage.

It’s been there as long as I’ve known.

So I don’t have a conscious memory of not having rage, right?

So earliest memories of life when I’m five years old,

I have rage like you can’t believe.

And it’s a problem all my life.

So as a teenager,

if I go more than two weeks without punching a hole

in the wall of our house, it’s a miracle.

I mean, I am so good at drywall.

You can’t believe how good I am

for all the stuff I have to repair around our house.

Like I’m breaking windows.

I’m breaking, it just doesn’t, like I just,

and so in a way, and of course I rationalized

how much boxing saved my life

because I had this amazing outlet for my rage, right?

If you, I got to basically exercise six hours a day,

I’m hitting punching bags in people all day long,

and it’s just a beautiful outlet that keeps me out of jail.

And a big part of that rage was inward, right?

So it’s not rocket science to understand

that a person who has that much hatred for everyone

has an enormous amount for themselves.

And so one of the things I didn’t realize was happening

was what my inner monologue was,

because as you can appreciate,

your inner monologue is so frequent

and ubiquitous and present

that it’s easy to almost forget that it’s there.

I mean, that’s the sort of dangerous part about it, right?

Is kind of the David Foster Wallace, this is water thing.

If fish are swimming through water,

the water’s everywhere,

they don’t even realize they’re in water.

You don’t realize the subconscious stream of thoughts

that constantly flow.

But eventually I became aware of just

what that self-talk was.

And it is, it was no longer the case.

It was the angriest, the most violent

self-talk you can imagine.

I mean, it was like,

there is no mistake that I could make

that was anything other than my perfect, perfect standard

that didn’t result in what I would call

my inner Bobby Knight going ballistic.

So it just didn’t matter.

Like it sounds silly under, it didn’t matter.

If I didn’t perfectly cook a steak,

if I didn’t perfectly nail something I was doing,

if I didn’t do anything that was perfect

at what I described as match grade perfect,

I mean, I would want to beat myself to a pulp

and I would scream at myself.

I mean, it just, again, it’s hard to describe

and I hope that most people listening to this

don’t understand what that feels like.

Well, it became very clear that that had to change

because when you are that,

when you hate yourself that much,

by definition you are going to be

an insufferable prick to everybody else.

Like, because you’re just,

that’s going to spill into how you interact with the world.

So I was working with a therapist

who was one of the people who was sending me

to this place in Arizona.

And basically it became clear that,

you know, they proposed that I could shed this trait

if I was willing to do a certain amount of work.

And I was like, there’s no chance.

Like, I’m 47 years old.

This is the only way I’ve ever interacted with myself.

How in the world could this be undone?

It would take another 40 years to undo this.

And they’re like, no, no, here’s this exercise

you’re going to do.

So the exercise was every single time I did something

where I would have that self-talk,

I would have to immediately stop myself

and pretend that it wasn’t me that just did that,

but it was one of my closest friends.

And instead I would audibly speak to that person.

There was nobody else there,

but speak to that person as though

they are the one that made the mistake.

And I was to record that on my phone.

So if I’m out there shooting my bow and arrow

and I don’t get a bullseye,

instead of screaming at myself,

I have to say, oh, imagine it’s my buddy JR

who just missed that shot.

What would I say to him?

Pick up the phone or pull out the phone

and say, of course, something different.

And of course, what I would say in that situation

was much kinder.

I mean, infinitely kinder.

It’s like, if I’m saying it to my closest friend,

I’m going to say it in a very kind way.

And I had to take a copy of that audio

and text it to my therapist.

Oh, wow.


Talk about vulnerability.

I was all on board this practice

until you mentioned that at which point.

And I trust my therapist to a very deep level,

but I thought, wow, that’s a mountain.

Well, this poor person got a lot of text messages,

a lot of audio files.

But here’s the part that just blows my mind.

It only took, I don’t know, I can’t remember exactly.

I’d have to go back to look at my journals.

It only took about four months to get rid of Bobby Knight.

Like, you know, again, we had kind of a mental model

for what this looked like,

which was Bobby Knight was the chairman of the board.

He sat in the boardroom and nobody else got to talk.

And for those that don’t know,

Bobby Knight had a terrible temper.

Yeah. Yeah.

The worst. Right.

This is the guy that was throwing chairs

across the basketball court.

Level 11. Yep.

Out of 10.

And all of a sudden, like we got to the point

where Bobby Knight is not even in the boardroom anymore.

In fact, as I say this today,

I don’t really remember what he sounded like.

I mean, it’s amazing to me.

And I’ve had some really amazing opportunities

to bring him back.

Like, it’s not like I’m making fewer mistakes, right?

It’s not like I’m better today than I was three years ago

at all the things that I do.

I’m not, I’m actually probably worse in many regards.

But the difference is, you know,

I can communicate with myself.

I think I can say this.

I think I can say lovingly, right?

And maybe not as lovingly as some people can.

I still think I’m probably

maybe just a little higher standard with myself

than maybe I need to be at times.

But I’m just not beating myself up like I used to.

And I think by extension,

I’m beating other people up a lot less.

Well, I don’t know the extent

to which your internal narrative

reflects the narrative that others have about you.

But first of all, I want to thank you

for sharing what you just shared.

I think as a practical step it,

first of all, it’s one I’ve never heard of before,

but certainly represents this incredible phenomenon

of neuroplasticity.

Because four months sounds like a bit of time

and yet you were 47 years old.

So that’s 47 years of accumulated,

just absolutely berating self-talk is what it sounds like.

So it’s something that people can think about

for their own purposes and their own challenges.

Also, I’ve read the book twice now and love it.

As I put in my endorsement of it,

I think it’s not just informative,

but it’s indeed important

because it centers on so many of the key actionable items

related to healthspan and lifespan,

vitality, longevity,

whatever people want to call these things

that are essential.

But also the section on emotional health

was absolutely profound for me.

It inspired a huge number of changes.

And the book as a whole

represents a very important contribution to everybody.

There are numerous points

and I would say every chapter is applicable to everybody.

And there are very few books out there

that are really like that.

So I want to thank you for that

and especially for including the section on emotional health

and especially for sharing what you did today

because I think it doesn’t just take a bit of vulnerability

but a ton of vulnerability and humility

to be able to share what you just shared.

And my only request or wish is that you also

hopefully internalize it,

the tremendous gift that you’re giving everybody

through coming on podcasts like this,

doing your own podcasts, writing the book.

I look out on the landscape of front-facing,

public-facing health out there

and you sit not alone,

but in a unique stance as the medical doctor

that I do believe that people trust the very most

because of the fact that you have that intense rigor,

I wouldn’t even say your desire,

your absolute obsession with measurement and precision.

Many of the things that a moment ago you were pointing to

as potentially hazards for your emotional life,

but that serve all of us, the general public,

so preciously and with just incalculable value.

So I hope that internalizes as well.

Maybe it’ll even weave into your self-talk.

Maybe I’d need to send you a script every day,

but in all seriousness,

I also want to thank you for taking the time today.

And even though it’s a personal thing,

I really want to thank you

for being an amazing colleague to me in the podcast space,

in the health and medicine space, whatever that is,

and also just an incredible friend.

You’ve been a tremendous source of support and guidance

in every one of the domains that we talked about today

and many more.

And again, I just want to say

that this emotional health component, I agree with you.

I think it’s not just vital.

I think it’s the most vital of all of them.

So you’ve just made numerous important contributions

and I’m just want to thank you for sharing

that you clearly put everything you have

into everything you do.

Thank you, Peter.

Andrew, thank you.

I really appreciate you making the time

for us to sit down and talk in a long form way,

which I enjoy and yeah, it’s an honor

and it means a lot to me that you have read it twice

and that you’ve appreciated it

and praised it as you have.

Thank you.

Thank you once again for joining me

for today’s discussion with Dr. Peter Atiyah.

I hope you learned as much

and enjoy the conversation as much as I did.

Please also check out Dr. Atiyah’s new book,

which is releasing on March 28th, 2023,

entitled, Outlive, The Science and Art of Longevity.

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