Dr. Chris Palmer: Diet & Nutrition for Mental Health | Huberman Lab Podcast #99

ANDREW HUBERMAN: Welcome to the Huberman Lab podcast,

where we discuss science and science-based tools

for everyday life.

[MUSIC PLAYING]

I'm Andrew Huberman, and I'm a professor

of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, my guest is Dr. Chris Palmer.

Dr. Chris Palmer is a medical doctor

specializing in psychiatry at Harvard Medical School.

He is the world expert in the relationship

between metabolic disorders and psychiatric disorders.

He treats a variety of different conditions,

including psychosis, including schizophrenia, as well

as attention deficit hyperactivity

disorder, obsessive compulsive disorder, anxiety disorders,

and depression among others.

He is best known for understanding

the relationship between how metabolism

and these various disorders of the mind interact.

And indeed, today, he describes not

only his own fascinating journey into the field of psychiatry

but also his clinical and research experience

using diet that is different forms of nutrition

in order to treat various psychiatric disorders.

He describes some remarkable case studies

of individuals and groups of people

who have achieved tremendous relief from the types

of psychiatric disorders that I just

mentioned a few moments ago, as well as new and emerging themes

as to how metabolism and the mind

interact to control things like obesity.

Indeed, he raises the hypothesis that perhaps obesity,

in many cases, is the consequence of a brain

dysfunction as opposed to the consequence

of a metabolic dysfunction that then impacts the brain.

During today's episode, he shares with us

his overriding hypotheses about the critical roles

that mitochondrial function and dysfunction play

in mental health and mental illness,

and how various particular types of diets--

ranging from the ketogenic diet to modified

ketogenic diet and even just slight

adjustments in carbohydrate intake--

can be used in order to change mitochondrial function

and bring relief for various psychiatric illnesses.

He also highlights the essential and important theme

that various diet interventions, including the ketogenic diet,

were not first developed for sake of weight loss

but rather were developed as treatments

for neurologic conditions, such as epilepsy.

Today, he shares with us how the foods

that we eat alone and in combination, and how fasting--

both intermittent fasting and more lengthy fasts--

can interact with the way that our brain functions

to strongly control the way that we think, feel, and behave.

What's wonderful is that Dr. Palmer not only explains

the science and his clinical expertise,

but also points to various actionable measures

that people can take in order to improve their mental health.

I'd like to mention that Dr. Palmer is also

the author of a terrific new book.

The title is Brain Energy: A Revolutionary Breakthrough

in Understanding Mental Health and Improving

Treatment for Anxiety, Depression, OCD, PTSD and More.

I've read the book, and it is a terrific read.

I came away from this book with a much evolved understanding

of how the various psychiatric disorders that I just

described, as well as ADHD, emerge in people.

And it has completely revised my understanding

about the possible origins of various psychiatric disorders

and the best ways to treat them, including

both with medications but also with nutritional approaches.

If you'd like to learn more about Dr. Palmer's

work and the book, please go to chrispalmermd.com.

We also provide links to the book

and to his website in our 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 for the general public.

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And now, for my discussion with Dr. Chris Palmer.

Chris, Dr. Palmer, thank you for being here.

CHRIS PALMER: Thank you, Andrew, for having me.

ANDREW HUBERMAN: I have a lot of questions for you.

And I'm really excited about this topic

because I think most people know what mental illness is--

or they have some idea what that is.

Most people have some idea what nutrition is.

Fewer people certainly know how closely

those things can interact.

And I think everybody is familiar with the feeling

of a food or the ingestion of a food

making them feel good in the short term.

When we eat a food that tastes delicious to us

or that we associate with something nice,

then we feel good mentally and physically.

Whereas, when we eat something that gives us

food poisoning or maybe even something that just doesn't

taste that great or that we associate

with a bad experience, we feel less good in the short term.

But I believe that very few people understand

or are familiar with the fact that nutrition

and our mental health interact in this very intimate, maybe

even causal, way and that is something that occurs

over long periods of time.

Meaning, what I ate yesterday or the day before, maybe

even 10 years ago, could be impacting the way

that my brain and body are making me feel now.

So if you would, I'd love for you to just tell us

about a little bit of the history,

in particular, your history with exploring

the relationship between nutrition and mental health.

And then we can dive into some of the more particulars

of ketogenic diets versus other diets,

and some of the truly miraculous findings

that you and others are coming up

with based on real patients and real experiences of people

who suffer and then find relief by altering their nutrition.

CHRIS PALMER: Sure.

This story really starts with my own personal story.

And I don't need to go into great detail.

But to set the stage, when I was a kid,

I definitely had mental illness, started with OCD.

A series of events happened in my family.

My mother had a horrible kind of psychotic break,

and all sorts of adverse childhood events for me.

She and I were actually homeless together for a while.

I went on to have subsequent depression, suicidality,

all sorts of things.

But somehow or another, I pulled myself together and got

through medical school-- actually

did quite well in medical school,

got an award for being one of the top students,

and then was doing my internship and residency at Harvard.

And at that point in time, I was diagnosed

with metabolic syndrome.

So I had high blood pressure, horrible lipids,

and pre-diabetes.

And I was doing everything right supposedly.

I was on a low-fat diet, and I was exercising regularly.

And year after year, my doctor kept

telling me diet and exercise.

I kept asking him, what diet?

What exercise?

I was doing everything he kept telling me to do.

Everything was getting worse.

My blood pressure kept going higher.

And at some point, he kind of said,

you're going to have to go on medication.

I need to put you on something for your pre-diabetes,

something for your cholesterol, and something for your blood

pressure.

So three pills out of the gate.

And I'm like, I'm only in my 20s.

ANDREW HUBERMAN: Were you overweight?

CHRIS PALMER: No.

Technically, no.

I had a gut, so that's a sign of insulin resistance, I know now.

I didn't know it then.

And he actually kind of leaned in at one point and said,

do your parents have diabetes?

Yeah.

Do your parents have high blood pressure?

Yeah.

Are your parents overweight?

Yeah.

Oh, I'm really sorry, it's genetic.

Basically, you're screwed.

It's your genes.

You're just going to have to bite the bullet and take meds.

And as a physician, I knew what that meant.

I knew that I'm in my 20s, if I'm already

on three meds for metabolic syndrome,

I'm going to be screwed by the time I'm 40 or 50.

And I'm probably going to be having heart attacks.

And I'd heard through the rumor mill

that the Atkins diet could somehow

help people improve their cholesterol in pre-diabetes.

I actually didn't really believe it.

I was highly skeptical.

And I believed everything I was taught in medical school.

Why would my professors lie to me?

They knew what they were talking about.

Low-fat diet was the thing to do.

And the Atkins diet was clearly dangerous and reckless.

But I had been trying the medical dogma for years,

and it wasn't working for me.

And so for whatever reason, I decided

this is going to be my last attempt at something different.

And then I'll just bite the bullet and go on meds.

So I tried the Atkins diet.

I did my own special version of it.

I still avoided red meat because I was terrified of red meat.

I tried to do a healthy version, which it's probably

more like the South Beach diet.

This was before the South Beach Diet was invented.

But within three months, my metabolic syndrome

was completely gone.

ANDREW HUBERMAN: So blood pressure normalized,

lipids normalized.

Did your weight change?

You mentioned that you were of healthy weight

but that you had a bit of abdominal--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --fat.

CHRIS PALMER: I lost the abdominal fat.

I probably lost about 10 pounds through this process.

But everything got normal.

And when I went back to my doctor, he was shocked.

He actually said, what the hell are you doing?

ANDREW HUBERMAN: During the time before

you switched to this new diet, how was your mental health,

if you don't mind me asking?

Because it sound like you're very clear that there

was metabolic syndrome or you were

headed towards more severe metabolic syndrome.

You mentioned OCD.

I actually am familiar with this.

As a kid, I had a low level kind of Tourette's grunt.

And probably me, obsessive still to some extent--

although not full-blown clinically diagnosed OCD,

so I can relate somewhat.

If you're willing, what was the context

of all that before and after this nutritional switch?

CHRIS PALMER: So before the nutritional switch,

I was still struggling with low grade depression and OCD.

Again, it wasn't necessarily interfering

with my ability to function because I was functioning

at a high level.

Anybody looking from the outside, you're a top student.

You just got into one of the most competitive--

actually, at that point, it was the most competitive residency

program in the country for psychiatry.

So they would have looked at me and said, you're fine.

But I wasn't.

I was actually on medications.

I was trying different medications,

trying to figure out how to feel better,

how to stop obsessing so much, how to not be so depressed.

And I found that those medications,

they actually came with more side effects for me

than benefits.

I was on Prozac for a long time.

It totally messed up my sleep.

And then the psychiatrist was like,

you need pills to help you sleep now.

And I'm-- I just--

I'm like, that doesn't--

that's not really resonating very well with me.

And I'm now a psychiatrist.

I'm in my psychiatry residency.

And I'm thinking, you know what?

That's just not sitting well with me

that you're going to prescribe more and more meds for all

the side effects that you're causing.

And yet at the same time, I wanted to feel better.

And I was learning chemical imbalances.

This is what we do to get rid of depression and OCD.

You're supposed to take your pills.

And so I was taking my pills.

I was in psychotherapy.

I had been in psychotherapy on and off for years.

I had received much more intensive treatment

when I was younger.

And that was essentially worthless for me.

It actually probably just caused harm at the end of the day.

ANDREW HUBERMAN: Psychoanalysis?

CHRIS PALMER: Various psychotherapies-- not

psychoanalysis per se, but some of them

were psychoanalytically-oriented psychotherapies.

I was actually hospitalized at one point.

I had been put on lithium and imipramine, which

is a tricyclic antidepressant, and other things.

And they were actually horrible.

They were horrible.

They did nothing beneficial for me.

I gave them a decent amount of time to work.

I really wanted to feel better.

So at the time that I tried this diet,

I certainly wasn't impaired in the same way.

I wasn't struggling that much.

But I was-- still have these low grade symptoms,

was trying to feel better.

And the thing that was the most striking to me,

after doing the diet for three months,

was not the fact that my metabolic syndrome was gone.

That was my goal, and it was a seemingly miraculous

achievement because I got rid of everything

with one dietary change.

But the thing that I noticed was dramatic improvement

in my mood, energy, concentration, and sleep.

I-- for the first time in my life,

I started waking up before my alarm went off

and feeling rested.

That never happened to me before.

I was meticulous about planning when my alarm went off

and how many times I could push the snooze button in order

to be on time for wherever I needed to be,

whether it was school or the hospital or whatever.

I had it.

I had this good system.

I was never late for anything.

But that was shocking to me, that I felt so good.

And one of the things that I've often said to people, prior

to the diet, I always felt like there are two types

of people in the world.

There are "haves" and "have-nots."

There are these happy, peppy people,

who just are so positive, and they've got energy.

And they have the saying, they like

to work hard and play hard.

And I always understood working hard.

I totally got that because I was a hard worker

and I understood the value of hard work.

And you got to do something useful with yourself.

But I never understood who the hell wants to play hard,

like who's got energy for that?

Aren't you tired from working so hard?

How on Earth do these people have energy

to go and play hard?

And I assumed that they were just part

of the "haves" in the world.

And they were just lucky and privileged.

They either had good genetics or maybe they

had good childhoods or good parents

or something-- something that I didn't have.

ANDREW HUBERMAN: The kids with genuine smiles

in the yearbooks.

CHRIS PALMER: Yes, exactly.

ANDREW HUBERMAN: [LAUGHS]

CHRIS PALMER: Yes.

ANDREW HUBERMAN: Whereas, the rest--

and by the way, I really appreciate

you sharing some of your personal story

because I think it is very important for people

to hear and understand that people like yourself,

who are extremely high functioning and accomplished,

that the road was--

from everything I'm hearing and understanding-- very choppy

internally at times, and that you've overcome

a lot in order to get there.

And also, have been going through what

sounds like a very long iterative process of trying

to figure out what works and what

doesn't work to finally arrive at a solution,

and then make that the basis of much of the work

that you're doing today for other people.

I think it's very important because I think many people

share with you this notion that there

are indeed two groups-- a happy group

and then fated-to-be unhappy group.

And it speaks to the fact that--

your story, rather, speaks to the fact that what we see

is not always what's going on internally with people and that

this notion of there just being two groups--

the happy or the haves and the have-nots--

can't be the way that it works, and there are probably

many more people suffering than we realize,

and that there is an important need for tools

to overcome that suffering.

So I really just hear you.

Even early in our discussion, I just

want to extend a genuine thanks because so much

of what I hear from people is questions about health,

and mental health, and physical health.

But that clearly point to the fact

that many people are struggling to varying degrees.

And even the people who are in this category

of great childhood and happiness could do far better

for themselves and then also for other people.

So thank you for that.

I want to know.

At the point where you realized that nutrition

can play a profound role in how you feel and operate

in a large number of domains, you

are still a student or a resident at that point?

CHRIS PALMER: I was a resident.

ANDREW HUBERMAN: At that point, did you

decide that you were going to explore

this in a professional context?

CHRIS PALMER: Not yet.

ANDREW HUBERMAN: OK.

So what was the journey forward into the work

that you're doing now?

CHRIS PALMER: So the next step was that I just

had friends and family who saw me,

saw that I had improved my health,

saw that I lost some weight pretty easily.

In particular, I remember my sister and sister-in-law,

they got really pissed at me one Thanksgiving

because I could resist all the pumpkin pie, and apple pie,

and everything else.

They were like, how the hell are you doing that?

How are you resisting all of this food?

And I said, I don't crave it anymore.

I don't want it, I'm fine.

I'm just-- I'm having turkey and green beans.

And that's good enough for me.

So I got them to do the diet.

And they too noticed dramatic improvement in their moods,

and energy, and sleep, and everything else.

So within a few years, the primary thing I noticed

is this powerful antidepressant effect.

And now, I'm an attending physician.

I've got all these patients in my clinical practice

with treatment resistant mental illness.

I'm in a tertiary care hospital.

So I almost never get somebody off the street

with their first episode of depression.

Out of the gate, as part of my career,

I get treatment resistant mental disorders.

So I get people who've already been to 6-plus psychiatrists,

therapists.

They've usually tried dozens of different medications.

They've been in decades of psychotherapy.

They've often had ECT and other things.

And nothing's working.

And I'm thinking, well, we're kind

of out of options for these other people.

And this diet is having this really powerful antidepressant

effect.

I think I'm going to try it and just see if any of my patients

are game to try it to see if it might help them.

Sure enough, it did.

Didn't help everyone and not everybody

was interested and/or able to do it.

But some of the ones who were able to do it

ended up having a remarkable and powerful antidepressant effect.

One woman actually became hypomanic within a month.

And she had been depressed pretty much

nonstop for over five years--

chronically depressed, suicidal, in and out of hospitals.

And I saw her become hypomanic.

And I'm thinking, wow, this really

is a powerful antidepressant effect.

This is amazing.

This is like a medication but better because it actually

is working for her.

But I laid low at that point because, at that point,

we didn't have many clinical trials of the safety

or efficacy of the Atkins diet for even weight loss

or diabetes, let alone any mental disorders.

And so I really actually felt like I'm on the fringe here.

And this is not going to be met with praise by anyone.

So I'm just going to lay low.

I'm going to offer it to patients.

And I went along that way up until 2016.

ANDREW HUBERMAN: And may I just ask about the diet?

When you say "Atkins diet," so this is low to zero starch,

so low carbohydrate diet, certainly low sugar.

CHRIS PALMER: Yeah.

ANDREW HUBERMAN: And was it traditional Atkins?

Were you tailoring it to the individual patient

depending on their psychiatric symptoms,

whether or not they were overweight or not overweight?

I'm assuming you're not a nutritionist,

so how did you prescribe a nutrition

plan for your patients?

And what was involved in making sure

that they adhered to that, maybe even

some of the things you observed in terms

of who was more willing to try this or not try this?

Any observations or maybe even data?

CHRIS PALMER: So early on, I was winging it.

And I was-- the first few patients,

it was try this Atkins diet.

I want to see ketosis, so I was going for ketones.

ANDREW HUBERMAN: So they were pricking their finger,

and they were doing a blood ketone test?

CHRIS PALMER: I didn't know about blood ketone monitors

if they existed back then.

So I was-- we were using urine strips.

ANDREW HUBERMAN: Which are not quite as accurate

but still useful as a general guide, from what I understand.

CHRIS PALMER: True.

ANDREW HUBERMAN: Is that right?

CHRIS PALMER: Absolutely.

ANDREW HUBERMAN: OK.

CHRIS PALMER: So I was strongly recommending that patients

achieve urinary ketosis.

And the interesting thing is I noticed a pattern,

that when they were trying the diet and not getting ketones,

they often did not get a clinical benefit.

It was once they got into ketosis

that I began to notice the clinical benefit

and the powerful antidepressant effect.

ANDREW HUBERMAN: So probably any nutrition plan, a.k.a diet,

that elevated ketones in the urine to the point where you

would say, this person is in ketosis--

or they would say I'm in ketosis--

that was a step in the right direction,

independent of exactly what they were eating or not

eating to get there, including fasting?

At that time, probably, fasting wasn't as popular now.

Thanks to the incredible work--

I think it's incredible, and he is a former colleague.

And I know there's a lot of controversy about fasting.

But I think, for many people, fasting is a powerful tool.

For others, it's a less useful tool

--of Satchin Panda and others.

But fasting certainly will limit your carbohydrate intake

and get you into ketosis.

Correct?

CHRIS PALMER: It will.

ANDREW HUBERMAN: Did you have any patients fast

or do intermittent fasting?

CHRIS PALMER: I did.

I had some patients who did what Atkins had called a fat fast,

where they eat primarily fat.

So they either fast and/or they eat primarily fats

to try to get into a state of ketosis.

So for some patients, it was actually

quite easy to get into ketosis, especially overweight

and obese patients.

They have a lot of fat stores on their body

and actually limiting carbohydrates

usually results in high levels of ketosis for them.

ANDREW HUBERMAN: And they probably

feel better too, I imagine, because when

we limit our starch intake, we start

to excrete a lot of water.

People can get some pretty quick weight loss

that even though it may not be fat loss,

makes them feel literally a little lighter

and maybe a little more energetic.

Is that right?

CHRIS PALMER: Absolutely.

And as the years went on, the field was advancing,

more research was coming out.

People were getting a little more sophisticated

with blood ketone monitoring, with different versions

of ketogenic diets.

And I was evolving my practice.

The thing that completely upended everything

that I knew as a psychiatrist, though, was when I helped

a patient in 2016 lose weight.

So this was a patient, 33-year-old man

with schizoaffective disorder.

He had been my patient for eight years now.

ANDREW HUBERMAN: Could you clarify

for people what schizoaffective disorder is?

I'm not a clinician.

But as I recall, it's like a low level of schizophrenia.

So there might be some auditory hallucinations.

If I met this person, I might think

they're kind of different, quote unquote, "weird."

But they would not seem necessarily

scary to me and to typically to other people.

And I mean that with respect, of course.

But oftentimes, people with schizophrenia

can seem just like-- you don't even

know how to interact with them because their world seems

so altered because they have all these so-called positive

symptoms-- hallucinations, and they're

talking to people that no one else can see, et cetera.

Is that schizoaffective?

CHRIS PALMER: So no.

So schizoaffective is the same as schizophrenia essentially.

The only difference is it's schizophrenia

with superimposed mood episodes.

ANDREW HUBERMAN: Oh, so it's actually more severe than--

CHRIS PALMER: It can be.

ANDREW HUBERMAN: OK.

So I have it backwards.

CHRIS PALMER: So schizoaffective disorder

is essentially schizophrenia and plus some mood episodes.

ANDREW HUBERMAN: Ah, maybe I'm thinking of schizotypal?

CHRIS PALMER: Schizotypal is the low grade,

kind of mild paranoia, or kind of eccentric beliefs,

and other things.

ANDREW HUBERMAN: OK.

Folks out there, I have my nomenclature backwards.

Schizotypal is the, quote unquote, lower--

"low level" schizophrenia or schizoid-like.

Schizoaffective is as or more severe.

CHRIS PALMER: Full-blown schizophrenia

plus full-blown usually bipolarism.

ANDREW HUBERMAN: And now, it's absolutely clear

who the clinician in the room is.

[LAUGHTER]

Thank you for that reminder.

CHRIS PALMER: No worries.

So this man had schizoaffective disorder.

He had daily auditory hallucinations.

He had paranoid delusions.

He could not go out in public without being terrified.

He was convinced that there were these powerful families,

that they had technologies that could control his thoughts.

They could broadcast his thoughts to other people.

They were trying to hurt him.

They had targeted him for some reason.

He wasn't quite sure why.

He had some suspicions and beliefs about maybe

when he did this bad thing when he was 11 years old, that's why

they decided to target him.

This man was tormented by his illness, tormented.

It ruined his life.

He had already tried 17 different medications,

and none of them stopped his symptoms.

But they did cause him to gain a lot of weight.

ANDREW HUBERMAN: These medications, as I recall,

for schizophrenia-- the classical ones are dopamine

receptor blockers-- caused people to--

huge increases in prolactin.

That's why sometimes men--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --will get breast development.

And they'll put on a lot of weight.

And they'll be catatonic-- or movement disorders.

CHRIS PALMER: Yes.

ANDREW HUBERMAN: They make you feel like--

I have to imagine, given how good

most things that release dopamine make us feel,

that blocking dopamine receptors with antipsychotics

makes people feel lousy.

CHRIS PALMER: Horrible.

And it's a huge challenge in our field because a lot of patients

don't want to take them.

And then you get these rebound effects.

If patients are on them for several months,

and then they stop them cold turkey,

they can get wildly psychotic and ill,

end up aggressive or hospitalized or sometimes dead.

So that's him.

He weighs 340 pounds.

And for whatever reason, he gets it in his head,

I'm never going to get a girlfriend

if I don't lose some weight.

He also recognizes, I'm never going

to get a girlfriend because I'm a loser.

I'm schizophrenic.

I live with my father.

I have nothing going for me.

But I could at least try to address

one of these awful, horrible things about myself.

And maybe I could lose some weight.

So he asked for my help.

For a variety of reasons, we ended up

deciding to try the ketogenic diet.

Now, at this point, I have no anticipation

that the ketogenic diet is going to do anything

for his psychiatric symptoms because this man

has schizoaffective disorder.

That's not depression.

Depression is very different.

They're totally different disorders.

So he decides to give it a try.

Within two weeks, not only does he start losing weight,

but I begin to notice this dramatic antidepressant effect.

He's making better eye contact.

He's smiling more.

He's talking a lot more.

I'm thinking like, what's gotten into you?

You're coming to life.

Like you're-- I've never heard you talk this much.

I've never seen you so excited or present or alive.

I haven't changed his meds at all.

The thing that upended everything

that I knew as a psychiatrist was six to eight weeks in,

he spontaneously starts reporting,

you know, those voices that I hear all the time?

They're going away.

And he says, you know how I always thought that there were

all these families who were controlling my thoughts

and out to get me, and they had targeted me?

And I'm thinking, oh, yeah.

We've been talking about that for eight years.

We can talk about that again.

He says, you know what?

Now that I think about it, I don't think that's true.

And now that I say it, it sounds kind of crazy.

It probably never was.

I've probably had schizophrenia all along

like everybody's been trying to tell me.

And I think it's going away.

That man went on--

he's now lost 160 pounds and kept it off to this day.

ANDREW HUBERMAN: Wow.

CHRIS PALMER: He was able to do things

he had not been able to do since the time of his diagnosis.

He was able to complete a certificate program.

He's able to go out in public and not be paranoid.

He performed improv in front of a live audience.

at?

One point, he was able to move out of his father's home

and live independently.

And that completely blew my mind as a psychiatrist.

And I went on a scientific journey

to understand what in the hell just happened.

ANDREW HUBERMAN: That is indeed mind-blowing.

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I have a couple of questions.

First of all, did he stay on any kind

of antipsychotic or other medication?

If so, were the dosages adjusted, excuse me,

while undergoing this remarkable transition?

Because as we know, it's not an either

or medication or nutrition changes, it can be both.

And then the other question is one of adherence.

I think about someone with schizoaffective disorder,

who's suffering from all the sorts of things

that you described.

How does somebody like that organize themselves in order

to stay on a ketogenic diet?

And I say this with all the seriousness in the world.

I think there are a lot of people

who do not have schizotypal or schizoaffective disorder

who have trouble, they claim, adhering to a ketogenic diet.

It's not the easiest diet.

Certainly in its extreme form at first,

it's not the easiest diet to stick to.

So how did he do it?

That sounds like a remarkable individual.

And I'd also like to just know your general thoughts

about adherence to things when people are back on their heels

mentally.

How do they get motivated and stick to something?

So the questions were, medication, yes or no?

If yes, dosage adjusted, yes or no.

And if people are suffering from depression

or full-blown psychotic episodes,

how does one ensure that they continue to adhere to a diet?

CHRIS PALMER: So in terms of medications,

he has remained on medication.

So early on, I wasn't adjusting anything.

I was just in disbelief and shock that this was happening.

I didn't know what was going on.

Over the years, we have slowly but surely

tried to taper him off his meds.

He has been on meds for decades.

He started medications when he was a young child.

His brain is as developed in response

to all sorts of psychiatric medications.

And it has not been easy to try to get him off.

We continue to try to get him off medication.

And it's challenging and difficult.

And I just want to say for any listeners, it is--

getting off your meds is very difficult and dangerous.

And you need to do it with supervision,

with a mental health professional or a prescriber

because it is dangerous.

When people reduce their meds too much,

they can get wildly symptomatic.

ANDREW HUBERMAN: Is that true for depression as well?

CHRIS PALMER: It's true for any psychiatric medication.

The brain makes adaptations in response

to psychiatric medications.

And when you stop them cold turkey--

some people are fine.

But I wouldn't recommend finding out

because I've seen patients-- when they stop antidepressants,

I've seen patients get flooredly depressed and suicidal

within three months.

I had one patient, almost quit her job

because she became convinced that, well, my life sucks,

and it's all because of my boss.

And I know that she's just a horrible human being.

And she's abusing me.

And I was like, whoa, whoa, whoa.

I think this is related to your medication change.

We got her back on her meds, within three days,

she said, oh my god, I can't believe that happened.

I almost quit my job.

And that would have been the most illogical and irrational

decision I've ever made in my entire life.

But somehow, it seemed so real just several days ago.

And now that I'm back on this medication--

and it doesn't mean that she needs the meds.

But it doesn't mean that he needs the meds.

It means that meds need to be adjusted very safely,

and cautiously, and gradually.

So that's the medication piece.

The adherence piece was not easy for him and for other patients.

It is very rare that I have a patient who I can say,

do the ketogenic diet.

Come see me in 3 months, and let me know how it was going.

That almost never happens.

It has happened, I think, on two occasions.

ANDREW HUBERMAN: But that is, if I understand correctly, what--

perhaps not you-- but many psychiatrists

do with medication.

It's, here's your prescription.

Let's talk in--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --a month or three months.

CHRIS PALMER: Yes.

ANDREW HUBERMAN: So that's a variable that is probably

worth us exploring a little bit here

as the conversation continues.

CHRIS PALMER: Absolutely.

ANDREW HUBERMAN: That frequent contact

and making micro adjustments or macro

adjustments to medication or nutrition, could be meaningful.

CHRIS PALMER: Absolutely.

So with this particular patient, early on, he

was actually pretty adherent.

I was seeing him once a week.

And so I could do a lot of education.

I was weighing him.

I was checking his ketones.

I was checking his glucose levels.

At that point, I had a blood ketone monitor in my office.

So I knew whether he was compliant or not,

which is so beneficial in doing clinical work

and research on this diet.

It's the only diet where within seconds, I

can have an objective biomarker of compliance or noncompliance.

ANDREW HUBERMAN: Such a key point and again,

brings to mind, for me, the parallel with medication.

A patient can say they're taking their medication,

and unless they're in a hospital setting,

where somebody's checking under their tongue and all of this,

they very well could not be taking it or taking more.

And you and I both know that blood

draws for neurotransmitter levels are complicated

because you want to know what's in the brain

and what's functional in the brain.

And then we have to imagine that most people there prescribed

drugs for any number of different psychiatric

conditions are not giving blood every time they

talk to their psychiatrist or psychologist.

No?

CHRIS PALMER: No.

On that front, when we've looked at studies of compliance,

the majority of patients are at least

somewhat noncompliant with prescription medications.

It's not on purpose.

They forgot.

They take it at night.

They were out late.

They were off their routine.

They forgot to brush their teeth--

because that's when they take their meds.

And so because it was so late, they just

crashed when they got home.

They forgot to take their meds.

Happens all the time.

If it's a medication that people take more than once a day,

the noncompliance rates are much higher because it's just

easy to forget.

So it's not that people are willfully disobeying

their doctors or anything else.

It's just hard to remember to take meds consistently

every day.

ANDREW HUBERMAN: When you say measuring ketones,

I want to drill into this a little bit

because it does seem that the presence of ketones

and somebody being, quote unquote, "in ketosis,"

it turns out to be the key variable.

Certainly, in your book, that's one of the major takeaways--

although there were many important takeaways--

that people get into ketosis.

Do they have to stay in ketosis?

So for instance, I've followed the--

I don't any longer.

But I've tried, in the past, the so-called cyclic ketogenic

diet, where every third or fourth day, get

some pasta, or rice, et cetera.

That was interesting as an experiment.

But to stay in ketosis, what sort of blood levels of ketones

do you like to see in your patients?

What is the range that you think most people could aspire to?

CHRIS PALMER: So it really depends on the patient

and what I'm treating, quite honestly.

And I don't think every patient needs the ketogenic diet.

For some patients, simply getting rid of junk food

can make a huge difference in a mood disorder, for instance.

ANDREW HUBERMAN: So a junk food, meaning, highly processed food,

food that could last on the shelf a very long time.

CHRIS PALMER: Highly processed foods

that are usually high in both sugar, carbohydrate,

and carbs, and fats.

Those seem to be the worst foods.

That combination-- high sugar, high fat--

seems to be the worst combination

for metabolic health.

And lo and behold, we've got emerging data that suggests,

that strongly suggests, it's also bad for mental health.

Depression and anxiety are the most common mental disorders.

And so we have the best data for those disorders.

But we actually have a lot of data with even bipolar disorder

and schizophrenia that insulin resistance, in particular,

and insulin signaling in the brain

is impaired in people with chronic mental disorders

kind of across the board--

all the way from chronic anxiety, depression,

to bipolar, to schizophrenia, and even Alzheimer's disease.

We know that patients with all of those disorders

have impaired glucose metabolism and that the insulin signaling

system in the brain, which is different than insulin

signaling in the periphery, seems to somehow

possibly be playing a role.

So to step back from that, so for some patients,

I might just want to decrease glucose and insulin levels.

And I can do that by getting rid of sweets.

For other patients, like patients

with schizoaffective disorder or schizophrenia or bipolar

disorder, especially if it's chronic,

if I'm using it as a brain treatment,

then I do want a ketogenic diet.

And I usually want reasonably high levels of blood ketones.

Usually, for depression, I want to see at least greater

than probably 0.8 minimal.

For psychotic disorders and bipolar disorder,

I usually want to see levels greater than 1.5.

That's what I'm shooting for, if at all possible.

So yeah, I think that's what I'd go for.

ANDREW HUBERMAN: Yeah, so--

and sorry, I didn't mean to imply

that people need to be in ketosis in order

to see some mental health benefits from changing

their diet.

You make very clear in your book--

and we'll go into this in more detail--

that avoiding insulin resistance,

reversing insulin resistance, and essentially trying

to reverse what earlier you described

as this metabolic syndrome, which

is a bunch of different things, is the target.

And for some people, getting rid of highly processed foods

and focusing mainly on nonprocessed or minimally

processed foods will really help.

For others, going straight to the full-blown ketogenic diet

will be of most benefit.

I'd like to back up a little bit in history

and get to something which I find incredibly interesting,

which is epilepsy and the longstanding use

of ketogenic diet and fasting to treat epilepsy.

And the reason I want to kind of rewind to that point in history

is that, I think that for a lot of listeners and people

out there who are familiar with how changing your diet

or changing your exercise can positively

impact sleep and weight and all these things,

and it cascades into feeling better--

that makes perfect sense.

But for a lot of the world still,

the idea that changing or using nutrition as a dissection tool

or as a treatment tool to understand and treat

mental illness, is still a kind of heretical idea,

that to them, it kind of falls in the,

OK, well, that's like a woo science or something like that.

Now, obviously you're a board-certified physician

or psychiatrist at arguably one of the finest medical schools

in the world, Harvard Medical School.

Even though I'm on the Stanford side, we acknowledge--

we acknowledge our East Coast--

CHRIS PALMER: You're the Harvard--

ANDREW HUBERMAN: --friends.

CHRIS PALMER: --of the West Coast.

ANDREW HUBERMAN: We're not going to talk--

OK.

CHRIS PALMER: [LAUGHS]

ANDREW HUBERMAN: We're not going to talk--

CHRIS PALMER: Or we're the Stanford of the East Coast.

ANDREW HUBERMAN: That argument could go back and forth

a number of times.

You're a serious clinician and a serious scientist.

And you're a serious thinker.

But for a lot of people out there,

the notion of using diet, they immediately

think, ah, well, that makes perfect sense.

Or I think there's a category of people who think, well, yeah,

didn't Atkins die of a heart attack?

I hear that a lot.

That was crazy.

People immediately discard the Atkins diet

for that reason, which I do think is throwing the baby out

with the bathwater.

But it's an interesting thing nonetheless.

And then I think that the majority of people

sit in the middle and just want to see

science and medicine come up with treatments that work.

And I have to say, I'm very relieved to hear what you said

earlier, which was-- you never said that people should come

off their medication and just become--

go on a ketogenic diet and everything will be cured.

You're certainly not saying that.

CHRIS PALMER: No.

ANDREW HUBERMAN: And rather you're

saying, if I understand correctly,

that nutrition needs to be considered

one of the major tools in the landscape of effective tools

and that it can be very effective,

evidenced by the story that you shared.

And there are many other stories in there

as well of truly miraculous transformations.

So let's talk about epilepsy and how the ketogenic diet is not

just used for epilepsy but is one

of the oldest, if not the oldest, examples

of the use of nutrition to treat a condition

of the nervous system that can be incredibly

debilitating, even deadly.

CHRIS PALMER: Yeah.

And the reality is that this literature,

and this clinical history, and all of the research we have

was the godsend that I needed to do the work that I'm doing.

Otherwise, I would have been discredited on day one.

Chris Palmer is claiming that a dietary change

can influence schizophrenia or schizoaffective disorder.

That's impossible.

And he's a quack.

But the thing that immediately got me credibility was I

didn't focus on it as a diet.

I did a deep dive into the epilepsy literature.

So the ketogenic diet, unbeknownst to most people,

was actually developed a hundred years ago, 1921,

by a physician for one and only one purpose--

to treat epilepsy.

It wasn't developed as a weight loss diet.

It wasn't developed as the diet that all human beings should

follow.

And the reason it was developed is

because of this longstanding observation,

since the time of Hippocrates, that fasting can stop seizures.

Now, fasting is not a healthy diet.

Fasting is the process of no diet.

So we now understand a tremendous amount of science.

Most people think going without food is bad.

And they equate it with starvation.

But in fact, when we go without food,

it causes tremendous shifts in metabolism--

both brain and body metabolism.

And it puts the body into a mode of autophagy, and conservation

of resources, and all sorts of things that

are beneficial to human health.

And this is why fasting has been used

as a therapeutic intervention in almost every culture,

in almost every religion for a millennia.

But for the most part, that was all

thought to be religious folklore.

That was just crazy talk.

And those stupid people way back then thought

God cured everything.

And so they fasted.

And they just assumed that they were getting better.

Well, in 1921, one physician used intermittent fasting

on a child with seizures and found that, oh, Lo and behold,

this religious folklore stuff has something to it.

It actually worked.

The problem with fasting is that you

can only fast for so long before you starve to death.

And that's not a very effective treatment.

ANDREW HUBERMAN: And this child was ingesting water, correct?

CHRIS PALMER: Yes.

ANDREW HUBERMAN: It was just food elimination fasting.

CHRIS PALMER: Food elimination.

ANDREW HUBERMAN: OK.

CHRIS PALMER: So no special diet.

But the problem with fasting for epilepsy

is that as soon as people start eating a normal diet again,

their seizures usually come right back--

oftentimes, with a vengeance.

And so it can be a good short-term intervention.

The fasting can take a few days because it can

take a few days to get ketosis.

And then you can get some relief from chronic seizures.

But it's not a good long-term treatment

because, again, people will starve to death.

As soon as they start eating, seizures come back.

So it was actually Dr. Russell Wilder at the Mayo Clinic

who developed the ketogenic diet with one and only one purpose.

He wanted to see, can we mimic the fasting state, using

this special diet, to see if it might stop seizures long-term?

And lo and behold, it worked.

Early results were extraordinarily positive.

50% of patients who use the ketogenic diet

became seizure-free.

And another 35% had a 50% or greater reduction

in their seizure frequency, so about 85% efficacy rate.

ANDREW HUBERMAN: Sorry to interrupt.

I didn't mean to do that there.

Was it just for pediatric epilepsy

or for adult epilepsy as well?

CHRIS PALMER: So back in the 1920s,

we didn't have many anti-epilepsy treatments.

And a lot of adults were struggling as well.

So they were using it on anybody who would do the diet.

By the 1950s, pharmaceuticals were coming out.

And we had many more anticonvulsant treatments.

And there's no question, they work for a lot of people.

That's great.

And taking a pill is so much easier than doing this diet.

So the diet pretty much fell out of favor.

And nobody was using it from the 1950s to about the '70s.

But lo and behold, even to this day, people with epilepsy,

about 30% don't respond to the current treatments

that we have available.

30% will have treatment resistant epilepsy,

which means they continue to have seizures

no matter how many anticonvulsants they're taking,

even if they've had brain surgery.

It just doesn't stop their seizures.

And so in the 1970s, the ketogenic diet

was resurrected at Johns Hopkins for these treatment-resistant

cases.

And lo and behold, it works--

not for all of them, but it works in--

about 1/3 become seizure-free.

And these are people who've tried everything and nothing's

working.

So 1/3 become seizure-free.

Another third get a clinical benefit,

meaning a 50% or greater reduction in their seizure

frequency.

And the other third, it doesn't seem to work.

It's not always clear if that's because of noncompliance

or if that's because the diet's just not working.

But about a third, a third, a third--

seizure freedom, reduction in seizures,

or it just doesn't work.

And so the reality, the godsend for me

is that we have decades of neuroscience research

on the ketogenic diet and what it is doing to the brain.

We know that the ketogenic diet is influencing neurotransmitter

levels-- in particular, glutamate, GABA, adenosine.

It changes calcium channel regulation and calcium

levels, which is really important in the function

of cells.

It changes gene expression.

It reduces brain inflammation.

It changes the gut microbiome.

Gut microbiome is a huge topic right now.

And there are some researchers who

argue that is the primary benefit of the ketogenic diet--

it's changing the gut microbiome in beneficial ways.

So it's doing a lot of things.

It obviously improves insulin resistance.

It lowers glucose levels, lowers insulin levels,

which improves insulin signaling.

The key for my research that I've outlined, the real magic,

is that this diet stimulates two processes that

relate to mitochondria.

It stimulates a process called mitophagy,

which is getting rid of old and defective mitochondria,

and replacing them with new ones.

And it also stimulates a process called

mitochondrial biogenesis, which means

that after people have done the ketogenic diet for a while--

months or years-- many of their cells in their bodies

and brains will have more mitochondria.

And those mitochondria will be healthier.

And I believe that is the reason the ketogenic diet is such

a powerful treatment not only for epilepsy but also

for people with chronic mental disorders.

ANDREW HUBERMAN: Would you mind listing off

a few of the mental disorders?

And I know this is not meant to be inside ball,

but we should distinguish between psychiatric disorders

and neurological symptoms and diseases.

The fields of psychiatry and neurology

hopefully someday will just emerge.

But for instance, typically if somebody

is presenting with something that

looks like Alzheimer's, dementia,

they'll talk to a neurologist.

Whereas, if somebody is presenting with symptoms,

like schizophrenia, bipolar, they'll talk to a psychiatrist.

But if you wouldn't mind wearing a dual hat,

could you just quickly list off some

of the neurologic and psychiatric disorders

for which ketogenic--

or let's just say-- nutrition changes

have been shown to improve symptoms significantly.

And then maybe we can dive into a couple of these

as well as get more deeply into these two very interesting

aspects of mitochondrial function and repair

and turnover.

CHRIS PALMER: Yeah.

In terms of nutritional psychiatry, it's a broad field.

And it's in its infancy, is the real answer.

If you're looking for randomized controlled trials documenting

efficacy in large numbers of patients with these disorders,

we don't have them.

They're underway now.

But we don't have them yet.

What we do have are case studies.

We have a lot of mechanistic science papers

by some of the leading neuroscientists

and psychiatrists in the world--

and neurologists in the world kind of outlining,

this is everything we know that the ketogenic diet is doing.

These are the problems in the brains

of people with these chronic mental or neurological

disorders.

So we know that they should work.

But the disorders range from chronic depression to--

we've got a trial underway for PTSD.

We've got one actually decent pilot

trial from the National Institutes

of Health for the ketogenic diet for alcohol use disorder,

of all things.

And we can go into that a little more.

We've got a couple of pilot trials of the ketogenic diet

for Alzheimer's disease.

And those are randomized controlled trials.

We've got case studies of the ketogenic diet

for chronic depression, bipolar disorder, and schizophrenia.

The largest study that we've got in that mental health sphere

is a pilot study of 31 patients admitted to a French hospital.

28 of those patients were able to do the diet

and stay on the diet.

So 10%, off the bat, noncompliant,

couldn't do the diet.

So we need to include that.

But of the 28 patients who were able to do--

and these are 28 patients with treatment-resistant mental

disorders, chronic depression, bipolar, and schizophrenia.

Of the patients who were able to do the ketogenic diet,

100% had at least some improvement in symptoms.

46% had remission of illness.

Remission of illness, that does not

happen with current treatments.

And 64%, I think, were discharged on less medicine

than they went into the hospital on.

So it wasn't that the people were prescribing more medicine

and that's why.

They were being discharged on less medication.

We've got at least--

again, a lot of the hard core scientists are going to say,

show us the randomized controlled trial

with hundreds of patients.

And we've got five randomized controlled trials underway now,

funded primarily through philanthropy.

I can tell you that--

we've talked about that one index patient.

But at this point, I have now treated dozens of patients.

And I've heard from hundreds of patients

who've been treated by other clinicians, researchers--

or I've just heard from patients from around the world--

who have shared stories of complete remission

of long, chronic mental disorders--

like bipolar disorder and schizophrenia--

off of psychiatric meds.

Some of them-- not all of them, but some of them

are able to get off all psychiatric meds

and remain in remission.

Again, I think I didn't say this before.

But it's really important to mention.

For people who might be unfamiliar

with the mental health field and its connection with epilepsy,

the reason that it's such an important connection

is that we use epilepsy treatments

in psychiatric patients every day in tens of millions

of people.

So a lot of people don't know this,

but I'll list off some names that a lot of your listeners

may have heard of.

And they probably know them as psychiatric drugs.

But in fact, these are epilepsy drugs.

Depakote, Tegretol, Lamictal, Topamax, Neurontin

or gabapentin, Valium, Klonopin, Xanax--

those are all medications that stop seizures.

And many of them were developed initially for seizures.

But we, in the mental health field,

quickly steal them and start using them in tens of millions

of people, even if they're off label.

So that means, we don't have research studies documenting

that they're effective.

But we go ahead and use them anyway

because the reality is far too many patients aren't getting

better with the FDA-approved treatments

that we do have to offer.

So psychiatrists are just winging it in some cases.

And we're just throwing whatever we can at them

and we absolutely include epilepsy treatments.

So in many ways, using the ketogenic diet

as a treatment for serious mental disorders,

is nothing new at all.

It's an established evidence-based treatment

for epilepsy.

We use evidence-based treatments for epilepsy

across the board for a wide range of mental disorders.

And so in many ways, that's all I'm

doing with the ketogenic diet.

It just happens to be a diet.

[CHUCKLES]

ANDREW HUBERMAN: I love it.

I love it.

And I should say, I love it because we

had a guest on here early days of the podcast.

He's a colleague of mine at Stanford.

He's a bioengineer, and a psychiatrist, phenomenal

scientist and psychiatrist, called

Deisseroth, who won the Lasker prize, and so on and so forth.

And he made a really important point,

which should have been obvious to me

but wasn't until he said it, which

was the psychiatrist has tools, just like the surgeon has

tools.

But the tools are language and observing behavior.

Those are the dissection tools for what's

going on in someone's brain.

And then as a neuroscientist, I'm

familiar with the neurotransmitters

and neuromodulators.

And you mentioned that--

and there are these tools of altering brain chemistry, which

are of the sorts of drugs you just listed

off, or antidepressants, or antipsychotics,

that fall into these major bins of adjusting

dopamine or adjusting serotonin or some combination

of dopamine, serotonin epinephrine, adenosine,

and on, and on, and on.

And it seems to me, it's an incredible field.

But that the field is still very much in its infancy

that it wasn't about a hundred years ago that people were

measuring bumps on the head as a way to diagnose phrenology,

and that there's still so much to learn.

And so when I hear you say, adjusting nutrition or putting

people into a ketogenic state or even just eliminating

highly processed foods, sugars, et cetera,

taking care of metabolic syndrome,

and then observing tremendous relief

in clinical syndromes of--

or symptoms, rather, of psychiatric disorders,

it makes perfect sense to me.

It's yet another dissection tool.

And a tool for altering brain chemistry.

If I think about the landscape, the sort of sociology out there

of--

again, there seem to be these bins, like a third of people

saying, of course, diet, and exercise,

and social connection, and limiting

stress, that's the good stuff.

That's the stuff that we really works.

And then about a third of people are sort of unclear.

And then a third of people think, well,

if it's not a prescription drug, then

it just has no place in medicine.

And hopefully, that's changing.

And certainly, the work that you're doing

is going to be important in that transition

that I think we will see.

I'd like to talk about mitophagy and mitochondrial biogenesis.

I think most people learn that the mitochondria are the energy

factories of cells and that indeed, they are.

As a neuroscientist, what I know about

them is that they are present everywhere in neurons.

Not just in the so-called cell body,

but you can find mitochondria in the furthest little bits

of neurons.

And neurons can be quite big, very large.

In fact, meters long or more in some cases and some species,

including us.

Depending on how tall somebody is, could be many meters--

or several meters rather.

And that mitochondria do a lot of stuff besides just

produce energy, because I think people

hear "mitochondria," "energy," and they think, oh, so

these patients felt better.

They lost weight.

They had more energy.

And then they're doing better.

But here we're talking about remission

of auditory hallucinations, people feeling suicidal

and then changing their diet and feeling like life

is something they can deal with, and maybe even function

extremely well, and et cetera.

So maybe we could just talk about mitochondria

for a moment.

And then talk about these two major effects.

What are some of the other things

that mitochondria are important for in neurons and maybe

other cells of the brain?

Because as an access point for all this,

I think it would be great if people could learn

a little mitochondrial biology.

CHRIS PALMER: So I guess the first thing that I'll say

is that this field is one of the most cutting-edge fields

in medicine right now.

20 years ago or so, I think the majority of research scientists

thought of mitochondria as nothing

more than little batteries.

They take food and oxygen and turn it into ATP.

And that's really important.

Yeah, we get that.

But they're just little batteries.

That's all they are.

And so one of the reasons that this work is so important

it's because it combines cutting-edge research

in the metabolic field in the aging field.

And we can start to pair it with a mental health

and neurological health field.

So mitochondria-- one scientist gave me this analogy.

He said, if you think of the cell as a computer,

a lot of people think of mitochondria

as the power cord to that computer

because they're providing the power.

And they are, in fact, the power cord to that computer.

But actually, their real function

is the motherboard of that computer.

So mitochondria are directing in allocating resources

throughout a cell.

That is their primary function.

And then they happen to be powerhouses as well.

And so to give some clear examples,

mitochondria play a direct role in the production, and release,

and regulation of some really key neurotransmitters,

including serotonin, dopamine, glutamate, acetylcholine.

Those are pretty powerful neurotransmitters.

ANDREW HUBERMAN: Yeah, I would call those--

I would consider those the--

I know you listed more than three.

But the sort of primary colors of neurotransmission.

CHRIS PALMER: Yes.

ANDREW HUBERMAN: Any one of those in excess or deficiency

is going to have profound negative effects

on a nervous system.

Or it's going to alter the way that people and animals feel,

think, move--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --remember, et cetera.

CHRIS PALMER: So mitochondria are providing both some

of the building blocks, if you will,

for some of those molecules that are

part of the Krebs, citric acid cycle.

Some of the intermediate products

actually go into making those neurotransmitters.

Much more importantly, mitochondria

provide the energy for the production

of those neurotransmitters.

And fascinatingly, mitochondria are directly related

to the release of neurotransmitters.

ATP alone is not enough.

There have been some research studies that have actually

found that mitochondria move along

the membrane of the synapse to release batches of vesicles

of neurotransmitters, and that if the mitochondria are removed

from the synapse and researchers flood that cell with ATP,

neurotransmitters usually are not getting released.

Mitochondria are doing other things.

We don't entirely even understand what all they're

doing or how they're doing it.

But they're doing other things than just providing the power.

Another really important example is

that mitochondria are actually the primary regulators

of epigenetics.

If you look at any one factor--

so one study actually found that they're

responsible for the expression of about 60%

of the genes in a cell.

And mitochondria do this through a lot

of ways that have been known for years and sometimes decades.

So mitochondria are directly related

to the levels of reactive oxygen species in a cell.

They are managing calcium regulation in cells.

And we know that those things play a role

in epigenetic expression.

We know the levels of ATP to ADP or AMP also play a role.

And mitochondria are doing those things.

But it turns out, mitochondria are actually

doing much more sophisticated things

than even those in terms of gene expression.

Mitochondria at least play a role

in all of the aspects of the human stress response.

So when humans are stressed, either

physically or psychologically, there

are several things that happen--

increased cortisol increased adrenaline, noradrenaline,

inflammation, and gene expression-- in particular,

in the hippocampus-- occur with the stress response.

And one group of researchers actually

genetically modified mitochondria

in four different ways, and found

that all of the stress response, all those four

buckets of stress response were impacted in one way or another,

implying that mitochondria are somehow

playing a role in those.

In terms of their role in cortisol,

we know that mitochondria actually

have the enzyme required for the synthesis of steroid hormones.

So that includes cortisol, estrogen, testosterone,

and progesterone, some names that maybe everybody's

heard of.

so that means that if mitochondria

are in short supply or dysfunctional,

the production of those hormones may become dysregulated.

Mitochondria play a direct role in inflammation.

And they turn the inflammatory system both on--

or they at least play a role in turning the inflammatory system

both on and off.

I'm not going to be able to quote the exact study

and author.

But one paper in cell actually identified mitochondria

as the key regulator in turning certain inflammatory cells off,

and that when you inhibit mitochondrial function,

those cells don't turn off, that mitochondrial levels

of reactive oxygen species are a key signaling process

to turn the inflammatory cell process off.

Another study found that macrophages--

so macrophages are an important immune cell

that play a role in healing.

So if you cut yourself, your body will get--

send inflammation that way and send immune cells that way

to try to heal your skin.

And macrophages play an important role in that healing.

One group of researchers tried to figure out

how do macrophages know to switch

between the different phases of wound healing

because the macrophages do different things

in the different phases of wound healing.

And the conclusion of all of their research

was that it's mitochondria.

Mitochondria are sending the essential signals

that change the state of the macrophages

to induce these different phases of wound healing.

So I've just talked about neurotransmitters, hormones,

epigenetic expression, inflammation.

For anybody familiar with the mental health field,

they know these are some of the key variables that researchers

have been struggling with for decades, trying to figure out

how do these fit together.

We know that all of those buckets

can be disrupted in people with mental disorders.

And our field has struggled to understand,

but how do they fit together?

How can we make sense of this disruption?

And I believe once you understand

the science of mitochondria, you can actually

connect all of the dots of the mental illness puzzle.

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Super interesting little subcellular goodies,

these mitochondria are.

I come from a field where people are often divided

into lumpers and splitters.

And I'm somewhere in between.

For those of you who don't know, lumpers

are people that like to make things really simple--

lists of no more than three functions or dividing brain

areas into no more than three.

Splitters are people that like to subdivide

into a ton of detail.

There's a history of scientists being splitters in order

to be able to name things after themselves because--

CHRIS PALMER: [LAUGHS]

ANDREW HUBERMAN: There's more territory

to go around if you're splitting than if you're lumping.

But we are doing neither here.

What I'm hearing is that mitochondria, in addition

to being important sources of energy production and output

in cells--

which, of course, they are--

probably have other roles.

Maybe someday, what we call mitochondria will actually

be two or three different little subcellular or organelles.

There may be little bits in there

that are controlling gene expression and little bits

in there that are controlling neurotransmitter production.

But at least for now, the name is mitochondria.

And thank you, by the way, for illustrating

some of the other things that they do because

in the landscape of science education,

oftentimes, people will think, OK, energy production.

There'll be a picture or a cartoon of mitochondria

flexing its muscles.

People go, OK, energy, mitochondria,

mighty mitochondria.

And then they'll think, oh, they're

just sort of like a dumb jock portion of the cell.

They're not doing anything sophisticated.

And everything you listed off is that they

are doing many sophisticated intricate things within cells.

So I think how things are cartooned and discussed

actually has an impact-- and not just on the general public,

but on the medical field and on the science fields.

Anyway, that's more science sociology.

But now that everyone is well aware

that mitochondria are doing a large number of very important

things in a very regulated way, let's talk about mitophagy.

A few years ago, because a Nobel Prize was given for autophagy--

sometimes called autophagy.

Look, people, you can say it either way.

People will know hopefully what it means is more important,

which is the gobbling up of one's own cells

that are dead or injured.

And this idea of autophagy, of cells

being eaten up within a system--

nervous system or other system--

has come up again and again.

I actually wasn't aware that mitophagy could

be such an important lever.

So tell us about mitophagy, which I have to presume

is the, intentional or not, gobbling up of mitochondria,

presumably to replace them with newer healthier mitochondria.

Is that right?

CHRIS PALMER: It is.

So in many ways, mitophagy is a subset of autophagy.

But it's got its own name because it

is specific to mitochondria.

There do appear to be some unique regulators of mitophagy

compared to autophagy more broadly.

Mitochondria actually are playing a role in autophagy

itself.

And this makes sense because one of-- so the global picture

of autophagy is stimulated by fasting states

or fasting-mimicking states.

So when your body senses that you don't have enough food,

it actually hunkers down and starts

to recycle dead old parts in this kind of carefully

orchestrated way.

And it takes them to lysosomes.

They get degraded.

And then those degradation products

get used for either energy or to build new things.

Autophagy is always occurring at a low level.

But you can really hyperstimulate the process

through fasting, calorie restriction,

fasting-mimicking diets, other things.

And this is why fasting and calorie restriction

is so kind of such hot topics in the medical field now.

It's because they've been shown to induce longevity.

And we think it's probably through that process

that you're stimulating the body to kind of become

lean and conservative in terms of its allocation of resources.

And the body doesn't just destroy the healthiest tissue

along with the old dead stuff.

It has these processes that identify the old and defective

parts first.

And they go first.

And that's what's beautiful about the whole thing.

And that's why fasting is so important.

So mitophagy we know plays a really important role because--

so there's this term called mitochondrial dysfunction,

which some researchers are actually wanting to get rid of

and move away from because, as you just said,

mitochondria do so many different things.

And different mitochondria even within the same cell

may very well be specializing in different tasks.

And mitochondria from one cell to another

are sometimes doing very different things,

like not all mitochondria can produce cortisol.

That's specific to specific cells

where those genes are getting turned on.

So it's not like all mitochondria

are producing cortisol.

Just the ones in your adrenal gland, for instance,

are producing cortisol.

But there is this term "mitochondrial dysfunction."

And it has long been known, for decades,

that mitochondrial dysfunction is associated with everything

that ails us essentially.

So in the 1950s, we had a theory of aging

that was based on reactive oxygen species.

And that's where all the inflammation is bad

for you comes from.

ANDREW HUBERMAN: And where all the noise about antioxidants--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: Like in the '90s,

it was like, it contains antioxidants.

Not to say antioxidants are bad, but they are certainly not

the be-all-end-all of health.

CHRIS PALMER: They are not.

But that's exactly where that research came from,

is that researchers were narrowing

in on these reactive oxygen species are highly, highly

correlated with all of the diseases of aging

and poor health outcomes.

It turns out, they're also highly, highly correlated

with all chronic mental disorders interestingly.

So researchers used the antioxidants

to see if, well, maybe if we can stop,

somehow tame these reactive oxygen species,

we'll improve health outcomes.

Doesn't seem to work.

By the 1970s, our understanding of mitochondria

and their role in the production of reactive oxygen species

expanded.

And that led to the mitochondrial theory of aging.

So in the 1970s, we had this mitochondrial theory of aging,

based primarily and exclusively on reactive oxygen species.

Fast forward a couple of decades,

that was disproven because we now reactive

oxygen species aren't all bad.

They actually serve a signaling process.

They're a normal part of human functioning

and cellular function.

So they're not all bad.

But we still know high levels of reactive oxygen species

are bad for you.

Fast forward to just, I think, maybe last year,

with this expanded role of all of the different things

mitochondria are doing.

So David Sinclair published a paper

in one of the cell journals, I think,

saying that, oh, mitochondria are actually

the unifying link of everything that we know about aging.

Mitochondria are the cause--

or defective mitochondria or defective mitochondrial

function, mitochondrial dysfunction,

is possibly the unifying cause of aging

and all of the aging related disorders.

So mitophagy is trying to address all that.

It's trying to say, OK, this is bad.

We don't want defective mitochondria and how can

we get rid of old ones or defective ones

and replace them with new ones.

And I think the most powerful signal and tool

that we have right now is, in fact, related to diet.

It's calorie restriction.

That is the oldest, truest, kind of best-proven way to prevent

aging in a wide variety of animal species--

fasting and intermittent fasting.

And again, you can only do those things for so long.

And then fasting-mimicking diets can also

stimulate this process of mitophagy.

ANDREW HUBERMAN: Before we talk about mitochondrial biogenesis,

if--

and I certainly accept the idea that mitochondria

are extremely important in physical health

and mental health.

That's, for me, is a straightforward conclusion

at this point, based on what you've said,

whatever and elsewhere, et cetera.

And if various diets, including ketogenic diet, including

fasting, reducing sugar intake, et cetera,

can assist in mitochondrial function and mitophagy--

and that's at least one of the levers by which diet

can positively impact mental health and physical health,

can we conclude that there's something special

about low blood glucose in the brain?

The sort of common pathway of all of those things-- fasting,

ketogenesis--

for some people, maybe they--

maybe some people have great insulin management,

so just removing sweets, refined sugars,

brings down their blood glucose level substantially.

They don't need to go on a ketogenic diet

in order to relieve a low level depression

or something like that.

Seems like the common theme here is

that glucose levels in the brain need

to be reduced, which for me, is surprising

because neurons love glucose.

There are some really nice studies.

One that I can think of recently that

was published in Neuron, if you just

look at the tuning of a neuron, how well a neuron in the brain

represents some visual image in the environment in terms--

here, we can just generalize and say,

more action potentials, more electrical signals

from the neuron generally correlates

with better high fidelity representation.

It's sort of if everyone's time someone says, shout,

and then someone shouts, the neuron

is the one responding to the order.

And these neurons just, when there's high glucose,

they are faithful representatives

of what's out there in the world.

But then when you fast an animal,

they become less faithful representatives

of what's out there.

And yet when I've done intermittent fasting,

and I do a kind of modified version of it,

my mental clarity is far better than when

I've had a big bowl of pasta--

probably for other reasons related

to serotonin and tryptophan.

So I think for the typical listener out there,

I have to imagine, it's got to be a little confusing.

We hear neurons love glucose.

They live on glucose.

And here, we're saying, let's deprive them of some glucose.

Or let's just bring glucose levels down.

Or let's switch the fuel source of the brain from glucose

to ketones.

And now the brain really works the way it's supposed to.

So this raises a little bit of just so story question,

like why would it be the case that neurons love glucose,

and yet if there's too much glucose around,

they become sick?

And of course, with any why-would-it-be story,

as I would say, I wasn't consulted at the design phase.

And I'm going to presume that you

weren't consulted the design--

CHRIS PALMER: I was not.

ANDREW HUBERMAN: --phase either.

And that if any of us say that we are,

then we are probably the patients that need evaluation.

So I think there's a name for that.

There's delusion--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --right?

OK.

I threw out my first correct clinical assessment of myself.

So how do I get my head around this?

You've got me sold on mitochondria--

not that I needed to be sold.

But that's an easy yes, yes, absolutely, yes.

The idea that diet can impact mental health

and physical health-- yes, absolutely--

by way of mitochondria-- at least in part, great.

But then neurons love glucose.

So what's going on?

Or what do you think is going on?

CHRIS PALMER: I am not convinced that glucose is the real story.

Glucose may, in fact, be a symptom.

We know that parts of the brain--

there have been a couple of studies that just came out

in the last couple of weeks, I think,

documenting that actually astrocytes in the hypothalamus

play a key role in glucose regulation throughout the body.

And it appears to be a metabolic role, which in my mind,

implies that the mitochondria in those astrocytes

are probably playing a key role because we know mitochondria

play a key role in sensing glucose levels.

They play a key role in the release of insulin

from the pancreas.

But mitochondria in the brain is also

playing a role in kind of balancing

how much glucose is around.

And so it's a difficult question because I think in some cases,

high glucose levels are actually a symptom

of metabolic dysfunction somewhere in the body or brain.

And when I think about, well, what does that mean?

In my mind, most of the evidence currently

is pointing to mitochondrial dysfunction

somewhere in the body or brain.

That is the most likely cause of that dysregulation

of glucose levels.

But we know that if you consume massive amounts

of junk food, sugar, and other things,

that you can get dysregulation of glucose levels.

The conundrum, though, is that that's not

a universal response.

ANDREW HUBERMAN: And what about the typical person?

I've never really liked junk food that much.

Maybe as a kid, I can recall liking candy.

But I was a sandwich for lunch person for a long time.

And as I've changed that out for salad

and maybe a small piece of meat with my salad or something

like that, I feel far better during the day, far more alert.

But I do eat carbohydrates.

I eat starches typically at night.

But I tend to do some very hard training at some point

during the day.

So I imagine I have some glycogen to repack.

OK.

That's me.

I only mentioned that because I'm not in ketosis

as far as I know.

I haven't-- unless you brought the strips,

I haven't done the blood glucose test today.

So what about the typical person who's

an omnivore eating some rice, some pasta, pasta

salads, people that are eating not junk food massive amounts

of sugar but have blood glucose that's

in kind of moderate range?

Do you think-- and here, feel free to speculate.

Do you think that those people might feel far better--

or even a little bit better-- if they

were in a lower glucose state?

And I ask this because I think there

are a lot of people out there who suffer

from full-blown depression.

But there are also a lot of people

who suffer from moodiness and feeling not so great,

subclinical depression.

CHRIS PALMER: Yes, burnout is what I would call it.

ANDREW HUBERMAN: Yeah, or just feeling some days are great,

and then other days, they feel lousy for reasons

they don't understand.

CHRIS PALMER: Yeah.

ANDREW HUBERMAN: And those make for less dramatic case studies.

And yet I have to assume that that description will

net a large fraction of the general public.

CHRIS PALMER: So the way that I kind of break this field--

and I'm probably getting too nerdy right now.

But I kind of break this field into cause--

what's the actual root cause--

and what are effective treatments.

And I really see them as two separate things.

Just because the ketogenic diet is an effective treatment,

does not imply that the cause of the problem

was eating carbohydrates.

And I think that's a really important distinction.

There are many people who disagree with me on that.

There's no doubt about it.

And everybody's heard people say,

sugar is the cause of everything that ails you.

Or carbs are the cause of everything that ails you.

If everybody does a low carb diet or a ketogenic diet--

and then they go to, so it must be sugar that was the cause.

I don't see it as clearly black and white as that.

Calorie restriction, ketogenic diet,

carbohydrate restriction are inducing metabolic changes

in the brain and body.

And regardless of what the person was eating,

they are inducing metabolic changes

that can be really beneficial to brain health.

So let me just give a clear black and white example

of this.

And then I can speak to the broader topic

that you brought up about just the general population.

The easy example of the ketogenic diet

being an effective intervention for somebody

who was not following a bad diet is an infant with epilepsy.

There are lots of infants who have uncontrollable seizures.

They are drinking breast milk.

To the best of our knowledge, that

is the primary, most beneficial food source

an infant could be consuming.

Now, some might say, well, maybe the mother is--

whatever, I don't buy that.

The mother's breast milk is, in fact, the optimal food source

for that infant.

And yet that infant is still seizing.

If we put that infant on a ketogenic diet,

a lot of those infants seizures will stop.

It doesn't mean that the cause of the infant seizures

was a bad diet.

But it means that dietary intervention

can change brain metabolism and improve symptoms

in that person.

So going to your broader question about adults,

modern-day, the real answer is-- there was just

this conference in London, the Royal

College of obesity medicine or something like that.

That's not the name.

But it's something along those lines.

The conclusion of that conference

that invited the greatest minds in obesity medicine,

the overarching conclusion of that conference was we

don't know what causes obesity.

It's really important that we sit with that.

We don't know what causes obesity.

ANDREW HUBERMAN: They don't think

excess caloric intake beyond one's daily metabolic needs

is causing obesity?

CHRIS PALMER: Some will argue that.

And so some will say yes, it's all energy balance.

But why do we have an epidemic of obesity?

ANDREW HUBERMAN: Oh.

Well, that's the N-gazillion dollar question.

CHRIS PALMER: Yes.

Some will say, it's all the junk food.

But we had junk food in the 1970s.

When I was growing up, I grew up on Kool-Aid, and Twinkies,

and King Dons, and HoHos, and--

[LAUGHS]

ANDREW HUBERMAN: I'm rewatching the Mad Men series now.

I love that series, and I'm rewatching it.

And I happen to know someone who worked on that series.

They researched everything for the props,

and the costumes, everything, right down to diet.

And if you look at the diet, it was terrible.

It was mostly-- yes, there was a lot

of excessive amounts of drinking and cigarette smoking.

But the diets were terrible.

It was pre-packaged foods.

It was frozen dinners.

That really came to prominence in the '70s and '80s.

But even in the '50s and, from what I've been reading, even

in the '30s and '40s, people were not

eating grass-fed meat and Brazil nuts

with a little bit of broccoli rabe on the side.

That's not the typical intake.

So something out there-- or maybe multiple things--

are at play to increase obesity.

CHRIS PALMER: And at the end of the day, I believe--

some will call this speculative.

But I actually think we've got a tremendous amount of evidence

that continues to point in this direction.

I believe that mitochondria are the key

to the obesity epidemic, that there is

something in our environment.

So that is either our food, environmental toxins, stress

levels, poor sleep, not getting adequate sunlight, whatever

you want to speculate on, all of the above, all of those things

are known to impair mitochondrial function.

And if parts of your brain that regulate metabolism and that

regulate eating behaviors are not metabolically healthy,

it means that they will not stop you from eating.

Or it means that your metabolism will not

rise to the challenge of 10 donuts,

because some people can eat 10 donuts

and go on staying thin and healthy.

ANDREW HUBERMAN: I totally agree.

Although, I would just like to say

that it seems to me that compared to when I was growing

up-- and again, I haven't run the statistics--

there are fewer and fewer of those individuals around now.

Just as when I was growing up, it was one or two kids in class

that were quite overweight.

And then there were some that were mildly overweight.

But most were of healthy weight.

Nowadays, that's dramatically altered.

The landscape is dramatically altered in the other direction.

It is rare when I encounter one of those can-eat-anything type

people.

I know one, he's actually an employee at Stanford.

He's in our media team at Stanford.

And this guy, when I take him to lunch, it's like--

he's in his early 70s, and he can eat.

And he's incredibly lean.

He exercises a little bit.

But he's one of these mutants that just can eat, and eat,

and eat, and he's lean and he's vital, and he's--

it's wild.

And he's an expensive lunch.

CHRIS PALMER: [LAUGHS]

ANDREW HUBERMAN: But those people are seem rare.

And even those kids are now seem rare.

CHRIS PALMER: They're getting increasingly rare.

And that leads me to think it may

be epigenetic factors in the womb environment,

so that kids are actually coming out predisposed to obesity.

ANDREW HUBERMAN: Well, let me ask you about

that because I had a note here to ask this later.

But I'm going to interrupt you now in order

to capture this moment.

My understanding is that--

well, as everyone knows, we inherit DNA.

We get genes from both of our parents.

And they mix.

Although there are incredible data from Catherine Dulac's

lab at Harvard and others showing that we actually

have entire regions of our brain that

carry neurons that are of purely of mom's or of dad's DNA,

depending on the brain region.

This is a wild finding.

But it's accurate.

And this has actually been known about in terms of heritability

of disease, et cetera.

Maternal DNA, DNA from mom, genes from our mother--

not to place blame on mothers at all.

My understanding is that the mitochondrial DNA

come exclusively through the maternal side.

Is that true?

CHRIS PALMER: So it's a great question.

And I've been asked this before.

And yeah, psychiatrists are known for blaming mothers.

And some might say that I'm trying to redo that whole thing

and blame mothers again.

ANDREW HUBERMAN: The data are the data.

I'm not trying to blame mothers here.

Mothers play an essential role in everything.

But if it is true that mitochondria

are the linchpin of all this and maternal DNA is what determines

the mitochondrial DNA, I think it's an important place

to look.

CHRIS PALMER: It's an important question.

And the answer is unequivocally no.

That's not the way it works.

ANDREW HUBERMAN: Well, then vindication for anyone

that was asserting that.

CHRIS PALMER: And so let me explain it.

So mitochondria have 36 genes unto themselves.

13 of those genes code for some of the mitochondrial machinery

of making ATP.

And the other 36 play roles in epigenetic regulation,

play roles in whole body metabolism, and other things.

So that is what you're inheriting from your mom.

It's the mitochondria and those 36 genes for the most part.

But the majority of proteins that make up mitochondria,

over, I think, 1,300 genes that make up mitochondria

are actually encoded in the nuclear DNA.

And so you inherit a copy from both your mother

and your father.

So the majority of people who have mitochondrial defects

or rare mitochondrial diseases actually

could inherit them from either mom or dad

because it can be a defect in the nuclear genes that code

for proteins that make up mitochondria.

The much bigger issue when--

so when I talk about mitochondrial dysfunction

being a primary driver of mental illness, metabolic illness,

it's not that people inherit a defective mitochondrion

or mitochondria from mom, and then

that just ruins their life forever.

That's actually not the way it works.

The beautiful thing about this theory

is that it connects all of the risk factors

that we already know play a role in mental health

but also metabolic health.

Sleep disruption impairs mitochondria and mitochondrial

function.

Stress, high levels of stress and trauma,

impair mitochondrial function.

Drug and alcohol use, alcohol, tobacco definitely--

in terms of the smoke--

and marijuana-- THC, in particular-- all impair

mitochondrial function.

ANDREW HUBERMAN: THC directly or the smoke?

CHRIS PALMER: THC directly.

Those studies have been done.

So mitochondria actually have CB1 receptors right on them.

And various researchers, a couple

of studies from Nature actually documented

this, that the mitochondrial CB1 receptors are primary--

kind of primary points of the influence of marijuana

on human behaviors and effects.

Because when they remove CB1 receptors in animal models,

these changes don't happen.

So the CB1 receptors--

we've got some large studies of adolescents

who use a lot of marijuana.

And the areas where the mitochondria have the greatest

number of CB1 receptors are areas of their brains

that actually are atrophied or shrunk compared

to normal healthy controls.

So that means their brain tissue is aging prematurely.

It's shrinking prematurely.

But the CB1 receptors on mitochondria

also seem to play a role in the memory impairment that

can be induced from THC.

And they also play a role in the kind

of lack of motivation, the behavioral amotivational state

from THC.

Now, again, for people who want to chillax,

that's what they're looking for.

They don't want to remember anything.

They don't want to think.

They want to be spaced out.

They want to relax.

That's great.

But it's important that they know

that they're actually harming the mitochondria in their brain

cells.

And that although there's always an opportunity

to repair mitochondria and always an opportunity

to stimulate mitochondrial biogenesis,

so you can get it back, but if you keep doing it chronically,

you're probably not helping your overall mental or metabolic

health.

ANDREW HUBERMAN: Yeah, I'm glad you brought up THC.

We did an episode on cannabis.

We also did one on alcohol--

probably lost some friends from that one.

When you look at the data, it's very clear.

I'm not arguing that people dislike

the effects of these compounds when they take them.

But it is clear that, at least to me,

based on the data that regardless of what people

have read about red wine, that not drinking any alcohol is

going to be healthier than drinking alcohol,

and that the thresholds for alcohol ingestion before people

start to negatively impact their health

is about one or two per week.

And then THC, because of the very high concentrations

of THC that are present in a lot of products now--

vaping and smoking THC and even edibles--

that it can be problematic.

You mentioned adolescents that predisposition,

and brain atrophy, psychosis, et cetera.

In any case, because you mentioned alcohol

because it is a commonly used substance,

I heard you give a talk in which--

I think I have this right-- in which alcohol can disrupt

the way that the brain uses fuels of all kinds,

which may disrupt one's response to alcohol,

make alcohol seem more rewarding to those that drink alcohol.

So drinking alcohol makes alcohol

more rewarding to the brains of alcohol drinkers,

but that it also might alter glucose metabolism,

that basically alcohol is not good for our brains.

Do I have that correct?

CHRIS PALMER: You do have that correct.

ANDREW HUBERMAN: OK.

What happens if you take an alcoholic or somebody that just

drinks two to four nights a week a couple

of drinks, which I think is pretty common out there,

and you put them on a ketogenic diet?

Has that experiment been done?

CHRIS PALMER: That experiment has been done.

ANDREW HUBERMAN: Ah.

CHRIS PALMER: It led by none other

than a woman named Nora Volkow, who

is one of the leading neuroscientists and addiction

researchers in the world.

She is the director of the National Institute

of Drug Abuse.

She's been hot on the trail of metabolic abnormalities

in the brains of people with alcohol use disorder, which

I will just refer to as alcoholics

because that's what everybody knows it as.

So she's been hot on this trail for many, many years.

And as you said, it turns out that the reward pathways,

in particular, are metabolically compromised in alcoholics.

And the metabolic compromise essentially, in a nutshell,

means they aren't getting enough fuel from glucose.

The interesting thing is that when people drink alcohol,

your liver converts alcohol into a molecule called acetate.

That acetate travels up to the brain and fuels brain cells,

in particular, some of these reward

pathway cells more than others.

And so chronic alcoholics have this chronic deprivation

of energy in these cells.

And so Nora Volkow and other researchers at the National

Institutes of Health did a study in which they set out

to see if we can change this brain metabolic problem

in alcoholics.

Will that affect clinical symptoms of alcoholism?

And will it do anything?

It's clinically useful.

And so they actually did a pilot randomized

controlled trial, admitted alcoholics to a detox unit.

Half of the patients got a ketogenic diet.

The other half got the standard American diet.

And then everybody else, all of them

got the same detox protocol.

The patients who got the ketogenic diet

required fewer benzodiazepines for their detox.

Despite that, they had fewer withdrawal symptoms

from the alcohol.

They reported fewer cravings for alcohol.

And the researchers did brain scans,

which showed improved brain metabolism in these key areas

that they were looking at.

And their brains showed reduced levels

of neuroinflammation, which was also something

they were really interested in.

And so that one study says to us that even though most people

would think alcoholism has nothing to do with diet,

alcohol is just drinking too much.

It's a matter of willpower.

Or it's somebody who's addictive.

They've got an addictive personality,

and it's that simple.

You come out of the womb with an addictive personality.

And those people are novelty seekers, and they're impulsive.

And they have no patience.

They have no discipline.

They can't sustain any kind of rewarding experience.

ANDREW HUBERMAN: Or childhood trauma.

There's a--

CHRIS PALMER: Yes.

ANDREW HUBERMAN: --story there, which there very well may be.

But--

CHRIS PALMER: And there may be.

ANDREW HUBERMAN: Yeah.

CHRIS PALMER: But what that research study strongly

suggests--

and again, yes, maybe we need larger controlled trials.

But this is one of the leading neuroscientists in the world

who's hot on this trail.

This is what she believes.

And this is what I believe.

It's that if we can correct the brain metabolic defects

from chronic alcohol use, we might

be able to help people be sober and give them a fighting

chance.

Or give them an edge up or pull a lever

that we can use in their favor, for their benefit.

There's one caution to all of this research

that I really do want to highlight.

And so now, I'm going to get hate mail

from all the keto community.

ANDREW HUBERMAN: That's OK.

I admire you for talking about nutrition at all

because anytime one talks about nutrition,

you're going to get hate mail from somebody.

CHRIS PALMER: So the caveat to all of this

is that as part of the research that those researchers were

doing, they actually wanted to see

what will happen to alcohol levels

if an animal consumes alcohol while on a ketogenic diet.

So they didn't do this in humans yet.

This is a fairly easy study to do.

So I'm hoping somebody will do this study soon.

But they instead put rats half of them

on a standard diet and half of them on a ketogenic diet.

And then they exposed them to the exact same amount

of alcohol.

The rats who were on the ketogenic diet

had a five-fold increase in blood alcohol levels.

Five-fold increase.

ANDREW HUBERMAN: Meaning, they drank more?

Or--

CHRIS PALMER: No.

ANDREW HUBERMAN: --it was metabolized differently.

CHRIS PALMER: It was metabolized differently.

The rats all got the same amount of alcohol.

ANDREW HUBERMAN: So for people out there who are ketogenic,

I'm chuckling, but who are not alcoholics-- please,

alcoholics, please do something about it

because it's so detrimental.

But I guess does this mean that they can drink less in order

to get the effect of alcohol that most people are seeking?

CHRIS PALMER: Cheap dates.

Cheap date is what you call that.

You only need a half a drink instead of three drinks.

ANDREW HUBERMAN: I would think the keto community would thank

you for this unless they somehow have a stake in the alcohol

industry.

CHRIS PALMER: The reason that I put it

as a caution is that if anybody is struggling with alcoholism

and thinks hey, I need an edge up.

I need a lever to pull because I'm really struggling

to give this stuff up.

I just find myself going back.

And if you're telling me my brain metabolism is messed up,

and this might help it, I'm all in favor of that.

And yes, that's what the researchers are pursuing.

And that's what I'm saying with the following caveat--

that if you relapse while on a ketogenic diet,

you better not drink the same amount of alcohol

that you think you can drink.

ANDREW HUBERMAN: It could be deadly.

CHRIS PALMER: It could be deadly,

and/or it could be really--

yeah, deadly to you or someone else because unfortunately,

a lot of times when people drink,

they get behind the wheel.

And they think that they can handle two drinks safely.

And they think, well, I can go out for dinner

and have two glasses of wine and drive home safely.

I know myself.

If you go to a ketogenic diet, please

don't drive with the same two drinks

because it means your blood alcohol level--

if it models anything that we found in the rat study--

your blood alcohol levels may be five times higher

than they would normally be.

And that means you are really wasted.

And you're probably not safe to be driving.

ANDREW HUBERMAN: Probably the same

is true for drinking on an empty stomach, right?

CHRIS PALMER: Yup.

ANDREW HUBERMAN: Yeah.

Now, it's a very important point.

And thank you for raising that.

I hear this again about mitochondria,

about blood glucose, you mentioned astrocytes.

And for those of you--

that earlier astrocytes are a non-neuron cell type

in the brain, a glial cell type that my postdoc advisor was

known for popularizing the modern science of glia,

which include astrocytes.

And I'd be remiss if I didn't say that they are considered

the cells that hold everything together in the brain

and are kind of passive observers.

But they do many things actively.

I think now people appreciate the astrocytes at least

as important as the neurons.

And certainly, for disease, they are often

implicated in warding off of disease, et cetera.

Everything that you're telling me about the fact

that the brain can regulate things that are happening

in the body, metabolism, et cetera, organ health, obesity,

et cetera, to me, as a neuroscientist,

that's not surprising.

All of it just screams hypothalamus, hypothalamus,

hypothalamus because here, you're telling me,

it's regulating these basal functions like metabolism.

It's regulating how much we crave things.

And of course, hypothalamus is involved

in motivation and craving.

There are other areas, too--

other areas of the brain, too, of course.

But I would imagine that someone ought to

or has mapped out where the receptors for all this business

are in the brain.

And I guess that raises the question of, when

one goes on a ketogenic or low blood glucose diet or fast,

has anyone observed changes in the brain?

Has anyone had neuroimaging of humans and their brains

under conditions of ingesting one diet or another,

whether or not they're psychiatric--

suffering from a psychiatric disorder or not?

I would think that's where the gold is.

CHRIS PALMER: We do have some of those studies.

When you do a neuroimaging study,

you can measure a lot of different things.

So one thing with a PET scan, you

can measure glucose metabolism.

So a researcher, Stephen Cunnane is

doing that research in particular in Alzheimer's

disease patients and Alzheimer's disease models but in humans.

And that's because we know that--

again, a common finding in patients

with Alzheimer's disease is this glucose hypometabolism,

some people are attributing it to insulin

signaling impairment.

And so some people are calling it type III diabetes.

At the end of the day, I think the clearest

signal that we have is that cells

aren't getting enough energy from glucose as a fuel source.

That is something that I think I can confidently

say that's backed by numerous research studies.

There's debate in the research field

about whether that's a primary driver of the illness.

I happen to believe it is.

And if you ask the question, well,

why would cells not be getting enough fuel from glucose?

You have to focus on mitochondria

because they're the ones producing

the fuel from that glucose.

So you somehow you have to implicate mitochondria

in that process one way or another.

Others will say, no, that's just a side effect of whatever's

causing Alzheimer's disease.

So Stephen Cunnane has done studies where he even

gives ketone supplements.

ANDREW HUBERMAN: These are liquid ketone esters?

CHRIS PALMER: Yeah, ketone esters or ketone salts.

And it has actually found that these brain metabolism deficits

can be corrected, at least short-term,

by giving a ketone supplement.

ANDREW HUBERMAN: Is this in the context of people

also ingesting some carbohydrate?

Because I confess, I've tried the ketogenic diet.

I probably did it wrong.

This was years ago.

And then the cyclic ketogenic diet.

But in the last year or so, I've started

using liquid ketone esters.

And I do eat some carbohydrates each day,

usually in proportion to how much high intensity exercise

I'm doing.

Those liquid ketone esters, for me--

at least subjectively-- I feel greatly

increase my energy levels and my ability to focus mentally.

And they improve my sleep.

This is my observation tracking some data

but just, again, subjectively.

So in this example, are you talking

about people taking ketone esters or ketone

salts on a backdrop of a ketogenic diet

or on the backdrop of a more typical diet?

CHRIS PALMER: So he's done both.

So he's done studies where patients aren't doing

anything special with the diet.

So they're eating whatever they normally

eat, absolutely nonketogenic, giving them

a ketone salt or ester, and then noticing

immediate and direct changes in the metabolism

of these metabolically compromised brain cells

as measured by PET imaging.

ANDREW HUBERMAN: These are not household pets, by the way.

Sorry, I have-- we have to just--

P-E-T, positron emission tomography, not pets.

Although, I'm sure that there are people out there

who have their dogs, or cats, or whatever,

or their pet kangaroos, whatever you might own,

on ketogenic diet.

OK.

CHRIS PALMER: Absolutely.

So he's actually moved further.

He's done a pilot trial in a nursing home

actually, where he did not put the patients

on a ketogenic diet.

He simply reduced carbohydrate consumption

at breakfast and lunch.

They still got the same dinner as everyone else.

And simply reducing carbohydrate consumption

at breakfast and lunch resulted in cognitive improvement

in a statistically significant way in some of those subjects.

ANDREW HUBERMAN: Oh, I love that result. I'm sorry,

I just have to highlight this.

I'm a huge believer in directing carbohydrates

to specific portions of the day when

one needs to be less focused and alert

and yet can replenish glycogen.

Limiting carbohydrates most of the time during the day,

for me, has been a game changer in terms of maintaining

alertness, et cetera.

I'm not aware that I have age-related cognitive decline.

But then again, I would-- people around me may argue otherwise.

CHRIS PALMER: Let me say, you are Andrew Huberman.

There is no way you have [LAUGHS] cognitive impairment.

ANDREW HUBERMAN: Although you didn't know me

as a six-year-old--

CHRIS PALMER: If you have cognitive impairment,

we're all screwed.

ANDREW HUBERMAN: Well, I have plenty

of flaws and impairments-- well over 3,000

documented by people very close to me.

But this is very interesting, I think,

in the context of everything we've been talking about

because could it be that supplementing

with liquid ketones or prescribing

liquid ketones to people who are challenged with mood

disorders-- or things of that sort-- could be beneficial,

even if they are not willing or able to adhere

to a ketogenic diet?

CHRIS PALMER: That is the million dollar question

right now.

And we don't have good trial data to say yes or no.

My speculation, my hunch, having tried that clinically

with patients, is it doesn't seem to work.

It's not the same thing.

The bigger reason for my feeling confident in saying that

is that we've had ketone salts and esters

available for over a decade now.

We have tens of thousands of children and adolescents who

are following a strict, ridiculously strict, ketogenic

diet to control their epilepsy.

Those kids would love to be off the ketogenic diet.

Their parents would love to have them off the ketogenic diet.

ANDREW HUBERMAN: They had no birthday cake, no ice cream.

CHRIS PALMER: There is not one case report

of any child controlling his or her seizures using

exogenous ketones without also doing the ketogenic diet.

I just find it hard to believe that at least some

of those people haven't tried it out to see.

I do know some patients with bipolar disorder

and even schizophrenia who are doing extraordinarily well

on a ketogenic diet.