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 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. In keeping with
that theme, I'd like to thank the sponsors
of today's podcast. Our first sponsor is Thesis. Thesis makes custom nootropics. And as I've said many times
before on this podcast, I am not a fan of
the word "nootropics" because it means smart drugs.

And frankly, there are no
specific neural circuits in the brain or body for
being, quote unquote, "smart." Thesis understands this. And they've developed
custom nootropics that are designed
to bring your brain and body into the state
that's ideal for what you need to accomplish. They use the highest
quality ingredients, things like
phosphatidylserine, alpha GPC, many ingredients
that I've talked about before on this podcast
and that I happen to use myself. I've been using Thesis
for over a year now. And I can confidently
say that their nootropics have been a game changer. For me, I like their
nootropic for clarity. I use that before
cognitive work often. And I like their
nootropic for energy, and I often use that
before workouts– in particular, workouts
that are especially intense.

To get your own personalized
nootropic starter kit, go online to Take their 3-minute
quiz, and Thesis will send you four
different formulas to try in your first month. Again, that's And use the code
Huberman at checkout to get 10% off your first box. Today's episode is also
brought to us by Eight Sleep. Eight Sleep makes smart mattress
covers with cooling, heating, and sleep tracking capacity.

I've talked many
times on this podcast about the critical relationship
between sleep and body temperature. That is, in order to fall
asleep and stay deeply asleep throughout the night,
our body temperature needs to drop by
about 1 to 3 degrees. And conversely, when we
wake up in the morning, that is, in large part,
because of our body heating up by 1 to 3 degrees. Now, people have different
core body temperatures. And they tend to run colder or
hotter throughout the night. Eight Sleep allows you
to adjust the temperature of your sleeping
environment so that you have the optimal temperature
that gets you the best night's sleep. I started sleeping on
an Eight Sleep mattress cover about eight months
ago, and it has completely transformed my sleep. I sleep so much deeper. I wake up far less during the
middle of the night, if at all.

And I wake up feeling far
better than I ever have even after the same amount of sleep. If you want to try
Eight Sleeping, you can go to to save up to $400 off their
sleep fit holiday bundle, which includes their
new Pod 3 cover. Eight Sleep currently
ships in the USA, Canada, United Kingdom,
select countries in the EU, and Australia. Again, that's Today's episode is also
brought to us by ROKA. ROKA makes eyeglasses
and sunglasses that are of the absolute
highest quality. The company was founded by
two All-American swimmers from Stanford. And everything about ROKA
eyeglasses and sunglasses were designed with
performance in mind. I've spent a lifetime working on
the biology, the visual system. And I can tell you that
your visual system has to contend with an enormous
number of challenges in order for you to see clearly– for instance, when you move from
a sunny area to a shady area and back again, whether or not
you're looking at something up close or often to the distance. ROKA understands the
biology of the visual system and has designed their
eyeglasses and sunglasses accordingly so that you always
see with perfect clarity.

ROKA eyeglasses and
sunglasses were initially designed for activities
such as running and cycling. And indeed, they are
very lightweight. Most of the time I
can't even remember that they're on my face. They're so lightweight. But the important thing to
know about ROKA eyeglasses and sunglasses is
that while they can be used during
sports activities, they also have a
terrific aesthetic. And they can be used just as
well for wearing to work or out to dinner, et cetera. If you'd like to try ROKA
eyeglasses and sunglasses, you can go to ROKA–
that's, and enter the code
Huberman to save 20% off on your first order. Again, that's ROKA,,
and enter the code Huberman at checkout. 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.

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.

I'd like to take a quick
break and acknowledge one of our sponsors,
Athletic Greens. Athletic Greens, now called AG1,
is a vitamin mineral probiotic drink that covers all of your
foundational nutritional needs. I've been taking Athletic
Greens since 2012, so I'm delighted that they're
sponsoring the podcast. The reason I started taking
Athletic Greens and the reason I still take Athletic Greens
once or usually twice a day is that it gets
me the probiotics that I need for gut health.

Our gut is very important. It's populated by
gut microbiota that communicate with the brain, the
immune system, and basically all the biological
systems of our body to strongly impact our
immediate and long-term health. And those probiotics
in Athletic Greens are optimal and vital
for microbiotic health. In addition, Athletic
Greens contains a number of adaptogens,
vitamins, and minerals that make sure that all of my
foundational nutritional needs are met. And it tastes great. If you'd like to
try Athletic Greens, you can go to, and they'll give you five
free travel packs that make it really easy to mix up
Athletic Greens while you're on the road, in the
car, on the plane, et cetera. And they'll give you a year
supply of vitamin D3/K2. Again, that's to get the five free travel
packs and the year supply of vitamin D3/K2. 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
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

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.

to take a brief break and thank our sponsor,
InsideTracker. InsideTracker is a
personalized nutrition platform that analyzes data
from your blood and DNA to help you better
understand your body and help you reach
your health goals. I've long been a believer in
getting regular blood work done for the simple reason that
many of the factors that impact your immediate and
long-term health can only be analyzed from
a quality blood test. The problem with a lot of
blood and DNA tests out there, however, is that
you get data back about metabolic factors, lipids,
and hormones, and so forth. But you don't know what
to do with those data.

solves that problem and makes it very easy
for you to understand what sorts of nutritional,
behavioral, maybe even supplementation-based
interventions you might want to
take on in order to adjust the numbers of those
metabolic factors, hormones, lipids, and other
things that impact your immediate and
long-term health to bring those numbers into the
ranges that are appropriate and indeed optimal for you. If you'd like to
try InsideTracker, you can visit to get $200 off an ultimate
plan or 34% off the entire site as a special Black Friday
deal now through the end of November.

Again, that's and use the code
Huberman at checkout. 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.

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.

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.

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.

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. They have tried to switch
off the ketogenic diet using exogenous ketones. Their symptoms came back. And so they found that
it just wasn't effective. Now, again, those are anecdotes. My scientific
speculation about why is because the ketogenic diet is
actually not necessarily about ketones themselves.

Ketones are one of a
multifaceted story there. And so when people
do a ketogenic diet, they're also improving–
they're lowering glucose levels. They're improving
insulin signaling. They're ramping up mitochondrial
biogenesis, in particular, in the liver because
mitochondria actually make ketones. That's where they're made. And they're primarily made
in the liver mitochondria. So when somebody is
on in a fasting state or on a ketogenic diet,
their liver mitochondria go through the roof because
they're being called to action.

It's like, hey, body's
in starvation mode. Get to work. And so the mitochondria– the cell senses we need
more mitochondria to process fat to turn it into ketones so
that those ketones can get up to the brain and keep
the brain fueled, because fatty acids
can't fuel the brain. Only ketones can. Now, so my sense is that–
and the gut microbiome changes and everything, the
changes in hormones– so if you're eating
a lot of donuts and drinking a
bottle of ketones, the donuts are going
to prevent your body from lowering glucose levels. You're still going to
have the high glucose levels from the donuts. You're still going
to probably have the impaired insulin signaling. You're probably still
going to possibly have some inflammation from
the inflammatory effects of that food.

And so just drinking ketones
alone won't be enough. I think for people who are
metabolically healthy, I'll include you in that, I think
ketones can play a really beneficial role, no doubt. I think exogenous
ketones may, in fact, proven valuable in
clinical use for patients who maybe can't follow a
super strict ketogenic diet but maybe could do
a low carb diet. And then given the
research that's happening with
alcohol use disorder, I could imagine a
situation– here's the million dollar
tip to whoever wants to go out and get this,
if it actually turns out to be true. I could imagine a scenario
where we use exogenous ketones with alcoholics. And that every time they have
a severe craving for alcohol, they drink ketones instead.

of tastes like alcohol. The ketone esters, when I take
them, I drink them straight. Sometimes I'll put
them in seltzer. And I'm not a big
drinker, as I mentioned. I might have an alcoholic
drink every once in a while. I just don't ever crave it. I just do it every maybe– I think 2020 was the last
time I had a drink of alcohol. So obviously, I'm not a
good representative example. But the ketones
taste good to me. And they obviously
don't get you drunk. They do seem to flick on my
alertness pretty quickly. My understanding is that they
are the brain's preferred fuel source.

Meaning, they are going
to be the first fuels used by the brain when there's a
buffet of fuels available. If there's glucose
in my bloodstream, there's circulating
liquid ketones, the ketones would be used
first or preferentially. Is that true? CHRIS PALMER: I think
it's a complex question. Some research that we have
suggest that there are brain areas or brain cells that
require glucose and cannot use ketones. So 100% of the brain cannot
be fueled with ketones as far as we can tell. So there are some areas
that require glucose.

And that's probably the
reason we have gluconeogenesis to keep the body going and keep
the brain going no matter what. But when ketones are available,
especially if ketones are high, the way I think about
it is not that ketones are the preferred fuel
source and glucose goes to the wayside. But the way I think
about it is that you have a range of
cells with varying degrees of metabolic health. And some of those
cells are going to be extraordinarily healthy
with appropriate healthy abundant mitochondria. And those cells
are probably going to continue to use
glucose as a fuel source. But if ketones
happen to be there, sure, they'll use that, too. Why not? But the real money
is metabolically compromised tissues,
whether it's brain cells or
other tissues that– we're talking about the brain. So if you've got metabolically
compromised brain cells– because it's not
across the board. Like with Alzheimer's
brain scans, there are specific regions
that are more metabolically compromised than others. And that's why we see patterns
of atrophy in specific brain regions.

It's because those regions are
dysfunctional metabolically for whatever reason. And we can get into
why that might be. But my sense is that if you've
got a metabolically compromised cell, that cell is sending
out a distress signal. That cell is calling resources
from the body, like feed me. Give me something. And if it can't use
glucose effectively, it is going to suck
up those ketones and then start running on all
cylinders or closer to it. And that process is so
critical because what it means is that if that cell
was barely getting by on 60% of its
real ATP requirement, it means that it doesn't have
enough energy for maintenance and repair functions.

As soon as you give that
cell a hundred percent energy or close to it, even
if you get it up to 90% of its preferred
energy amount, it can start to repair itself. That's the beauty
of the human body in living organisms,
is that they have a priority list of
what they're going to do. If that cell senses that
there are defective molecules, defective proteins
in this cell that need to be replaced,
once it gets enough fuel, it will start repairing
itself and doing that work. ANDREW HUBERMAN:
That makes sense. Thank you for that

I'd like to talk
about Alzheimer's and age-related cognitive
decline generally. I know many people
out there are just terrified of losing their
memory for the obvious reasons. Memory sets context, et cetera. And many people
have relatives that suffer from Alzheimer's or
other forms of dementia. I've heard that the
ketogenic diet and diets like it can be very
effective for helping to offset some of the
symptoms of Alzheimer's and age-related
cognitive decline. In fact, I even have a friend
I won't out by institution, who's the chair of
Cardiology, who contacted me, of all people, asking whether or
not I was aware of any studies or whether or not I knew of
anybody who had benefited from ketogenic diet for Alzheimer's. And I thought, well, why don't
you ask one of your colleagues in neurology? But his response was
really interesting. He said there are many books out
there for the general public. There are a lot of online
discussions about this.

There are a lot of
assertions about this, and some animal studies. Again, these are his words. There are very few, if any,
controlled clinical trials exploring the role
of the ketogenic diet for the treatment or
reversal of Alzheimer's and age-related
cognitive decline. I'm hoping that statement
was incorrect or soon will be incorrect– because those
trials are ongoing– but he said, yeah, the people
are most popular for telling us about the important role
and positive role of being in ketosis for Alzheimer's,
for some reason, they just won't do
a clinical trial. And that's been frustrating
to the community. So this is a very educated,
very accomplished person who's a physician of
heart medicine as opposed to something else
related to the brain. But what is the story there. And for goodness' sake, why
aren't there clinical trials on ketogenic diet
and Alzheimer's? I don't expect you to be
responsible for that fact. But goodness, I would
think this would be the obvious thing for NIH.

I'm on study section but not
for these sorts of experiments. Why isn't money just avalanching
into this area based on all the anecdotal evidence that
people are talking about? CHRIS PALMER: So
we've got a couple of small pilot clinical trials. The best one was a
randomized controlled trial. I think it only included 26
subjects, something like that, randomized to 12 weeks of a
low fat diet, 10-week washout, 12 weeks of ketogenic diet. Some of the participants got
keto first and then low fat. Other participants
got low fat then keto. And that trial actually
found that when patients were in ketosis, they had
statistically significant improvement in activities
of daily living and quality of life. And they did have improvement
in cognitive function. But it didn't reach
statistical significance, that improvement did not.

We've got other trials. We've got several animal models
showing that the ketogenic diet can improve biomarkers
of Alzheimer's disease in Alzheimer's models. So it can reduce
plaques and tangles, can even improve cognitive
impairment in animal models. And we've got a couple
of other small pilot trials of ketogenic
diet in humans, showing that it improves
biomarkers compared to, say, the low fat diet or
the American Heart Association diet. So we've got those. I think one of the
biggest challenges that I'll just share openly– and this is– I'm
somebody who's pretty passionate about this research. And I believe it has
a lot of potential. But Johns Hopkins'
researchers attempted to do exactly this kind of a
study, Alzheimer's patients' ketogenic diet
versus the, I think, American Academy of Aging– or something like that–
diet, is the controlled diet.

Which presumably has starches in there. CHRIS PALMER: Yes. ANDREW HUBERMAN: I think
that's the key variable. CHRIS PALMER: Probably
lots of– yeah, lots of– ANDREW HUBERMAN:
And some potatoes– CHRIS PALMER: Whole grains,
lots of whole grains. ANDREW HUBERMAN:
Yeah, some potatoes. CHRIS PALMER: And they spent,
I believe, over three years. They screened over 1,300
people who expressed interest. At the end of the
day, I think they only got 27 people to enroll. And only 14 of those
people completed the study. ANDREW HUBERMAN: Wow. CHRIS PALMER: Despite
that, what they found was that the subjects
who achieved ketosis had cognitive improvement.

But people on study
section are going to look at a study like that
and say, even if the science is there, if you can't get
people to do this diet, why would we spend money
on researchers trying to get people to do this diet? ANDREW HUBERMAN:
I should mention, study section is this closed
door panels of 40 or so people. There are many of these panels. Different divisions in the
National Institutes of Health use different panels. And then grants are
evaluated in a very small, because of the size of the
federal budget for research, a very small percentage. Usually, about 10% of
these studies are funded. The rest generally
don't end up happening. That is very informative. What you just described
is very informative because now it
makes sense to me. There's no conspiracy. It's not big pharma,
I don't think, is trying to suppress
trials of ketogenic diets on Alzheimer's because
I would imagine the first thing that
pharma would want to do is to see that study done.

So they didn't have to. And then the moment it was done,
if it showed a positive effect, they'd probably want
to isolate the molecule and wrap it up in something
that people would take, right? CHRIS PALMER: Yes. ANDREW HUBERMAN:
So I don't think there's any active
suppression by pharma. I think pharma would probably
be cheering from the sidelines because they could capitalize
on it, because ultimately, the studies are
done by scientists. But the treatments are
generally doled out by pharmaceutical companies
and/or physicians. So I don't believe there's
a conspiracy there. That is very interesting. And it's kind of amazing,
given our discussion of earlier, which is that
you had a patient that was having schizophrenic
symptoms who managed to stay on this diet. So is there something special
about Alzheimer's patients and people with age-related
cognitive decline? Presumably, they're
very dependent on others to cook for them
and shop for them. I think that this is almost
perfect controlled environment for getting this study done.

that is the key issue. So again, I got patients– I get patients with bipolar
disorder, schizophrenia, extraordinarily impaired
people to do this diet and stay with it. But it's because I'm providing
a weekly session for them. And I imagine this
study did not provide that kind of intensive support. In the pilot trial that
I described to you, they actually got, I
think, over 90% compliance with the different
dietary interventions. So some of it is going to
be dependent on the research group. And does the research group
understand that this is not– it's not like
prescribing a pill. Here, take this pill. And take it every day and
come back in three weeks. And even then, we
don't know for sure that the patient took
the pill every day.

We just assume they
took the pill every day. And studies say they
probably didn't. So I think when we think
about a dietary intervention, we need to think about
more intensive support and education. And that support could be a
health and wellness coach. It could be a dietician. It could be education
of the family. It might even be providing
them with dietary meals. That maybe for six months,
we actually provide them with ketogenic meals– once a week, put
them in your freezer. Microwave them when needed– to make this diet as easy
and doable as possible.

Because if we can get
people to do the diet, if we can get them through
the first couple of months, most people can learn
how to do this diet. More importantly– I
didn't mention this before. But the number one reason I
am so successful at getting patients to stay on
this diet for years, is because of the consequences
to them when they go off of it. That is the reason I can
get schizophrenic patients and bipolar patients
to do this diet, whereas other people can't
get an everyday human being to do it for weight
loss because the weight loss patient doesn't experience
devastating tormenting symptoms when they break the diet.

Oftentimes, they are rewarded. They eat something
they really enjoy. And they get a little bit
of a dopamine rush from it. And they're off to the races. They're like, I'm going to–
oh, I've already cheated. I'll cheat again. I'll get back on it someday. And they never get around to it. My patients, when
they go off the diet, they start hallucinating
within 48– or 24, 48 hours. And they quickly realize that
was a really stupid thing to do. That piece of cake
was not at all worth the torment that I'm
experiencing now. So they get back on the diet. I suspect with
Alzheimer's disease, we might notice
something similar. Some of these people
have very mild symptoms. So maybe they won't
have that kind of a reinforcement, negative
reinforcing kind of experience. But I think some of them will. Some of them recognize that
they are impaired cognitively. And if this diet could
help them remember better, if this diet could help
them function better– and again, that's what
the pilot trial showed, is activities of daily living.

That means these
people are able to go to the bathroom on their own. They're able to get
themselves dressed. Whereas, they needed help
with those things before. Those are actually
really important things to both the patient
and the caregiver. And if they go off
the diet and then quickly revert into a
more symptomatic state, that might be reinforcing
enough for them to figure out a way to
do the diet on their own. And if we think
about, if this really is an effective
intervention– and yes, we need longer trials,
larger trials, all of that, because there are
plenty of stories in the medical field where
pilot trials looked really spectacular and promising. And then larger trials just
failed to show the benefits. I believe, based on all
the science of metabolism, mitochondria, glucose
hypometabolism, all of that, I believe the science makes
this an obvious treatment that has real potential. So people will call me biased. That's fine. I've got my bias. ANDREW HUBERMAN: No, based
on clinical observation and extensive clinical
observation at that– I think biases that
are simply because we want to feel a certain
way or believe something are worth critiquing.

But bias based on
observation– here, I should mention that most of
what we know about human memory was sparked by one patient,
a famous HM, who I think was living in Harvard Medical,
in one of the hospitals around. There are many hospitals
on Longwood Campus. But one patient, the
reason we associate the hippocampus with memory
is because we knew that HM's the hippocampus
was intentionally damaged for epilepsy treatment. So this idea that
everything has to be a randomized clinical
trial, to me, is crazy.

Of course, that's
a gold standard. And it's essential. But there's so much information
in textbooks, medical textbooks in particular, that are gleaned
from single-patient case studies or from three-patient
neurostimulation in the brain or something of that sort. So to me, I'm still
perplexed as to why there's this insistence on
only one form of evidence. Clearly, what you're
doing, the important work that you're doing clinically,
and in the research side, and in public communication,
is assisting this. I have a question about– or more of a statement/question
about the ketogenic diet. Based on everything
that we've talked about, seems to me that the
ketogenic diet for weight loss is a very interesting
aspect of the diet as is intermittent
fasting for weight loss even though it might just be
by way of caloric restriction that occurs with fasting. But then in some
ways, the effects of the ketogenic
diet on weight loss are a bit of a decoy
for most people. That's where their mind goes.

This person lost X
amount of weight. Maybe that made
them feel better. Maybe that actually
made them underweight. I think you've talked about it. For some people, it can actually
bring them under weight. I'm glad that we got
the chance to dive into the description of
ketogenic diet for epilepsy because it really is a
medical intervention that has a side effect of
weight loss or could be used to treat obesity
and induce weight loss. But it's really about
far more than that. And that raises a question
for me, which is– we've been talking about the
ketogenic diet as one thing. But I've heard you
discuss this before, where just as a physician will
prescribe different dosage ranges of a given drug, you
can prescribe different dosage ranges of a nutritional
plan, a diet. It's not one thing. It's not necessarily
zero carbohydrates or 100 grams or 50 grams. It depends on the patient
and a lot of other factors. I've heard you list off
various things classic keto. Maybe you could just briefly
tell us what that typically is, because I think
most people think it means eating a lot of
meat and not carbohydrates.

But it might not be that. Fasting and then some
of the other– you mentioned Atkins earlier. We don't have to go into
each of these in detail. And I know in your
book, you talk about not just the science and
clinical background but also some actionable steps that
people could consider. So they can refer
there for more detail. But for somebody
who, let's say, is depressed– they've had
some rounds of depression. Maybe they're on
antidepressants, maybe not– and they want to try
something like this. Obviously, this has to be done
in concert with a physician observing all this. But what is the typical thing
that you probe with first? Just like with a
drug, you might probe with 20 milligrams of a drug. What's your typical initial
dietary intervention probe? Terrible languaging, I realize. And I'm criticizing
myself for that. But I think people get the idea. CHRIS PALMER: The real
answer is that I don't have a one-size-fits-all
recommendation for any person. So the first thing
that I'm going to assess with the patient is,
what symptoms are they having? What is their current diet like? And what are they willing to do? I try to meet them
where they're at.

So if somebody– and
I want to point out. You mentioned the
all-meat version of this diet, which
is often referred to as the carnivore diet. ANDREW HUBERMAN: Very
controversial diet. CHRIS PALMER: There is
no doubt that exists. Some people swear by it. They swear they've tried other
versions of ketogenic diets and only when they went
to a carnivore diet did they get benefits. But there are vegetarian
and vegan versions of the ketogenic diet. So in my mind,
this is not at all about the diet wars
of animal-sourced versus plant-sourced foods. It's about inducing a
state of ketosis, which is mimicking the fasting state. That is what it's about. And you can do that by
not eating anything, by fasting and/or
intermittent fasting. And you get your results. So no diet is a ketogenic diet. So it's not about the
foods or the types of foods that you're eating. It's about inducing
a state of ketosis. The first variable I'm going to
look at when I recommend this or prescribe this is the
person's current weight.

If somebody is obese
versus somebody who's thin, I'm going to use different
dietary strategies for those two situations. In the obese patient, they
have tons of fat stores on their body already. Usually, it is a goal of theirs
to tap into some of those. And they'd like to
lose some weight if they're going to try a
ketogenic diet for brain health anyway. And so I'm going to use that. So that person, really, the diet
is carbohydrate restriction. And that usually is a
sufficient intervention. ANDREW HUBERMAN: Both
simple carbohydrates, meaning sugars
and fructose also? CHRIS PALMER:
Fructose, definitely. So no added sugars, essentially. You can have added natural
sweeteners like stevia or monk fruit. You might use
artificial sweeteners. Years of doing
this, I'd probably recommend steer away
from them if you can because I think
they tend to stimulate cravings for high carb foods.

So if you can kind of get
through a couple of weeks without sweet things,
your cravings for those will go down. And it'll make the diet easier
and a little more sustainable. But let's say you can have
your artificial sweeteners, if that's what you really want. So I'm going to say less
than 20 grams of carbs a day for those people. They can have all the
protein they want. They can have vegetables. And they can have all
the fat they want. But I'm not going to
push fat on those people. I'm not going to tell them, eat
a lot of fat, at the same time because I want to use the fat
on their body as the fat source, at least early on.

Are you encouraging healthy fats like
monounsaturated fats, like olive oil? Are you encouraging people
to eat a little less butter, et cetera? CHRIS PALMER: I tend
to encourage, again, a wide range of fats. And it's going to
depend on the person. A lot of times, people come to
me with very specific ideas. But I'm going to tend to
encourage olive oil, avocados, nuts, which are
usually considered, even by the American
Heart Association, healthy sources of fat. The more controversial
thing are things like coconut oil or coconut
cream, which the American Heart Association might say
is not a healthy fat, I kind of disagree with
that and don't think it's unhealthy at all actually. And when you look at the
epidemiological studies of saturated fat
causing heart disease or causing adverse outcomes, at
best, maybe increases your risk 10% to 15%– at best.

How much coconut oil can people ingest, anyway,
before they either develop diarrhea– no joke–
or just sort of get tired of coconut oil? Anyway, your point is taken. But they can eat meat
if they like meat? CHRIS PALMER: Absolutely. ANDREW HUBERMAN: Or
they can eat eggs. Or if they don't
like meat and eggs, they could eat sardines
or things of that sort. I personally can't– I can't even stomach the– I don't even like
the word "sardine." I have nothing against
the actual fish. But that's just me. But obviously, people have– I say this because people have
different preferences, right? CHRIS PALMER: Yes. ANDREW HUBERMAN:
I'll eat a steak. But I'm not going
to eat a sardine. CHRIS PALMER: And I'm
going to go with that. And again, there are vegan
sources of protein that– people can eat tempeh
and other things. So that's the obese person. It's carb restriction as
the primary initial phase. The thin person is going
to need to eat a lot of fat because they don't have a lot
of fat stores on their body.

And if I want them in
ketosis, clinical ketosis, I'm going to have
to feed them fat. So that's the person
that I'm going to say, make sure
you get in avocados, olive oil, butter,
maybe heavy cream. So heavy cream is delicious. It's a delicious way
to get your fats in. I have one patient who
just drinks it straight, to just try to get it in. ANDREW HUBERMAN: I get it. I've never had an
appetite for sweets. I absolutely love
savory fatty food. When I was in high
school, I was thin. So I was able to do this. But I used to drink
half-and-half. Sometimes I wake up in
the middle of the night and drink it just because
it tastes so, so good. CHRIS PALMER: It
does taste good. So if they're on
a ketogenic diet, I'm going to push them
away from half-and-half and toward heavy whipping cream. So you can whip that up.

You can freeze it. It turns into ice cream. You can add vanilla. You can add cocoa powder. You can add all sorts of things. And you're off to the races
with shakes, and ice cream, and mousse, and all sorts
of things that you can have. With any of these patients,
the beauty of this diet is I have objective biomarkers. I'm going to have them
measuring ketones. And I'm going to adjust the diet
based on their state of ketosis and/or the clinical benefits
that I'm looking for.

If it's an average person,
who is not currently under psychiatric care, not
taking prescription medicines but is saying, I'm burned out. I'm exhausted. I want some of that brain
energy that Andrew Huberman is talking about. He talks about feeling good. I want some of that. I'm probably actually
going to recommend the protocol you
describe, which is, let's see if we can just
carb restrict for a while and see if that produces
clinical benefit. I have one– he's
not even a patient, just somebody who read my book. I didn't tell him anything. And he came away
from it saying– he was ready to start an
antidepressant for his anxiety.

He had chronic anxiety,
was trying meditation, was trying all sorts of things. Nothing– those
things weren't enough. He was ready to go on
prescription medicine. He read an early
copy of the book. He took it upon himself without
consulting with me to restrict carbohydrates alone. He did not go ketogenic. He is a vegetarian. He restricted carbs. Within three weeks,
said, I don't need prescription medicine.

I can't believe how
much better I feel. And all I did was cut
out some of the high carb foods in my diet. So I think for some people,
it can be that simple. For people with serious
mental disorders, if they are chronically
depressed, if they're on lots of prescription
meds, if they're disabled by their
symptoms, and certainly, if you're bipolar or have
schizophrenia or something, those are the people
I really do want them to work with a
medical professional because meds may
need to be adjusted. They need a real
shot at this diet. It's not like weight loss. Weight loss, everybody wings it. And either you're
successful or you aren't. You look on the internet or
you read a book or you do– even the colleague
that you mentioned, he's probably just reading– who knows whether it's
credible information or not– and just winging it, and
seeing whether it works or not. For people with serious
mental disorders, I want you to treat it like you
have epilepsy because you do have a serious brain disorder.

It's impairing your ability
to function in the world. It's impairing your
health and happiness. You deserve a competent
medical treatment. And we have that. We have a hundred-year
evidence-based. We've got dieticians
who know this like the back of their hand. They can monitor your
level of ketosis. They can help look for vitamin
and nutrient deficiencies that can be a
consequence of the diet, and make sure that you're
not developing those. They can help tweak
the diet if needed. They can give you ideas if
you're getting bored with eggs every morning. They can give you ideas for
what else you might have. And if you're using it to
treat a serious disorder, I think you need serious help. ANDREW HUBERMAN: A
couple of questions, a little more detailed,
but I think a lot of people will have this on their mind. Is it ever the case
that you'll prescribe somebody the ketogenic
diet in conjunction with intermittent fasting? So eat keto but eat
between the hours of, whatever, 11:00 AM and
8:00 PM or something like that.

That's the first question. CHRIS PALMER: Absolutely. And I have one patient with
type 2 diabetes and chronic depression. And he will try to follow
the ketogenic diet. And sometimes, his blood
sugars are still very high. And sometimes I
will ask him to do either intermittent fasting or
even a three or four day water fast. And it is shocking. When he does a three or four
day water fast, the first day or two, he feels like crap.

I'll just say up front,
don't do it if you've got an important meeting or
business trip or anything. Don't be– ANDREW HUBERMAN: So this
is just consuming water. CHRIS PALMER: This is
just consuming water. ANDREW HUBERMAN:
No black coffee? CHRIS PALMER: I usually tell him
he can have plain black coffee or tea. But– ANDREW HUBERMAN: You
have mercy after all.

a tiny ounce of mercy. But when he does it, his blood
sugars plummet in a good way, his blood sugars
are normalizing. But the last time he did it,
he actually got to seven days at one point. And he said, I feel great. I want to keep going. I can't believe
that I'm not hungry. But I am not hungry at all. I don't miss food at all. And at seven days, I
kind of cut the cord. I was like, no, no. We're done. ANDREW HUBERMAN:
He needs to eat. CHRIS PALMER:
[LAUGHS] We're done. ANDREW HUBERMAN: You got to eat.

Well, I find it
really interesting that the intermittent
fasting, of course, controversial at some level,
but as to whether or not it's just beneficial by way
of caloric restriction– because it is one way to
achieve caloric restriction– whether or not has
additional benefits. But I'm very interested
in the neural side of it. And it does seem
that the fasted state can start to take on its
own rewarding properties, where people get
dopamine release not from eating, as
most everyone does, but from abstaining from food. Now, this can be pathologic
in the sort of example of anorexia nervosa, which
is we both know as the most deadly psychiatric illness. But for non-anoxerics,
I think it's interesting to note that
eventually not eating can have its own rewarding properties
to it that aren't just related to weight loss. But in the short-term, feeling– in other words, feeling
really good by way of abstaining from eating.

CHRIS PALMER: Yes. And that's actually– it
raises an important risk that I haven't mentioned yet. But at least in
psychiatric patients– but even in some
patients who just use the keto diet
for weight loss, I have seen definite hypomania. ANDREW HUBERMAN:
So these are people that aren't sleeping very much. Are they also getting
kind of delusional, thinking they're going
to run for president? CHRIS PALMER: No. So the distinction between
hypomania and mania– so mania, you might become
psychotic and delusional. Mania, by definition,
is problematic. It's causing a problem
in some way or another. And if you have
psychotic symptoms, it's definitely called
mania, full-blown mania. Hypomania, for
better or worse, is something every human
being probably craves. So it is feeling
extraordinarily good. It's getting by on less sleep.

But you don't need to sleep. Who needs sleep? I've got things to do. My brain is running
on all cylinders. I feel so creative. There have been lots
of famous people through the ages who have been
bipolar, probably bipolar. And some of their most
productive periods of time, whether it's art or
creating scientific models or what-have-you, were probably
during hypomanic episodes.

do you do in that case? I'm obsessed with getting
sufficient quality sleep. It's a kind of a repeating
theme in our podcast and many of my
social media posts. And I always recommend
behavioral tools first, then exercise, viewing
sunlight, et cetera, at appropriate times,
avoiding late night artificial light exposure,
et cetera, and occasionally, for people who
are doing all that and still struggle with
sleep, supplementation. One of the things that
I've seen some data on is that for people who are
following a low carbohydrate diet, that inositol,
in particular, can be helpful for
getting into sleep probably because it's
a bit of an– has a bit of an anti-anxiety effect.

But presumably, there are
other things out there, too. The magnesiums will
generally do that. A hot bath will do that,
too, for that matter. But what you're talking about
is people who are going, what, a day and a
half without sleep? Or they're just two
hours of sleep a night? CHRIS PALMER: So
the worst case I saw was actually a mental
health professional who didn't recognize it initially. He went six months with
two to four hours of sleep every night. ANDREW HUBERMAN: Because they
were on a ketogenic diet? CHRIS PALMER: He was
on a ketogenic diet, was getting by on two to four
hours of sleep every night, did not initially recognize
that this was a problem.

He was feeling great. He was feeling that keto high. And he was actually
waking up at 4:00 AM, going for 10 to 20
mile runs most days. He finally stopped the ketogenic
diet after about six months because he said, I can't
maintain my weight. I'm losing too much weight. ANDREW HUBERMAN: Sorry, I
didn't mean to interrupt. I was just thinking there
are some social media personalities associated
with nutrition that might be hypomanic. I'll let you do the
clinical evaluation. So what does somebody
do in that case? So I don't know that
I've ever been hypomanic. But as I mentioned
earlier, unless I've done a very high intensity
workout early in the day and I need to replenish
carbohydrates, I typically eat meat, fruit, and
vegetables throughout the day– minimum amounts
of fruit but some. And then at night, I switch
over to mainly carbohydrate. It really helps me sleep. It replenishes glycogen stores. I sleep really well, wake
up the next morning, repeat. And of course, this goes
against a lot of the dogma that, oh, you're not
supposed to eat carbohydrates late in the day and [MUMBLES].

This is what works for me. And so I do it. For somebody like this mental
health professional, who is hypomanic, would going off
the ketogenic diet entirely be the best idea? Or could it be
that adjusting when they eat their carbohydrates
would be advantageous in order to make
sure that they felt alert and great during the day? Maybe not hypomanic
but then could have a four to eight-hour a
night sleep as opposed to a two to four hours a night, which
is really very little sleep. CHRIS PALMER: Yeah, it's not– ANDREW HUBERMAN: It
can't be healthy. CHRIS PALMER: It's not healthy. ANDREW HUBERMAN: Even if you
can do it and feel great, I imagine that the
brain is suffering. CHRIS PALMER: It is. And the body is suffering. ANDREW HUBERMAN: And
your friends and family are suffering. CHRIS PALMER: The body is
repairing itself with sleep. And so yeah, it's– if it's somebody who
is not a patient, they're not a mental
health patient.

They're not using
the ketogenic diet as a mental health treatment. They're simply doing
it for whatever. I actually start with
everything you've just outlined. Let's start with
behavioral measures first. And the first
intervention is education. You need at least six
hours of sleep a night. Period, end of story. That's non-negotiable. If you're not getting at least
six hours of sleep a night, we need to consider
this a problem. So figure out a way to
get 6 hours of sleep. For some people, that's
enough, just the education. They don't get out
of bed at 3:00 AM. It might take them an hour
to fall back to sleep. They fall back to sleep. For most people, if you can get
three nights of decent sleep in a row, the
hypomania goes away. That is the way
to extinguish it. And then they still go on
feeling a high from it. They feel great. Their brain feels good in
terms of memory, concentration, motivation, all of those things. But they're not
hypomanic anymore. And then I might use
supplements, melatonin, others that you mentioned,
magnesium is a big one.

And for some, I will recommend
exactly what you're doing– eat some carbohydrates
in the evening before you're going to bed. Either have them at dinner
and then wait a few hours before you're going to go
to bed or have them right before you're going
to go to bed, just to try to calm your body
down and get it going. When I'm using this as
a clinical intervention, especially with patients
with serious mental illness, I actually want them in a
state of ketosis long-term. So I'm not going to do the
carbohydrate intervention. I'm going to try
all the other ones. But if they still can't
sleep even with supplements, over the counter
supplements, then I'm probably going to go with
prescription, sleeping medicines, as a
temporary stopgap to try to get them three to
seven days of decent sleep. That usually breaks
the hypomanic cycle. And then they stay
on the ketogenic diet because it ends up resulting in
all of these other improvements that I've described. Their illness can sometimes
go in to full remission.

dose trazodone as a first line prescription? CHRIS PALMER: I would
not use trazodone. I would actually
specifically avoid trazodone because it's an antidepressant. And they're already hypomanic. And I certainly don't
want to push that further. So as long as it's somebody
without a history of addiction, I'm going to use
a benzodiazepine or either commonly called
the Z medicines for sleep– zolpidem or Ambien or
something like that. ANDREW HUBERMAN: Those tap
into the opioid pathway? GABA opioid? CHRIS PALMER: GABA. I usually start with something
like Ativan or Klonopin or something like that– probably Ativan because
it's shorter-acting.

And again, I'm only looking
to use it short-term. I let them know that up front. We're looking for three to
seven days of decent sleep. And then we're going to try
to get them off that medicine. And usually, people
are off to the races and can sustain it well. ANDREW HUBERMAN: A
question about hormones. Many of the Huberman Lab
podcast listeners will ask– any time we're talking about
something like exercise or a drug treatment or
behavioral training, people will say, what
about the menstrual cycle? How is that impacted by this? How does the menstrual cycle
impact its efficacy, et cetera? Carbohydrates and
caloric restriction have been implicated in
different interactions– are known to interact
with the endocrine system. So what do you do if you have
a patient who is depressed or could have
psychotic symptoms– but let's go with depression
because that's probably a bit more familiar to most people– and then they're on
a low carbohydrate or full ketogenic diet, but
their menstrual cycles cease.

How do you deal with
those adjustments? And I guess we could
expand this conversation and say, what about
male fertility also? Because some caloric
diets seem to– my understanding is that
submaintenance caloric diets, so weight loss
diets, will improve testosterone-estrogen ratios
in males that are obese. But for someone
that's not obese, to go on a sub-caloric diet,
that it can start to impair testosterone levels and– probably not render
them infertile but certainly adjust
that whole axis. So what about interactions
between ketosis, diets, et cetera, and the
endocrine system? CHRIS PALMER: The
real answer is, I don't think anybody knows. And there's not a
one-size-fits-all answer because I've seen examples. And I'm aware of science to back
up polar opposite conclusions. So the first general
observation that I'll make– I know so many couples,
husbands and wives, boyfriends and girlfriends,
heterosexual couples, who have tried the ketogenic
diet to lose weight together– ANDREW HUBERMAN: And
end up with a baby? No, I'm just kidding.

[LAUGHS] CHRIS PALMER: No. Almost universally, the men
have a much easier time with it than the women. It's not across the board. But I know so many examples
where the women say I couldn't tolerate that diet. It did not make me feel better. It actually made me feel worse. And I think in those
cases, it probably does relate to hormones. I'm aware of animal
models, of mice– in particular, ketogenic
diet in mouse models. One researcher shared with me,
the thing that was striking is that the female
mice never got pregnant on the ketogenic diet.

Whereas, the mice
on the standard diet were just having
babies right and left. And it was just
shocking, the difference. On the surface, it makes sense. The ketogenic diet is
mimicking the fasting state. Women who are
trying to reproduce should not be fasting. If your body is in
a fasting state, it probably does not
want to expend resources, metabolic resources, calories,
nutrients, and other things, to creating a baby
because your very life is being threatened
by, quote unquote, "fasting" or starvation. That even though
the ketogenic diet is a sustainable,
nonstarvation diet, we're really using
that diet to trick the body into thinking that it
is in a fasting or starvation state. And so just from a kind
of evolutionary stance, it makes sense that
women's bodies may actually have significant changes
in hormonal status to prevent pregnancy
because a woman should not be having a baby when
she's starving to death.

I know of examples of women
who are the opposite, though, who have benefited
dramatically and tremendously from the ketogenic
diet, have put schizophrenia, bipolar
disorder into full remission. And I do actually know of
one case, at least one case. A woman, infertile,
she and her husband had been trying for three
years, no pregnancy. She went keto. Within four months,
she was pregnant. How do I make sense of that? I don't know. And unfortunately, I
don't think we really have good control data on what
does the ketogenic diet do to male hormonal systems, what
does the ketogenic diet do to female hormonal systems. But clearly, I think
changes are happening. I don't have a way to
predict it, at least. If somebody else has great
insights, I welcome them. But I haven't seen
them published. ANDREW HUBERMAN: It's
a terrific answer because when things are all over
the place and bidirectional, depending on one
circumstance or the other, I think it screams for
controlled studies, and more descriptions
of case studies, and anecdotal data, too.

So I think it's an
excellent answer. It also calls to mind the
important public service announcement that because of
these bidirectional effects that you described,
please don't use fasting or the ketogenic
diet as a reliable form of contraception. CHRIS PALMER: [LAUGHS] ANDREW HUBERMAN:
Yes, please don't. I have a final
question, which relates to something that is very much
starting to get buzz now– and maybe more so
for people that hang out in the Twitter
space or the nutrition space. But there's a new
class of drugs that I think initially were
developed to treat diabetes but are now being evaluated
for their efficacy to treat obesity.

And these are the semaglutide
drugs that are involved in– they tap into these glucagon
related GLP-1 pathways. And it is a story that we've
talked about a little bit on the podcast before. But many people, I
imagine, probably haven't heard that conversation. I would simply like to know what
you think about these drugs. They obviously adjust the way
that glucose and insulin are managing energy, both in
the body and the brain, and can produce weight loss. So that to me, when I look
at the data, it's impressive. But a good logical shift
in diet and exercise could achieve
similar weight loss.

But a lot of people
just won't do that. So the question I have
is, what are your thoughts on semaglutide and other GLP– I think I might have said
GLT before, excuse me– GLP-1 related compounds? And do you ever prescribe
these in conjunction with these dietary shifts? Because it seems
to me, they would fall right in with the
catalog of other approaches that you have available. CHRIS PALMER: The
real answer is, I am not at all an expert
on these medications. ANDREW HUBERMAN: But what
are your thoughts about them? They seem to be
weight loss drugs, not unlike the fen-phen
drugs of the '90s that then were banned because a few
people didn't handle them well. CHRIS PALMER: They are. We had fen-phen. And even before
that, in the 1950s, and '60s, and '70s, Dexedrine– ANDREW HUBERMAN: Amphetamine. CHRIS PALMER: Amphetamine– ANDREW HUBERMAN:
Mother's little helper.

yes, was the treatment of choice for women
across the United States to keep their slim figures. And we created addicts
and all sorts of problems. But they were widely used and
probably millions of women because they work. ANDREW HUBERMAN: Because
they kill appetite. CHRIS PALMER: They
kill appetite. My overall thoughts are this. There is zero doubt in my
mind that the obesity epidemic is a threat to human health and
potentially the human species. If it keeps going at
the rate it's going, it is a threat to our species. We have to figure out what
on Earth is happening, and what can we do about it.

These medications,
in early studies, are highly effective
over a year or two. That's promising. I am worried, though,
that we're not attacking the root cause of obesity. If the root cause
of obesity ends up being some kind of poisoning
of the metabolic machinery in the brain or body– and I would argue that probably
relates to mitochondrial health and mitochondrial function– I have every reason to believe
that taking a medication that helps you lose weight may not
be addressing that problem. And therefore, may
not be addressing all of the negative health
consequences of what we call obesity. So obesity, in it
of itself, we know that excess fat can
become inflammatory and can cause problems,
in and of itself. But I actually see
obesity as a symptom. I see obesity as a symptom
of metabolic derangement in the body or brain. And that is why
people become obese. And that if we're really
going to get anywhere, we need to identify
what is causing that metabolic derangement.

Using a symptomatic treatment
like a GLP-1 medication, to the best of my
knowledge, is not addressing that core problem. And we're just ignoring it. Maybe I'll be wrong. And maybe these will
be the wonder drug that saved the human
species, and everybody will be thin and healthy
forever and ever. I'm not hopeful, because
we've never– we've had so many promising
drugs come along. Fen-Phen, Dexedrine,
and other things, we've had so many
promising drugs. And at the end of
the day, when you try to muck with
human metabolism using a single processed
molecule, manmade, I can't think of even one
example where it's been great for large numbers of people.

manufacturing insulin is life-saving for people
with type 1 diabetes. So that would be an example. But giving massive
doses of insulin to people with type 2 diabetes,
actually is a downward spiral. I would much rather see people
with type 2 diabetes control their diabetes through
diet and lifestyle. And that might be a ketogenic
diet, or a low carb diet, or exercise or good sleep,
or all of the other thing. All of it. I'd much rather see
that because when people try to control their
type 2 diabetes with a molecule, even though it's a
natural molecule insulin, we know that thats results
in really poor health consequences, results
in higher rates of cardiovascular
disease, higher rates of mental
disorders, higher rates of premature mortality. Do I think GLP-1 molecules
are going to be different? No. I don't have any reason to
think they are going to be. So that would be my two
cents, but we'll see. Time will tell. ANDREW HUBERMAN: Time will tell. Meanwhile, I want to
thank you for doing what is, without
question, pioneering work.

Again, I'm not a clinician. But I've been around
this space long enough to know that indeed there
there are no wonder drugs. There are drugs that certainly
can help alleviate symptoms in some individuals. But that lifestyle and in
the case of your work– in particular, in the
discussion today– diet and, the ketogenic diet,
in particular, it's clear, can have incredible
effects, miraculous effects, in some individuals. And positive effects
in others that might not be of
the same magnitude but nonetheless are
extremely important, so on behalf of myself, and the
listeners, and and certainly, just on behalf of everybody out
there– because everyone does need to be concerned about
mental health issues, whether or not they have them
and in their family themselves.

Or otherwise, because
they impact everybody. Just really want to thank
you for viewing the work that you're doing because
it really is pioneering. And it's brave. And I can see now, based on our
discussion, why it would work. You've given us a lot of hints
into the underlying mechanisms that suggest as to
why it would work. And you're going to
given us examples as to how it has worked
in patients that you've worked with. And this field is
expanding fast. I think this is an area
of psychiatry and medicine in general. Meaning, behavioral,
nutritional interventions, that is expanding very fast. So thank you for being brave and
for taking this on, and doing it in such a structured way,
and for communicating it here today.

And with the general
public, through your book, and your online presence. We will certainly point
people in the direction of those valuable resources. Thanks so much. CHRIS PALMER: Yeah, I know. ANDREW HUBERMAN:
I appreciate it. CHRIS PALMER: Thank you, Andrew,
for being brave and having me on your [LAUGHS] show– ANDREW HUBERMAN: And a pleasure. CHRIS PALMER: –and for
a great conversation. ANDREW HUBERMAN: Thank you for
joining me for my discussion with Dr. Chris Palmer. I hope you found it to be
as informative, actionable, and exciting in terms of
the various treatments that we can now think about
when considering treatments for psychiatric disorders. Once again, if you're interested
in his work or his new book, Brain Energy, I encourage
you to go to his website. That's You can also find
the book Brain Energy by Chris Palmer on Amazon
and other sites where books are sold. And we provide links to the
book and to Dr. Palmer's website in the show note captions. If you're learning from
and/or enjoying this podcast, please subscribe to
our YouTube channel. That's a terrific zero
cost way to support us. In addition, please subscribe
to the podcast on Spotify and on Apple.

And on both Spotify
and Apple, you can leave us up to
a five star review. If you have questions
or suggestions about topics and
guests you'd like me to include on the
Huberman Lab podcast, please put those in the
comments section on YouTube. I do read all the comments. In addition, please
check out the sponsors mentioned at the beginning
of today's episode. That's the best way to
support this podcast. During today's episode, we
did not discuss supplements. But on many previous episodes
of the Huberman Lab podcast, we do discuss supplements
because while supplements aren't necessary for
everybody, many people derive tremendous
benefit from them for things like enhancing
sleep, and focus, and hormone augmentation, and so forth. The Huberman Lab
podcast has partnered with Momentous Supplements
because they are of the very highest quality. And they ship internationally. And in addition
to that, they have single-ingredient
formulations that allow you to devise the
supplement regimen that's most effective and most
cost effective for you. If you'd like to see the
supplements discussed on the Huberman Lab
podcast, please go to The Huberman Lab also has
a zero cost newsletter that you can access.

It includes summaries
of podcast episodes as well as summaries
of various protocols for mental health, physical
health, and performance. You can sign up
for the newsletter by going to Go into the menu and look for
the Neural Network Newsletter sign-up. You just provide your email. And I assure you we do not
share your email with anybody. And again, it's
completely zero cost. Again, go to and
sign up for the Neural Network Newsletter. And if you're not already
following us on social media, we are Huberman
Lab on Instagram, Huberman Lab Lab on Twitter,
and Huberman Lab on Facebook. And at all of those
sites, I provide science and
science-related tools for mental health, physical
health, and performance.

Some of which overlap
with information covered on the
Huberman Lab podcast. But often which is distinct
from information covered on the Huberman Lab podcast. So again, that's Huberman
Lab on Instagram, Twitter, and Facebook. Once again, thank
you for joining me for today's discussion
with Dr. Chris Palmer. And last, but
certainly not least, thank you for your
interest in science. [MUSIC PLAYING].

Click here Now


Please enter your comment!
Please enter your name here