Our Episode

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday

[Music] life I’m Andrew huberman and I’m a professor of neurobiology and

Opthalmology at Stanford School of Medicine my guest today is Dr Chris Palmer Dr Chris Palmer is a psychiatrist

and researcher at Harvard University he focuses on how metabolic health and mitochondrial Health in particular can

be leveraged to treat and in some cases cure psychiatric disorders including schizophrenia autism depression bipolar

and ADHD today we discuss how metabolic Health something we hear a lot about nowadays is really about mitochondrial

health and the specific lifestyle and other factors that you can use to improve mitochondrial number and

function we talk about things like exercise sleep sunlight which you’ve heard about before but we talk about

those from a different perspective and we discuss some things that have never been discussed before on this podcast at

least in light of mitochondrial health things such as creatine methylene blue nicotine and we talk about the key role

of specific B vitamins and iron in brain function we also have a very direct discussion about vaccines and whether or

not inflammation caused by vaccines can potentially damage mitochondria which then leads to mental health challenges

and of course in that context we discuss the vaccine autism debate we also discuss public health and what is needed

to truly change the way people exercise and eat and the rapidly changing landscape of the National Institutes of

Health and the CDC as you’ll soon hear Dr Palmer gives us a master class on mitochondrial function and how to

improve this vital aspect of our health if you’ve heard about metabolic Health you’ve heard about the Obesity crisis

that’s important but looking at all of that and approaching it through the lens of mitochondrial Health you’ll soon

learn is absolutely the way to go it’s a New Perspective that will change the way that you think about mental and physical

health and that no doubt will impact your health practices in very positive ways before we begin I’d like to

emphasize that this podcast is separate from my teaching and research roles at Stanford it is however part of my desire

and effort to bring zero cost to Consumer information about science and science related tools to the general

public in keeping with that theme this episode does include sponsors and now for my discussion with Dr Chris Palmer

Dr Chris Palmer welcome back thank you so much for having me back I credit you

with leading the Call to Arms the public awareness

and the implementation of what some people call medic olic Psychiatry but

what we could easily just call the relationship between mental and physical health and the use of nutrition

supplementation and where appropriate prescription drugs for the treatment of mental health but what do you call this

field that you’ve basically founded and that you’re pioneering there are others right but uh that you’re pioneering and

how should the general public think about the relationship between mitochondria and their Mental Health for

for those that are not aware educate us I could talk for hours on this um so

first of all thank you for um I I think you’re actually giving me way too much

credit though um I don’t know about that I uh I’m I’m talking a lot about it and I think I will accept that maybe I’m

able to talk about it in a way that helps people understand it that other scientists haven’t been able to

but you know one of the more important reasons I want to say this is because unbeknownst to a lot of people this

field has actually been around for about a century and a half researchers in the 1800s around the

turn of the century well up into the 1960s were hyperfocused on the role of

metabolism in severe mental illness schizophrenia bipolar disorder they were

actually measuring levels of lactate and glucose and um and other kind of metabol

biomarkers in people with schizophrenia and bipolar disorder documenting differences really kind of H honi in on

the these metabolic disruptions is potentially the cause of mental

illness and then our field lost its way we we became focused on

neurotransmitters and assumed that they were the primary cause of mental

illness while other fields were focused on psychological and social social factors you know we got cognitive

behavioral therapy we still had psychodynamic Psychotherapy um but people were doing

research on adverse childhood experiences that was really taking off documenting that that’s related and

so you know the field kind of splintered into these biological psychological

social camps um and people really hyperfocused in all of these

ways to me this field of integrating

metabolism with mental health with physical health is about

unifying that whole story it’s about unifying and building

on what these researchers a hundred years ago were pursuing it’s about integrating the

biological psychological and social camps it’s about putting it all together

and stop being so reductive C istic and simplistic to suggest that it’s all

biological or it’s all psychological or it’s all social and that if one if it’s one it can’t be the other it can be all

of them um and it’s different combinations for different people so in many

ways I’m just standing on the shoulders of giants who have done groundbreaking

work to create the science that allows us to put this all together um

with that said I do firmly believe that we are on the cusp

of a revolutionary change in the Paradigm of the mental health field of

how we think about mental illness you know there are Myriad biological

things the psychological and social things are all obvious and true yes stress trauma loneliness adverse

childhood experiences all of those things come together our field is long known that

all of those things play a role in mental illness which exactly which mental illnesses it’s essentially all of

them every one of the labels in dsm5 can be impacted by biological

psychological and social factors so trauma in childhood increases risk for

posttraumatic stress disorder duh everybody knows that trauma in childhood

also increases risk for neurodevelopmental disorders if it occurs early enough it increases risk

for substance use disorders personality disorders psychotic disorders mood disorders anxiety disorders dementia

later in life and everything else every label what else do adverse childhood

experiences increase risk for all of the metabolic disorders obesity type 2

diabetes cardiovascular disease autoimmune disorders premature

mortality you know we have statistics that just sticking with that theme

adverse childhood experiences if you have six or more adverse childhood

experiences compared to somebody who has no adverse childhood experiences now that’s a rare group granted but for the

people who have six or more on average they live 20 years shorter they lose 20 years of life

because of those adverse childhood experiences and so is that a mental

health issue I would say it’s a physical health issue it’s both it’s both a

mental health issue and a physical health issue and so how can we understand that how can we understand that trauma in childhood increases risk

for heart disease and obesity and diabetes and dementia and PTSD and ADHD

and sub use disorders and the only way to connect it is through

metabolism and ultimately through mitochondria unfortunately people like

simple answers and they’re like so diet will fix everything I’m like no I never said diet will fix everything but it can

help it can help and it can be lifechanging and life saving I I don’t

want to I don’t want to minimize or step back from my work with dietary

intervention there is no doubt in my mind it can dramatically change people’s

lives but it’s not just diet it’s lots of other things and um and so it’s

putting it together and trying to make sense of the science for what does cardiovascular disease have to do with

depression or PTSD on the surface a lot of people scratch their heads and they really

don’t know they they assume that well one’s a brain disorder and one a heart disorder and it’s like no we need to

integrate that because all of the risk factors this this essentially the same

bioc psychosocial risk factors that increase risk for heart disease also increase risk for brain disease and we

just we need to start putting it together we need to be more sophisticated we have computers we have ai it’s 2025 we can do better yes well

first of all uh I and I’m sure the listeners really appreciate your human regarding who’s responsible for the uh

big surge in uh the interest in this field um so thanks for crediting your

predecessors and um the others in the field uh at the same time I credit you um with really popularizing a lot of

these terms being willing to go public facing and and share about metabolic Psychiatry for lack of a better uh way

to put it U metabolic Psychiatry and and and really championing these ideas and

uh being open into being part of a medical and Science and public discourse community so I’d be remiss if I didn’t

say that so hopefully you’ll take that in and if you won’t then I I very much appreciate it it’s true thank you very

much it’s true and and I’m not alone in in that sentiment I’d like to take a quick break and acknowledge our sponsor our place

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condition like depression let’s take depression um uh to start off I can just

broadly create two you know Columns of of things or approaches that one might

take uh one is this U mental model of sort of a molecule deficiency like I’m

not saying this but there are many who at one point thought uh depression is related to a deficiency in serotonin or

depression is related to a deficiency in dopamine either levels regulation enzymatic control whatever

the the the level of control just this idea that these molecules are somehow lacking if you put

them back you can relieve some symptoms of depression the other column that comes

to mind for me having looked at the data on cognitive behavioral therapy on the data

on uh psychedelics in the clinical setting for the treatment of depression ssris and other um so-called

anti-depressants is this notion of neuroplasticity the idea that neural circuits can change and that neural circuits control our sense of well-being

our perception of self perception of others feelings of agency Etc and it’s now very clear that if you change levels

of neuromodulators like dopamine like serotonin you don’t necessarily cure

depression but you open a window for plasticity and then perhaps the therapy

that you’re doing can modify brain circuits more robustly so I think in terms of molecule deficiency maybe it’s

a vitamin deficiency a neuromodulator deficiency and then I also think about plasticity that these treatments are

just allowing for more brain change more rapidly what other columns would you add

to that picture um and perhaps first do you think that picture is um woefully

inadequate or just partially inadequate because I think this is the way most people think about the treatment of

mental health they think oh there’s something missing you take a drug and you get that thing back and then like

ADHD you don’t have enough dopamine or what you put it in and then all of a sudden attentional circuits work better

this kind of thing versus plastic which is the modification of those circuits and the two things are not

mutually exclusive but I I think until now they really hasn’t been a a clear

understanding that there are other columns for um for mechanistic change in in mental health I would

say the concept of metabolism metabolic

regulation mitochondrial function mitochondrial Health

actually is an umbrella concept for everything you’ve just said it’s an

umbrella concept for well how do we create neurotransmitters where do these

neurotransmitters come from what regulates their production release from

cells and then even to go further what impact do those neurotransmitters have

on other cells they are largely regulating brain

metabolism and the way we usually think about it is they are regulating brain

activity but if you ask the question well what is brain activity brain activity is either is fueled by

metabolism that a a neuron cannot be active unless it has the capacity to

increase its ATP kind of production and then when you

suppress a neuron when you when you inhibit its function the TP production

goes down so whether you want to think of metabolism as just a consequence of neural activity I actually think about

it as an integral part of neural activity it’s kind of like your car can’t go without the

engine a cell can’t go without mitochondria um a cell can’t do what

it’s supposed to do without mitochondria the other concept that you mentioned neuroplasticity neuroplasticity is all

about energy and met metabolic resources to create new

connections new neural connections between axons

dendrites Somas other other aspects of neurons and cells and other types of

cells asites oligodendrocytes um but in order to get

neuroplasticity neuroplasticity implies growth and modulation and even pruning

but it involves change and in order for an living organism to change that

requires this foundational concept of metabolism now on the surface to a lot

of people that sounds too abstract and it sounds like well that’s ridiculous then if you’re you’re saying that metabolism is everything in biology and

I kind of am of course it is you you can’t talk about biology without talking about

metabolism but when you talk about metabolic Health it becomes much more concrete

pragmatic and real with real tools that you talk about

all of the time on this podcast

exercise promotes metabolic Health exercise promotes

neuroplasticity they are inseparable you can’t improve your metabolic Health

without also at least opening up the opportunity for

neuroplasticity improving your diet does the same thing sleep or lack thereof can

impact this substance use can impact this and so you know in a way it it

basically says let’s connect all of the dots let’s not hyperfocus on serotonin

and a serotonin imbalance or deficiency as the singular cause of depression

because for those of you who don’t know that is ridiculously

reductionistic and it is absolutely not true we know that we know that with

certainty now you know the the whole serotonin hypothesis of

depression came about not because researchers identified serotonin

deficits in the brain that entire concept came from the observation

that medications that modulate serotonin

activity or inhibit its reuptake into neurons those medications ssris other

types of anti-depressants those medications can reduce the symptoms of depression in some people that was just

a purely serendipitous finding

it was Serendipity the first anti-depressant was actually a tuberculosis

treatment they were giving it to patients on a tuberculosis Ward and an

astute infectious disease doctor noticed some of these patients are really

depressed but when I give them this tuberculosis treatment they perk up like within a few

weeks they start looking a lot less depressed and I don’t think it’s a coincidence I

think it’s the medication I’m giving them do you recall what the drug was aoide it’s the first MAO inhibitor and

um I could be saying the name wrong but uh it’s first MAO inhibitor and uh that

became the first anti-depressant which makes sense uh MAO inhibitors inhib of the enzymes that

break down or let’s just speak about these enzymes broadly either I think most anti-depressant drugs or treatments

for ADHD typical prescription treatments uh either reduce the breakdown of

neuromodulators like serotonin dopamine acetylcholine depending on which one we’re talking about or they um they

reduce the reuptake so that there’s just more neurom modulator around for longer

yes tell us about mitochondria in the framework of mental health so most

people know mitochondria as the PowerHouse of the cell if if if they know that it at all so these tiny little

organel and the PowerHouse of the cell reference means that mitochondria take

the breakdown products of the food that we’re eating they are the primary thing using the oxygen that we’re breathing in

they are creating the carbon dioxide that we’re breathing out and that they are turning food into ATP which is the

energy currency of the cell so they’re taking food and oxygen and lots of other

things but let’s just simplify food and oxygen converting it into ATP and that

is what the PowerHouse of the cell kind of refers to there is no doubt they do

that there is no doubt that when that process stops humans have about six

minutes or so and then we’re dead that process is critical to life

there is no other process in the body that you can disrupt that will kill the organism

faster it is Central to living organisms this production of ATP so I don’t at all

mean to take away or minimize that function but research over the last 25

years has completely upended that simplistic notion of what mitochondria

are doing they are actually doing so much more some people have created the reference that MIT are like the workers

inside a cell that in order for a cell to work you need a Workforce because there’s so

much that needs to be done signals need to be sent thing like all this work all

of these different things need to be functioning and mitochondria are

absolutely providing the energy for those things to happen but they’re also orchestrating a lot of it so for example

they play a direct role in in converting food into some of the substrates for the

production of neurotransmitters um but they also go

further they store like some neurotransmitters like Gaba within themselves and that plays a role in

gaba’s release from a neuron they actually go to the cell membrane and

move along the membrane dispensing vesicles of neuro

transmitters and when you take the mitochondria away from the

synapse but provide that synapse with ATP vesicles don’t get released

neurotransmitters aren’t getting released the mitochondria are doing more we don’t exactly know what but they’re

doing more than just providing the energy they they play a role in turning

inflammation and immune cell both on and off they help start the process but they

also help coordinate the cessation of that process

they play an instrumental role in both the first and the last step in the

synthesis of cortisol and they play a role in the first step in the synthesis of all of

the steroid hormones which include estrogen testosterone progesterone

so that if you have disregulation of cortisol or if you have disregulation of testosterone or

estrogen or progesterone you must understand the role of mitochondria

in that disregulation because they are critical in the production and release

of these hormones they are the primary regulator

of epigenetics so epigenetics are the expression of genes from the cell

nucleus and researchers have long known that that’s related to levels of reactive oxygen species it’s related to

levels of calcium it’s related to other cell signals those cell signals are mostly

originating within mitochondria during the development of any cell

mitochondria they are like a universe unto themselves and there’s so much we don’t know about them but what what

researchers have found is that mondria actually line up literally line up in an

organized fashion around the cell nucleus and take on different confirmations and that is somehow

sending signals to the Gen to result in the expression or the

suppression of different genes from the nucleus and that when

researchers take these mitochondria and like mess them up or something the cell does develop normally you know they’ve

been implicated in all of the phases of the human stress response to psychological stress so that includes

cortisol release noradrenaline release it includes inflammation and it includes

epigenetic changes so those are kind of the four buckets of the human stress

response cortisol adrenaline inflammation and epigenetic

changes and researchers actually manipulated mitochondrial genes two

genes in the cell nucleus that control for mitochondrial proteins and two genes in mitochondria themselves and by

manipulating these four different genes one at a time in mice they could impact all of the four

aspects of the stress response and so what that means is that mitochondria are

somehow involved in regulating the human stress

response and so the way that I think about it is that and the way that many researchers

actually think about it now is that mitochondria you know there are hundreds

sometimes thousands of them in our cells in each of our cells most neurons have

thousands of mitochondria the mitochondria are actually moving around they use the

cytoskeleton to move around the cell they fuse with each other

they it’s called mitochondrial Dynamics they like change shape they do all sorts

of things and again that impacts all of these signaling processes but that’s just within one

little cell so you can think of one cell is like almost a village of

mitochondria that they’re all just doing different things things and working together to help that cell function but

in fact when you think about hormones like cortisol you can think about it as a way

for mitochondria in one cell to produce cortisol that they can get sent to mitochondria in another cell to to make

that other cell do something to either increase its activity or decrease its

activity some people actually think about human cells as just a network of

mitoch all kind of the mitochondria throughout the body and brain are just doing all

sorts of things and at the end of the day we come back to just common sense at

the end of the day it’s about helping the organism adapt and survive ultimately

organisms rule number one they need to survive rule number two they need to

reproduce and rule number three they need to adapt and mitochondria are playing a

foundational role in all of those basic aspects of organismal

survival and again to some people that well that’s so high level that’s like well you’re saying it’s everything I’m

like yeah it kind of is and mental health falls under it how could we think

about mental health without thinking about the big picture like let’s start with the big picture and then let’s put

Health into it and let’s put the lack of adaptation or the lack of survival or

the um these other things I’d like to take a quick break and thank our sponsor

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