The Dr. Hyman Show - Fix Your Brain by Fixing Your Body: Metabolic Psychiatry Explained by Dr. Shebani Sethi
Episode Date: September 24, 2025For too long, psychiatry has treated mental illness as if it lives only in the brain. But what if the real story begins in the body? My guest today, Dr. Shebani Sethi, is a Clinical Associate Professo...r at Stanford and founding director of the Metabolic Psychiatry Program, the first clinic to unite psychiatry with nutrition and metabolism. On this revealing episode of The Dr. Hyman Show, we explore how shifts in metabolism affect the brain and why this whole-body lens could transform how we prevent, understand, and treat mental health. Watch the full conversation on YouTube, or listen wherever you get your podcasts. We discuss: • How to recognize metabolic red flags behind mood and focus • Tests you can ask for to uncover hidden drivers of mental health • Everyday steps to restore brain energy and resilience • Foods and nutrients that calm inflammation and support cognition Dr. Shebani Sethi coined the term Metabolic Psychiatry, capturing what I’ve long believed and explored: that mental health begins in the body. Embracing this shift could reshape how we treat the mind and how we live each day. View Show Notes From This Episode Get Free Weekly Health Tips from Dr. Hyman https://drhyman.com/pages/picks?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Sign Up for Dr. Hyman’s Weekly Longevity Journal https://drhyman.com/pages/longevity?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Join the 10-Day Detox to Reset Your Health https://drhyman.com/pages/10-day-detox Join the Hyman Hive for Expert Support and Real Results https://drhyman.com/pages/hyman-hive This episode is brought to you by Big Bold Health, Sunlighten, Function Health, Paleovalley, Timeline and AirDoctor. Get 30% off HTB Immune Energy Chews at bigboldhealth.com and use code DRMARK30. Visit sunlighten.com and save up to $1400 on your purchase with code HYMAN. Join today at FunctionHealth.com/Mark and use code HYMAN100 to get $100 toward your membership. Get nutrient-dense, whole foods. Head to paleovalley.com/hyman for 15% off your first purchase. Support essential mitochondrial health and save 10% on Mitopure. Visit timeline.com/drhyman to get 10% off today. Get cleaner air. Right now, you can get up to $300 off at airdoctorpro.com/drhyman.
Transcript
Discussion (0)
One and three people have insulin resistance in the United States.
And that doubles your risk of developing depression, even if you have had no psychiatric history.
This is this sort of weird moment in psychiatry where I think we're converging these two massive paradigm shifts.
One is around psychedelic medicine, metabolic psychiatry.
You can't do one without the other.
Dr. Shabani Sethi is the founding director of Stanford's Metabolic Psychiatry Program,
where she unites nutrition, metabolism, and mental health care.
She's rewriting mental health by fixing the body first.
What is metabolic psychiatry?
Metabolic psychiatry is thinking about metabolism and mental health connection,
but it's the study of all of the metabolic dysfunctions, both systemic as well as central.
So you can have dysfunction in the brain, and you can have dysfunction outside the brain in the body.
And those two elements are important in thinking about how that affects psychiatric disease and mental health.
The thing that I think people are wondering about it is where do I start?
Like, I'm depressed, I'm anxious.
Maybe I have bipolar disease.
Maybe I've got it from schizophrenia.
Like, what do I do?
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Welcome, Shemining to the podcast.
It's good to have you back.
We had a chance to talk about your work a few years ago, and I just wanted to revisit it because
it's such an important piece of work you're doing in the world to look at mental health from a new
lens, which is how the body affects the brain. It's something that, you know, is kind of this
weird anomaly in psychiatry because historically, psychiatrists never looked at the body. I mean,
the joke in medicine is neurologist pay no attention to the mind and psychiatrists pay no attention
to the brain. And also, I would say psychiatrists pay no attention to the body. And,
terms of what's happening that could be influencing the brain. You're sort of highlighting the
opposite of the mind-body effect, which is the body-mind effect. And it's bi-directional, but mostly
we focus on the mind-body effect. Yes, stress can cause illness and so forth. But physiological change
in the body that are emerging because of our lifestyle and our crappy diet and stress and toxins
and all these things have an effect on the brain. And we really have neglected this area. And the body
has only so many ways of saying, ouch, and the brain even less. You know, when your, when your knee
hurts if you're spraying your knee, you know, it hurts, right? But if your brain is inflamed,
what happens? It doesn't hurt and they don't get a headache. It creates mental illness. And so I want
to unpack with you today, this whole feel that you sort of are deeply involved in that you coined
the term for, which is metabolic psychiatry. So maybe you can start out by saying, how did you come up
with this? Where did it like originated from in your mind? And what is metabolic psychiatry?
Well, thank you, Mark, for having me back on your show.
You actually wrote a book 20 years ago or 15 years ago making some of these connections.
Yeah, the ultra-mind solution, right?
Here we are, 15 and 20 years later are talking about it.
These ideas of metabolism and mental health being connected, they're not new.
They've been around for 100 years, 100 years ago in psychiatry.
We had seen that there were levels of lactate that were elevated in,
serious mental illness, and that there were levels of glutathione, which were low. They were
low, and it is an antioxidant. And so these markers were markers of bioenergetic dysfunction.
And so... Lactate is like when you exercise too much and your calves hurt because you've got lactic
acid in your muscles. That's happening in your brain. And so there's also a preferential area of
energy production towards glycolysis that produces lactate, and that tends to be more common
in certain diseases. So we see that in neurodegenerative conditions. We see that in serious
mental illness, like bipolar disorder and schizophrenia and major depression. So when I say
serious mental illness, I'm talking about these three illnesses primarily. Knowing that these were
biomarkers that we saw 100 years ago, and then we went in different directions over the last
hundred years focused on neurotransmitters and, you know, other systems, which are only just
part of the picture. There's a much bigger picture when we think about metabolism. So
metabolism is really just thinking about food, breakdown into energy, and everything that
happens in between is detail. Metabolic psychiatry is thinking about that metabolism and
mental health connection, but it's the study of all of the metabolic dysfunctions, both
systemic as well as central. So you can have dysfunction in the brain and you can have this function
outside the brain in the body. They're connected, right? And those two elements are important
in thinking about how that affects psychiatric disease and mental health. And so when we look at how
that dysfunction affects psychiatric symptoms, whether it's prevention, whether it's
progression of disease or treatment of disease, that's really what metabolic psychiatry is about.
I think other instances, metabolic psychiatry has been defined as brain energy metabolism only,
or it's been defined as just the ketogenic diet, for example. And I want to clear that up because
metabolic psychiatry really is a more holistic term that incorporates all systemic as well as
central metabolic dysfunction and how that affects psychiatric disease. Yeah, so just for people,
In medicine, we talk about metabolism,
and people say, I have a slow metabolism,
and the lay culture, and I have fast metabolism.
They mean a little bit different things.
So metabolism is, yes, how you eat food
and it conversion to energy.
But there's an enormous number of metabolic pathways.
If you were to put on a wall in basically microprint,
it would be a giant wall, all the metabolic pathways.
You know, these set of things we see in medical school,
and every single one of those pathways are part
the biochemical reactions that happen across every system in your body. And there's 37 billion
trillion chemical reactions every second in your body. All those are part of your metabolic system.
And all those things, I think, affect our mental health and everything else in terms of disease.
So understanding that is really important and it's kind of a neglected thing in medicine.
We sort of give lips of us to it in the first year medical school. We pretty much ignore it after
that. We don't learn much about things like insulin resistance, but even less about.
nutrition, which is driving a lot of the metabolic systems, right? Because every one of those
biochemical pathways requires a nutrient to actually work. So since metabolic psychiatry,
you're saying, is the bigger rubric that encompasses all of that, not just sugar and glucose
and metabolism from that perspective, right? Exactly. Yeah. So I think that's important
understanding. And those metabolic pathways affect everything. So it's very complicated. We kind of
look at that chart and maybe learn a little bit about it, but it's kind of not this thing that we pay
attention to, but it ends up being the kind of, I would say, holy grail of how to actually think
about health in general, and particularly psychiatry. And the fact that you sort of are pointing
in the fact that the way we thought about mental illness might not be totally accurate. And I think
this is part of the problem in our society is that, you know, if someone has rheumatoid arthritis,
their joints are damage, we don't say, oh, there's something wrong with you. Like, we go,
too bad. I'm sorry, you're suffering from this. And they're going to help.
With mental health, there's a lot of stigma around it, and there's a lot of judgment around it,
and there's a lot of attribution of meaning to it.
And I think through history, there's been this phenomenon of different views of mental illness throughout history.
And I think we're in this new era of understanding mental illness to the lens of metabolic psychiatry.
And also, I don't know what you call it, trauma-informed psychiatry or, you know, psychedelic medicine,
which is addressing a lot of these other aspects.
Yeah, I think one of our, the dean of our medical school at Stanford Medicine had said,
I think during a medical school graduation,
that the greatest discoveries are discovered
in between, in this intersection between fields.
And sometimes I think we forget
that the body is related
and, you know, organs are not just isolated
and they're working in a whole system.
Yeah.
So, you know, if your city is, you know,
running and it's not,
if there's an issue in the power grid
and you're not having enough power
and the light's flickering somewhere,
there's something that's wrong. And even though it's working, it's not working optimally. And so
medwall psychiatry takes different fields of endocrinology, immunology, and so forth. And we really wanted to
have, as Stanford, we wanted to put a name to it so that more clinicians and researchers and, you know,
people out there do more work in this area. It really gives us a communication tool and map to be able to label
something and to be able to work in a more collaborative way.
And the truth is, you know, for the serious mental illnesses that you're talking about,
I mean, then people suffer from anxiety, depression, major depression, more serious
psychiatric illnesses from that spectrum.
But then there's things like schizophrenia and bipolar disease, which are pretty intractable
and chronic and the medications come with a lot of downside effects and obesity.
It kind of makes it even worse.
We're seeing, you know, studies that show and some of the work, some of the work,
you've done, you see profound changes in these and treatable mental illnesses using this approach
of metabolic psychiatry and nutrition and food. Can you kind of talk about how did you,
because you kind of came from the field of obesity medicine and also psychiatric medicine. So was that
what kind of got you thinking about this? Yeah. So for me, I think I was one of those really lucky
at an early point in my career when I was in medical school. I had exposure to nutrition, which
usually is not typical. I think normally it's maybe two days of lectures of nutrition and medical
school, although I'm optimistic as changing. I had an opportunity to really delve more into obesity
medicine starting in medical school, and that got me very interested in nutrition as well because
I started seeing differences in patients when it came to psychiatric symptoms. And one patient in
particular who had schizophrenia and treatment resistance schizophrenia. I spent a lot of time
talking to these patients in an obesity clinic. From there, I learned more about obesity treatments,
and so I really just follow my heart in a lot of ways. I didn't have plans to be a physician
scientist or an entrepreneur. I just had plans to treat patients, and I did that, and I really
enjoy it. But I felt that a lot of times these things were not being treated, whether it was
metabolic syndrome or insulin resistance or metabolic issues. And I thought it would be,
you know, helpful to do that. And so I started really with a strong interest. And that just led me
with my curiosity to go further into obesity medicine. I knew I wanted to do psychiatry.
and I went into psychiatry with an interest in metabolism.
So I veered towards obesity medicine because that was what I had a great mentor in medical school.
And I went in that direction.
He was an obesity medicine specialist.
And from there, that's how I learned about ketogenic therapies for seizures.
And then I worked with some of the folks who were neurologists who do that for epilepsy.
And then understood how I could adapt it for psychiatric conditions.
And then I started studying that.
I did it with my patients. I started studying it. And here I am many years later, doing research trials. And I started a program at Stanford, which is focused on metabolism-based interventions for those with bipolar or schizophrenia or depression and also eating disorders. I had done some work in eating disorders and trials and with obesity drugs. And I have realized over time that there are other options and tools.
which I do believe is important to integrate into psychiatry.
I felt that it was missing, that we oftentimes kind of segregate ourselves a little too much from
other fields, and there's just, there's so much connection and relationship.
And I'll give you one example.
Yeah.
So in primary care, I saw a lot of patients that had diabetes, right?
Diabetes or hypertension.
But the folks that had the more severe depression tended to have insulin resistance,
or they had some other metabolic condition.
And so in primary care, the folks with diabetes who weren't doing well had depression.
So that's the thing that I saw, and then I just got more curious about this and that connection.
Yeah, there's a big crossover, like about 40% of people with diabetes have mental illness, right?
It's pretty high.
So in bipolar illness, about 37, almost 40% have metabolic symptoms.
syndrome. Pre-diabetes, essentially, yeah.
Full-blown metabolog syndrome.
Yeah. You know, if you have insulin resistance, one in three people have insulin resistance
in the United States, and that doubles your risk of developing depression, even if you
have had no psychiatric history. So there's a lot of relationships.
And it depends on how you define pre-diabetes, too, because I think if you look at some of the
workout of Tufts, they looked at people with what they determined was metabolic dysfunction, which
which is either you have a high blood sugar,
high blood pressure, abnormal cholesterol,
you're overweight or obese,
or you've had a heart attack or stroke.
And if you combine all those,
which are all related to the fundamental biology
of insulin resistance, which I want to unpack with you,
that's 93.2% of Americans.
So it's more than one in three
that have some degree of this.
That's concerning to me
because our diet is so bad,
it's so high in sugar and starch.
It's such a destructive force
for not only our body, but also our brain.
And people don't understand that.
People don't understand that, yeah, okay,
I guess if I eat too many cookies or have too much soda,
I'll gain weight and I'll get overweight,
but they don't connect the dots with mental health.
And then it becomes a vicious cycle.
The more depressed you are,
the less like you are to take care of yourself,
and you spiral, and that's what happens a lot in these patients.
So can you talk about, like, the dive into this whole phenomenon
of insulin resistance in the brain,
and how it affects you and how it's somehow different
than peripheral insulin resistance?
Because you talk about like cerebral hypometabolism,
which means low metabolism in the brain, right?
And how it affects the brain
and how insulin resistance plays a role in this.
Can sort of unpack that.
So cerebral glucose hypometabolism in the brain globally
is a central pathological characteristic
of neurodegenerative conditions
and also present in schizophrenia and bipolar in particular.
And that's really when the certain areas of the brain cannot use glucose for energy.
Even though glucose is present, it can't process the glucose well.
And you develop insulin resistance as well.
And when you have insulin resistance centrally, there's a problem with insulin signaling
and glucose signaling in the brain. And we see this even before the diagnosis of psychosis.
Before medications are given and before the diagnosis, it's present. So we think there's a relationship
between psychiatric illness and insulin and glucose handling in the brain. When you have
insulin resistance in the brain, that doesn't necessarily mean that you'll have insulin
resistance in the body. You know, measures of that differ. And a lot of the medications that
we tend to use in psychiatry, unfortunately, some of them do have effects on insulin resistance
peripherally, which is different than insulin resistance centrally. It can affect the hypothalamus,
the nuclei, the hypothalamus. It can increase food intake. So it makes you, it increases your
appetite. Hungry, yeah. Yeah, it makes you hungrier. And with the peripherally,
it can increase insulin so that you are releasing more insulin and become insulin resistant
by nature of the medication. But there's also elements of the medication that occur in the brain
as well where it improves insulin signaling depending on the drug. So it's actually kind of complicated.
And I'll give an example is lithium. It also improves insulin signaling in the brain. But to get back
to, you know, this insulin resistance concept in the brain and why it's important, it's really important
because it's important for neuronal plasticity.
A neuron, neuronal growth, remodeling, shaping.
It's extreme insulin signaling is critical for that.
It's one of the reasons why it's important.
When you have insulin resistance peripherally, so outside the brain,
it leads to degeneration and atrophy of some of the hippocampal neurons as well.
And so it's structurally altering the brain when you have insulin resistance
peripherally. So that doesn't necessarily mean that the insulin resistance centrally is doing that.
It's the peripheral insulin resistance that's leading to that. So there is this bidirectional
relationship that you mentioned earlier. And that bidirectional relationship is that, you know,
on one side, you have, if you have type 2 diabetes or obesity or insulin resistance, it's leading
to symptoms, psychiatric symptoms, it leads to a psychiatric diagnosis eventually. It's affecting
the brain. But then there's also intrinsic metabolic dysfunction and insulin.
insulin resistance as part of that in psychiatric disease that then leads to HPA access
dysregulation or it leads to sleep disturbances and it leads to the obvious peripheral signs
of metabolic dysfunction as well.
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So basically what you're saying in English is that is that, you know,
You know, you've got the insulin resistance in the body that affects the brain structurally.
It can shrink in memory centers and other key areas of the brain that make it not work well.
But you can also have the psychiatric symptoms making you have worsened ability to regulate blood sugar and insulin peripherally too because it affects your stress response.
It affects your whole metabolic system.
Yes, in addition to medication side effects and so forth.
But even the intrinsic metabolic dysfunction that exists in psychiatric conditions can also make someone more vulnerable in developing those other conditions.
And when you look at type 2 diabetics, their mitochondria function at half the rate as regular people who don't have type 2 diabetes.
So mitochondria essentially the little energy factories inside your cells and there's anywhere from hundreds to thousands and tens of thousands in the brain, it's the most dense per brain cell is the most mitochondrial.
of any cell in your body.
So energy is really important in the brain.
What we find is if you're a type of diabetic
or if you have insulin resistance,
your mitochondria don't work as well.
And that creates a whole downstream set of consequences.
It can create more oxidative stress.
It potentially can create more inflammation.
And it's also inflammation.
It can cause mitochondrial dysfunction.
So it's a kind of virtuous or maybe a vicious cycle.
It's a vicious cycle.
It's a vicious cycle of dysfunction.
Yeah.
But on the other hand,
that you can create a virtuous cycle
by the interventions that you're finding with your team and group at Stanford looking at metabolic
interventions of diet nutrition like keto diets for helping reset the brain energy system.
Generally, there's four mechanisms of metabolic disease.
There's plasticity, you mentioned, the inflammation, there's oxidative stress, and there's
mitochondrial dysfunction.
And so anything that's going to target these areas, whether it's a diet or whether it's,
you know, medications that target these pathways,
there is a potential for improving both the metabolic disease and the psychiatric disease
because there is a shared relationship.
There's a shared pathogenic relationship between mental health and metabolism.
Yeah.
So that's really what we're studying, and that's what we're trying to, you know, go further into
with a lot of mechanistic, you know, studies as well as looking at clinical outcomes and metabolic markers and so forth.
I can go into that in detail, but...
I mean, I think the inflammation piece is really important
because when you look at people with type 2 diabetes
or insulin resistance,
they often have a high C-reactive protein,
a marker of inflammation,
and they often have systemic inflammation.
And when we start to look at all these neurodegenerative
and neuropsychiatric illnesses,
a common feature is inflammation.
And I've even seen some stupid studies
looking at like TNF alpha blockers for depression,
which is like a drug we use
for rheumatoid arthritis or severe autoimmune diseases,
it's 50 grand a year, and there's a lot of side effects.
And they're, you know, they're saying,
well, that's inflammation in the brain.
Let's give you an anti-inflammatory.
But it doesn't work like that.
I think we have to think about what's causing the inflammation,
get to the root cause of it.
And it's this metabolic dysfunction that tends to be both the cause
and the consequence of it.
Yeah, and I think we can think about all of these,
whether they're drugs or even dice,
there are different tools in the toolbox that we can use.
used to target a metabolic pathway or an improvement in symptoms. For example, you could take
metformin, a lot of us know, right? Metformin improves glucose. It improves insulin sensitivity,
but it also crosses the blood-brain barrier, and it has a neuroprotective effect. It helps in the
TCA cycle, you know, within the mitochondria, we have machinery to produce energy, to produce ATP,
and there are deficits in that energy pathway, whether they're enzymes or cofactors, they're
not present. Metformin helps support that to some degree. And it also does decrease inflammation.
So in some studies, it's been shown to reduce TNAF alpha, or reduce interleukin 6, reduce other cytokines.
And we know cytokines also are pro-inflammatory, right? And they end up also affecting serotonin synthesis.
It affects tryptophan metabolism.
Yeah.
Hey, that's neurotransmitter, right?
And that's one part, but that's one part of the equation.
Yeah.
And so there was a study, a colleague of mine did, looking at metformin and treatment-resistant
bipolar depression.
And that showed an improvement in those who were treated with metformin and also had
the psychiatric medication on board.
It allowed the psychiatric medication on board to work better.
So that's just one example of how a metabolic interview.
prevention or tool can improve psychiatric symptoms that goes beyond just, you know, let's improve
insulin resistance, but there's so many other pieces that are also being affected by it.
And basically what you're talking about is this up until now, most of psychiatry has been
sort of downstream. Oh, neurotransmitters may be a problem, but the question is, why are they so
messed up in the first place? Right. And what's causing that? And it seems like what
your work is finding is that a lot of our lifestyle and diet related problems that are driving
blood sugar dysregulation and mitochondrial dysfunction, inflammation, our ultra-processed diet and
sedentary lifestyle, and all these things that sort of accelerate the problem actually makes
these sort of neurotransmitter problems worse downstream. And you can treat the neurotransmitters
or you can treat the cause, right? You can treat the symptom or you can treat the cause. And I think
The metabolic psychiatry approach, you know, like you said, has many tools, like metformin
is a drug that helps improve it, but there are many other things, right, that are including
diet, lifestyle exercise, we know, is very effective for mental health.
And how does that work?
It may partly work by improving insulin sensitivity, right?
Yeah, that's one.
And, you know, increasing BDNF, which you and I talked about last time, I think, on your
show, like now five years ago, the time is flow.
Yeah.
But you described it as miracle grown.
I really love the way you described it.
Because that's exactly what it is.
That was one, you know, with exercise, it's shown to, you know, improve those levels and improve cognition and so forth.
So there's a lot of tools.
And the mitochondrial therapies, I mean, you know, there's a woman named Suzanne Goh, who's looked at a lot of mitochondrial dysfunction, autistic brains.
And whether you have ADD or autism or you have Alzheimer's or Parkinson's or depression or bipolar or schizophrenia, it's all this spectrum of brain dysfunction.
And there's a lot of common pathways involved in all these.
And her workers found that, yeah, there's energy deficits in these kids in the brain, just like, and it may show up in one subset of people as autism and another subset is schizophrenia, but essentially it's the same mechanism.
You know, she talks about using mitochondrial therapies, essentially cofactors that are involved in these metabolic steps, these biochemical steps, require helpers.
And so they use nutrients like amino acids or COGU10 or other compounds that actually help improve brain function.
So I wonder, are you exploring any of these sort of nutraceutical approaches that are using the body's own things that uses to actually make energy, but giving them a sort of a higher doses or through supplementation as a tool for helping metabolic psychiatry of patients?
Yeah, it's an interesting question.
And I love her work, by the way.
And I think looking at mitochondrial dysfunction, it's a lot of shared mechanisms with these different conditions.
So it does make sense when we're studying serious mental illness and other conditions to be looking at vitamins, co-factors, things.
So we test for that in our clinic.
We test for all of these things and we optimize.
So we have an approach that we use to make sure that people are not deficient in these things.
Because if someone's deficient, does that make sense to treat them only with medication and ignore the fact that they're deficient or malnour?
nourished in some way. If they have insulin resistance, obesity, metabolic syndrome, sure,
let's treat that. But let's make sure they're also not malnourished. Most of them are malnourished.
And you mentioned 90-something percent of the population is having some kind of metabolic abnormality.
Overfed and undernourished. Right. Yeah. So calories, not enough to nutrients, yeah.
It's almost like a crime to not be thinking about it. And that's why I think it's really important
to have that approach. And to answer your question, well, I'm not specifically,
looking at one supplement in its effect on psychiatric outcomes. I'm really looking at the whole
kind of the whole picture and making sure they're optimized. Give an example of research that's
been done in our field by colleagues who looked at omega-3 supplementation, at least one gram,
including EPA per day for, I think it was a total of eight to 12 weeks period, which
significantly had a good, it was modest evidence that showed benefit for psychosis, early phase
schizophrenia, early phase psychosis. And it's also been a treatment as an adjunctive treatment for
depression. Things like this are helpful for us to know about. Unfortunately, didn't have the same
effect for chronic schizophrenia. But that's why prevention is so important. And mentioned earlier about
fasting insulin, right, and development of depression, like, why aren't we checking these things
more routinely or more frequently to prevent conditions or prevent exacerbation of, you know,
symptoms that are so severe like psychosis?
Yeah, I mean, I think what you're bringing up is important, and, you know, medicine's very
reductionist, and it likes to go, let's look at omega-3s, let's look at vitamin D, let's look at
magnesium, let's look at whatever B vitamins. And the body is so complex that it requires all
ingredients. It's like if you want to grow a healthy plant, you can't just have soil, you need
water and light, you know, and vice versa. Like, the human body is very much the same way. And I think
we often will not be sophisticated in how we think about providing all the components needed
for optimal function of mitochondria, of your immune system, of insulin resistance. And I think that
one way to navigate that is sort of emerging from our understanding of metabolomics,
and proteomics and gene expression products
that are helping us understand the body
in a more nuanced way.
And I think one of the things I think a lot about
is what are the biomarkers of mental illness?
And one of the things we should be looking at
that can play a role,
rather than just treating one thing,
you have to find everything that's off and fix it.
In other words, if your omega-3 is low
and you take it, great.
But if your vitamin D and magnesium are also low,
might not work as well, right?
And so you kind of have to think holistically about all the various factors.
So can you talk a little bit about your work in the frame of the biomarkers of mental illness
and what you're thinking about in terms of evaluating that?
You know, you talk about lipids and triglycerides and HDL and blood sugar and anyone's seen all that.
But it goes deeper than that.
It does.
And I'm glad you're pointing that out about the, you know, optimization can't just be a reductionist approach of one thing.
We really have to look at everything.
and that's what we are doing with our treatment approaches.
It is important to, you know, obviously monitor those things as well.
But biomarkers are biomarkers.
They're in psychiatry, I don't believe that there's just going to be one biomarker.
It's going to be, it's a group of markers.
And thinking about certain metabolic disease states, certain conditions,
how much the progression is based on those biomarkers is really where I think
we're heading. And also part of the effort in our trial, we're starting a randomized controlled trial
generously funded by some philanthropists, including Peace Guard philanthropies at Stanford. And we're
looking at mechanistic approaches for a metabolic intervention like a ketogenic diet in schizophrenia,
bipolar, and depression. And we're looking at a lot of these biomarkers. I'll give you one example,
and that is looking at triglyceride HDL ratio, for example.
That's been something that has been shown with a lot of good data
that depression's severity and chronicity
is associated with that marker.
And that's directly related to insulin resistance.
So you've got higher triglycerides and lower HDL,
and the ratio becomes higher as you get more insulin resistant.
So it should be like one to one.
That's right.
And you can go to one, four to one.
10 to 1, you know, if your triglycerides are 150 and your H.GEL's 30, that's a 5 to 1 ratio.
That's not good.
What was interesting about that study is that insulin sensitivity wasn't associated with the
chronicity of depression, but it was for the severity.
But the triglyceride HGl ratio was associated with both.
So there are some interesting nuances in the literature about kind of looking at the biomarkers
a little bit differently. And I think there's a lot of different biomarkers that will be
helpful in, and even, for example, with insulin resistance, since we're talking about that,
when we look at insulin resistance, we see that even with bipolar disorder, you have more
rapid cycling, you have more treatment resistance, and you have more suicidality. So that's another
thing that we could use as a biomarker as well. Yeah, I think it's so many different things.
I mean, when I think about it, you want to check your nutrient levels.
that affect mental health, like vitamin D and homocysteine
and methamotic acid and omega-3 fats and omega-3 index
and hormonal effects like thyroid and sex hormones
and your iron levels and zinc levels and insulin measurements
and some resistance scores which now are available through Quest
that you do at function health, which measures C-peptide and insulin
with mass spectrometry, which is a really accurate way of measuring insulin
insulin insulin insulin insulin insulin insulin and some resistance
and triglystria-hdl ratio and particle size and particle number,
inflammation levels, CRP.
So all these things are blood tests that actually can help clue you into many different problems.
But actually, if you see there's abnormalities, and we see a lot of it.
Like with function health, we're seeing like 70% have a nutritional deficiency at the minimum
level that's actually recommended by the dietary.
Not surprised.
It's not like what's an optimal level of vitamin D or what an optimal level of homocysteine is,
but like almost 60 levels are in the lab up to 14 or 15
and should be probably, you know, six to eight
that measures your folate or B12 or B6 status.
And so we're seeing a lot of that.
We're seeing, you know, 95% with metabolic dysfunction
through the lipid particle size,
and we're seeing 46% with high CRPs,
and we're seeing a lot of really significant inflammation.
So we started to go, wow, the population is at large as sick.
We're seeing an increase in mental illness,
and no one's really talked about how do we think differently
about treating things systemically.
And I think what you said is really important
because it's a paradigm shift from thinking of the body
is a bunch of different organs and parts
to how the body's a network and everything is connected.
And we have to treat the network, not the symptom.
Exactly, yeah.
And so that's a lot of what your work is doing.
And I wonder also the schizophrenia part,
you know, 17% of people with schizophrenia
have elevated gluten antibodies, which can drive a lot.
a lot of brain inflammation and create a lot of neuropsychiatric symptoms.
Absolutely.
And then again, you're taking that out when you get people a keto diet.
It's a good thing that we should test before and after too, which we're doing in our next
study.
So we will be doing that.
And also looking at...
Looking at gluten antibodies?
Yeah, we're planning to.
Amazing.
Yeah.
Just looking at mitochondrial deficits, too.
So we'll be looking at that.
So how are you doing that?
Because it's something in medicine we don't really pay attention to.
We learn about mitochondria in the first year.
medical school. We learn about the Krebs cycle. You call the TCA cycle, which is the energy cycle,
how you turn food and oxygen into energy in the body. And then we kind of forget about it. And it's not
part of clinical medicine. We don't talk about how do we evaluate mitochondria, how do we test them,
how do we treat dysfunctional mitochondria? Yet it's one of the central features of most illnesses
that are chronic, from mental health to neuropsychiatric disorders to metabolic disease like diabetes to heart
failure, many, many problems are mitochondrial issues. Yeah, I don't have an answer as to why we don't do
it more, but I think it's, you know, something that is probably difficult and hard to treat in some
ways. But the more research, I think, that we have in this area, the better it's going to be for
more targeted interventions. So I'm hopeful, you know, for that. One thing that I thought would be
helpful in when you're describing the mitochondrial dysfunction in various conditions, what we are seeing
in psychiatry also is that, you know, the brain is volume-wise, it makes up 2% of our body,
but it consumes 20% of our energy. And it's so delicate, extremely delicate, that if there
are deficits in insulin and glucose handling and that, you know, crept cycle machinery to produce
energy, then there's more metabolic vulnerability in psychiatric conditions. There's more
metabolic vulnerability in specific areas of the brain. You and I talking right now,
we're maybe using 80%, you know, our capacity. We have, if we're, you know, talking a little bit more
deeper in science, you know, it'll be a 5% increase, our daily, you know, activities, but less.
And for someone that maybe has genetic predispositions or have environmental stress, it's going to be
a little harder to have that, you know, perfect machinery producing energy. And there's more
metabolic vulnerability there. And so those differences between one region or the brain,
and another, is pretty critical for functioning, cognition, mood, and mental health symptoms.
And how are you thinking about measuring mitochondrial function, as you're talking about in your
upcoming studies?
I believe in a lot of collaboration.
I love collaborating with other scientists.
So University of Toronto, Mayo Clinic, a lot of other departments at Stanford.
I have a faculty member, chair of genetics, who at Stanford will be looking at all Omec profiling,
So all expression of proteomics, metabolomic data, wearable, HRV data, another faculty member
is going to be looking at ketone metabolites because downstream of ketone metabolism,
there may be, say, an amino acid called phenylalanine attached to beta-hydroxybutyrate,
which is what ketones will break down into.
And if you have that, the end effect of appetite reduction or weight loss is present.
If not, it doesn't work as well.
the mitochondrial testing is a collaboration with Mayo Clinic and University of Toronto,
and that's looking at all the different metabolites in the mitochondria lactates one of them,
but there are a lot of other sexnal co-way, different dehydrogenases,
so we'll be looking at all the levels of that before and after.
You normally can get at a regular lab test.
No.
Is there a research-based test looking mitochondria?
Yeah.
I mean, clinically, it's been a tough thing for us to look at because you could do a V-O-2-Max test,
which is basically an exercise treadmill test that measures sort of indirectly your mitochondria.
You can measure organic acids, which are urinary metabolites.
And I think, you know, we all have sort of subtle changes in our metabolic pathways that affect different things.
And we can see some of those changes.
But there's now, you know, cheek swabs that look at the respiratory chain, which is, you know, basically the assembly line that turns food and oxygen into energy.
And there's some interesting, you know, kind of ways to start to think about how do we sort of clinically measure this in people?
because it's such a big, it's such a big black box, and it's so important.
And then you can actually even be specific and say, oh, this pathway that requires
Koku 10 is a little slow.
So what if I give extra Koku 10 is going to speed it up?
And it becomes more personalized that way, right?
Like, and more specific.
And I forgot to mention, we're also looking at epigenetic data.
So looking at DNA methylation and gene expression, it's 120 patients, randomized control
trial, and we'll be collecting a lot of data, continuous ketone monitoring, Abbott
donated the devices.
So we're grateful for that, yeah, glucose monitoring and getting more.
We're still fundraising for the trial, but we have gotten enough to get started and we're
looking at all these measures and it's exciting.
We're excited about it.
You know, what you're offering to people is not here take this pill for your mental illness,
but here's a lifestyle change that can have profound effects.
How do you do that?
Because these are patients who are often mentally ill, which makes it harder for them to make
good choices, right? And so you're asking them to do a ketogenic diet or you're asking
them to do severe lifestyle changes. How are you getting people to do that? Yeah, that's a good
question. And, you know, I do want to recognize that it's not always easy, especially when you
have a condition like schizophrenia. But there's a lot of support that is involved in providing
care that's important in those cases and caregivers that get involved. So we do support groups. We
really help them with, you know, adjusting to making changes in the home, to be able to,
not necessarily thinking about it as a diet, but really think about it as a lifestyle change and
a metabolic therapy for their illness, which is improving their quality of life, which is
our primary outcome is the thing we care about most as clinicians, right? So, you know, we, we want
them to have a better quality of life. They want a better quality of life. And that's what also
motivates them to stay on the diet or the approach as well.
So I think a combination of that.
A lot of good side effects, yeah.
Yeah, a lot of good side effects, yeah.
I mean, in your clinical trial, you're doing on the ketogenic diet for bipolar and schizophrenia that recently published with 20 few patients, you had 100% reversal of the metabolic syndrome or prediabetes.
You had 12% reduction in body weight.
You had a 36% reduction in belly fat, 27% reduction in insulin resistance, which, by the way, the Homa IRS is probably as good as this new insulin resistance score that,
quest is doing through the mass spec.
We're doing that now.
But, you know, dramatic reductions in psychiatric symptoms and so improved sleep,
life satisfaction, all these great side effects, you know.
Yeah, in four months.
Yeah.
And when you take a drug for schizophrenia, all the side effects are bad, right?
You know, all the side effects are good.
And does that encourage people to stick with it more because they're seeing positive effects?
It does encourage people to stick with it more.
And I think, you know, over time also organically, the more mutual patients with other clinicians in cardiology, endocrinology, or primary care see their patients improving with reduction in visceral fat and improvement of, you know, other metabolic markers, aside from the psychiatric markers, and people start to appreciate it and are grateful that their patients are doing better.
And the patients themselves also themselves feel like they have more control over their lives.
It gives them hope. And a lot of the patients that were in that pilot study that I did was published last year, but are still in my patients today. A lot of them are still my patients today. And a lot of them are still on a ketogenic diet. So it does speak to, I guess, the feasibility of being on it over time. And I said earlier that my goal was, I like seeing patients, I enjoy, seeing them get better. A lot of these conditions are hard to treat. Having a tool like this and seeing that it's helpful is very encouraging.
I thought that doing research is important for our field in order for it to, you know, go past
just beyond me and other people do it.
Yeah.
I want it to just die with me.
I really want this to be out there.
So when I'm not around, my son can grow up in a world where there are more things that, you know,
his disposal and, you know, that my patients have at disposal and, you know, people that we can
reach beyond just the academic centers, beyond research.
I think that's why it inspired me to.
go outside of that too and start something and found a company that's really just focused on
providing that care. Because otherwise, research just stays in research and in academia. It isn't,
not going out doesn't feel, doesn't feel right to me, I guess. I mean, it takes decades for
scientific discovery to end up in clinical practice. So I think the fact that you started
Metabolic Psychiatry Lab, which is an online platform for engaging people who want to try this out is
important and it allows it to scale up and people to get access to it and to and what you're doing
is so revolutionary I mean think about the fact that you know nutrition has not been a topic in medicine
that is really thought to be a serious subject and it's sort of the sort of stepchild fourth cousin
once from who not science enough yeah not but what you're talking about is a nutritional therapy
that has effects that orders of magnitude more than our traditional therapy.
So it's not like it's an equivalent therapy.
It's so much better.
And I wonder in terms of your work at Stanford,
are you finding resistance,
or are you finding encouragement or openness to this idea?
Because it's sort of a...
Yeah, a lot of people ask me that question,
and I appreciate that.
I have found a lot of support.
With anything, there's always waves, right?
But I have found a good amount of support,
especially with all the activities I'm involved in.
And I'm in Palo Alto in Silicon Valley, right?
It's pretty common for professors to spin out companies outside academia as well.
I love doing the research.
I believe it's important to have evidence-based science.
So I'll still continue to do that.
But also, you know, having the support to be able to move between these worlds is something that I'm grateful for.
So your psychiatry colleagues are not going.
what are you doing using food in medicine?
You should be using drugs?
I think some people are like, how do you stay on that?
How do you stay on a eugenic diet, right?
But again, I think it's the way you approach it.
I think understanding, I think education understanding around it's a therapy,
not a diet really.
In my mind, it's really a therapy, just like a drug would be.
It requires monitoring, it requires physician or as someone trained in that area.
And there are other metabolic tools.
wrote this in Nature paper along with 12 other authors focused on, you know, what is metabolic
psychiatry, why is this important, but also what are the, what is the current evidence for
these different metabolic based treatment interventions and why should we care and where are we
going in the future? I'm more hopeful because there's a global group of scientists and researchers
that do care about this and are working on this. And I think it was just yesterday that
the Senate Appropriations Committee came out with a recommendation.
for the NIMH to put more money and funding into, guess what,
nutritional science or nutritional ketosis work in serious mental illness specifically.
I'm psyched about that.
I can't wait to apply.
And I hope that I can do more research with metabolic psychiatry labs or at Stanford.
But I care about the science and I care about patients getting access to these treatments.
And so, you know, I love that function health has been able to.
to really improve the access to get these labs.
Yeah.
And what we're doing at MetaBalk Psychiatry Labs is putting together the biomarkers,
the personalization, using AI, machine learning algorithms to improve the disease states of someone
with schizophrenia versus someone with bipolar and really provide that wraparound care for
them and work with their psychiatrist or their therapist or their PCPs so that they're
not alone in this whole world.
and I think, or in the health care system, which I don't know how much we want to go into that.
But I wanted to share with you that the reason why I was, I think, compelled or felt obligate to go on this is myself, after I had a child, I had a really significant tailbone injury.
And I couldn't sit for nine months.
And so, yeah, it was horrible.
But a lot of people couldn't see that I was injured or suffering in some way because, you know, I wasn't walking around with a cat.
or, you know, I didn't have, it was invisible, right?
There was a colleague of mine that sent me a book on tailbone pain.
And there was a chapter on the psychology of tailbone pain.
And when I read it, it just felt so validating.
It was like an advocacy of how do you walk through the health care system
and how do you tell your OB-guide or like what the issue is because it gets often missed.
It was so helpful for me that book.
So I decided that I wanted to do something similar, like a patient advocacy.
manual or book, and I'm still writing it, and who knows, when I'm going to be done. But I wanted
to do that for those with serious mental illness. Starting metabolic psychiatry labs is part of that
reason. And I mean, you're starting with the sort of most extreme case, right? Schizophrenia, severe
bipolar disease. But, you know, the spectrum mental illness goes from just a little anxiety and
depression, to OCD, to more serious things. So across that whole spectrum, this approach can work,
right? It's not just serious mental illness. It can be depression, anxiety, that may be less severe,
but still debilitating for someone and they're suffering from it.
And having a metabolic approach, especially if 90-something percent have metabolic abnormalities,
why couldn't they not benefit from something that's tangible and targeted and specific and evidence-based?
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I mean, it's really interesting because I first to start to understand these ideas
when I was treating people with a lot of chronic illnesses that were not really
psychiatric in nature, like an autoimmune disease or insulin resistance or microbiome issues
or gut issues, and all these psychiatric problems would go away or get better.
And I said I was sort of shocked.
And it's really why I wrote this book,
The Ultra Mind Solution,
How to Fix Your Broken Brain by Fixing Your Body First,
because I was like, wait a minute,
nobody's talking about this.
And I don't know if this is the thing or not,
but it's certainly repeatable in my practice.
And if you pay attention and observe what's happening
with your patients and listen to them,
it's like, holy cow, you know,
you treat someone's microbiome
when their OCD gets better
or you treat someone with some nutritional deficiencies
and they get better
or you fix their blood sugar
dysregulation
and their anxiety goes away
and their panic attacks get better
and like...
And see, I think the reason
why you ended up
maybe putting that together
is because you're probably,
you know, you were treating patients,
you were coming up with something
for them, you saw them get better,
and it went from there.
And I think really where the heart is
of, you know,
when you're really seeing patients
and treating them,
you see that.
Probably motivated you to do
what you're doing today.
Totally.
I mean, I joke and you call myself
the accidental psychiatrist
just because I just didn't treat people's mental health issues,
but then I started to.
And then I wrote a book, and then, boy, I got a flood of patients
who had mental health issues and autism and ADD and Alzheimer's.
You're trying to find solutions.
And it was amazing to see how much they got better
when we just applied this sort of systems approach
to dealing with all the variables that go wrong
and not just being a reductionist sort of single vector.
I think you'll be excited to know.
know, that we're also looking at microbiome.
We're testing the microbiome also before and after with the trial.
So genetic, you know, data, too.
So it's really like a big library of data that will collect and happy to collaborate.
Yeah, very fascinating.
I mean, I think, you know, our data set as function health is interesting because we won't
share it or sell it or use it for any purpose other than, you know, just helping learn.
And, you know, anything we learn will be from an anonymized data set that's, you know,
You can't tell who's who, but we're learning so much about the population, and it would be, it's
going to be an interesting strategy to how do we start to study what's happening and actually
had to talk with Lloyd Minor, who's the dean of Stanford, about collaborating on some research
projects.
Oh, good.
Because, you know, it's hard to do a study.
I mean, you want to do a study with 120 people.
It is.
It's millions of dollars.
It's a lot of effort, and, you know, the costs are really high to do the diagnostics.
But here we have almost 300,000 members and hundreds and biomarkers on each one,
which is tens of millions of biomarkers.
A really good way to collaborate.
Yeah.
Literally, we have available to sort of figure out what's happening with the population
when they change things or do this.
And I think it's going to be an interesting data set.
We should talk more about that, and I'd love to.
Actually, Lloyd Miner is a huge supporter of the work.
And actually, it wrote me a very nice email after the podcast.
pilot study came out and was really grateful for what I was doing. So it's very encouraging. That actually
answers your other question about how supportive is Stanford. I think people who have an open mind,
I found this at Cleveland Clinic, that, you know, people who are in these sort of elite institutions
typically had more open minds because they were curious. They were asking questions. They were willing
to challenge orthodoxy. And of course, there was always the pushback. But this is this sort
a weird moment in psychiatry where I think we're kind of converging these two massive
paradigm shifts. One is around psychedelic medicine, trauma, and then metabolic psychiatry at the same
time. And it feels like they're complementary. I'd love to see them sort of combine all the pieces
because, you know, you can't just do one thing. Like, you know, if you have some serious trauma,
yes, you have to fix your metabolic function, your nutritional status, get your thyroid working,
get the toxins out of your system, then your brain can work better.
Right.
I always say it's a lot easier to be enlightened if you're not mercury poisoned or your thyroid's
working, you're going to be 12 deficient, right?
Absolutely.
But if you also have to look at the other end of the equation, which is, you know,
one of the psychological impacts that imprint on the brain and on our genes and epigenetics
that actually drive our psychiatric symptoms.
So it's sort of bidirectional, and you can't kind of do one without the other.
You know, one of the things that you talk about is eating disorders, and I was sort of curious about that, because the orthodoxy in eating disorders is don't restrict anything for these, often young girls, sometimes boys.
And yet you're talking about putting these kids on a ketogenic diet, which is extremely restrictive, right?
So what have you found with these?
Yeah, I have some colleagues.
This is one of the most life-friendly illnesses, is anorexia.
I have a colleague who's doing a trial looking at ketogenic diet and anorexia specifically.
You know, as a whole, when we look at eating disorders, whether it's anorexia or bulimia or binge eating, there are disruptions in several different pathways.
There's serotonin, dopamine, and opioid pathways as well.
A lot of the literature on anorexia and restriction has been largely, and with bulimia too, is that you would.
would exacerbate the symptoms when you're restricting a diet. But a lot of that literature is based
on low fat, low calorie diets, not necessarily thinking about, well, if you add fat back in
and you have moderate protein and, you know, you have kind of, you nourish yourself in kind of the right
way. So to me, it's not a diet. It's actually the way we should, we should be eating more like
this. Is that changing neurocognition? Is that changing the obsessions or compulsions, for
example, that you sometimes do see in anorexia and the rigidity. And that data isn't quite out
yet, but there is some preliminary data that is showing improvements, especially with binge eating
and Binge Eating and BLEMEA, we published some case series on this and recently published an article
a couple of weeks back on improvement and food addiction symptoms, which is a separate clinical
entity from binge eating disorder and obesity. But it tends to be in a subgroup in both conditions. And
And in that subgroup tends to be worse outcomes when you have the food addiction as well.
So there are reductions in binge eating and purging and, you know, so forth.
So we know, we have been looking at that and researching that data.
But it's not easy to do a ketogenic diet.
That's the hard part.
It's like you have to get rid of grains and beans and sugar.
And it's a personal choice.
If that's some, if someone wants to go down that path, you know, we will support it as long as it's clinically appropriate for them.
I did a trial in the past with a colleague in mine, Deborah Safer, at Stanford, which we looked at a obesity drug, FDA-approved obesity drug called Casimia, and we looked at that in binge eating disorder and bulimia and achieve abstinence rates of 63% while on the drug versus the control group was about 6%.
So there was a pretty significant difference between those that were taking the medication because it affects reward pathway, it affects
glutamate and GABA transmission, it was shown to be helpful for them.
That's amazing.
Where are the big gaps in our knowledge that we have to fill in this field?
How do we do the types of studies that are needed?
Because I remember Thomas Insull, who I met once, who was the former head of the National
Institute of Mental Health.
I said, what do you think of the DSM-5, which is the diagnostic and statistical manual
that used to describe psychiatric illness?
So essentially it's describing symptoms and categorizing people according to their symptoms, not causes.
He goes, well, I think it has 100% accuracy, but 0% validity.
Meaning it's great at putting people in categories of symptoms like you have schizophrenia, you have ADD, you have bipolar disease, you have depression, you have anxiety, you have OCD.
But it doesn't tell you anything about why.
And also it doesn't help you differentiate in those groups the different causes because you could have 10 people with depression with 10 different causes.
and you need to treat each one differently
instead of this one-size-fits-all medicine
which is kind of what we do.
Yeah, I remember him saying that before too
and, you know, he's right.
It's one way that we have as a field
to categorize the symptoms.
Where we would like to go is, you know,
you talked about biomarkers earlier
and thinking about what are the right biomarkers
and, you know, what's the right way
to have a tool that you can predict
certain symptoms arising
and thinking about
the metabolic pathways that are involved specifically looking at more mechanistic understanding
of that energy, vulnerability, and differences in diagnosis and disease state can be helpful.
But again, there's a lot of shared pathology, shared characteristics, and thinking about
more of that rude cause of what are the dysfunctions and why it's occurring.
And is it happening in all conditions?
A lot of times with psychiatry, there's a lot of different.
different causes, and it's heterogeneous, right? And so it can be quite complex. But I think the more
targeted we can be, and the more specific we can be with our treatments, who's going to do
better on what treatment. I think that's where we want to go and collecting our data. So, you know,
with the data that you guys are collecting with labs and the outcomes and the treatment, you know,
that we're collecting, I think that would be a really good way of figuring it out.
100%. I mean, and we're seeing this conversion.
of like the understanding of sort of the measurement of a sort of different metabolic pathways
that are off, but also sort of the personalization. So we sort of combine metabolic psychiatry
with personalized psychiatry, it becomes much more effective. More precision, yeah. Right. And I think
that's what I've always done with functional medicine is, you know, everybody's got a different
treatment, even if they have the same disease, because it depends on what their particular
their dysfunctions are, and you can actually assess those and measure those.
We can look at the microbiome.
We can look at the mitochondria.
We can look at, you know, the gut and food sensitivities.
We can look at nutritional status and different people.
We can look at all these different things that play a role.
I think we need to sort of better accelerate this because so many people are suffering.
Yeah.
And, you know, around the margins, there's these cracks in our conceptual framework in medicine.
There's a crack in the ideas that we all were trained in medical school, which is that diseases are these entities that show up, that we have to treat with drugs, that we don't really know why they happen necessarily, and we don't understand the causes, and we just kind of have to do our best downstream.
We have to get to upstream medicine, root cause medicine, systems medicine, network medicine, whatever you want to call it.
Yeah.
And I think, you know, the work that you're doing at Stanford around Metablock
psychiatry kind of breaks that through, but it's true across all of medicine.
You know, this is, this cracks are happening everywhere, whether it's autoimmune disease or
the other disease is.
The thing that I think people are wondering about, I'm sure if you're listening, is where do I start?
How do I, like, I'm depressed, I'm anxious, maybe I have bipolar disease, maybe I've got
a form of schizophrenia.
Like, what do I do?
What would you advise people to?
First understanding that there are tools out there right now that can be delivered and over time obviously will be refined and improved, but that there is a place to go to get care. We have a, you know, we have a line for people to contact us. We will recommend where we think it makes sense for them to get care. We offer care both at Stanford and at Metabolic Psychiatry Labs. And so there's a lot of, you know, research trials. I'm involved in several now. So,
that's also an avenue that patients can take. Hopefully we can get to a place where I have a
manual recommendation where they can kind of navigate. But for now, I've been able to set up,
you know, a line where people can contact and get information and if they want to enroll in care,
they can. Not bound by a geography, not bound by one academic center, right? And it's scalable and digital.
Yeah, every state. And that's the metabolic psychiatry labs.
Yeah.
And is that operational now?
Are people able to join?
It's operational.
It is venture-backed, and it is going to grow.
That's pretty exciting.
I mean, because I think talk therapy is helpful, but it's not going to fix people if they don't have these underlying things.
No, it's just one tool.
So I think we have to use all the tools in our show kit, whether it's trauma-informed therapy, whether it's psychedelic medicine, whether it's metabolic psychiatry, nutritional psychiatry, microbiome psychiatry, you know, which one of call it.
The job guy says, you know, your psychiatrist doesn't check your poop test when you go to the doctor
and you have depression, but they probably should.
I actually, speaking to the microbiome, I don't know how much you're looking at that,
but it was such a huge unlock for me to understand when we looked at people's bowel overgrowth of bacteria
or breast metabolites, you could check in organic acids, and you would treat them.
And sometimes I would treat psychiatric problems with antibiotics.
You clear out bacterial overgrowth.
or fungal overgrowth and people would come back to life.
I remember this little girl I had who was a beautiful nine-year-old little girl who was
just a terror and she was kicked out of her class like routinely in school on the bus
ride home.
They have to stop the bus 15 times to deal with her disruptive behavior and violence, aggression.
I did a urine test which looked at metabolites of bacteria and yeast in the gut and she just
was off the chart, like with fungal metabolites and bacterial metabolites and so I'm just going to
go back to first principles and reset her gut and give her an antibiotic and any fungal and give her some
probiotics. Good she had you. It was like the lights just came on in this girl overnight. She went from
like this terror to being this sweet little girl. And I was like, oh, wow, this is more here than I
understand in terms of what's affecting the brain and how the brain responds to different things
that are happening in the body that we haven't really begun to uncover. And so I'm exciting to
see, you know, 20 years later, now this is actually emerging as a field of inquiry, you know,
as something that people are paying attention to in major academic centers like Stanford. It's pretty
exciting. It's about time, right? It's about time, yeah. It's about time. Actually, the pans autoimmune
with OCD and depression. Pandas. Pandas, yeah. It's.
It's a call it Pans Clinic at Stanford.
But I've seen a lot of cases there where antibiotics really helpful were the psychiatric symptoms.
Yeah.
There was another biomarker like L. Acetyl carnitine that my colleague actually at Stanford had looked at as a marker of depression.
Yeah.
And with slow on depression, and so with antidepressants, it resolved the marker with treatment response.
Yeah.
I mean like, like, as is there, has improved carnitine levels?
Mm-hmm.
Interesting.
Yeah, the acetyl-al l-carnatine level, yeah.
So it's interesting that, you know, we might be giving drugs thinking they work one way,
but they might work another way.
Like statins may not really work by lowering LDL, but they work by lowering inflammation.
Exactly.
So that's why metabolic psychiatry is really thinking about the whole picture
and that there's multiple tools, both with medication and nutrition
and how it all gets put together.
Yeah, and I'm excited doing the omics work and depatomics and mitochondrial testing
because before we really had a hard time.
It was like looking at the sky without a telescope
or looking at bacteria without a microscope.
It's hard to see.
And now with the advent of deep diagnostics
that are available, not just regular biomarker testing,
but looking at what we call the omics,
which is your metabolomics,
all the metabolites you have in your blood,
the proteins you have in your blood, proteomics,
epigenetic expression,
we can start to map out
what was happening and see these patterns and then use AI and machine learning to help
us make sense of them and then kind of see how we can create more targeted solutions for people
based on these large data sets, which are becoming radically deflationary.
I mean, I think your whole genome sequence you can do for 300 bucks an hour used to be
a billion dollars.
Yeah, so we're poised at a very good time right now to be able to use technology to really
understand, you know, the science and the mechanisms.
And it's not just the sky.
There's a whole universe now, right?
Between the, you know, breaking down of food
and production of energy and waste products,
what we call metabolism, right?
So there's a whole universe out there
and excited to continue to explore it.
Exciting work.
I'm going to keep following what you do.
I'm going to maybe see if we can work together
to figure out the mental health biomarkers.
That would be something, right?
Yeah.
You see a psychiatrist to make a stand-of-care
to get a panel of biomarkers for mental health.
Let's make sure you don't miss anything.
Yeah.
You know, it's love to.
It would be amazing.
I mean, it really takes multiple brains and energy since we are all in limited supply to create something really wonderful.
Well, thank you.
How can people learn more about your work?
Metabolicpsychiatry.com or Metabolicpsychiatrylabs.com is the two websites.
It's a free resource.
Metabolicsychiatry.com is a free resource through Stanford that we created and happy to help anyone looking for anything specific.
and metabolic psychiatrylabs.com is, of course, the virtual remote care for metabolic psychiatry care that's nationwide.
And then there's a, for those nerds listening, there's a great article that you've written called metabolic dysregulation and metabolism-based approaches to mental health,
a narrative review of metabolic psychiatry, sort of trying to lay out a whole field, what it is, what we know, where we are now,
what are the options for therapy from nutrition to metabolic therapies to drugs that can modify these pathways?
and I think everybody should have a good look at that paper.
We'll put it in the show notes so we can track it.
Thank you for your work.
I'm going to keep on what you're doing.
We'll have you back maybe a few more years.
Another five years.
I really appreciate what you do in the world.
Yeah, likewise.
Thank you for having me, Mark.
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