Fix Your Brain by Fixing Your Body: Metabolic Psychiatry Explained by Dr. Shebani Sethi

For 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 Professor 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.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  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.

• 0:08Dr. Mark Hyman?

  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.

• 0:20Speaker 02

  Dr. Shebani 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.

• 0:32Dr. Mark Hyman?

  What is metabolic psychiatry?

• 0:33Speaker 00

  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.

• 0:57Dr. Mark Hyman?

  The thing that I think people are wondering about is where do I start? Like, I'm depressed, I'm anxious, maybe I have bipolar disease, maybe I've got a forms of schizophrenia, like, what do I do?

• 1:11Dr. Mark Hyman?

  Welcome, Shebani, 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 neurologists 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 in 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 bidirectional. But mostly, we focus on the mind-body effect.

• 1:55Dr. Mark Hyman?

  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 you're... When your knee hurts, if you sprain your knee, you know, it hurts, right? But if, 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 field that you sort of are deeply involved in, that you coined the term for, which is metabolic psychiatry. So maybe you can start off by saying, how did you come up with this? Where did it like originate from in your mind?

• 2:38Dr. Mark Hyman?

  And, and what is metabolic psychiatry?

• 2:41Speaker 00

  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.

• 2:50Dr. Mark Hyman?

  Yeah, the Ultra Mind Solution, right?

• 2:52Speaker 00

  Here we are, 15 and 20 years later, 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-

• 3:26Dr. Mark Hyman?

  Lactate is like when you exercise too much and your calves hurt because you're, you've got lactic acid in your muscles, that's happening in your brain.

• 3:33Speaker 00

  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 100 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

• 4:16Speaker 00

  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 dysfunction 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

• 4:58Speaker 00

  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.

• 5:31Dr. Mark Hyman?

  Yeah. So just for people listening, in medicine, we talk about metabolism and people say, I have a slow metabolism and lay culture, or I have fast metabolism. They mean a little bit different things. So metabolism is, yes, how you eat food and it converts into energy. But there's an enormous number of metabolic pathways. If you were to put on a wall in basically micro print, it would be a giant wall, all the metabolic pathways, you know, these sort of things we see in medical school. And every single one of those pathways are part of 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

• 6:11Dr. Mark Hyman?

  of the 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 lip sugars to it in the first year of medical school. We pretty much ignored 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 in a sense, metabolic psychiatry you're saying is, is the bigger rubric that encompasses all of that, not just sugar and glucose and metabolism from that perspective, right?

• 6:49Speaker 00

  Exactly.

• 6:50Dr. Mark Hyman?

  Yeah.

• 6:50Speaker 00

  Exactly.

• 6:51Dr. Mark Hyman?

  So I think, I think that's important to understand. And those metabolic pathways affect everything. So it's very complicated. We kind of like, look at that chart and maybe learn a little bit about it, but it's, 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, and the fact that you've, you sort of are pointing to the fact that the way we thought about mental illness might not be totally accurate. And, and I think this is part of the problem in our society is that, you know, if someone has rheumatoid arthritis, their joints are damaged. 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 like, how can I help? Well, 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

• 7:36Dr. Mark Hyman?

  to it. And I think through history, there's been this, this phenomena of different views of mental illness throughout history. And I think we're in this new era of, of understanding mental illness through 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.

• 7:55Speaker 00

  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 bodies related and, you know, organs are not just isolated and they're working in a whole system.

• 8:16Dr. Mark Hyman?

  Yeah.

• 8:17Speaker 00

  So, you know, if your city is, you know, running and it's not, if, if there's a

• 8:25Speaker 00

  Issue in the power grid and you're not having enough power and the light's flickering somewhere, there's, there's something that's wrong. And it, even though it's working, it's not working optimally. And so metabolic psychiatry takes different fields of endocrinology, immunology and so forth. And we really wanted to have at 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.

• 8:53Dr. Mark Hyman?

  Yeah.

• 8:53Speaker 00

  It really gives us a communication tool and map to be able to label something and, and to be able to work in a more collaborative way.

• 9:01Dr. Mark Hyman?

  And, and the truth is, you know, for the serious mental illnesses that you're talking about, I mean, 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 in the work, some of the work you've done, that you see profound changes in these intreatable mental illnesses, uh, when using this approach of metabolic psychiatry and nutrition and food is, can you kind of talk, how, how, how did you, cause you, you kind of came from the field of obesity medicine and also psychiatric

• 9:44Dr. Mark Hyman?

  medicine. So was that what kind of got you thinking about this or?

• 9:48Speaker 00

  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, um, which usually is not typical. I think normally it's maybe two days of lectures of nutrition in medical school, although I'm optimistic is changing. I had an opportunity to really delve more into obesity medicine, uh, starting in medical school. And that got me very interested in nutrition as well, because I started seeing differences, um, in, in patients when it came to psychiatric symptoms. And, uh, 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.

• 10:32Speaker 00

  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 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.

• 11:14Speaker 00

  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 are 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

• 11:57Speaker 00

  for those with bipolar, 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.

• 12:30Dr. Mark Hyman?

  Yeah.

• 12:31Speaker 00

  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.

• 12:53Dr. Mark Hyman?

  Yeah.

• 12:54Speaker 00

  That's, that's the, the thing that I saw. And then I just got more curious about this and that, than that connection.

• 13:01Dr. Mark Hyman?

  Yeah, it's a big crossover, like what, 40% of people with, with diabetes have mental illness, right?

• 13:07Speaker 00

  It's pretty high. So in bipolar illness, about 37, almost 40% have metabolic syndrome.

• 13:15Dr. Mark Hyman?

  Pre-diabetes, essentially, yeah.

• 13:17Speaker 00

  Full-blown metabolic syndrome. Yeah. You know, if you have insulin resistance, there, 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.

• 13:33Dr. Mark Hyman?

  And it depends on how you define pre-diabetes too, because I think if you look at some of the work out of TOFS, they looked at people with what they determined was metabolic dysfunction, which is either you're, 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, 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.

• 14:17Dr. Mark Hyman?

  And people don't understand that. People don't understand that, yeah, okay, I guess if I ate 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 I think, and then it becomes a vicious cycle. The more depressed you are, the less likely 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, the, the dive into this whole phenomenon of insulin resistance in the brain and how it affects you? And how it's somehow different than in peripheral insulin resistance? Cause you talk about like cerebral hypometabolism, which means low.

• 14:54Dr. Mark Hyman?

  Metabolism in the brain, right? And how it affects the brain and how insulin resistance plays a role in this. Consider unpack that.

• 15:02Speaker 00

  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.

• 15:44Speaker 00

  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.

• 16:28Speaker 00

  It can affect the hypothalamus, the nucleus of the hypothalamus. It can increase food intake. So it makes you, it increases your appetite.

• 16:37Dr. Mark Hyman?

  Hungry, yeah.

• 16:37Speaker 00

  Yeah, 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 you an example, 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, neuron

• 17:16Speaker 00

  Neural 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,

• 17:59Speaker 00

  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 resistance is part of that in psychiatric disease that then leads to HPA axis dysregulation or it leads to sleep disturbances and it leads to the obvious peripheral signs of metabolic dysfunction as well.

• 18:34Dr. Mark Hyman?

  So basically what you're saying in English is that, 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'd also have the psychiatric symptoms making you have worsened ability to regulate blood sugar insulin peripherally too, because it affects your stress response. It affects your, your whole metabolic system.

• 19:03Speaker 00

  Yes, in addition to medication side effects and so forth, but even the intrinsic metabolic.

• 19:10Speaker 00

  Dysfunction that exists in psychiatric conditions can also make someone more vulnerable in developing

• 19:17Dr. Mark Hyman?

  Yeah.

• 19:17Speaker 00

  those other conditions.

• 19:18Dr. Mark Hyman?

  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 are essentially the little energy factories inside your cells, and there's anywhere from hundreds to thousands and tens of thousands, the brain is the most dense per brain cell is the most mitochondria of any cell in your body. So energies are really important in the brain. What we find is if you're a type 2 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 can cause mitochondrial dysfunction. So it's a kind of virtuous, or maybe vicious cycle.

• 20:01Speaker 00

  It's a vicious cycle.

• 20:02Dr. Mark Hyman?

  It's a vicious cycle of dysfunction.

• 20:03Speaker 00

  Yeah.

• 20:04Dr. Mark Hyman?

  But on the other hand, 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.

• 20:17Speaker 00

  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 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.

• 20:49Dr. Mark Hyman?

  Yeah.

• 20:50Speaker 00

  So that's really what we're studying, and that's what we're trying to go further into with a lot of mechanistic studies, as well as looking at clinical outcomes and metabolic markers and so forth. I can go into that in detail, but.

• 21:07Dr. Mark Hyman?

  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 T N F alpha blockers for depression, which is like, you know, 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, you know, they think, well, it's inflammation in the brain. Let's give you an anti-inflammatory like, 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.

• 21:51Dr. Mark Hyman?

  And it's this metabolic dysfunction that tends to be both the cause and the consequence of it.

• 21:57Speaker 00

  Yeah. And I think we can think about all of these, whether they're drugs or even diets, they're different tools in the toolbox that we can use 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.

• 22:43Speaker 00

  And it also does decrease inflammation. So in some studies, it's been shown to reduce T N F alpha, reduce interleukin six, reduce other cytokines. And we know cytokines also are pro-inflammatory, right? And they end up also affecting serotonin synthesis. It affects tryptophan metabolism.

• 23:02Dr. Mark Hyman?

  Yeah.

• 23:03Speaker 00

  Hey, that's neurotransmitter, right? And that's, that's one part, but that's one part of the equation.

• 23:07Dr. Mark Hyman?

  Yeah.

• 23:08Speaker 00

  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 psychiatric medication onboard. It allowed the psychiatric medication onboard to work better. So that's, that's just one example of how a metabolic intervention 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, that are also.

• 23:43Speaker 00

  Being affected by it.

• 23:45Dr. Mark Hyman?

  And we basically what you're talking about is this up until now, most of psychiatry has been sort of downstream. Like you're, oh, neurotransmitters may be a problem, but the question is, why are they so messed up in the first place?

• 23:56Speaker 00

  Mm hmm.

• 23:56Dr. Mark Hyman?

  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, all these things that sort of accelerate the problem.

• 24:16Speaker 00

  Yeah.

• 24:16Dr. Mark Hyman?

  Actually.

• 24:17Speaker 00

  Exactly.

• 24:18Dr. Mark Hyman?

  Makes like these sort of neurotransmitter problems worse downstream. And you can treat the neurotransmitters or you can treat the cause, right?

• 24:25Speaker 00

  Yeah.

• 24:26Dr. Mark Hyman?

  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?

• 24:43Speaker 00

  Yeah, that's one. And, you know, increasing BD, BDNF, which you and I talked about last time, I think on your show, like now five years ago, the time has flown.

• 24:52Dr. Mark Hyman?

  Yeah.

• 24:53Speaker 00

  But you, you, you described it as miracle grow. And I really love the way you described it because it's exactly, it'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.

• 25:08Dr. Mark Hyman?

  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 schizophrenia, it's all this spectrum of brain dysfunction. And, and the, there's a lot of common pathways involved in all these. And then her work has 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 has autism and other subset is schizophrenia. But essentially, it's the same mechanism. She talks about using mitochondrial therapies, essentially cofactors that are involved in these metabolic steps. These biochemical steps require helpers.

• 25:49Dr. Mark Hyman?

  And so they use nutrients like amino acids or CoQ10 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 patients?

• 26:14Speaker 00

  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, cofactors, 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 malnourished in some way? If they have insulin resistance, obesity or metabolic syndrome, sure, let's treat that.

• 26:59Speaker 00

  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 abnormalities.

• 27:09Dr. Mark Hyman?

  Overfed and undernourished.

• 27:11Speaker 00

  Right, yeah.

• 27:11Dr. Mark Hyman?

  Too many calories, not enough nutrients, yeah.

• 27:13Speaker 00

  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, while I'm not specifically looking at one supplement and 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. My 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,

• 27:57Speaker 00

  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?

• 28:35Dr. Mark Hyman?

  Yeah, I mean, I think what you're bringing up is important. And, you know, medicine's very reductionist. And 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, and the body is so complex that it requires all the ingredients. And 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, 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, and I think that one way to navigate that is sort of emerging

• 29:18Dr. Mark Hyman?

  from our understanding of metabolomics and proteomics and, and gene expression products that are helping us understand the body in a more nuanced way. And I, I think one of the things I think a lot about is, what are the biomarkers of mental illness? And what are the things we should be looking at that, 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-3s Low and you take it, great, but if your vitamin D and magnesium are also low, might not work as well, right?

• 29:51Speaker 00

  Yep.

• 29:51Dr. Mark Hyman?

  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 A1C and all that. But it goes deeper than that.

• 30:09Speaker 00

  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.

• 30:51Speaker 00

  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.

• 31:35Dr. Mark Hyman?

  And that's directly related to insulin resistance. So the higher, 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.

• 31:46Speaker 00

  That's right.

• 31:46Dr. Mark Hyman?

  And you can go to two to one, four to one, 10 to one. You know, if your blood, if your triglycerides are 115, your HDL is 30, that's a five to one ratio. That's not good.

• 31:55Speaker 00

  What was interesting about that study is that insulin.

• 32:00Speaker 00

  Sensitivity wasn't associated with the chromicity of depression, but it was for the severity. But the triglyceride HDL ratio was associated with both. So there are some interesting nuances in the literature about about kind of looking at the biomarkers a little bit differently. And I think there's, there's a lot of different biomarkers that will be helpful. 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.

• 32:42Dr. Mark Hyman?

  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 methylmalic 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 are now available through Quest, which you do at Function Health, which measures C-peptide and insulin mass spectrometry to really accurately measure insulin resistance and triglyceride HDL ratio and particle size and particle number, inflammation levels, CRP. So all these things are blood tests that that actually can help clue you into many different problems.

• 33:26Dr. Mark Hyman?

  But, 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.

• 33:37Speaker 00

  I'm not surprised.

• 33:38Dr. Mark Hyman?

  It's like, not like what's an optimal level of vitamin D or what an optimal level of homocysteine is, but like homocysteine 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 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 is sick. We're seeing increasing mental illness and no one's really. Talked about how do we, how do we think differently about treating things systemically? And I think your, your, what you said is really important because it's a paradigm shift

• 34:22Dr. Mark Hyman?

  from thinking of the body as a bunch of different organs and parts to how the body's a network and everything's connected. And that we have to treat the network, not the symptom.

• 34:31Speaker 00

  Exactly.

• 34:32Dr. Mark Hyman?

  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 of brain inflammation and create a lot of neuropsychiatric symptoms.

• 34:45Speaker 00

  Absolutely.

• 34:46Dr. Mark Hyman?

  And then again, you're taking that out when you give people a keto diet, that's even part of it, you know?

• 34:50Speaker 00

  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, and also looking at-

• 34:57Dr. Mark Hyman?

  Looking at gluten antibodies?

• 34:58Speaker 00

  Yeah, we're planning to.

• 34:59Dr. Mark Hyman?

  Amazing.

• 35:00Speaker 00

  Yeah, just looking at mitochondrial deficits too. So we'll be, we'll be looking at that.

• 35:05Dr. Mark Hyman?

  So how are you doing that? Because it's, it's something in medicine, we, you know, we don't really pay attention to. We learn about mitochondria in the first year of 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.

• 35:40Speaker 00

  Yeah. I don't have an answer as to why we don't do it more, but I think it's, uh, you know, something that is probably difficult and hard to, 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-

• 36:09Speaker 00

  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 Kreb 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% of our capacity. We have, if we're talking a little bit more deeper in science, it'll be a 5% increase. Our daily activities, a bit less. And for someone that maybe has genetic predispositions or have environmental stress,

• 36:54Speaker 00

  it's gonna be a little harder to have that perfect machinery producing energy. And there's more metabolic vulnerability there. And so those differences between one region of the brain and another is pretty critical for functioning, cognition, mood, and mental health symptoms.

• 37:13Dr. Mark Hyman?

  And how are you thinking about measuring mitochondrial function as you're talking about in your upcoming studies?

• 37:20Speaker 00

  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 omic profiling, so all expression of proteomics, metabolomic data, wearable HRV data. Another faculty member is gonna 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.

• 38:05Speaker 00

  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, lactate's one of them, but there are a lot of other, there's sexinyl CoA, different dehydrogenases. So we'll be looking at all the, all the levels of that.

• 38:23Dr. Mark Hyman?

  It's not something you normally can get at a regular lab test.

• 38:25Speaker 00

  No.

• 38:26Dr. Mark Hyman?

  Is there a research-based test looking mitochondria?

• 38:28Speaker 00

  Yeah.

• 38:28Dr. Mark Hyman?

  I mean clinically, it's been a tough thing for us to look at because you could do a VO2 max test, which is basically an exercise treadmill test that measures

• 38:35Speaker 00

  Yeah.

• 38:36Dr. Mark Hyman?

  sort of indirectly your mitochondria. You can measure organic acids, which are urinary metabolites. And I think, you know, we all have subtle, 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, 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? Cause it's such a big, it's such a big black box and it's so important.

• 39:06Speaker 00

  Yeah.

• 39:06Dr. Mark Hyman?

  And then you can actually even be specific and say, oh, this pathway that requires CoQ10 is a little slow. So what if I give extra CoQ10, it's going to speed it up?

• 39:15Speaker 00

  And it becomes more personalized that way, right? Like a bit 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 controlled trial, and we'll be collecting a lot of data, continuous ketone monitoring. Abbott donated the devices.

• 39:34Dr. Mark Hyman?

  Glucose monitoring.

• 39:35Speaker 00

  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 of these measures. And it's exciting. We're excited about it.

• 39:46Dr. Mark Hyman?

  You know, what, what you're offering to people is not here, take this pill for your mental illness, but here, here's a lifestyle change that can have profound effects. How do you do that? Because th- 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, how are you getting people to do that?

• 40:10Speaker 00

  Yeah, that's a good question. And, you know, I do want to recognize that it's, 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

• 40:54Speaker 00

  to stay on, on the, on the diet or the approach as well.

• 40:57Dr. Mark Hyman?

  Yeah.

• 40:58Speaker 00

  So I think a combination of that.

• 41:00Dr. Mark Hyman?

  A lot of good side effects. Yeah.

• 41:02Speaker 00

  Yeah, a lot of good side effects. Yeah.

• 41:04Dr. Mark Hyman?

  I mean, in your clinical trial, you know, like ketogenic diet for bipolar schizophrenia that recently published with 23 patients, you had a hundred percent 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 IR is probably not as good as the, this new insulin resistance score that Quest is doing through.

• 41:28Speaker 00

  Oh, yeah.

• 41:29Dr. Mark Hyman?

  Through the aspect.

• 41:30Speaker 00

  We're doing that now. Yeah.

• 41:31Dr. Mark Hyman?

  But, you know, dramatic reductions in psychiatric symptoms and so improved sleep, life satisfaction, all these great side effects, you know?

• 41:40Speaker 00

  Yeah, in four months.

• 41:41Dr. Mark Hyman?

  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, and does that encourage people to stick with it more because they're seeing the positive effects?

• 41:53Speaker 00

  It, 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 life. It gives them hope. And a lot of the patients that were in that pilot study that I did, it was published last year, but are still my patients today. A lot of them are still my patients today. And I, and a lot of them are still on a ketogenic diet. So it does speak to,

• 42:38Speaker 00

  I guess, the feasibility.

• 42:40Dr. Mark Hyman?

  Yeah.

• 42:40Speaker 00

  Of being on it over time. And I, 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.

• 43:04Dr. Mark Hyman?

  Yeah.

• 43:04Speaker 00

  I don't 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, 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, and start something and found a company that's really just focused on providing that care.

• 43:34Dr. Mark Hyman?

  Yeah.

• 43:34Speaker 00

  Cause 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.

• 43:42Dr. Mark Hyman?

  I mean, it takes decades for scientific discoveries 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, 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 this sort of stepchild, fourth cousin, once for who?

• 44:13Speaker 00

  Not science enough.

• 44:14Dr. Mark Hyman?

  Yeah, not, but what, what you're talking about is a nutritional therapy that has effects of orders of magnitude more than our traditional therapies. So it, it's not like it's an equivalent therapy. It's, it's so much better. And I wonder if in, in terms of your, your work at Stanford, are you, are you finding resistance or are you finding? Encouragement or openness to this idea because it's it's sort of a

• 44:40Speaker 00

  Yeah, a lot of people ask me that question and I appreciate that I I have found a lot of support. With anything, there is, there's always waves, right? But but I have found a good amount of support, especially with all the activities I'm involved in. And I'm in Palo Alto, Silicon Valley, right? It's pretty common for professors to spin out companies outside academia as well. I love doing the research. I I believe it's important to have evidence based science. So I'll still continue to do that. But also, you know, having having the support to be able to move between these worlds is is something that I'm grateful for.

• 45:18Dr. Mark Hyman?

  And so so your psychiatry colleagues are not going. What are you doing using food in medicine? This you should be using drugs.

• 45:26Speaker 00

  I think some people are like, how do you stay on that? How do you stay on a ketogenic diet, right? But again, I think it's the way you approach it. I think understanding, I think education, understanding around. It's a 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 someone trained in that area. And there are other metabolic tools. I wrote this in a 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?

• 46:08Speaker 00

  I'm more hopeful because there is 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 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 really

• 46:52Speaker 00

  Improve the access to get these labs.

• 46:55Dr. Mark Hyman?

  Yeah.

• 46:55Speaker 00

  And what we're doing at Metabolic 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 healthcare 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 obligated to go in this is myself, after I had a child, I had a really significant tailbone injury.

• 47:37Dr. Mark Hyman?

  Oh.

• 47:38Speaker 00

  And I couldn't sit for nine months.

• 47:40Dr. Mark Hyman?

  Okay.

• 47:41Speaker 00

  And so, and 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 cast or, you know, I, you know, I didn't have, it wasn't visible.

• 47:53Dr. Mark Hyman?

  Right.

• 47:54Speaker 00

  There was a colleague of mine that sent me a book on tailbone pain.

• 48:00Dr. Mark Hyman?

  Oh.

• 48:01Speaker 00

  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 healthcare system?

• 48:10Dr. Mark Hyman?

  Yep.

• 48:10Speaker 00

  And how do you tell your OB-GYN 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 it might be done, but I wanted to do that for those with serious mental illness. Starting Metabolic Psychiatry Labs is part of that reason.

• 48:30Dr. Mark Hyman?

  And you mean, you're starting with the sort of most extreme case, right? Schizophrenia, severe bipolar disease, but you know, the spectrum of mental illness goes from just a little anxiety and depression.

• 48:39Speaker 00

  Absolutely.

• 48:39Dr. Mark Hyman?

  To OCD, to more serious things. So, you know, across that whole spectrum, this approach can work, right?

• 48:44Speaker 00

  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, and having a metabolic approach, especially if 90, you know, something percent have metabolic abnormalities, why couldn't they not, you know, benefit from, from something that's tangible and targeted and specific and evidence-based?

• 49:18Dr. Mark Hyman?

  I mean, it's really interesting because I first started 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 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 and their OCD gets better.

• 50:02Dr. Mark Hyman?

  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.

• 50:12Speaker 00

  And like, And see, I think the reason why you ended up maybe putting that together is because you were 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 that 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.

• 50:32Dr. Mark Hyman?

  Totally. I mean, I joke and call myself the accidental psychiatrist 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.

• 50:50Speaker 00

  You're trying to find solutions.

• 50:51Dr. Mark Hyman?

  And they, 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.

• 51:05Speaker 00

  I think you'll be excited to know that we're also looking at microbiome. We're testing the microbiome also before and after with the trials. So genetic, you know, data too. So it's really like a big library of data that we'll collect and happy to collaborate.

• 51:20Dr. Mark Hyman?

  Yeah, very fascinating.

• 51:23Dr. Mark Hyman?

  I think our data set is 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 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. How do we start to study what's happening? And we actually had a talk with Lloyd Minor, who's the dean of Stanford about collaborating on some research projects.

• 51:50Speaker 00

  Oh, good.

• 51:51Dr. Mark Hyman?

  Because, you know, it's hard to do a study. I mean, you want to do a study with 120 people, 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 in biomarkers on each one, which is tens of millions of biomarkers.

• 52:13Speaker 00

  Really good way to collaborate.

• 52:14Dr. Mark Hyman?

  That literally we have available to sort of figure out what's happening with the population when they change things to do this. And I think it's going to be interesting.

• 52:23Speaker 00

  Absolutely. Yeah, we should talk more about that. I'd love to. Actually, Lloyd Minor is a huge supporter, you know, of the work and actually wrote me a very nice email after the 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?

• 52:42Dr. Mark Hyman?

  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 is this sort of 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

• 53:26Dr. Mark Hyman?

  nutritional status, get your thyroid working, get the toxins out of your system, then your brain can work better.

• 53:32Speaker 00

  Right.

• 53:32Dr. Mark Hyman?

  I always say it's a lot easier to be enlightened if you're not mercury poisoned or your thyroid's working, you're not B12 deficient, right?

• 53:38Speaker 00

  Absolutely.

• 53:39Dr. Mark Hyman?

  But, but if you also have to look at the other end of the equation, which is, you know, what are the, what are the psychological impacts that imprint on the brain and on our genes and epigenetics? That actually drive our psychiatric symptoms. So it's it's sort of bidirectional and you can't kind of do one without the other. You know, one of the things that you talked about is eating disorders. And and I was sort of curious about that because the 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?

• 54:19Speaker 00

  Yeah.

• 54:20Dr. Mark Hyman?

  This is a life threatening. This is one of the most life threatening illnesses is anorexia.

• 54:24Speaker 00

  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 is 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 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,

• 55:03Speaker 00

  well, if you add fat back in and you have moderate protein and you have kind of you nourish yourself in kind of the right way. So to me, it's not 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 you see in anorexia and the rigidity? And that data isn't quite out yet, but there are there is some preliminary data that is showing improvements, especially with binge eating and bulimia. 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.

• 55:46Speaker 00

  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, we have been looking at that.

• 56:06Dr. Mark Hyman?

  That's incredible. 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.

• 56:12Speaker 00

  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 of mine, Deborah Safer, at Stanford, which we looked at a obesity drug, FDA-approved obesity drug called Cosimia, and we looked at that in binge eating disorder and bulimia and achieved 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.

• 56:56Dr. Mark Hyman?

  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 Insol, 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? 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.

• 57:38Dr. Mark Hyman?

  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.

• 57:52Speaker 00

  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

• 58:35Speaker 00

  more of that root 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 causes and it's heterogeneous.

• 58:49Dr. Mark Hyman?

  Yeah.

• 58:50Speaker 00

  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 in 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.

• 59:15Dr. Mark Hyman?

  A hundred percent. I mean, and we're seeing this convergence of like the understanding of sort of the measurement of our sort of different metabolic pathways that are off.

• 59:25Speaker 00

  Yeah.

• 59:26Dr. Mark Hyman?

  But also sort of the personalization. So we sort of combine metabolic psychiatry with personalized psychiatry, it becomes much more effective.

• 59:36Speaker 00

  More precision, yeah.

• 59:37Dr. Mark Hyman?

  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 dysfunctions are. And you can actually assess those and measure those.

• 59:48Speaker 00

  Exactly.

• 59:49Dr. Mark Hyman?

  We can look at the microbiome, we can look at mitochondria, we can look at, you know, the gut and food sensitivities, we can look at nutritional status in different people, we could toxin load in different people, we could 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.

• 1:00:07Speaker 00

  Yeah.

• 1:00:08Dr. Mark Hyman?

  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.

• 1:00:36Speaker 00

  Yeah.

• 1:00:37Dr. Mark Hyman?

  And I think, you know, the work that you're doing at Stanford around metabolic 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 neurodegenerative diseases. The thing that I think people are wondering about, if 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?

• 1:01:04Speaker 00

  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.

• 1:01:45Speaker 00

  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.

• 1:02:01Dr. Mark Hyman?

  And that's the Metabolic Psychiatry Labs?

• 1:02:03Speaker 00

  Yeah.

• 1:02:04Dr. Mark Hyman?

  And is that operational now that people able to?

• 1:02:07Speaker 00

  It's operational. It is a venture backed and it is gonna grow.

• 1:02:12Dr. Mark Hyman?

  That's pretty exciting. I mean, because I think talk therapy is helpful, but it's it's not gonna fix people if they don't have these underlying things.

• 1:02:20Speaker 00

  No, it's just one tool.

• 1:02:22Dr. Mark Hyman?

  So I think we have to use all the tools in our toolkit, whether it's trauma informed therapy, whether it's psychedelic medicine, whether it's metabolic psychiatry, nutritional psychiatry, microbiome psychiatry, I don't know which one to call it.

• 1:02:33Speaker 00

  Integration.

• 1:02:34Dr. Mark Hyman?

  The job Gary 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 of 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 various metabolites, you can check in organic acids and you would treat them. And sometimes I would treat psychiatric problems with antibiotics. Clear out bacterial overgrowth or fungal overgrowth and people would come back to life. You know, I remember this

• 1:03:07Speaker 00

  That's right. Yeah.

• 1:03:08Dr. Mark Hyman?

  Little girl I had who was beautiful nine year 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 had 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's just off the chart, like with fungal metabolites and bacterial metabolites. And so like, I'm just gonna go back to first principles and reset her gut and give her an antibiotic and an A fungal and give her some probiotics.

• 1:03:45Speaker 00

  Good she had you.

• 1:03:46Dr. Mark Hyman?

  It was like the lights just came on in this girl overnight. And 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 excited to see, you know, 20 years later, there's now this is actually emerging as as a field of inquiry and, you know, as something that people are paying attention to in major academic centers like Stanford. It's it's pretty exciting.

• 1:04:18Speaker 00

  It's about time, right?

• 1:04:19Dr. Mark Hyman?

  It's about time. Yeah. About time.

• 1:04:21Speaker 00

  Actually, the PANS autoimmune, OCD and depression.

• 1:04:25Dr. Mark Hyman?

  Pandas.

• 1:04:26Speaker 00

  Pandas. Yeah.

• 1:04:28Speaker 00

  Call it Pan's Clinic at Stanford, but I've seen a lot of cases there where antibiotics really helpful for the psychiatric symptoms.

• 1:04:34Dr. Mark Hyman?

  Yeah.

• 1:04:34Speaker 00

  There was another biomarker like L-acetyl-carnitine.

• 1:04:38Dr. Mark Hyman?

  Yeah.

• 1:04:39Speaker 00

  That my colleague actually at Stanford had looked at as a marker of depression.

• 1:04:43Dr. Mark Hyman?

  Yeah.

• 1:04:44Speaker 00

  And with anti, it's low on depression. And so with antidepressants, it resolved the marker.

• 1:04:51Dr. Mark Hyman?

  Really?

• 1:04:52Speaker 00

  With treatment response. Yeah.

• 1:04:53Dr. Mark Hyman?

  You mean like, does her eyes improve carnitine levels?

• 1:04:56Speaker 00

  Mm hmm.

• 1:04:56Dr. Mark Hyman?

  Interesting.

• 1:04:57Speaker 00

  Yeah, the acetyl L-carnitine level.

• 1:05:00Dr. Mark Hyman?

  So it's interesting that, you know, we, we might be giving drugs thinking they work one way, but they might work another way.

• 1:05:05Speaker 00

  Exactly.

• 1:05:05Dr. Mark Hyman?

  Like statins may not really work by lowering LDL, but they work by lowering inflammation.

• 1:05:09Speaker 00

  Exactly. So that's why, 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.

• 1:05:21Dr. Mark Hyman?

  Yeah. And I'm excited doing the omics work and the metabolomics and mitochondrial testing because before we really had a hard time, like it was like, it was like looking at the sky without a telescope and, or looking at, you know, bacteria without a microscope. It's hard to see. And now with the advent of, of deep diagnostics that are available, not just regular biomarker testing, but

• 1:05:45Speaker 00

  Yeah.

• 1:05:46Dr. Mark Hyman?

  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's happening and see these patterns.

• 1:05:58Speaker 00

  Yeah.

• 1:05:59Dr. Mark Hyman?

  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, these large data sets, which

• 1:06:09Speaker 00

  Exactly.

• 1:06:09Dr. Mark Hyman?

  are, are becoming radically deflationary. I mean, I think your, your whole genome sequence, you can do for 300 bucks an hour. It used to be a billion dollars.

• 1:06:17Speaker 00

  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 food and production of energy and waste products, what we call metabolism.

• 1:06:35Dr. Mark Hyman?

  Yeah.

• 1:06:35Speaker 00

  So there's a whole universe out there and excited to continue to explore it.

• 1:06:41Dr. Mark Hyman?

  It's exciting work. I'm gonna keep following what you do. I'm gonna maybe see if we can work together to figure out the mental health biomarkers. That would be something, right?

• 1:06:47Speaker 00

  Yeah.

• 1:06:48Dr. Mark Hyman?

  See a psychiatrist to make a standard of care to get a panel of biomarkers for mental health. Let's make sure you don't miss anything.

• 1:06:53Speaker 00

  Yeah.

• 1:06:54Dr. Mark Hyman?

  You know, it's

• 1:06:55Speaker 00

  Love to.

• 1:06:56Dr. Mark Hyman?

  Be amazing.

• 1:06:56Speaker 00

  I mean, it really takes multiple brains, energy.

• 1:07:00Dr. Mark Hyman?

  Yeah.

• 1:07:01Speaker 00

  Uh, since we are all in limited supply, uh, to, to create something really wonderful.

• 1:07:05Dr. Mark Hyman?

  Well, thank you. How can people learn more about your work?

• 1:07:07Speaker 00

  Metabolic Psychiatry.com or Metabolic Psychiatry Labs.com. Um, it's the two websites. It's a free resource. Metabolic Psychiatry.com is a free resource through Stanford, uh, that we created and happy to help anyone looking, uh, for, you know, anything specific. And Metabolic Psychiatry Labs.com is of course the virtual, uh, remote care for metabolic psychiatry care that's nationwide and

• 1:07:31Dr. Mark Hyman?

  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 in mental health. And there to 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, I, I think everybody should have a, 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 gonna keep following what you do. I'll have you back maybe a few more years.

• 1:08:00Speaker 00

  Another five years.

• 1:08:02Dr. Mark Hyman?

  Having next. I really appreciate what you do in the world.

• 1:08:05Speaker 00

  Yeah, likewise. Thank you for having me, Mark.

• 1:08:07Dr. Mark Hyman?

  When it comes to supplements, you only want the best for your body, the kind with the highest quality, cleanest and most potent ingredients you can get. That's exactly what you'll find at my supplement store where I've hand selected each and every product to meet the most rigorous standards for safety, purity and effectiveness. These are the only supplements I recommend to my patients and they're also what I use myself. Whether you want to optimize longevity or reduce your disease risk, or you're looking to improve your sleep, blood sugar, metabolism, gut health, you name it. Drhyman.com has the world's best selection of top quality premium supplements, all backed by science and expertly vetted by me, Dr. Mark Hyman. So check out Drhyman.com because when it comes to your health, nothing less than the very best will do. That's Drhyman.com, D R H Y M A N dot com.

• 1:08:50Dr. Mark Hyman?

  If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health, where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional.

• 1:09:35Dr. Mark Hyman?

  This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center, at ultrawellnesscenter.com, and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.