Good Life Project - The Surprising Link Between Metabolism & Mental Illness | Dr. Chris Palmer

Episode Date: June 29, 2023

Discover the compelling link between mental health and metabolic dysfunction with Harvard psychiatrist, Dr. Chris Palmer and author of the book Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health--and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More.After years of treating patients, he stumbled upon a paradigm shift - a schizophrenia patient's symptoms went into remission with a ketogenic diet, pushing him toward the metabolic roots of mental health. Could mental illnesses be metabolic disorders caused by dysfunctional mitochondria in the brain? Join us to explore this revolutionary breakthrough, blending diet, lifestyle changes and metabolic interventions, and how it can redefine treatment for millions globally suffering from mental disorders.You can find Chris at: Website | InstagramIf you LOVED this episode you’ll also love the conversations we had with Aviva Romm, MD about how hormones control health, and what we can do about it.Check out our offerings & partners: My New Book SparkedMy New Podcast SPARKEDVisit Our Sponsor Page For Great Resources & Discount Codes Hosted on Acast. See acast.com/privacy for more information.

all mental disorders appear to share one common pathway. I am very boldly and audaciously asserting that the common pathway is actually metabolism, that mental disorders are metabolic disorders of the brain. And once you understand the science of mitochondria, we can actually begin to connect the dots of all of the different risk factors that we know play a role in mental illness. And we can also begin to understand exactly how and why the brain might malfunction if it is metabolically compromised. But the much more exciting news in my mind is that it leads to an entirely new way to understand and treat mental illness. So big, powerful, and potentially provocative question

for you. What if mental illness, mental disorders like depression, anxiety, and schizophrenia were actually metabolic disorders of the brain? And treating metabolic dysfunction at the level of mitochondria, those power plants of the cell, could potentially help millions suffering from mental illness. My guest today, Chris Palmer, has spent three decades treating mental health disorders, only to find that most patients did not get better with conventional treatments. And that all changed when a patient with schizophrenia saw his symptoms go into remission from a ketogenic diet, sparking Chris's journey into understanding what was actually happening. What were the metabolic roots of mental health beyond the behavioral roots? So Chris is a Harvard psychiatrist,

researcher, and author of the book Brain Energy, a revolutionary breakthrough in understanding mental health and improving treatment for anxiety, depression, OCD, PTSD, and more. After 27 years of clinical practice, Chris has integrated metabolic interventions into his treatment plan and now champions a comprehensive lifestyle approach focused on diet, exercise, sleep, and stress management. And this really inspired Chris to investigate how all different ways of eating, including the ketogenic approach, could help severe mental illness, which led him eventually

to the discovery that mitochondria, those cells power plants that we all learned about in, I think, middle school probably, how they play this incredibly important role in regulating neurotransmitters and brain function. And that plays a powerful role in how we feel. Chris came to believe that mental disorders may actually be metabolic disorders caused by dysfunctional mitochondria that just can't produce enough ATP to fuel brain cells. And numerous studies show that metabolic abnormalities in people with mental illness and abnormalities in mitochondria function coincide. However, as Chris is very clear on, this isn't just about diet. Diet alone isn't enough. We explore that as well as factors like sleep, stress, substance use, relationships.

They all impact mitochondrial function and metabolism and in turn, mental health. With Chris's holistic metabolic perspective, he believes we can finally solve the century old mystery of mental illness, move beyond just symptom management and truly improve the lives of the 1 billion people worldwide suffering from mental health struggles and challenges. This was such a powerful and eye-opening conversation. I am so excited to share it. I'm Jonathan Fields, and this is Good Life Project. The Apple Watch Series X is here. It has the biggest display ever.

It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you 8 hours of charge in just 15 minutes. The Apple Watch Series X. Available for the first time in glossy jet black aluminum.

Compared to previous generations, iPhone XS or later required. Charge time and actual results will vary. Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were gonna be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the

difference between me and you is? You're going to die. Don't shoot him, we need him. Y'all need a pilot. Flight risk. We're having this conversation at an interesting moment in time and culture, emerging from three years that have been fairly brutalizing on a lot of different levels for a lot of different people on a global

scale, not the least of which is people's mental health. And if folks were saying that there was a profound crisis in the state of mental health before these last few years, I think only exacerbated. Let's zoom the lens out a little bit because you have an interesting take, I think, on sort of like the general state of mental health and culture today. Talk to me a little bit about what you're seeing. You know, as you said, I think most people are aware that we have a mental health crisis and some people are thinking it's due to the pandemic, but unfortunately has been going on for a few decades now.

Mental disorders have been increasing in prevalence really throughout the world. And in 2017, as a snapshot, which is some of the last comprehensive data that we have from the World Health Organization, approximately 1 billion people on the planet had a mental disorder. And mental disorders are now the leading cause of disease burden and the leading cause of disability on the planet. What that means is that although we have a lot of treatments that do work for people, and I am not here to bash them, I am not here to bash the mental health field, I have been a psychiatrist for over 27 years. I am deeply passionate about this work and about this field. But if we really take a hard look

at how we're doing as a mental health field, the real answer is that far too many people do not get better with the treatments that we have to offer. You know, I think most people understand that diagnoses like schizophrenia and bipolar disorder are lifelong chronic disorders that can ruin people's lives. But in fact, plain old depression is now the leading cause of disability on the planet. It tops the list of all medical diagnoses that disable human beings. So we're really in a crisis and we need new answers and new solutions. I'm curious, as you described, this is not new. Many people may have surfaced and piled on through external circumstances over the last years, but this is a multi-generational, if not like it's been following us for the history of humanity type of thing. And it seems like the last generation or two, there've been new

medications, new therapeutic approaches, as you suggested, like they're doing a good job for some people on some level. It doesn't feel, and I'm curious, because I'm sort of like looking at it from the outside in, you're looking at it from the inside out. From the outside looking in, it feels like the last decade or two, there hasn't been sort of like the level of big ahas or big breakthroughs or therapeutic modalities where you could say there has been an exponential increase in the efficacy of the way that we step into a wide variety of mental illness. Is that a valid observation or is that just sort of like my jaded lens? No, unfortunately, that is a very astute and accurate lens. And here's the even more disturbing sad truth. You know, we have, for example, if we look at psychopharmacology, medications to treat mental illness, whether it be anxiety medications or depression medications or schizophrenia or bipolar medications, the reality is that many of them, most of them, in fact, were discovered through serendipity, meaning that we really didn't expect

to find an antidepressant, but we just happened to notice that, for example, a tuberculosis medication was making tuberculosis patients less depressed. And that was actually the first antidepressant that we got. Some astute infectious disease physician noticed, wow, these tuberculosis patients who are depressed are getting less depressed, and maybe we should use it in those patients on the psychiatry ward and see if it helps them. Lo and behold, it did help at least some of them, And we were off to the races. That was now an antidepressant. And even though we have had an explosion of neuroscience research looking at, well, exactly what are these medications doing? Maybe if we can figure out what these medications are

doing, we can develop new pills. There's no doubt we developed a lot of new pills. We developed pills that focus on serotonin receptors or dopamine or norepinephrine, other neurotransmitter levels or receptors, but all of that was through serendipity. The reality is we still cannot definitively explain how or why do these medications work. The first antipsychotic was an anesthetic medication. Mood stabilizers were discovered serendipitously. And that is part of the challenge. So your point about we haven't had any major breakthroughs, the reason is because we're winging it with all of these serendipitous findings. And the reality is that the crux of the problem is that if you ask the leading psychiatrists and

neuroscientists in the world a fairly simple question, if you ask them, what exactly causes mental illness, they can't give you a definitive answer. And that's a problem. That is a problem because if we don't understand the cause, we can't develop more effective treatments. I mean, it makes sense then. If you don't understand what is the root, then the only approach is really to just say, let me try a whole bunch of these different things and see if it affects the symptomology. If it does, great, we've got

something, but you never actually understand the causal reason why or what's actually happening here. Because not only can you not understand why is it working, but you don't even understand why the dysfunction is there in the first place, which makes it really hard to build a science-based intervention that you can track and build on in a robust way. That is exactly the crux of the problem in the mental health field today. I would imagine this is not for a lack of people really devoting tremendous resources and time and energy and desire to figure this out. Is it just that thorny a problem?

I think it's a couple of things. So one is it is that thorny of a problem. We have spent billions of dollars on research over the last century, easily, trying to understand what is happening in the brains of these people with mental illness. We've done all of these neuroimaging studies. As soon as they map the human genome, neuroscientists and psychiatrists were on that project, trying to figure out where are the genes for mental illness. Maybe now we can finally once and for all figure it out because we know these disorders run in families. So it's not for a lack of trying, and it's not for a lack of some resources and reasonably large resources. You can probably tell I'm being careful about the way I

phrase that. And I just want to point out one statistic. Approximately four years ago, which again is probably the time that we have the most comprehensive data, about four years ago, the global healthcare research budget, if you looked at all of the research dollars going to health conditions, diseases and disorders, only 4% was allocated to mental health, even though mental disorders are the leading cause of disease burden and disability on our planet. In many ways, that is unconscionable. But I think part of the problem is that the researchers all seem to be shooting in the dark. And without a clear path to more rapid advances in our field, the powers that be don't really want to spend a lot of money on research because the billions of dollars that they have spent don't seem to have anything new to show for it, which goes back to the point you made earlier. We don't really have any breakthroughs in treatment. And if anything, the tragic reality is we're losing ground. We're not developing new revolutionary blockbuster treatments, but the existing treatments that

we have seem to be increasingly less effective or mental disorders are spreading like the plague because, again, the prevalence statistics are skyrocketing. And this goes across the board for numerous diagnostic categories, depression, anxiety, bipolar disorder, autism. Autism spectrum disorder has tripled in prevalence in the last 15 years. And researchers are scratching their heads, what's going on? How can this be? And so I don't think the politicians and the funding sources want to spend a tremendous amount of money because they're not really seeing results for the money that they are spending. Yeah. It's interesting also, we've sort of been talking about these under the general umbrella of mental illness for many of these different conditions, they're still viewed as separate things. Like if you have depression, oh, it's

this. If you have anxiety, oh, it's this. If you have OCD, oh, it's this. If you have living with bipolar, oh, it's this. That's not the way you look at them. No, that's not the way I look at them at all. That's not the way the science actually says they really exist. So, although on the surface, those diagnostic labels are very descriptive of symptoms to us. So, if I say somebody has anorexia nervosa, you get a very clear picture quickly, probably of a woman who's thin and starving herself. If I say somebody has schizophrenia, you might picture somebody who's talking to himself, hearing voices, delusional.

If I say somebody's depressed, you get a clear picture of what that looks like. The shocking thing for people who aren't familiar with this field is that mental disorders are actually not as distinct and separate from each other as most people think, or as I just articulated. And there are two primary reasons for that. So they really fall in categories of something called heterogeneity and comorbidity. Heterogeneity means if I look at two people with the same diagnostic label, they can have very different symptoms and look and function very differently from each other. And it can be really difficult to believe that they have the same brain disorder or disease or illness or whatever we want to call it. So, two people

with autism spectrum disorder, we have billionaires in our society who have been labeled on the spectrum. And then at the same time, we have other people who are completely devastated by that diagnosis. They're living in group homes. They're unsafe. They may have cognitive impairment. They may have seizures on top of it. And they look and function very differently. And it can be hard to imagine that somehow those people have anything in common. The other issue is this issue of comorbidity. And what that means is that if you have one mental disorder and you're getting treatment, the people who seek treatment for mental health disorders are much more likely to have more than one. One study of a clinic actually found that on average, people have about three

and a half different diagnoses. So that means if you come in for your depression, you might also have symptoms of a substance use disorder. You might also have OCD. You may have an anxiety disorder. But then when we follow people longitudinally, they develop new disorders that are seemingly unrelated. So one shocking statistic, people who start off with an anxiety disorder are anywhere from 8 to 13 times more likely to go on to develop schizophrenia. And on the surface, most people would think anxiety has nothing to do with schizophrenia. But when you look at statistics like that, it starts to become much murkier.

This actually gets extraordinarily detailed and complicated because when researchers look at any of the risk factors for mental illness, it turns out that almost every risk factor confers risk for numerous mental disorders, not just one. So I'll give you one easy example that some people probably are aware of, but I'll just really try to drill this home. So most people think of post-traumatic stress disorder as, well, that's people who've been traumatized. Well, it turns out that people who've been traumatized, yes, absolutely, they are more likely to go on to develop post-traumatic stress disorder, but they're also more likely to go on to develop depression, anxiety disorders, schizophrenia,

bipolar disorder, substance use disorders, alcoholism, opioid use disorders. They're more likely to develop personality disorders. And so one risk factor confers risk for numerous disorders, seemingly very different disorders. And shockingly to most people, this goes to the level of genetics. A lot of people know that bipolar disorder runs in families, but when researchers have zeroed in on exactly which genes confer risk for bipolar disorder, it turns out it's not specific to bipolar disorder. Those same genes also confer risk for schizophrenia and depression and anxiety

disorders and epilepsy and learning disorders and all sorts of disorders all at the same time. And there's a whole body of research that has looked at everything that I've just talked about, and they have actually come to the conclusion, several different researchers using different methods, research methods, different data sets, have come to the conclusion that actually all mental disorders appear to share one common pathway. Okay. So then we need to know what that common pathway is. They seem to share something in common. So I am very boldly and audaciously asserting that the common pathway is actually metabolism, that mental disorders are metabolic disorders of the brain. And in order to understand what that means,

you have to understand these tiny things in our cells called mitochondria. And once you understand the science of mitochondria, we can actually begin to connect the dots of all of the different risk factors that we know play a role in mental illness. And we can also begin to understand exactly how and why the brain might malfunction if it is metabolically compromised. But the much more exciting news in my mind is that it leads to an entirely new way to understand and treat mental illness. Which is so powerful. The Apple Watch Series 10 is here. It has the biggest display ever.

It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you eight hours of charge in just 15 minutes. The Apple Watch Series 10, available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required.

Charge time and actual results will vary. Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is? You're going to die.

Don't shoot him. We need him. Y'all need a pilot. Flight risk. So this over time in your work has coalesced into a sort of a unified theory of mental illness, both in how we understand it and also how we might go about treating it that you term brain energy, the brain energy theory. It seems like there was a case or a patient who you were working with back

in 2016. It sounds like that interaction served as almost an inciting incident for you to really deepen into this theory in a very practical applied way. It did. So I had actually noticed probably 20 years ago that certain dietary patterns, such as low carbohydrate or ketogenic diets can sometimes have an antidepressant effect. Some people feel less depressed when they're on those diets. And I'd actually been using it clinically for a while, but kind of under the radar. I wasn't really all that public about it.

And in 2016, I had a longstanding patient. He had been my patient for eight years at that point with what's called schizoaffective disorder, which is a cross between schizophrenia and bipolar disorder. This man had tried 17 different medications, but none of them stopped his psychotic symptoms. He had been in and out of hospitals. He had been in residential treatment programs. He had hallucinations every day, had paranoid delusions, and he was tormented by his illness. His life was essentially ruined. And a lot of those medications come with a side effect of weight gain. And so in 2016, he weighed 340 pounds and he asked for my help to lose weight.

And at that point, we decided to try the ketogenic diet. He had actually tried a few other weight loss methods earlier and they didn't work for him. So we decided to try the ketogenic diet. And although I had had experience with it and had seen some antidepressant effects, I had no concept or notion that this would do anything for this man's psychiatric symptoms because he had schizophrenia, essentially. So within two weeks, not only does he start losing weight, but I begin to notice this powerful antidepressant effect in him. And I haven't done anything with his medications or other treatment. He's coming in to see me once a week, but he's

lighting up. He's making better eye contact. He's talking more. He's more positive to see me once a week, but he's lighting up. He's making better eye contact. He's talking more. He's more positive. And I'm thinking, wow, I've never seen you like this. What's going on? This is really amazing. And there's a part of me thinking, well, maybe it's just he's feeling good about losing some weight. Isn't that nice? Isn't that nice that he's feeling so good about losing weight? The thing that upended everything that I knew as a psychiatrist was about two months into it, he spontaneously starts reporting that his longstanding hallucinations are going away and that his paranoid delusions are also going away. He is beginning to realize that they're not true and probably never had been.

That man, he's lost 160 pounds and has kept it off to this day six years later. He was able to do things he had not been able to do since the time of his diagnosis. He was able to complete a certificate program, go out in public and not be paranoid. He actually was able to move out of his father's home for a time. He was able to perform improv in front of a live audience. And those things would have been impossible for him prior to this diet. And that set me on a journey to not only start using this with other patients, which I have now done abundantly, but it set me out on a journey to understand what on earth just happened. Because this is impossible. This can't be happening.

Yeah. Because based on everything that we had known up till that point, there should be no relationship between this nutritional metabolic intervention and the state of mental health or dysfunction, but you're witnessing it there in front of you in a very real applied way. Before sharing this story, you brought up this notion of the mitochondria. So let's close the loop here. You see this experience, you're kind of figuring out like what is happening here? Because I can't deny the fact that something profound is changing purely by, it sounds like really the only change you made was nutritional. So how do you go from there into diving deep into the relationship between nutrition, metabolic state, and mental health? You know, the next step actually was just to close the loop on the clinical aspect of that so that people don't think this is just a

single anecdotal case. I've now used this treatment in dozens of patients personally, myself, researchers, and I'm collaborating with researchers from around the world for the last six years. So we have animal models, mice studies and other animal models showing us what exactly the ketogenic diet is doing. I didn't say this yet, but for those who don't know, a lot of people have heard the keto diet is a weight loss diet, or they think it's a fad diet, or they think it's a dangerous diet where people eat lots of meat and bacon and nothing else. But in fact, it's an evidence-based treatment for epilepsy.

The ketogenic diet can stop seizures even when medications fail too. And that's important because we use epilepsy treatments in psychiatry all the time. All sorts of medications that we use in the mental health field are in fact epilepsy medications. They were developed to stop seizures, but we use them abundantly. And that was actually a gift because we have a tremendous amount of neuroscience already on exactly what is this diet doing to the brain to stop seizures. And it turns out that neuroscience is highly relevant for people with mental disorders as well. So we now have over five controlled trials of the ketogenic diet underway for people with serious mental illness. We've got

additional trials on PTSD, alcoholism, Alzheimer's disease. So that field is rapidly advancing. A lot of people are interested in it, but I didn't want to stop there. Number one, I realized, oh, everybody hates this. At least the medical establishment, they hate the keto diet. They're not going to buy this. But at the same time, I recognize this is a miraculous treatment for some of my patients who had tried dozens and dozens of medications and their lives were ruined. I have to figure this out. I have to make this available to more people. And if I just go running around saying the keto diet can help schizophrenia, I'm going to sound like a quack and nobody's

going to take me seriously. So I ended up going on this deep dive initially simply to understand how and why would the ketogenic diet help to put schizophrenia into remission or bipolar disorder into remission? How can I try to convince the scientists along with the world that they should take this seriously? And as I was doing all of that research, again, I was initially led to neuroscience and we know about all of these effects of the ketogenic diet on neurotransmitters and inflammation and hormones and the gut microbiome. So all of these very relevant hot topics in the mental health field.

So there were easy connections already, but I wasn't satisfied with those. I was like, but why? How? Like, what is going on? Schizophrenia is not supposed to go into remission, and it doesn't go into remission for the millions of people who are getting standard treatments. Most of them do not get a remission of symptoms. And so what can this diet tell me about the cause of schizophrenia?

And because that might be really important information for our field. And so as I continued this scientific journey to understand what is happening, how is the ketogenic diet changing neurotransmitters? How is the ketogenic diet reducing brain inflammation? Exactly how is that working? I was led to these tiny things in most of our cells called mitochondria. And I had heard about, when I was in medical school even, I was taught mitochondria are the powerhouse of the cell. Right. That's every ninth grade bio class. That's like probably one of the three things anyone might remember from it. Exactly. And for the most part, that's all I

was taught they are. They're just powerhouses. They take food and oxygen and turn it into ATP. And that's really important, but they're kind of just like little batteries. Some people even call them that. Some researchers refer to them as little batteries for the cells. But in fact, what blew my mind is that there has been an explosion of research over the last 20 years in particular on all of the different roles that mitochondria play in the function of cells and in human physiology, and this includes brain function. And the more that I dove into the science of mitochondria, the more I was just completely, I don't know, I'm dumbfounded because I learned that mitochondria actually play an instrumental role in the production and regulation of neurotransmitters

like serotonin and dopamine. And I'm thinking, whoa, I never learned that. That's huge for mental health, like serotonin and dopamine. The more functions that I learned about mitochondria, the more of the dots of mental illness I could connect. And at the end of the day, the soundbite conclusion that I've come to again is that mental disorders are metabolic disorders of the brain. And what that means is that mitochondria somewhere in some cells, maybe a lot of cells, are not functioning properly, or there aren't enough of them. And that results in brain

dysfunction that we call symptoms of mental illness. When you start out from the mitochondria and you move past this rudimentary understanding of they are the power plants of the cell, the batteries, and you realize they actually affect so many different systems in the body. From there, I'm thinking about, and fundamentally also, even if you just take them at their root level as energy providers for the body, there is this syndrome that has been kicked around, I think, for the last 10, 15 years that in the early days, I think a lot of people were calling it syndrome X. I think it's sort of evolved into metabolic syndrome. It was looked at as sort of

like being tied to a lot of the factors that you just listed out, systemic inflammation, all sorts of different things. So what you're kind of doing is drawing a line from all of these different indicators of like warning alerts that exist in the body through the mitochondria, and then from the mitochondria to that causing metabolic dysfunction, and then from metabolic dysfunction saying the metabolic dysfunction, the dysregulation of your metabolism and these things are actually leading to mental illness disorder, which sounds amazing. Like if that was actually mechanistically, you could say like, yep, check, check, check, check, check. I'm curious about that final gap though, between saying, okay, so a metabolic disorder is then going to, you can actually mechanistically

say this is going to lead to the expression of anxiety or depression or any number of actual symptoms of mental illness. Talk to me more about this. The thing that is probably shocking to most people, because most people have never heard this, and so they're going to think, Chris Palmer, you're just making stuff up. What are you talking about? Is this some theory that you pulled out of thin air that you're just highly speculating on what might be going on? The shocking thing is that this evidence goes back to the 1940s. So since the 1940s, we have had an abundance of clinical, epidemiological, basic science, neuroscience, neuroimaging, and even genetics research, all suggesting that there are metabolic

abnormalities in the brains and bodies of people with mental illness. And in fact, people with mental illness are more likely to develop the metabolic disorders of obesity, diabetes, and cardiovascular disease. And on average, they are dying early deaths across the board, across all diagnostic categories. Men are losing 10 years of life. Women are losing seven years of life if they have a mental illness, and they're primarily dying of metabolic disorders. In order to create or kind of hone in on this theory, I had to go to the cellular level to understand what would make a brain cell malfunction. Because in essence, that's what I am arguing a mental disorder is.

And it's important that I clarify, our brains have experiences for good reason. We are hardwired to get depressed and anxious if the circumstances call for that. So if you have a tragic loss in your life, you are going to get depressed. That is not a brain disorder in my mind. That is not a mental illness per se, although DSM might say it is. But I'm arguing that's not your brain malfunctioning. That is an adaptive response to adversity. But what I'm arguing is that the only way to understand why would the brain malfunction in people with real brain disorders that we call mental illness or mental disorders,

it's metabolic in nature. And numerous lines of evidence support this. But to answer your big picture question that you asked, like, how can we be sure? How can we be sure that it's metabolic in nature? Let me walk you through one example. I can walk you through many more if it's helpful. But let me walk you through one example. There's this thing called hypoglycemia, low blood sugar. And I'm going to take an extreme example, and I'm going to use the example of somebody with diabetes who is injecting insulin. And the reason I'm going to use that example is because

insulin injections can make blood sugar go dramatically low, like really, really low, in a toxic way that most of us can't experience because our bodies are programmed to create sugar, to release glycogen stores if our blood sugar is going that low. So most of us can't experience this on our own, even if we're not eating, even if we're starving. Our bodies don't do this. But with diabetes, it does. A lack of blood sugar is a metabolic problem. There is no way around it. So when your blood sugar starts going down, it becomes a metabolic problem that results in less and less ATP in the cells. And when people develop mild hypoglycemia, we start to see the first cascade of mental symptoms. People can feel lethargic. Some people might feel depressed. Some people might get a headache. Some might develop brain

fog. Some, interestingly, might develop anxiety or panic symptoms. So those are all very different symptoms, but they can all happen with relatively mild to moderate hypoglycemia. So the reason I'm using this example is because I'm using hypoglycemia. This is a clear assault on metabolism and our brain energy. And already, I've just described, wow, that's a lot of symptoms because we could put ADHD symptoms in there, anxiety symptoms, depression symptoms, cognitive symptoms. If the hypoglycemia continues to progress because this diabetic person has injected a lot of insulin and maybe they're not eating anything. Their blood sugar continues to plummet. They can develop what's called delirium, which means anything goes. They can develop any symptom

of mental illness with that label. And this includes hallucinations, delusions. They can actually start having seizures. And if that isn't rectified and addressed soon, they'll die. And I've essentially just outlined most of the symptoms of what we call mental illness in one very quick cascade that could occur over the course of an hour in a person with diabetes by inducing hypoglycemia, which is a metabolic problem. So then if you take that and you extend that out and you say, instead of a moment where somebody can address it and relatively quickly rebalance the level of blood glucose and insulin so that it's healthy and then bring whatever psychological

symptoms back online. If you extend that out and say, well, but what if this was a chronic state? What if you weren't necessarily, what if you weren't type one or two diabetic or you weren't hypoglycemic, but you were someone who had insulin resistance, which a lot of people do these days. So you just weren't properly processing glucose. And this became a persistent state. And a lot of people have no idea that this is actually going on in their bodies. It's a metabolic issue. And then all of these symptoms of the mind that you just described become part of the chronic state of an individual's sort of like state of mind as well. And over time,

I would imagine that they could end up compounding. I mean, it's fascinating because then you're talking about like a single source for what could be experienced as multiple different psychological symptoms and maybe even diagnosed as multiple different DSM conditions in a person, yet you can trace it back to a single metabolic point. Is that right? right. So we have strong evidence that insulin resistance, type 2 diabetes, for instance, is highly associated with depression, anxiety disorders. That is unequivocal. People with diabetes are much more likely to develop depression. And when they get it, it lasts much longer. They're more likely to have anxiety, insomnia, other symptoms of mental illness. But here's the shocking thing for people who maybe are skeptical still and thinking this can't possibly be true. So we have data from a longitudinal study of over 5,000 children who were followed from birth to age 24. The children who had the highest levels of insulin resistance beginning at age 9

had a five-fold increased risk for developing what the researchers called a psychosis at risk mental state. They were three, and that means schizophrenia and bipolar disorder, and they were three times more likely, so 300% more likely to already be diagnosed with schizophrenia or bipolar disorder by the time they turned 24. Insulin resistance was also associated with a higher rate, about double the rate of plain old depression, but that did not reach statistical significance in the sample. The sample size just wasn't large enough or depression has other causes as well that can contribute to the metabolic brain dysfunction, I would argue. So, there's more to metabolism than glucose. There's more to metabolism or metabolic health than insulin resistance. Put all of those

examples, tiny snapshot of some research that I just shared with you and that you described, all paints a picture. Metabolic abnormalities can start and then mental symptoms follow. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch,

getting you eight hours of charge in just 15 minutes. The Apple Watch Series 10, available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required. Charge time and actual results will vary. And as you just offered, there could be any number of contributors to metabolic dysfunction ranging from genetics to chemical imbalances to, I would imagine, even just daily things like how well did you sleep last night to your regular use of substances. And you write about this, actually, you talk about even things like the depth and quality of your relationships, the adversity. Having a sense of purpose in life can literally affect

metabolic function, which then feeds back into potentially your state of mental health. The interesting thing here is that most of those things we have some level of agency over, which is really good news. It is great news. I want to highlight one of the things you just said, because a lot of times when people hear me talking about mitochondria, they think I'm being reductionistic and I'm a biologist and that's all I am. And I don't get that there are psychological and social factors that play a role in mental health and nothing could be further from the truth. I am acutely aware. And in my mind, that was one of the beautiful things about mitochondria as the connecting factor, because lo and behold, mitochondria play a role in the human psychological

stress and trauma response. So when people are stressed and traumatized, mitochondria are being affected by that stress and trauma. They, over time, can become dysregulated or dysfunctional as a result of that trauma and stress. And that can lead to people developing mental disorders. Coming back to the main point you were making, the great news about this is this is not an abstract theory that's interesting to ponder and debate with scientists. This comes with real solutions for people with mild, moderate mental illness like depression or anxiety or ADHD, but all the way to serious mental disorders like bipolar disorder and schizophrenia, which most people think are incurable and really not even treatable. The treatments that we have

just reduce symptoms or keep people out of the hospital or keep them out of jail. They don't restore people's health and lives. And the great news is that I started this whole journey trying to understand how did this diet make schizophrenia go into remission? But I've expanded way beyond that. And I really want to be clear too, because some people hear about my work or hear about the book and they think that you're just selling the ketogenic diet and that's all you're about. And I'm not, because I'll be the first to say, I've seen some people for whom the ketogenic diet, at least at first glance, does not work for them. And so that also sent me on a

journey. Well, how can I understand that? If this theory is true, why isn't it working for some people? What are the other factors that are involved? And as you said, there are lots of them. Smoking cigarettes, alcohol use, sleep, stress, relationships, hormones. So yes, it's a little bit complicated. But the great news is you kind of most people already know this stuff. It's not earth shattering stuff. It's not that revolutionary. These are basic health and wellness requirements for human beings. We kind of sort of all know them. But let me give you an example because a lot of people think, well, but, you know, so if the keto diet doesn't work, then it's hopeless. And what I say to people is for somebody who's got schizophrenia and they're trying the ketogenic

diet and it's not working, I ask them about all of those other factors. And initially, they almost always blow me off. Like, well, those things don't matter. Sleep doesn't matter. My substance use doesn't matter. The pills that I'm taking don't matter. Relationships don't matter. Sleep doesn't matter. My substance use doesn't matter. The pills that I'm taking don't matter. Relationships don't matter. None of that matters. And I'm thinking, you're not getting it. Those things really do matter. And this treatment isn't going to be powerful enough to overcome all of the kind of negative consequences of those adverse lifestyle things.

So when people aren't getting enough sleep, that's a really easy one. Sleep is essential to human health, including your brain health. And if you're not getting enough sleep, you are fighting an uphill battle in trying to restore your brain health. And the statistics, sadly, are that the majority of Americans aren't getting enough sleep. So for people who are trying to recover, I let them know, you can't be one of those statistics anymore. You've got to prioritize sleep. You have to take care of your brain and your body and at least give it a chance to heal.

And if all of those different lifestyle things or genetic contributors as well, they all have the potential to sort of pile on to the potential for your mitochondria to become more and more dysregulated. It would make sense that the more of those contributors you have, the more potential dysregulation you have on the metabolic side. So maybe a dietary intervention isn't going to be enough. Maybe it flicks it on more than it was, but that's actually not enough to pass the threshold where you're actually starting to experience a remediation and symptoms. Maybe you actually have to go at it from multiple different angles. And my understanding from what you described is you sort of cherry picked the ketogenic diet because it's been studied for many years and there's an identifiable mechanism from that way to fuel your body to certain metabolic changes in the body. So you can kind of trace it that way. Who knows? Maybe down the road, there are other nutritional interventions that we

discovered that may have also alternative or complementary metabolic impacts that would be really beneficial as well. I actually think we already have some of those. So for some people, it really is just getting rid of the processed junk food. We've got a couple of trials of the Mediterranean diet, helping some people recover from chronic depression, and sometimes just getting rid of sugar, getting rid of high glycemic index foods, eating more whole foods. So there are lots of dietary strategies we can use. One thing that's really maybe will be helpful for me to point out. This applies to a lot more than just mental illness. This is about metabolic health. And so in the same way that you said, sometimes maybe diet isn't going to be enough to help restore brain health in somebody with a mental illness,

because we need to look at their substance use or their sleep or stress levels or other things. I'm going to say that applies for people who are just trying to lose weight. People who don't have a mental illness, but they're overweight or obese, and they want to lose weight. Far too often, they focus only on diet. And when they fail, they just think they haven't found the right diet, or they're just a lazy slacker who can't do a diet like everyone else. And what I would say to those people is that if you understand how all of these different lifestyle factors contribute to your metabolic health, you can actually develop a better weight loss strategy. So if you want to lose weight, you need to pay attention to your sleep. You need to pay attention

to your stress levels. You need to pay attention to your use of substances. You might want to think about some of the medications you're using to make sure that they don't cause weight gain. Because you're kind of fighting an uphill battle if you're trying to lose weight while you're doing any of those things that are harming your metabolism. So it's really about a comprehensive lifestyle strategy. Yeah. So here's what is flashing in my head right now. And it ties into something that is very of the moment, which is we're now seeing all over the news, all over the media, all over social media, especially in celebrity culture, a particular class of pharmaceuticals that was originally greenlit by the FDA for use in diabetes,

which is now being used in an off-label way under a lot of different brand names now for weight loss. And it's being touted as sort of a miracle by various different people. I'm not making any commentary about that or people who choose to opt into it or opt out of it. I'm purely curious on the science of it. Are you familiar enough with the science of those, how that category of meds work to know whether while they may cause meaningful and sustained weight loss in a large number of people, will they also lead to the type of positive metabolic change that you're talking about here that would potentially lead to improvement in psychological symptoms? It's early days still with those medications, like semaglutide and others. It's early days, and I don't think we have robust data for me to be

able to definitively say whether they are't think they are doing the work that I want them to do. I don't think they are improving mitochondrial and metabolic health. And the reason that I say that, and I'm fairly confident in that assertion, is because when people stop the medications, they rapidly regain the weight, very rapidly. And unfortunately, more often than not, people have also lost muscle mass from those medications. So when they lose weight from semaglutide, no doubt some of that weight loss is fat tissue, which is great and that's desirable. That's what everybody wants. So yes, we're getting a benefit, but some of the weight loss is muscle tissue, which is not what we want. When people stop the medication, they regain the weight, but more likely they are not regaining

that muscle weight. They are simply regaining even more adipose tissue or fat tissue, which is not good for health. The reason that I said what I said, so I don't think it's improving long-term health, is because if an intervention improves metabolism or metabolic health or metabolic flexibility or mitochondrial health or function, those are all different labels, but they're all highly interrelated and some might say they're all synonymous or some of them are synonymous with each other. If a treatment is doing those things, when the person stops the treatment, they should be more resilient and robust

than they were before they started the treatment. And the symptoms should not necessarily come back with a vengeance. And so I'll at least just point out, because I know a lot of people probably aren't familiar with this, but I'll at least just point out, because I know a lot of people probably aren't familiar with this, but I'll point out the ketogenic diet, when it is used in epilepsy, the initial recommendation by neurologists is that patients do the diet for anywhere from

two to five years, and then they stop the diet. And that is the beauty of a metabolic intervention. So most of the people with epilepsy, if they become seizure-free from the ketogenic diet, and then they do the diet, let's say for three years, and their neurologist says, it's time, let's stop the diet and see how you do, more than 50%, their seizures never come back. Wow. The ketogenic diet restored their metabolic brain health. It regulated metabolism in the brain again, so that they can go back to a normal diet or whatever diet they want to go to and remain seizure-free. And that's the beauty of a metabolic treatment.

But exercise is a metabolic treatment. I mean, there are so many metabolic treatments. But at the end of the day, you should come out healthier when you stop the treatment. And unfortunately, with semaglutide, we don't see that. Interesting. While we're talking about medications, one other thing that pops into my head is, circling all the way back to the beginning of our conversation, we talked about this notion that there are medications that emerged, as you described, from completely different

use cases that somehow started to be ported into the world of mental health, SSRIs, like medication for depression and anxiety, that can be quite effective for a decent number of people. If the metabolic theory is really at the core of mental illness, mental disorder, and the symptoms, how are those medications working for so many people? We actually have a lot of data on this and a lot of evidence for this. So before I go into this, I just want to say, because I'm going to say some stuff that might upset people or make people feel like, maybe I want to get off this medicine now. So before I go into more detail, I just want to say, if you are taking medication, please, please, please work with discussion with them and make a safe strategic decision plan

to see what can happen. Because I have seen innumerable times when people take matters into their own hands and stop their medications, if they go down too fast, it can be a disaster. People can become manic, depressed, psychotic. Some people end up dead. Others end up in the hospital. Some end up in prison. So please don't do that. With that said, we actually have a lot of evidence, and we've had this evidence for decades for some of the antidepressants. Some of the antidepressants are directly stimulating mitochondria. So, stimulants do that. So, ADHD medicines commonly do that.

There's a class of antidepressants called MAO inhibitors. Those, actually, MAO is located on mitochondria. So, those medications are working at the level of mitochondria. So that was kind of very low-hanging fruit to understand, well, that's why those would work. Some shocking news is that even things like SSRIs, the serotonin antidepressants like Prozac, Zoloft, Paxil, we have good evidence that those increase mitochondrial biogenesis or the production of new mitochondria in the brain. And that they result in when they work, they appear to be increasing the number of mitochondria

in brain cells, and that results in increased neuroplasticity in the brain. And so, it may be the mechanism of action is really not a serotonin imbalance per se, but that when we elevate serotonin levels somewhere in the body or brain, that can increase mitochondrial function in brain cells. So that's consistent with the theory as well. The thing that is really disturbing, and there was actually quite a challenge for me early on, was we have other classes of medicines, some mood stabilizers, but in particular, the antipsychotic medications. We know that they impair metabolism and they impair mitochondrial function. And what does that mean? It means people gain weight on them. People develop type 2 diabetes or at least insulin

resistance. They can have premature cardiovascular disease. And in the elderly, it's actually listed on the package insert that they can cause premature death. So those are all really concerning and those are harming metabolism. And that was one of the biggest challenges in developing this theory is I had to try to figure out, well, that doesn't make sense then. My theory must be wrong. This can't possibly be true if that's right. And at the end of the day, I came to the conclusion, again, based on a fair amount of science, but to the best of my knowledge, I haven't seen anybody else put it together so clearly and concretely. So I really do feel like I certainly figured it out on my own.

If somebody else has already figured this out and published it, I haven't seen it. But it speaks to this paradox that when a cell is metabolically compromised, it can become underactive or not very functional, but it can also become overactive or hyper excitable. And it's that hyper excitability, an overactive brain cell that produces a lot of the symptoms that we see in the mental health field. That accounts for things like bipolar mania. It accounts for things like psychotic symptoms. It even accounts for panic attacks or anxiety symptoms when somebody shouldn't be having panic or anxiety symptoms. So shouldn't be having panic or anxiety symptoms.

So an overactive brain cell. And the reason those medications work, I believe, is because they are suppressing metabolism in those cells. There are two ways to reduce symptoms of a hyperexcitable cell. One is to restore the health of the cell through these metabolic interventions like diet, exercise, good sleep, all those things. And then you're restoring the health of the brain. And then that person might be able to, quote unquote, go into remission, not have symptoms anymore, and live happily ever after. But the other way to stop hyper excitable cells is to actually completely shut down their metabolism or strongly suppress their metabolism.

And if you do that, it'll make it so that that cell can't function at all. And if that's an anxiety cell in your brain and you're suffering from a panic attack, that can feel really good to have something turn that cell off because that's what you want. But unfortunately, the process of suppressing the metabolism in that cell might end up making that cell weaker and more vulnerable over time. And that is one of the alarms that this theory does raise. So a short-term intervention, but long-term, we could actually be worsening the problem without even realizing that we're contributing to it. Fascinating. I mean, really, really interesting. As we start to come full circle in our conversation, because the question is going to be in a lot of

people's minds, where do I go from here? You offered, I think, a very wise first big flag, which is if you are already working with a qualified healthcare professional in any sort of therapeutic basis or medication, work with somebody who... Don't just say like, hey, I'm going to go try a whole bunch of things and experiment. Really do this in an intelligent and guided and sound way. What are some of the major, somebody walks away from this conversation and is like, how do I take this further? What are a couple of things that you would say, think about? So the first thing I would say is I would love for you to understand the theory and all of the different treatment options all together, especially if you're somebody suffering from a chronic disorder. It's been going on for a long time for you. You deserve a competent strategy.

I don't want you just shooting in the dark and winging it. I want you to understand, okay, here are the 15 different things I need to assess or pay attention to. Where am I at with these? How is my sleep? Am I getting any light exposure? Do I feel like I have purpose in my life? Do I have hormonal imbalances? Any of that. So, how's my diet? Obviously, people could read the book to get that. You can go to a website, brainenergy.com, and we're offering a lot of free information there. And you can listen to this podcast, lots of others. I've done articles.

There's all sorts of resources that you can find at the website for free. But if you can at least understand an outline of here are the things I need to consider. And then if you have a serious disorder with life-threatening or dangerous symptoms like suicidality or hallucinations or delusions, I want to just reiterate what you said. Please work with a healthcare professional. You've got a serious disorder. You deserve serious help. But if you've got mild or moderate symptoms, you're not suicidal. But if you've got mild or moderate symptoms, you're not suicidal, you just got mild depression or anxiety, maybe the treatments aren't working all that well for you and you want some new ideas or new strategies. Once you learn the overall

map, you can actually assess your diet, maybe get some light exposure. Maybe reprioritize your sleep if that's a problem. So I want you to just kind of do an assessment. Where do I maybe have the biggest problems with all of these things? Pick one or two areas where you think, yeah, I could use some change in that area. And I'm going to try it. I'm going to experiment. And I'm going to see. Give it two or three months.

See if it makes a difference in my symptoms. The really great news is that, you know, one person, I won't name him, but he's like an executive, had been struggling with anxiety for a long time, has been in psychotherapy for a while, practices meditation and mindfulness, does all sorts of things, and was actually ready to go on medications for his anxiety because those things weren't working enough for him. They had helped, but they just weren't working enough. He read an early copy of the book. I didn't have to tell him anything. And he came to me six weeks later and said, Chris, I read your book. I changed

my diet a little bit. He didn't do a ketogenic diet. He did some other interventions. I changed my diet a little bit. I got some light exposure in the morning. And I'm really just making sure I get eight hours of sleep a night. And I haven't felt this good in years. I can't believe it. There's no way I need anxiety medicine. I was ready to go to a psychiatrist and be put on medication. And now I realize, no, I don't need medication. I just need to do this. And since the book has come out, I have had so many other people approach me, same deal. So it really is about empowerment.

I'm not a big fan of proprietary supplements and everything else. I'm really like, these are free accessible treatments. Like you can do this. I'm not looking to make money. I'm looking to help people. I love that. And it feels like a great place for us to come full circle in our conversation. So I always wrap with the same question in this container of good life project. So I always wrap with the same question in this container of Good Life Project. If I offer up the phrase to live a good life, what comes up? I think for me, it's kind of the theme of it's a wonderful life and it goes along with this. But to know that I'm making enough of a difference in people's lives, that there are at least some people, at least one or two, who would say they love me, they respect me, they admire me, they something,

they hold me in some regard, they care about me in some way. I think that's it. I think it's connecting with other people and helping them, helping them live better lives. And then having that somehow be reciprocated, at least on some level. Thank you. Hey, before you leave, if you love this episode, safe bet, you will also love the conversation that we had with Dr. Aviva Ram about how your internal chemistry hormones affect all aspects of your wellbeing. You'll find a link to Aviva's episode in the show notes. And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app. And if you found this

conversation interesting or inspiring or valuable, and chances are you did since you're still listening here, would you do me a personal favor, a seven second favor and share it? Maybe on social or by text or by email, even just with one person. Just copy the link from the app you're using and tell those you know, those you love,

those you wanna help navigate this thing called life a little better so we can all do it better together with more ease and more joy. Tell them to listen. Then even invite them to talk about what you've both discovered because when podcasts become conversations and conversations become action, that's how we all come alive together. Until next time, I'm Jonathan Fields, signing off for Good Life Project. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist,

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