Transcription
Welcome to the Metabolic Link, a medical and science-focused podcast that explores the common thread of metabolism in health and disease. This is where science beats society. Welcome to the Metabolic Link podcast. I'm your host, Victoria Field, and I'm so excited you're joining me today because today, we've got an incredibly important topic that we're covering. This is something that affects all of us: mental health.
Did you know that it's estimated more than 1 billion people worldwide are suffering from a mental or neurological disorder? We have a complete crisis on our hands, one that's gotten significantly worse over the last few years. And that's why today's episode is so important and special because it's a full presentation for Metabolic Health Summit 2024 by world-renowned Harvard psychiatrist, Dr. Christopher Palmer.
Now, his presentation is titled "Brain Energy: The Metabolic Theory of Mental Illness." And in this episode, Dr. Palmer digs into how current treatments often fall short, why that is, and his groundbreaking perspective around mental illness and how it's linked to metabolic dysfunction in the brain. He also talks about the potential of using ketogenic diets, metabolic-based therapy, and other new treatments to really tackle this crisis head-on.
I know you're going to enjoy this episode. I know you're going to enjoy this presentation. If you're listening to it on any major podcast player, be sure to watch it on YouTube as well because we are offering all of the slides as well, so you can follow along with Dr. Palmer's presentation.
I also want to quickly mention and say that we do have several sponsors who support our podcast that we truly believe in, that we carefully vet, and that who make episodes like this one possible. So, thank you for supporting our sponsors. If you go and check them out, you're also supporting us and this podcast.
If you want to listen, however, to private episodes or episodes that are completely free from ads, including this one, be sure to head over to our membership platform dedicated exclusively to metabolic health and metabolic-based therapies. It's called The Metabolic Initiative, and you can find it at membership.metabolicinitiative.com. That's membership.metabolicinitiative.com. And in addition to private and ad-free episodes, we offer incredible benefits by joining, and really, the latest science around metabolic health and metabolic therapy. So, you won't want to miss it. Until you check that out, please enjoy this episode with Dr. Christopher Palmer.
Dr. Palmer is a Harvard psychiatrist and researcher working at the interface of metabolism and mental health. He's the director of the Department of Postgraduate and Continuing Education at McLean Hospital and an assistant professor of Psychiatry at Harvard Medical School. He's been pioneering the use of the medical ketogenic diet in the treatment of psychiatric disorders, conducting research in this area, treating patients, writing, and speaking around the world on this topic. Most recently, he has proposed a comprehensive theory of what causes mental illness, integrating existing theories and research into one unifying idea: the brain energy theory of mental illness. His new book, "Brain Energy," pairs cutting-edge science with practical advice and strategies to help people reclaim their mental health. His talk is titled "Brain Energy: The Metabolic Theory of Mental Illness."
[Music]
[Applause]
So, hello everyone. Thank you for being here. Um, so, just as a stage, I have no disclosures, um, other than royalties for a book. I've actually been asked to sit on lots of advisory boards for biotech companies and supplement companies and other things, and I'm actually turning them all down right and left, um, because I don't want anybody to ever question my motives for doing this work. So, I, whatever, wasn't looking for applause, but letting people know because, you know, everybody's like, "What's in it for you, Dr. Palmer? What are you going to make off of this?" And I'm like, "Well, I'm going to try to help people get better."
So, mental health today. For those who don't know, we have a mental health crisis. Prior to the pandemic, mental and substance use disorders affected about a billion people on the planet, throughout the world, and that represents about 13.3% of the world's population. Since the pandemic, rates are even higher now. Mental disorders are one of the leading causes of disease burden and disability worldwide. And if you talk to some authorities, like the World Health Organization, they will say, taken as a whole, mental disorders are, in fact, the number one leading cause of disease burden and disability worldwide.
The problem is not always a lack of treatment. For some, it's that our treatments fail to work. And there's this curious thing: the rates of mental illness have been rising for decades across a wide range of diagnostic categories. The rates of autism in the last 20 years in the United States have quadrupled. The rates of ADHD prescriptions for stimulant medications in the United States have doubled, doubled in the last 15 years. We have an Adderall shortage, in case you hadn't heard. Bipolar disorder, over the last 20 years in adults, rates have doubled. In children and adolescents, they are up exponentially. Now, in fairness, that's because it was a, not ever diagnosed disorder in the 1970s, and we are increasingly diagnosing this in children and adolescents. And what about plain old bread and butter major depression, depression? What's happening with that? The Gallup poll, as an annual survey, and just last year, 2023, rates of major depressive disorder, both current prevalence and lifetime prevalence, reached an all-time ever recorded high. And you can see that the pandemic took a toll, but rates were already going up before the pandemic.
What are we doing about this? Well, we have treatment, and we have a lot of treatments. We've got a wide range of medications, we've got psychotherapies, we've got hospitalization, group therapies, electroconvulsive therapy, transcranial magnetic stimulation, ketamine and psychedelics, addiction recovery programs. And let me be the first to say, in no uncertain terms, to this audience, these treatments save millions of lives every year. There is no doubt about that. Unfortunately, for far too many people who are getting the best treatments available, they just don't work for everyone. Treatment resistance affects about 20 to 60% of all patients with psychiatric disorders. Why such a wide range? Because it depends on what population you look at, what criteria you're using, how many years you're looking for treatment resistance, what are the diagnostic categories you're including, all of that. But our field is fairly clear and certain: psychiatric treatments do not cure mental illness. They are not disease-modifying therapies. At best, they reduce symptoms.
And this begs the question: why can't we do better? And I would argue it's because our profession has been unable to answer two fairly simple questions. The first: what causes mental illness? What exactly causes it? If you talk to the leading psychiatrists and neuroscientists of the world right now, they will say, "No one knows. It's just too complicated." All we know are risk factors, and we put them into the biopsychosocial model. We say that there are biological things like neurotransmitters, genetics, and hormones, psychological and social factors, trauma, stress, adverse childhood experiences, loneliness, that all come together to cause all of the mental disorders. How do these all fit together to cause mental illness? Like, how exactly does this all work? It's too complicated. Nobody can figure it out.
But the second simple question that our field has struggled to answer is, well, what exactly is mental illness? We have DSM-5-TR. This is often called the Bible of Psychiatry, and it has all of these different diagnostic labels. And the labels are household words to most people: schizophrenia, bipolar disorder, major depressive disorder or depression, anxiety disorders, OCD, personality disorders, alcoholism, also called alcohol use disorder, anorexia nervosa. These are household words. Everybody kind of knows what they mean, right? And those are totally different things. Anorexia has nothing to do with schizophrenia, and that has nothing to do with alcoholism. So, on the surface, it makes sense. We have all of these different labels. They're all different. Different types of people get these things. We have different treatments for them. They're all different.
We have three primary problems in the mental health field with these diagnostic labels, and they are heterogeneity, comorbidity, and a lack of validity. Heterogeneity says that if two people have the same diagnostic label, they can be wildly different from each other. So, you can have a child with autism spectrum disorder whose parents can't take care of him. He lives in a group home. He bangs his head against the wall to the point of bleeding, so the group home has to put a football helmet on this child. This child also has seizures and profound cognitive impairment. And when somebody asks, "What's wrong with this child?" we would say, "He's autistic." Somebody else with this same diagnostic label can be a billionaire businessman that we see in the news every day. Does anybody in their right mind really believe that those two human beings have the same brain condition?
The second problem is something called comorbidity. Comorbidity says that if you have one mental disorder, you're more likely to have another. In large population surveys across the United States, if you have one mental disorder, there's a 50% chance you have more than one. Now, if you're actually getting treatment for a mental health disorder, on average, you have between three and four different psychiatric diagnoses. So, what does that mean? That means that if you have schizophrenia, you're more likely to have OCD and an anxiety disorder. If you have major depression, you're more likely to have OCD and an anxiety disorder. If you have anorexia nervosa, you're more likely to have OCD and an anxiety disorder. Wait, schizophrenia and anorexia? Those are totally different diagnoses. But when you start to consider the comorbid diagnoses, real patients living real lives with these symptoms begin to look more similar than different sometimes.
And in fact, Tom Insel and many other leading psychiatrists and neuroscientists have been saying for decades, the reason we fail to make progress in the mental health field is because these are not valid disease constructs. These labels have to go. We will never make progress in our field if we cling to these labels. Yes, the labels describe symptoms. The symptoms are real. So, psychosis is real. Chronic psychosis is real. We call that schizophrenia. Are the psychotic symptoms real? Absolutely, they are. Is schizophrenia an accurate and effective term to describe everybody who meets those symptomatic criteria? Absolutely not. They are heterogeneous when you look at people with that diagnostic label. They are heterogeneous in terms of the causes, in terms of the symptoms, in terms of the comorbidities, and all of it. And in fact, you know, the National Institute of Mental Health has moved on from DSM and developed the Research Domain Criteria. There are competing models, the Hierarchical Taxonomy of Psychopathology, and these are transdiagnostic models. They say that we need to move beyond schizophrenia, bipolar, anorexia, and we need to look at symptom domains and broader constructs that are transdiagnostic.
So, let me stop there. All of that basically says the mental health field is a mess. It is an unequivocal mess. We have over a billion people affected in any given year. It is a growing crisis. Our treatments can sometimes work, but far too often, they fail to work. And we can't even figure out what exactly a mental illness is to begin with. How are we ever going to make progress?
Let's take a quick break now to say thank you to Timeline Nutrition, who is the sponsor of this episode. Timeline is a Swiss-based life science company and a global leader of urolithin research. In fact, they've spent the last 10 years doing research just to bring their product, Mitopure, to market. Mitopure is a really incredible product. It's the first of its kind to offer a precise dose of urolithin A. And urolithin A is a powerful postbiotic that you really can't get from your diet alone. So that's where Mitopure comes in. It's been clinically shown to give our mitochondria new power by triggering the body's natural process of removing and rebuilding damaged mitochondria, also known as mitophagy. You've probably heard of it. Timeline is actually offering our listeners 10% off your first order of Mitopure, which is, it's really exciting. Go to timelinenutrition.com/metaboliclink, use the code METABOLICLINK. That's T-I-M-E-L-I-N-E nutrition.com/metaboliclink and use the code METABOLICLINK to take advantage of the discount. And now, back to our episode with Dr. Christopher Palmer.
Now, let me tell you about a few different lines of research that suggest something both shocking, but also, in my mind, filled with hope for for our field. Many lines of research suggest that mental disorders share a common pathway. Now, this includes the genetics from the Human Genome Project, to childhood trauma, to stress, to hormones, to neurotransmitters, to brain imaging studies. When you put all of that evidence together, all of these lines of evidence suggest, "Wait, these disorders aren't so different from each other after all." Even though the symptoms can be wildly different, and even though the impact on people's lives can be wildly different.
Now, in 2012, Lahey and colleagues first proposed this as a general factor. They suggested that there was some kind of a unifying general factor that leads to all internalizing and externalizing mental disorders. In 2018, Caspi and Moffitt expanded upon this. They looked at all of the diagnostic labels in DSM and they said, "Wait, this applies to all of them." And they called this the P factor, P standing for psychopathology. And then just last year, 2023, Brandt et al. suggested, "Wait, it's not just those mental illnesses. There are lots of physical illnesses that also appear to share this common pathway."
Now, none of this research could tell us what the common pathway is. It's simply the, these were mathematical models looking at all of the different risk factors, all of the heterogeneity, all of the comorbidity, and it all comes to the same conclusion: that there is some common thing driving mental illness. What exactly that common thing is, is largely unknown right now. And in fact, Caspi and Moffitt, two years ago, said, "Maybe it's childhood trauma. Maybe that's the unifying P factor for mental illness." But in fact, there are lots of people who have mental illness who had perfectly happy childhoods. And there are also people who have horrible, abusive childhoods who don't develop a mental illness. So, in my mind, childhood trauma is not sufficient, and it's not necessary, and therefore, in my mind, it is not at all the P factor.
But there are lots of experts, Gay and Aron, and others, who will say, "No, it is trauma. Trauma is the root cause of all mental illness." I disagree. I think the root cause of mental illness is metabolic dysfunction affecting the brain. And I am arguing that, in fact, the only common sense way, the only scientific way to unify all of the risk factors that we know play a role in mental illness is through metabolism. That metabolic dysfunction in cells can actually explain all of the symptoms of mental illness. This is a way to integrate the biopsychosocial risk factors. And once and for all, it is a way to integrate what we call mental illness and what we call physical illness.
And so, let me help you come away, because I'm not going to go into the Research Domain Criteria and HiTOP models. Those models get ridiculously complicated fast because there are so many brain symptoms. And so to even begin to discuss that could take a five-day conference. But I don't need you to come away with the complex details. Instead, I want you to come away with just a concept. And what I am arguing is that we need to think about mental states and mental disorders in the same way that we think about pain.
So, pain is perfectly normal. All of us have it. If we injure ourselves, we will experience pain. It is not a disorder. It is not the body malfunctioning. When we have pain, we might take a pill for it. We might need some help. We might want some comfort. That doesn't make it a disorder. Yet, we still might even need medical attention if we have severe pain. You can have extreme pain if you get surgery. You may have extreme and prolonged pain. That, too, is not a disorder. It is not a disorder of pain that you're having extreme and prolonged pain. But there are, in fact, pain disorders in which the pain system is malfunctioning. Either the nerves or the brain regions that control and sense pain are, in fact, malfunctioning, and they are producing the sensation of pain when a person should not have pain.
What I'm arguing is that mental states and mental disorders can be understood in exactly the same way. So, for instance, we all have anxiety. That's normal. If you're being traumatized or bullied and teased relentlessly, you may have extreme anxiety. That's normal. Neither of those is a disorder. And yet, there are people who experience anxiety disorders. They have anxiety for no reason because the brain regions that code for anxiety are firing when they shouldn't, just like a pain nerve cell might be firing when it shouldn't. And I could go through each and every mental symptom and help you understand how every mental symptom can either be normal, extreme, or a disorder.
And now, let me take you through just a whirlwind tour of some of the evidence that supports what I am asserting. And I'm going to start with correlations. As we all know, correlation doesn't equal causation. But when we see strong bidirectional correlations, we need to consider a common pathway or a common pathophysiology. And in fact, we see strong bidirectional relationships between mental illnesses, all of them, and all of the disorders on the right-hand side of the screen: obesity, diabetes, cardiovascular disease, and Alzheimer's disease.
When I say bidirectional relationship, what do I mean? I mean that if I go to a mental hospital and look at people with mental illness, they are more likely to currently have or in the future develop obesity, diabetes, cardiovascular disease, and Alzheimer's disease. But on the flip side, if I go to a Weight Watchers group and look at a group of people with obesity, they're more likely to have a mental illness. They're also more likely to have diabetes, cardiovascular disease, and Alzheimer's disease. And on and on I go. I go to a diabetes clinic, a cardiovascular disease ward, and a nursing home with Alzheimer's patients, and all of these things can be mixed and matched. People with any of these labels are more likely to have another one of these labels.
Let me walk you through just a snapshot of some of the statistics. People with chronic serious mental disorders, two to three times the rates of obesity and diabetes. More likely to develop cardiovascular disease, and depending on the diagnosis, it can be anywhere from like 30% all the way up to almost 200%. Alzheimer's disease: if you have chronic depression, two to three times more likely to develop Alzheimer's disease. If you have the diagnosis of schizophrenia and you live to the young age of 66, you're 20 times more likely to be diagnosed with dementia on top of your schizophrenia.
What about the other way around? Obesity: anywhere from 50 to 350% increased risk for a wide range of mental disorders across the lifespan. Diabetes: two to three times more likely to develop depression and anxiety disorders. Cardiovascular disease: three to five times more likely to develop depression and anxiety disorder. Alzheimer's disease: if you have Alzheimer's disease, there is close to a 100% chance that you will have mental health symptoms: anxiety, depression, OCD, agitation, insomnia. There is a 40 to 50% chance you will have hallucinations and delusions. Those are the cardinal symptoms of what we call schizophrenia.
So, I want you to think about it: if you have schizophrenia, you have a 20-fold increased risk of developing Alzheimer's disease by the time you turn 66. If you develop Alzheimer's disease, there's a 50-50 chance you're going to have the hallmark symptoms of what we call schizophrenia. What I would argue is that we cannot talk about the root cause of mental illness without talking about the root cause of all of these other disorders. And in fact, metabolism is not just those metabolic disorders. Metabolism impacts every cell, organ, and tissue in the human body.
And this large population study of over six million people finds that if you are diagnosed with a mental disorder, you're more likely to develop all of these other physical disorders. All of the metabolic ones are on here, but autoimmune disorders and all sorts of other things are on this screen. Now, in many ways, this is nothing new. We have known all of this. People with chronic mental disorders are more likely to die early deaths. Depending on what population and what study you look at, anywhere from 7 to 30-year life expectancy reduction. But in fact, a large population study of over 7 million people, published in The Lancet a few years ago, suggests something more dire. No, it's actually not just those, you know, it's not just schizophrenia folks. It's every mental disorder. Every mental disorder. All of the labels in DSM-5 are associated with premature mortality. On average, men are losing 10 years of life. Women are losing seven years of life.
What are these mentally ill people dying of? Everybody thinks suicide. Yes, they are more likely to kill themselves. Yes, that plays a role in the statistics. But that, in fact, is not the explanation. The primary cause of death in the mentally ill at these premature ages is a heart attack or a stroke. Why? Why is this happening? This has not gone unnoticed. The World Health Organization put together a task force in 2016 and issued a report. It is due to factors related to the individual's behavior. That means the mentally ill overeat and under-exercise. Or maybe it's due to their disorder medication side effects, problems at the health system level. The mentally ill don't go to their primary care doctors and do what they're told and take their statin. Wider societal issues. The mentally ill are more likely to be unemployed and poor. And we know from large population studies, unemployed, poor people die early deaths. So maybe that's it. It's a social class issue.
I actually believe this is about blaming the victim. All of this says the mentally ill are lazy slobs. They overeat, they under-exercise. If they just tried harder, maybe they could resist that weight gain from those medication side effects. They are not good patients. They don't go to their primary care docs, and they're unemployed and they're poor. If they just pull themselves up by the bootstraps and tried a little harder, everything would be fine. I believe we are, in fact, missing the elephant in the room. And we have over a century of scientific evidence to support this. Metabolic problems have been identified in the brains and bodies of people with mental disorders for over a century. We have clinical epidemiological evidence. The basic science research dates to this says 1940s. I haven't updated this one. It's actually the 1930s. Plethora of basic science neuroimaging studies. The diagnoses span a wide range, including depression, anxiety, PTSD, schizophrenia, bipolar, anorexia, alcoholism.
What do I mean when I say metabolic problem? Differences in lactate, glucose metabolism, the ATP to ADP ratio, reactive oxygen species, redox markers, levels of NAD to NADH, inflammation, cortisol, brain insulin, and mitochondrial function. It gets complicated fast. That is what metabolic abnormalities look like and how they can be measured. Now, a lot of people still have trouble getting beyond this concept that the mentally ill are either just lazy, maybe it's because of their illness, Dr. Palmer, you know, they are unmotivated. That's a symptom. That's a symptom of schizophrenia. It's a symptom of depression. Don't make too much out of this stuff, Dr. Palmer. They're really unmotivated. I see it. Or it's the meds. It's the meds. The meds are doing it. It's the meds.
This study says something very different. A longitudinal study of over 5,000 children followed from the ages of 1 to 24. The children with the highest levels of insulin resistance beginning at age 9 had a 500% increased risk for having a psychosis at-risk mental state by the time they turned 24. And they were 300% more likely to already be diagnosed with bipolar disorder or schizophrenia by the time they turned 24. Children who gained the most weight around the time of puberty were 400% more likely to develop major depressive disorder by the time they turned 24.
Let's take another brief break to say a special thank you to Genova Connect, who is the sponsor of this episode. Goova Connect is powered by Genova Diagnostics, which is a lab company that is really leading the charge when it comes to taking control of our metabolic health. It's a company that offers online testing that you can use in the comfort of your own home. So whether you're looking to optimize your metabolic health, achieve performance with personalized recommendations, this lab testing company is for you. You can check hormones, you can check your gut microbiome health, nutritional insights. I mean, it's really endless the testing that they offer is just so comprehensive and, um, really amazing. If you want to establish and understand, uh, sort of setting a health baseline and then trying to improve that baseline over time, this is the company that's going to help you achieve your goals. Um, because without doing lab testing, you really don't know what's under the hood, right? So, I've personally used Genova Connect, um, and it's just incredible the wealth of information their tests offer. I've done their Metabolomics Plus test as well as their gut health test. Both were incredibly insightful and so helpful just as a standalone because they not only give you results, but they also give you action items, and just really beautifully explained, uh, results. It's not just like, "Here's your number." It's, it's giving you information that you can take, go to your physician, work with your care provider, and really start to make big moves towards improved health. And I'm excited to share Genova Connect is offering you 15% off any of their test kits when you use the code METABOLICLINK at gdx.net/themetaboliclink. That's the code METABOLICLINK at gdx.net/themetaboliclink to take advantage of that discount. Now, let's get back to our episode with Dr. Palmer.
This is one of the, I'm, I'm going to tell you now, this is one of the more important slides. I really want you to pay attention to because so many people just have trouble with this. So many people think in terms of linear relationships: A leads to B. So, what are you saying, Dr. Palmer? Are you saying that insulin resistance always comes first, and then people develop a mental illness? Is that what you're saying? No, that's not what I'm saying. Are you saying all the mentally ill people will become diabetic? No, that's not what I'm saying either. What I'm saying is that it is a complicated feedback loop. That mental leads to metabolic, and metabolic leads to mental.
So, people like simple things. People like simple concepts. And I am begging you to move beyond simple. So, on this slide, I have some of the simple concepts that people have. Mental illness is either a neurotransmitter imbalance or it is trauma, stress, psychological stuff. It's that simple. It's either a chemical imbalance or it's psychological and social, end of story. And you see that in the news. You see that from experts every day, every day. Metabolic disorders, obesity, diabetes. That's a diet and exercise issue. Dr. Palmer, if everybody just went keto, we'd be all fine. If the human species was on the ketogenic diet, we would eliminate all death and disability, and we would be immortal and forever healthy. Everything would be great. Dr. Palmer, it's diet and exercise. Of course, the vegans will say, "No, no, no, it's the vegan diet." And then the Mediterranean people, "Oh, no, it's Mediterranean diet." Everybody's got their opinions on what diet, what exercise plan is like, deal. We need to move beyond that.
We have long known that there is this "both" category that plays a role: genetics and epigenetics, hormones, inflammation, sleep, the gut microbiome. What I am here to say is let's integrate all of it. Adverse childhood experiences increase risk for just about every mental disorder, and they increase risk for obesity, diabetes, type type 2 diabetes, cardiovascular disease, and premature mortality. Trauma and stress lead to metabolic and mental disorders, and we call those the social determinants of health. I'm not making this up. Decades and decades of massive studies support this, prove this. But should we be thinking about metabolic health, diet and exercise, and brain function? That is actually somewhat heretical to suggest. And some will call this nutritional psychiatry or metabolic psychiatry. Lots of different labels. But this is, most people are skeptical. "That has nothing to do with the brain."
So, I'm saying metabolic, metabolism. What is metabolism? It's more than just burning calories, and it's more than just metabolic syndrome. It is a fundamental process that all living organisms use to convert food into energy or building blocks used to maintain your grow cells. And it involves the management of waste products. It is fundamental to the definition of living organisms. It is ridiculously complicated. I've given you a kind of somewhat simplistic diagram of metabolic pathways, and to give you a flavor, this is complicated, folks.
So, on that sense, a lot of people will say, "So, Chris Palmer, you're saying it's metabolism is everything, and you're saying mental illness is somehow related to it. Okay, so what? Who cares? That's not really helpful." If we ask some more common sense questions, though, we can get something a little more helpful. So, what exactly controls metabolism? What regulates metabolism in the human body? And if you really do a detailed dive into the science, if you really ask yourself that, it's not insulin, folks. It's not insulin resistance. If you really want to understand metabolism, you must be led to mitochondria.
And the reason most people don't know this is because this is a cutting-edge area of research over the last 20 years that has completely shattered our simplistic understanding of mitochondria and what they do. So many people know them as the powerhouse of the cell, but they are so much more than that. They are critical players in metabolism. Hundreds or thousands of them in each cell. They are highly dynamic. They don't just sit there and turn out ATP. They are moving around cells, fusing with each other, budding off from each other, forming confirmations around the DNA and nucleus to influence gene expression and cell development. They are a universe unto themselves, and there is so much we don't know about them. And yet, what we do know is that they, once and for all, can unify everything that we know about the mental health field.
They play a direct role in the production, regulation, and release of key neurotransmitters, including serotonin, dopamine, GABA, glutamate. And those neurotransmitters influence mitochondrial function. They play a role in genetics and in epigenetic expression. And genes that put people at risk for mental and metabolic disorders affect mitochondria. They play a role in turning inflammation both on and off. And yet, chronic infections and high levels of inflammation influence them. The gut microbiome influences them. Diet and exercise influencing influence them. Shockingly, mitochondrial function in specific brain cells influences whether you you are hungry or satiated. Whether you have a mitochondrial function in your muscles determines whether you have energy to exercise or not exercise. But adverse childhood experiences, stress, trauma, these influence mitochondria. Drugs and alcohol, sleep, hormones. In all hormones, impact mitochondrial function. But mitochondria are instrumental in key hormones known to play a role in mental illness. They control the first step in the synthesis of cortisol, estrogen, testosterone, and progesterone.
And in many ways, this really is nothing new. I'm not pulling this from out of thin air. This is about integrating a century or more of science. In 1879, before we had pills for mental illness, diabetes is a disease that shows itself in families in which insanity prevails. Within 10 years of the discovery of the molecule insulin, we were injecting it into mentally ill people. It was the most widely used treatment in the Western world for severe mood and psychotic disorders from the 1930s to about the 1950s. Its use persisted to the '60s. In the 1930s and '40s, abnormalities in lactate and glucose metabolism were first identified in people with bipolar disorder and schizophrenia. The mitochondrial theory of autism first proposed in 1985. In the 1990s, we had the neuroimaging explosion. What, what is neuroimaging? What, what are we measuring when we do all these brain scans? We're measuring brain metabolism. That's what all of that research is showing us. The mitochondrial theory of bipolar disorder was first proposed in 2000. And since then, there has been an explosion of research, tens of thousands of articles published in the best medical, biological, scientific journals that we have on the planet.
So, what can we do? The fact is that a new theory completely opens up a way to disrupt the mental health field, develop better treatments, refine our understanding, improve people's lives. Could we do anything with this today? And I think most of you know my answer is yes. There are many treatment options. And for this audience in particular, I want you to take a look at this slide. I do not have one bubble that says "ketogenic diet will cure all mental illness." Let me say that again: I do not have a bubble that says the ketogenic diet will cure all mental illness. Problem solved. Put people on keto and, oh, we're done. We're looking for the miracle cures right and left. That is not what I am saying. I am saying that we need a sophisticated and refined and advanced way to understand and treat mental illness.
We may very well continue to use psychiatric medications and psychotherapy. They are effective for millions of people. They will continue to be effective for millions of people. Those are gold standard treatments. They should play a role. Substance use, sleep, stress reduction, social connection. Many of these things are part of our routine standard armamentarium. But of course, mental health professionals never talk about diet or nutrition with their patients. Vitamins are supplements. We don't use metabolic medications. We usually don't measure too many hormones. So, there are a lot of new, innovative treatments.
So, let me come back to this concept. Treatment resistance is common. Now, this comes from an academic article looking at, "What are we in the mental health field get to do with all these treatment-resistant patients?" Any good mental health clinician already knows this to be true. The new ones think that they're just not good. The new mental health clinicians think, "I just, there must be something wrong with me as a clinician because I'm not getting all these people better." The good ones already know this. This is this is the standard. And what are the three core components? Number one, maybe we don't give the correct diagnosis. Number two, maybe we're not providing adequate treatment. And number three, maybe, in fact, yes, sometimes our treatments just fail to work for people.
So, let me rethink this using the brain energy theory. Correct diagnosis. So, not only do we need to identify all of the symptoms that people have, so you might put those into DSM categories, that's fine, because based on symptoms, we do know some treatments that can be helpful for those symptoms. But instead, we need a much more comprehensive way of diagnosing people. And that means a comprehensive assessment. We need to be measuring in all people with mental illness, mental disorders, we need to be measuring metabolic biomarkers like glucose, lipids, weight, blood pressure, visceral fat. We need to be measuring hormones, vitamins, and nutrients. We need to be thinking more in in more sophisticated ways about sleep and circadian rhythms, substance use. We really, really need to take a hard and disruptive look at the medications that we are prescribing. Because in the field of psychiatry, we often prescribe medications that cause metabolic harm. They cause weight gain, they cause type 2 diabetes, they cause cardiovascular disease, and they cause premature mortality. What are we doing to their mental symptoms when we prescribe those medications?
We need to do the standard stuff. Trauma, childhood adversity, adequate treatment. So, if you're going to use a psychotropic medication, let's be reasonable. Reasonable meds at reasonable doses for reasonable amounts of time. When I see patients who are getting medication after medication changed week after week or month after month, and when they come to me six months later, and they've been on seven different medications over the past six months, and they are a mess, guess what my diagnosis is? Irresponsible psychopharmacology. That is the reckless use of psychotropic medications. Putting people on them, taking them off, can cause mental harm. That should not be debatable. That should not be controversial. Yet, unfortunately, it is. And there's a lot more to mental health treatment than pills. Psychotherapy, housing, employment, relationships, stress reduction, substance use treatment. People need to have meaning and purpose in their lives.
Let's take one more quick break to say a special thank you to AirDoctor, who's a sponsor of this episode. If you breathe air, well, it's highly likely that you probably know that the air you breathe indoors is up to 100 hundred times more polluted than outdoor air. This is according to the EPA. And it's kind of wild when you think, kind of gross when you think about it, right? Right. That's where AirDoctor comes into the mix. AirDoctor filters out 99.9% of dangerous contaminants, so your lungs don't have to. This includes, uh, allergens, pollen, pet dander, dust mites, mold spores, even bacteria and viruses. I will tell you, from firsthand experience, I absolutely love our AirDoctor machine. It's got these indicator lights of whether or not your air quality is poor, and then you can actually see it doing work. You can keep it in auto mode, which is my favorite mode, because it just does the work and cleans up your air. And you can tell a complete difference once it's done cleaning the air, and the indicator light shows you're in the clear for for good air. I highly recommend, um, this device. It's pretty incredible. And I'm really excited to share that if you head on over to airdoctorpro.com and use the promo code METABOLICLINK, you'll receive up to $300 off select air purifiers, which is amazing. Also, exclusive to our podcast listeners, you'll receive a free three-year warranty on any unit, which is an additional $84 value. You can get this special offer by going to airdoctorpro.com. That's A-I-R-D-O-C-T-O-R-P-R-O.com and use the code METABOLICLINK. Now, back to our episode with Dr. Palmer.
So, let's rethink current treatments. So, first and foremost, a new theory doesn't replace what we already know. So, if this theory is really going to hold water, I have to be able to defend, "Well, why would an SSRI work? Why would Prozac work for anyone?" And what I am arguing is that we need to take a closer look and really radically rethink what, in fact, we are doing. So, we have lots of medications that impact serotonin. They can increase levels through SSRI, increased levels at the synapse. That's Prozac, Zoloft, Paxil. We have other serotonergic agents. Some antipsychotics block serotonin receptors. Does serotonin have anything to do with metabolism or mitochondria? If you actually look it up, it has everything to do with metabolism and mitochondria. Serotonin, about 90 to 95% of the serotonin in the human body is produced in our digestive tract, not in our brain. Serotonin plays a profound role in mitochondrial function. Serotonin is circulating around the human body, going into mitochondria in potentially every cell that has mitochondria. And that serotonin is being converted into melatonin, which serves an antioxidant function within mitochondria. We know that serotonin is a hot player in the gut, in the gut and the gut microbiome. And we know that the gut and the brain are connected. And more and more research is telling us, maybe a gut issue can cause anxiety or binge eating or other things in the brain. And SSRIs, we have known for decades, they're not just working in the brain. They're working in the brain and the body. And so, we need to completely rethink that. When you take Prozac, it's correcting a serotonin deficiency up here because we've got decades of research that has been unable to find that serotonin deficiency up here. And maybe it is about modulating serotonin, kind of serotonin physiology, to influence metabolism and mitochondrial function. And for some people, that can be immensely helpful and beneficial. And that is why when they go on Prozac, they're fixed. And they will argue with every one of us in this room if we try to take their Prozac away from them. They want their Prozac. And I want them to keep their Prozac. But I want them to think about why is that Prozac working for you? And I want them to think, "It's not a serotonin deficiency. Maybe serotonin is modulating your metabolism in a beneficial way for you."
Dr. Ian Campbell just published this paper in 2022. Lithium. Lithium is a known mood stabilizer. We know some of its mechanisms of action. It targets certain molecules. What exactly is a common theme? What is a unifying theme for these molecules that insulin is acting at? Oh, the insulin signaling pathway. And what does the insulin signaling pathway have to do with mitochondria? Well, everything. So, maybe when lithium works as a mood stabilizer for somebody, it is because it is having a metabolic effect on the insulin signaling pathway, which is beneficial to them in some way or another on their mitochondrial function.
But let's get, so again, I, I want us to look at what works. We're not going to throw the baby out with the bathwater. We want to look at what works. But I want us to rethink it completely. Upend the way we think about it. And make no mistake, that upending becomes highly disruptive because of the medications that cause metabolic harm. So, it, it may make some classes of medications obsolete, or maybe very rarely used in the future.
But let's ask more kind of novel treatment questions. Can a metabolic treatment play a role? And I could go through lots of this. There's hot areas of research: GLP-1 agonists, other diabetes medicines, statins for the mentally ill, to treat their mental symptoms, not just to prevent heart attacks, but to treat their mental symptoms, to prevent them from self-injuring. We've got evidence for all of that. But I am just going to hone in on diet. And the first and foremost thing that I need to just impart to this audience, because I know you guys are all sold on keto. I'm sold on keto. I love keto. But keto is not a one-size-fits-all solution for every human being on the planet. Dietary interventions need to be tailored to the individual in front of us.
And here are some broad goals. Goals for dietary interventions. Some patients need to lose weight. People who are obese might benefit from losing weight. That may improve their metabolic and mental health. Other patients are at the opposite end of the spectrum: people with underweight, anorexia nervosa, people with crippling depression and cancer who are cachectic and have lost, they are emaciated. They need to gain weight. We need, we might need to address nutritional deficiencies. Some people have allergies to there are toxic things and chemicals and ultra-processed foods. Removing those might be beneficial. We can talk about healthy diets like the Mediterranean diet. We can talk about the gut microbiome and changing that. And we can talk about changing metabolism. And I believe the ketogenic diet falls in that last category.
The ketogenic diet, all of you probably know, high fat, low carb, moderate protein. First developed not as the fad weight loss diet, not even as a type 2 diabetes treatment, although low carb diets were used in the 1800s for the treatment of type 2 diabetes and for weight loss. But the term ketogenic diet was coined by a physician who developed this treatment for epilepsy. It mimics the fasting state. If you talk to your primary care docs and they say that keto diet is dangerous, please let them know. Actually, doctor, it's an evidence-based treatment for weight loss, type 2 diabetes, and epilepsy. If you believe in medical literature, um, we have over 100 randomized controlled trials. Over 100 randomized controlled trials. Is it always better than the other diet? No. But almost always, it's at least equal, equal to if not better. That means it is a highly effective, safe intervention and treatment.
Now, as a psychiatrist, the reason I love the ketogenic diet is because it is an epilepsy treatment. And we use epilepsy treatments in tens of millions of people with mental disorders, sometimes FDA-approved indications, and more often than not, off-label. How does a diet stop seizures? We actually know more about the, the ketogenic diet on the brain than we do any other dietary intervention. The ketogenic diet is changing neurotransmitter systems, decreasing brain inflammation, changing gene expression. It is modulating the gut microbiome, which recent research, just in the last couple weeks, shows that modulation of the gut microbiome, when transplanted to a mouse, can actually affect brain metabolism in that mouse and reduce seizures. So, all of the dots are connecting, which is great for me and my theory. Um, but, uh, I focus on the essential thing: the ketogenic diet is inducing mitophagy, which is getting rid of old and defective mitochondria, and it is inducing mitochondrial biogenesis. So that when people do the ketogenic diet for anywhere from one to five years, their cells will have more healthy mitochondria at the end of the day. And I believe that is foundational to the healing potential of the ketogenic diet.
Do we have any evidence that this keto diet works? This is probably the best published study. There are many others underway for Alzheimer's disease. 26 patients randomized to 12 weeks of keto versus low fat. Everybody got the same diet. When they were on the ketogenic diet, they had improvement in activities of daily living, quality of life. They did have improvement in cognition, but the cognition score did not reach statistical significance. What about
Alcoholism. Dr. Wirers is here, who led this study. But this study was under the direction of Dr. Nora Vula, the director of the National Institute of Drug Abuse. What does alcoholism have to do with a diet? Well, alcoholism can result in, or can be the result of, brain glucose hypometabolism. Animal models already showed a signal. They admitted a group of patients with alcoholic M to a detox unit. Three weeks. Half get the ketogenic diet, half get the standard American diet. The patients who got the ketogenic diet required about 50% fewer benzodiazepines for their detox. Nonetheless, they had fewer withdrawal symptoms from alcohol. They reported fewer cravings for alcohol. When they did brain scans, they had lower, they had improved brain metabolism, and they had lower levels of brain inflammation.
Schizophrenia, bipolar disorder, and depression. I have reported several cases now of complete and lasting remission of the ketogenic of of schizophrenia, um, on the ketogenic diet. Patients are sometimes able to get off of medications. The, the most striking patient was one who had suffered from schizophrenia for 53 years. She put her schizophrenia into full and lasting remission, off of psychiatric medications for 15 years until she passed away. She also lost 150 pounds. So isn't that a nice side effect? Um, um, the largest published case series, 31 patients admitted to a French hospital. 28 were able to do the diet. These are patients who had treatment-resistant bipolar disorder, major depression, schizophrenia. Of the patients who were able to do the diet, 100% had improvement in symptoms. 43% achieved clinical remission. That doesn't happen with current treatments today. 64% were discharged on less medicine. So it wasn't that they were just medicating these people, and oh, what a nice side effect. 96% lost some weight.
This is a hot area of research. I am proud to announce that we got a $3 million gift to start the Metabolic and Mental Health Program at McLean Hospital. If any of you are researchers, or know of researchers who want to come join our team, we will be hiring. I will be hiring soon. This is a global effort, spearheaded in no small part by the Bazooki Brain Research Fund and Metabolic Mind. We have clinical trials now taking place at Harvard, Oxford, Hopkins, Stanford, NIAAA, all sorts of places. And with that, I thank you.
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