The Dr. Hyman Show - The Gut-Brain Connection: Why Your Mental Health Starts in the Microbiome

Episode Date: March 24, 2025

The connection between mental health and metabolic health is far deeper than once believed, with growing evidence showing a powerful, bidirectional relationship. Inflammation, poor diet, and gut dysfunction are now recognized as key drivers of both physical and psychological illness—often hiding in plain sight. By addressing root causes such as blood sugar imbalances, nutritional deficiencies, and microbiome disruption, many chronic mental health conditions can improve or even resolve. This emerging science challenges the traditional separation of mind and body, pointing instead to an integrated approach where healing the body becomes essential for healing the brain. Recognizing this link is crucial in shifting the future of mental health care. In this episode, I discuss, along with Dr. Chris Palmer and Dr. Shebani Sethi, why our diet is so closely related to the state of our mental health. Dr. Chris Palmer is a psychiatrist and researcher working at the interface of metabolism and mental health. He is the Director of the Department of Postgraduate and Continuing Education at McLean Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. For over 25 years, he has held leadership roles in psychiatric education, conducted research, and worked with people who have treatment-resistant mental illnesses. He has 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. More broadly, he is interested in the roles of metabolism and metabolic interventions on brain health. Dr. Shebani Sethi is a double board-certified physician in Obesity Medicine and Psychiatry. She is the Founding Director of Stanford University’s Metabolic Psychiatry program and Silicon Valley Metabolic Psychiatry, a new center in the San Francisco Bay Area focused on optimizing brain health by integrating low carb nutrition, comprehensive psychiatric care, and treatment of obesity with associated metabolic disease.  This episode is brought to you by BIOptimizers. Head to bioptimizers.com/hyman and use code HYMAN10 to save 10%. Full-length episodes can be found here: The Hidden Connection Between Gut Health & Mental Health That Therapy and Drugs Cannot Fix A Harvard Psychiatrist Rethinks Mental Health As A Metabolic Disease How Does Ultra-Processed Food Affect Our Mental Health?

Coming up on this episode of the Dr. Hyman show. The relationship between mental health and metabolic disease is bidirectional, which means if you have a mental illness, you're more likely to have metabolic disease and vice versa. And if you have a metabolic disease, you're more likely to develop a mental illness. You're more likely to have a heart attack, for example, if you have depression. And you're more likely to develop depression after you have a heart attack. Did you know that over 75% of people are deficient in magnesium?

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body gets exactly what it needs, where it needs it. I take magnesium breakthrough every night and I've noticed a huge difference in my sleep, stress, and muscle recovery. It's a game changer. Right now, bioptimizers is offering my listeners a special discount. Just go to bioptimizers.com slash Hymen and use code HYMEN10 at checkout. Don't wait, your body will thank you. Before we jump into today's episode, I'd like to note that while I wish I could help everyone

via my personal practice, there is simply not enough time for me to do this at scale. That's why I've been busy building several passion projects to help you. If you're looking for data about your biology, check out Function Health for real-time lab insights. And if you are in need of deepening your knowledge around your health journey,

check out my membership community, the Hymen Hive. And if you're looking for curated and trusted supplements and health products for your health journey, visit my website at drhymen.com for a summary of my favorite and thoroughly tested products. We have a mental health crisis. Globally, 300 million people are suffering from anxiety. 280 million people are suffering from depression.

Now from treating thousands of patients over the last 30 years, I've learned that depression is mostly not in your head. It's in your body. When I treat patients' gut issues, and this is something I just discovered almost by accident, their mental health would magically get better. But it wasn't magic. It was science. I just didn't understand at the time. It's not magic. Gut dysfunction is not the only cause of our mental health crisis. There's a lot of things that are driving it, but it's a major factor that's often unaddressed. Now when your gut is unhealthy, when it's inflamed, your brain is unhealthy and also inflamed. When we fix the gut, then brain health, mood, memory, focus and mental health all improve. Now why is

this important? Inflammation is a huge driver of most of our mental health issues from depression, anxiety, autism, ADD, even things like Alzheimer's, schizophrenia, bipolar disease, all linked to inflammation of the brain. And where's this inflammation coming from? Obviously our diet, but also from our microbiome. Now, I learned this early in my medical practice. In fact, one of my early books called The Ultramind Solution, a deep dive into the way the body affects the brain including the gut and the microbiome. Now conventional medicine views these two things as completely separate and unrelated. And typically if you have GI symptoms, you go to the GI doctor, a gastroenterologist.

And if you have mental health issues, you go to a psychiatrist to help with balancing your mood. They prescribe different drugs for each condition instead of understanding the root cause and treating that. And then we're gonna talk about how this works, why it's important, what the science is, and some of my clinical case studies, which are quite compelling. Now in functional medicine, we know the gut and the brain are infinitely connected

and that the health of one directly impacts the other. So you can't fix the brain without fixing the gut and you can't fix the gut without fixing the brain. So it's bidirectional. It's not mind-body, body-mind, body-mind, mind-body. It's both, right? When we do that, and I've done this in thousands of patients,

and the studies back this up, and more and more data's coming out, guys like Chris Palmer, Uma Naidu, and a psychiatrist from Stanford, and integrated psychiatrists, functional psychiatrists are all seeing this, and data is really exploding on this. When I wrote the book 15 years ago,

there was data, but it was limited. But I saw it, and I saw the kind of whispers in the wind, let's say, the sort of tea leaves. And I was like, okay, this is really something. And when I started to do this with my patients and when we do this now, we see profound improvements in mood and obviously digestive health and all other areas of health. So gut is just linked to everything. So fix the gut, fix the body, fix the gut, fix the brain. I know how powerful this is and how powerful functional medicine is for fixing depression because I also had it myself. And it wasn't because of something that had to do with my psycho-emotional health, but

my physical health. My brain literally broke one day in 1996. I felt like I had ADD, depression and dementia all at once. I saw lots of doctors, psychiatrists. No one could find the cause, although they wanted me to take Prozac for my symptoms and no one could agree on the diagnosis. Some said I had depression, others said I had chronic fatigue. In fact, I did have chronic fatigue and I started to dive into the literature. I consulted with other doctors and scientists, people on the leading edge of medicine and

I started to do some experimentation. When I came to understand that it wasn't just one thing that caused my brain to break, it was accumulation of a lot of things. Diet stuff, stress, environmental toxins like mercury was a big factor. My gut was just a mess. In fact, that's what happened. I had mercury underlying all this. And then one day I got some kind of gut infection up in Maine at a camp and then boom, my gut was off. And it didn't get back on track for many years until I figured out how to fix it. And all that leads to inflammation. So rebalancing my gut microbiome, getting rid of the mercury. It was messing up my gut because mercury interferes with the gut function.

It was the key to getting my brain and health back. I also saw this with so many of my patients. I had a woman who had severe OCD. She wouldn't clean up her house for years because she didn't want to move things around on the floor. Looked at her health and her biology and tried to see what was going on. And in functional medicine, we just take out the bad stuff, put in the good stuff. So I saw she had a lot of bad bugs in her gut, a lot of overgrowth of yeast.

And I gave her basically an antibiotic and an effungal that was designed to kill those particular bugs. And literally overnight, her OCD went away and she was able to clean up her whole house after decades. I also had a little girl who was a sweet little girl, nine years old, but was a terror. She would get kicked out of school all day

on the bus ride home. They'd have to stop the bus 10 times. She was terror her little sister tearing up pictures the family just kind of little nuts I did testing and she didn't have any gut symptoms But we found really high levels of bacterial overgrowth and bad bugs in her gut and yeast overgrowth And again, I gave her an antibiotic and an e fungal and literally overnight. She turned into this beautiful sweet little girl So that made me think oh my god There's a whole untapped world here that we're missing of how to help people who not only have physical health issues, but also have mental health issues.

So today we're going to dive deep into the gut-brain connection. We're going to share some functional medicine tools that will help support your gut health and obviously your mood and mental health too. So what is this gut-brain connection exactly? Well, let's go into the science. The human brain contains approximately 100 billion neurons, brain cells, nerve cells. The gut also has a nervous system. It's called the second brain, also known as the enteric nervous system. Enteric just means gut, fancy medical word. And this contains, get this, 500 million neurons. So there's five times as many

neurons in your gut as in your brain. Now, there's a bi-directional highway between the brain, brain, and the gut brain. And this is called the vagus nerve. And it links our enteric nervous system with our brain and our central nervous system. And it's sending and receiving signals all the time. So whatever's happening in your brain, mood, stress, emotions, impacts your gut function.

And what's ever happening in your gut impacts your brain function, right? Mind, body, body, mind. We talk about this. I felt sick to my stomach. I have gut feelings. Maybe you're so nervous you had to run to the bathroom, right? This is the gut-brain connection at work. There was a study that looked at more than 1.2 million hospitalizations for irritable

bowel and 4,000 hospitals. And people with IBS or irritable bowel syndrome had three times higher risk of anxiety, two times greater risk of depression, and had two times greater risk of suicide ideation, meaning they were thinking of suicide versus the general population. Now we used to think that anxiety caused IBS, but now we know it's the other way around and a little bi-directional. So think about that.

It's not really the stress or anxiety or mental health issues that's causing irritable bowel. It's the change in the microbiome and the irritation, inflammation to the gut lining and the enteric nervous system that feeds back to the brain. It creates an irritable brain. So irritable bowel leads to an irritable brain. So before we dive any deeper, let's define the features of this gut brain axis.

The gut, which basically we talked about, is the GI tract. It starts at your mouth and it goes to your anus. It includes esophagus, stomach, small intestine, large intestine, all the way down to the bottom. The vagus nerve is the longest nerve that comes from your brain called the cranial nerve, which travels through the brain stem to the gut and it connects the gut to the central nervous system and it goes through the entire GI tract. Think about it, you've got huge amounts of gut. If you laid out your small intestine flat, it would be the surface area of a tennis court.

And then there's your large intestine and then your esophagus. So all of that is really important. The vagus nerve connects to other things like your heart and lungs and so forth. But this vagus nerve is a really important part of your nervous system called the parasympathetic nervous system. This is the relaxation nervous system. It also is called the autonomic nervous system

or automatic nervous system. So it's not usually under our willful control, although we can regulate it through various practices. The yogis have been doing this for centuries. It regulates involuntary sensory and motor functions. You say, I'm gonna move my arms, you move your arm. But you don't go, oh, I wanna digest my food. Can you please digest the food in there?

Can you please regulate my heart rate? Can you control my blood pressure? You don't really think about it. These things happen automatically. A lot of this happens through this automatic system. There's a lot of signaling that happens through this nervous system. For example, it helps control appetite. And how does it do that? Through a peptide hormone called GLP-1. Right? You might have heard about this. This is ozempic, gobi, and so forth. Lingerie. These are drugs now, quote drugs.

But they're not really drugs. They're just mimicking your body's own GLP-1 at a much higher concentration. This is also known as the satiety hormone. I mean, it makes you feel full, which is why people don't eat, because they take this shot and they don't feel full. And this is also why people lose weight, because they take this shot, they feel full, they don't want to eat as much, and they lose weight. And this is typically secreted in the lower part of the intestine, but it basically reduces your appetite and promotes satiety.

And it's single via the vagus nerve. So this is really important, this drug, right? It's ozempic. So this is something your body makes. Also, there's other hormones that are regulated called CCK or cholecystokinin, peptide YY, really important. And other compounds called short chain fatty acids. We're gonna talk about why they're important.

But these are made by your gut. It suppress appetite by making you feel full by activating the vagus nerve. And these are things that you can regulate. Leptin is another hormone produced in fat cells and in the gut. And it's also the feel-full hormone. There's many of these redundant pathways in your body. And it exerts its effects through the vagus nerve.

This network, this gut brain, this second brain, or enteric nervous system is a vast network of, like I said, almost 500 million neurons that's embedded in the lining of the GI tract. What's in them not only is nerve cells, but also hormonal cells, enteroendocrine cells. And they're throughout the entire GI tract. And they're involved in sensing all sorts of signals, right? What nutrients you're taking in, taste,

mechanical stimuli, fiber. They detect the microbes, what's going on in there. They help sense toxic compounds. So it's really a critical system. And as I mentioned, this is called the second brain. It operates independently, but also with the brain brain, right? The central nervous system by the vagus nerve, and it controls everything, right?

Gut motility, right? Whether you're constipated or have diarrhea, enzyme secretion, digesting your food, hormone release. It regulates appetite and then makes sure to fill full hormones or the hungry hormones like ghrelin. And it also affects blood flow that aids in digestion and absorbing nutrients so it's super important. The microbiome consists of about a hundred trillion microbes maybe about

five thousand different species and you got about two pounds of poop in there of microbes in your GI tract. So what do these microbes do? Well they help you digest your food, they produce vitamins, they regulate hormones and they help you get rid of toxins. It interacts with your whole enteric nervous system and central nervous system. So the microbiome is a whole nother thing that's involved. You don't just have your brain brain and your second brain, you have your microbiome brain, let's call it.

It's really important. And it helps regulate everything in your body and it regulates mood particularly a lot. The composition of your gut microbiome, and I'm going into this because it's important to understand if you're gonna understand what to do about fixing your gut and how this all works, because I want you to understand the importance of understanding your gut as it regulates regulating your mood and brain health and pretty much everything else. So the composition of your gut

flora, it varies from person to person. It depends on their diet, right? So if you're a hunter-gatherer and eating meat or bison all the time, or if you're a vegan, all that changes based on what you're eating. It changes based on your lifestyle, stress, toxins, genetics, all regulate the microbiome. Now there's a large research project going on called the Human Microbiome Project. It helps map out the gut microbiome of individuals who are healthy and who are sick to understand better their gut bacteria species. So what defines a healthy gut?

What defines a sick gut? And how does that relate to different diseases? Now what's amazing also to me, this blew my mind when I learned about it, is it a third to a half of all the metabolites in your blood, all the thousands of molecules floating around your blood that regulate everything in your body, are not human. They're from your gut microbiome. In other words, these molecules produced from bacteria in the gut are absorbed and then impact your whole biology, including your brain and your mood. There's still a lot we don't know about

what makes a healthy gut or a sick gut, but we know a lot. Now your gut microbiome can produce healing metabolites that keep your gut immune system healthy. Things like short chain fatty acids, we'll talk about those soon. Vitamins like B12, for example, riboflavin made in your gut, enzymes, or it can produce harmful metabolites.

So bad bugs produce bad stuff, good bugs produce good stuff. And the bad metabolites from bad bugs can be things like cytokines. We've learned about from COVID, the cytokine storm. These are inflammatory messenger molecules of your immune system. Endotoxins, literally poisons, we call these lipopolysaccharides.

These are endotoxins, things that are toxic, produced by bacteria that can be absorbed across a leaky gut, cause you to be inflamed and create disease, including obesity, mental health issues, and much more. So bad bugs make you inflamed and almost all issues related to mental health. And it's really important to understand almost all mental health issues and brain issues, whether it's Parkinson's, Alzheimer's, autism, ADD, depression, anxiety, bipolar disease, schizophrenia are all caused by inflammation in the brain. So if we fix the inflammation,

we can fix many of these things. And we'll talk about how to do that soon. Now, what is this gut mood connection? We talked about, so what is the gut and what is the gut brain and the second brain and the first brain and the hormones. Okay, we talked about all that. So the gut microbiome actually influences brain health

and function and it impacts your mood, impacts your stress level. So literally you can have stress molecules produced in your gut that are not because of something happening outside, but something happening inside. And it increases the risk of depression, mental illness via a complex network of things. Nerve cells, endocrine cells or hormone cells, immune pathways. It's the psycho neuro endocrine immune system. We talked about this a lot. It involves all sorts of activities like the transport of neurotransmitters,

tabloids, cytokines, and certain species of gut bacteria are directly involved in the production of neurotransmitters affecting both the gut and the brain. Let's talk about some of them. So dopamine, for example, is best known for its role in reward pathways, leisure, motivation. For example, we know about Adderall or these ADD drugs. They all stimulate dopamine pathways. Sugar does. All the addictive compounds we like to. So does algorism, by the way way. By the way there are certain bacteria that help increase dopamine. Things like lactobacillus plantarum, bacillus subtilis, bacillus serius, and certain strains of E. coli that are beneficial. Pretty cool.

What about serotonin? Another important neurotransmitter involved in mood. It's involved in regulating various physiological processes including secretions of your intestinal tract, peristalsis, you know, motility, respiration, blood vessel regulation, behavior, mood. We know all about Prozac. That's how it works through inhibiting serotonin, reuptake in the nerve cells in the brain, which makes you have more serotonin. Now, certain bacteria that are good can actually help improve

the concentration of serotonin. And by the way, 90 to 95% of serotonin in the body is produced in the gut. But bacteria like Lactobacillus plantarum or Streptococcus thermophilus, which are healthy bacteria you can get through supplements or you can help grow their diet, actually help with improving serotonin. What about GABA? This is the relaxation neurotransmitter. It's sort of the receptor upon which volume and the benzos work. So GABA is sort of a relaxation neurotransmitter and it helps reduce neuronal excitability, helps reduce anxiety and stress, sleep.

And a lot of bacteria can help produce this in your gut, like Bifidobacterium, Lactobacillus plantarium, Lactobacillus ruderi, Lactobacillus rhamnosus, even things like acrimansia. We talked about this a little bit with Darlene from Pendulum Therapeutics. She basically was growing acrimomancia in this big vat to be a probiotic, and they started to analyze

what was in, what were the metabolites that the acromancia was producing. And they actually found a big spike and it turned out to be GABA. So this acromancia bacteria, which is so important for so many reasons and can have many podcasts and things we've written about it, I'll share it in the show notes,

acromancia actually produces GABA. So it's like a natural valium. Other bacteria can influence the levels of neurotransmitters by encoding genes for enzymes that produce neurotransmitters or directly impacting the synthesis of neurotransmitters or the breakdown of neurotransmitters. So the microbiome plays a huge role in all sorts of neurotransmitter function. For example, the conversion of neurotransmitter precursors like tryptophan you get from your diet into serotonin, which is the happy mood chemical. They're also involved in the production of a really important compound in the body called

BDNF. BDNF means brain derived neurotrophic factor. This is like miracle growth for your brain cells, increases in neuroplasticity, neurogenesis, meaning the making of new brain cells and the connections between brain cells. Also bacteria can produce really important compound called short chain fatty acids. These are called postbiotics. A lot of these things are postbiotics, right? Prebiotics fertilize good bacteria, probiotics are the bacteria,

and postbiotics are the compounds produced by the bacteria that are bioactive molecules or metabolites that are produced by healthy gut bacteria and impact our bodies and brains. Now, short chain fatty acids are one of the most important of these. Why? Because they affect every level of our health, regulating cancer, metabolism, inflammation, and gut health, but they also cross the blood-brain barrier and they affect brain health

by regulating neurotransmitter levels and they reduce inflammation, which again is at the root of all this mental health stuff. Are you feeling stressed, sluggish, or struggling with sleep? You might be low on magnesium and trust me, it's a bigger deal than you think. Most magnesium supplements miss the mark, but magnesium breakthrough by Bioptimizers gives you all seven essential forms in one capsule.

So your body gets the full benefits, better energy, stress relief and deep restorative sleep. I take it every night and it's a total game changer. Try it now with an exclusive discount. Go to Bioptimizers.com slash Hymen and use code HYMAN10. Your body will thank you. I take it every night and it's a total game changer. Try it now with an exclusive discount. Go to bioptimizers.com slash Hyman and use code HYMAN10. Your body will thank you. Depression is the leading cause of disability.

So this, you know, most people think of depression as a fairly straightforward illness and we have tons of antidepressants and we've got psychotherapy and we've even got shock treatments and we've got so many treatments available they have to be effective right? Well actually wrong. The majority of people with depression, bread-and-butter depression, are not getting better with our current treatments and it's not because they're not getting treatment. It's because our treatments fail to work for far too many of them.

And so I think that, you know, it was really interesting because the way that I went about unpacking all of this was, you know, I started with the neurology literature and because this is an anti-seizure treatment and we use anti-seizure treatments in psychiatry every day in tens of millions of people. And so, that was really low-hanging fruit and it was a great resource to tap into because we've got a hundred years of clinical and neuroscience evidence on the ketogenic diet and what is it doing to the brain. And so I could tap into that and lo and behold, sure enough, the ketogenic diet rebalances

neurotransmitter imbalances, it decreases brain inflammation, it changes the gut microbiome in beneficial ways, it, you know, improves- it's people off gluten. Yes, it gets people off gluten. It gets people off lots of other toxic foods probably. It improves insulin signaling and insulin resistance in most people. And so it has a wide range of effects, but still this is where the field of psychiatry is. It's like all of these different things. And so I went on a deeper search for how do these connect? Because at first I started off with a mission to how am I going to convince other mental

health clinicians to use the ketogenic diet for serious mental disorders? Because nobody's going to believe this. They're just not going to believe it. Unless I can present a clear and plausible mechanism of action based on science, nobody's going to buy this. And this miraculous treatment that I am seeing in front of my eyes is going to go wasted. I felt like I'm an academic. Not like that. You might lose your job.

Yeah. I did worry about that many times. I wouldn't go to jail like Galileo, but you might lose your job. I worried about that. The good news now is that I have the full support and endorsement of McLean Hospital actually. Amazing. That's unbelievable.

They are very enthusiastic and supportive of this. When I heard about what you're doing, I just did the happy dance. I was like, and I've been telling everybody, I'm like, wow, finally somebody's getting it where it counts. That's awesome. So the way that I ended up coming to the sciences, I ended up focusing on mitochondria and mitochondrial function and more broadly what we call metabolism. And so I came at the science from that perspective and ultimately viewing mental disorders as metabolic disorders of the brain. And that in order to

understand metabolism, you have to understand mitochondria. But in fact, you have to understand everything that you have known about for decades, functional medicine, how it's all interconnected, how diet, toxins, hormones, the gut, stress, all of that come together to result in illness. So functional medicine has been doing this for decades and yet I was holed up in my Harvard position and evidence based medicine and so we didn't learn a lot about functional medicine and certainly functional medicine protocols are not being used in psychiatric hospitals for the most part around the world.

Most psychiatric hospitals are not using these protocols or this paradigm. And so, but at the end of the day, even looking at mental disorders as metabolic disorders, which revolve quite a bit around mitochondria and mitochondrial function, I ended up coming to the same conclusions that you did. Mm-hmm. It's quite extraordinary.

And, you know, I don't know if you're aware of this, but right at Harvard, there is Uma Nadu, who has a whole department of nutritional psychiatry talking about the microbiome and the brain. There's another physician who's been on my podcast at Stanford. They have a department of metabolic psychiatry. It's starting to happen, and more and more psychiatrists are becoming aware of the data because there is data. There's a lot of literature now that supports this notion. When I sort of the mitochondria, it's really about metabolism and energy. And I'd like you to sort of unpack how that actually connects to psychiatric diseases. Because I first heard this concept when I talked to Martha Herbert,

who's a neurologist. And I think she's also, what's about in psychiatry, I might be wrong, neurologist, and I think she's also, what's her name, psychiatrist, I might be wrong, who was treating autism. She was doing brain scans on these autistic kids. She saw their brains were swollen and inflamed on biopsies. These kids got killed on a car accident or something. These brains are just full of inflammatory cells and the immune cells, the white blood cells called the glia. She also called what they have a metabolic encephalopathy. She said that autism is not a brain disorder, it's a systemic disorder that affects the brain. That's what I hear you saying, that psychiatric illness for the most part is a systemic disorder that affects the brain. The causes can be many. It could be with your diet, it could be your microbiome. I

was with a gentleman this weekend whose family was a Hungarian Jew whose family was killed in the Holocaust. He says, I know 150 members of my family were killed in the Holocaust and everybody's name. I lived in a constant state of trauma and stress my whole life. I was like, wow, this is the epigenetics of this. Scientific American just came out with a paper, with a paper, not a paper, but an article, sort of documenting some of the research in New York after 9-11 where they saw women who were pregnant

when 9-11 happened, their children were incredibly affected by the stress and trauma that happened to the mothers when they were pregnant and was registered in gene expression patterns and epigenetics and in cortisol levels and cortisol receptor function. I was like, wow, this data is really coming along in this. There's a lot of things that can affect it, but often the psychiatric problems are so

misdiagnosed and mistreated, honestly, and it creates so much suffering. What you're talking about is really a revolution. It is. It certainly was for me and it certainly is for psychiatrists that I speak with. I don't think they've really considered this. The reason that I am so passionate about mitochondria in particular is because they actually are responsible for much more than just energy production. So most people know mitochondria as the powerhouse of the cell, and so they create ATP, which is our energy source. And there's no doubt they do that, and they are instrumental in that role, and without that, we would not live.

But they actually do so much more than that. So they are primary regulators of hormones, for instance, key hormones like cortisol, estrogen, testosterone, progesterone, and others, that the production of those hormones actually begins inside mitochondria. And as those hormones travel through the body and influence cells throughout your body, the primary influence ends up converging on mitochondria. And so in many ways, the reason that I became ridiculously excited about this theory is because it is a way to connect all of the dots, the biopsychosocial models of mental illness.

It is a way to connect all of them. So mitochondria are instrumental in neurotransmitter function, neurotransmitter production, the release of neurotransmitters, the influence of neurotransmitters. They play a significant and powerful role in inflammation, but inflammation in turn affects mitochondria. effects mitochondria. And so it all, at least in my mind, once I started diving deeper, I was kind of flooded with all these questions. But wait, this can't, it can't be this simple. Like this, this is too simple. There's no way that this complex issue and the complexity of psychiatry and the brain, there's no way it can end up being this simple. And, you know, for the last five years, I have tormented myself in

some ways with questions, like if this is really true, then this should be true or that should be true or this should be true. And At the end of the day, everything in my mind seems to converge on these issues. Yeah, it's so true because I was reflecting on a previous podcast, who was a pediatric neurologist trained at Harvard, Oxford. She works at the University of San Diego now. She did brain imaging, functional MRI imaging of the brain in autistic kids and found they had energy problems, that mitochondrial energy deficits were evident in the brain of autistic kids. Then by giving them mitochondrial nutrients, basically the cofactors and helpers that actually

help you turn food and oxygen into energy, like CoQ10, for example, or B vitamins and just some really simple things that are brain expensive, that these kids would literally get better from autism. That's not to say that all autism is just caused by these nutrition-efficient or mitochondrial issues, but it's one of the things that we see. So there's a lot of people coming at this from a lot of different areas. You're in the psychiatric lane, but the neurologic lane is seeing this too and so is pretty much every other issue. Whether it's your weight or whether it's heart disease or diabetes or Alzheimer's or Parkinson's, so many diseases

are really related to mitochondrial dysfunction. It's great. It's really amazing. I think that this is such a breakthrough and I think there I think how besides the ketogenic diet are you approaching addressing mitochondrial function? Because for example, in autism, they're using these mitochondrial cocktails and supplements to help. That's where when I read your book, I was a little embarrassed because if you want the roadmap to, if you want the self-help version of how can I fix my mitochondria, I feel like your book, Ultramind Solution, is that roadmap. It involves improving your diet, exercise plays a role, stress reduction plays a role, toxins can

play a role, hormonal dysregulation can play a role. These can be wildly different in different people. I think that's a point that you made in your book. It's a point that you make commonly. It's not that there is a one size fits all solution for people. So one person could have an autoimmune thyroid disorder and have a horribly low thyroid hormone. And that person will suffer from both metabolic and mental symptoms. And fixing that problem is replacing thyroid hormone or somehow addressing

the autoimmune disorder and correcting that. Another person could have an autoimmune disorder related to intrinsic factor and they could have malabsorption of vitamin B12, regardless of what they're eating. That person too could have both metabolic and mental symptoms or disorders as a result of vitamin B12 deficiency. The treatment for that might be vitamin B12 injections because they can't absorb B12. Very different treatments, but you're addressing the same root problem or the same root cause which is metabolic, in my mind, metabolic dysfunction or mitochondrial dysfunction. But lots of different things can cause mitochondrial dysfunction. And so, that's the way I'm thinking about it is I, in my mind, mitochondria are front and center. But there are hundreds of different inputs that can influence how well

mitochondria function and how they're doing. And then the consequences of mitochondrial dysfunction are widespread and they can have numerous effects on the brain, resulting in very different symptoms. Some people might have ADHD, other people might have depression, others might have seizures, and others might have schizophrenia. And that probably depends on a variety of factors. What are the different components or environmental factors that are contributing to these problems?

Or genetics or other things, we may not even understand them. Yes. Right? Yeah, it's so true. And I just remember being in my clinic, you know, looking at the patients I saw and not really treating their psychiatric problems, but they would come in with autoimmune disease or digestive problems or arthritis or whatever migraine. And I would just do what I did.

And they would get better from other stuff. Like you're saying, you're treating this guy's weight loss and his schizophrenia got better. And I was like, wow, I call myself the accidental psychiatrist. I never intended to figure this stuff out, but I could not ignore what was in front of me. And I had a patient with ADD once who was so severe

and he had really terrible inflammatory symptoms as well as asthma and allergies and gut issues and migraines. And of course the doctor who was treating him, the psychiatrist just treated ADD with a stimulant and ignored the other things because of course they're not related. But I treated it, I just cleaned up his diet, I gave him some vitamins, I cleaned up his gut,

very simple things. And the mother brought his homework and we'll post it in the show notes because it's pretty impressive. Brought his homework before and after two months just of changing these few things. And these kids often have what we call dysgraphia. They're handwriting, you can't read it, he's 12 years old. It looks like somebody, you know, who's got some kind of severe disorder with writing or something. I don't know. It went from like severe dysgraphia to perfect penmanship in two months. I'm like, holy crap, what is going on in the brain? How does it go from being chaotic and disorganized and

asynchronous to being completely coherent? It was really a mind blowing concept for me and that's where it gave me the idea of the book. I don't know if you know this Chris, but the origin of functional medicine was in psychiatry from Abraham Hoffer. I did not know that. Yeah, so I'm gonna tell you this quick story. I don't wanna dive into some more of your work.

I don't wanna take too much of a sidetrack, but it's fascinating. Abraham Hoffer was a Canadian psychiatrist who treated schizophrenia. And he sort of somehow got the idea that there were some abnormal molecules going on in the brain and that it was related to some kind of nutrient problem. He gave high dose of niacin and zinc and B6 and magnesium. Many of these patients would improve or get better. He began to write about this, talk about this. Then he was friends

with Linus Pauling. Linus Pauling is a two-time Nobel Prize winner. He discovered the structure of proteins and he almost discovered the – well, he kind of did discover the double helix of the DNA and he told his son about it, but then they went – his son went to London and hang out with Watson and Crick and they kind of took it. That's a whole other story. Then he wrote an article in Science magazine, which – I mean, Science, which is a very prominent medical journal, which I don't know if you've actually seen, it's called Orthomolecular Psychiatry, written by Linus Pauling. Have you seen that article?

I have, actually, yes. Yeah. Well, that was the genesis of that. Essentially, the idea was that we could correct ortho means to straighten and molecular means molecules to straighten the molecules of the brain by using high dose of nutrients to move chemical reactions to their completion. Now, it was a very simple idea and it was super complicated paper, very scientific, but it sort of started this process. Then, Jeffrey Bland, who was really the father of functional medicine, was a student of Linus Pauling's.

Linus Pauling was thought of as a crackpot later in his life. I mean, I don't know if you're going to call anybody who won two Nobel Prize a crackpot, but he was kind of dismissed for his ideas about vitamin C and everything, but he was onto something and this is what we're seeing now. So I think your work is so important and your ability to actually communicate this, to look at the science is so important. So talk about how we can think about some of the inflammation process in mental health and metabolic health and what we need to do to fix that. People are listening, well, I hear this, my mitochondria aren't working, inflammation is connected. How do

I start to address that in myself? It's a great question. And inflammation is, as you know, is a complicated topic because so there are some clear causes of inflammation. You can get an infection, for instance, and that causes an inflammatory reaction in your body. And lo and behold, we have an abundance of evidence that when a woman is pregnant, if she experiences a serious infection, sometimes even a mild infection like with the influenza virus, her baby will be at increased risk for mental disorders later in life. If young children experience serious infections, especially if it's serious enough to be hospitalized,

they are about twice as likely to develop a mental disorder, oftentimes within three months of that hospitalization. The mental disorders are not trivial disorders. It's not anxiety because you are hospitalized. The disorders include things like autism, schizophrenia, mental retardation, obsessive-compulsive disorder, and others. These can become lifelong disorders. We know in those cases, the inflammation appears to be doing something that takes a toll or that changes neurobiology or changes kind of whole body function. And my hypothesis right now is that inflammation takes a toll on your metabolism, plain and

simple. For sure. And that it dramatically, we have very good direct evidence that inflammation takes a toll on mitochondrial function. It actually inhibits the function of mitochondria in some brain cells, and we have direct evidence for that. And by the way, the brain has got the most mitochondria per cell of any organ in the body, so it's really important. Yeah, it is.

And the brain is exquisitely sensitive to even slight fluctuations in mitochondrial impairment. So whenever people have a metabolic problem, usually the brain is the first organ to suffer and it might just be trivial symptoms. So clear causes of inflammation can result in metabolic or mitochondrial impairment and then result in mental symptoms or mental disorders. Even people with runny noses or hay fever are like 86% more likely to have chronic depression than people without that. So in some cases, these

things are unavoidable. And I just have to say that. I mean, a woman getting an infection while she's pregnant, there aren't a lot of things that she can do to necessarily, I mean, there are some things she can do to avoid an infection, but it's not going to be 100% and I don't want to get into a situation where we're trying to blame pregnant women for getting an infection. No. But you can do something about it when the baby is born and you can fix the baby afterwards. Yes. And you can even do something about it immediately after that infection.

So there are lots of ways to improve metabolism and mitochondrial health. And most of them are lifestyle related and they include things like diet, removing, as you say, removing the bad stuff from your diet and putting in the good stuff. So easy. It's easy. It's probably more complicated than most people realize because then they question, well, what's the bad stuff? Is it just fat? If I remove fat from my diet, am I going to be good? No, it's not that simple. And it's not as simple as carbohydrates. As somebody who's using the ketogenic diet, some will say, if you just remove carbohydrates, that will solve all of the world's ills. I

don't believe that at all. No, no. So, it's about removing bad things from the diet, adding in good things. But it could also include exercise. It can include prioritizing sleep, getting more rest, allowing your body to recover from that process. So, if you are usually a workaholic, if you are highly stressed and you have an infection, maybe it's time to just prioritize self-care for even a month or so after that, and really make sure you're getting good nutrition, you're exercising maybe more than you normally even do. Getting good rest, trying to decrease stress levels,

those types of things in order to allow your body to reset, in order to allow your body to recover from that assault on it. One of the best doorways to the mitochondria is exercise, right? It stimulates the growth of new mitochondria, improves the function of mitochondria. It's quite important and it also cuts down inflammation and activates your antioxidant enzymes. It has so many benefits and we know it's better, they quill into many drugs for depression

if you just exercise regularly, vigorously, right? And we know that diet also plays a role. And one of the challenges, I wonder how do you address this with your colleagues? Because this is something I've found even at Cleveland Clinic working with some of the researchers, they're like, well, we can how do you address this with your colleagues? Because this is something I've found even at Cleveland Clinic working with some of the researchers. They're like, well, we can't do everything at once. We can't do diet and exercise and supplements and sleep. I'm like, we can only do one thing at once because we don't know what's going

to work. I'm like, wait a minute. If you want to grow a nice garden, you don't just go, I'm going to give the water, the plant water only, but no soil or sunlight. Then I'm going to give it sunlight, but no soil or water. Then I'm going to give it sunlight, but no soil or water. It doesn't respect the laws of nature. How do you battle that within the medical paradigm? Because it's really tough. We're looking for the single drug, for the single disease, or the single outcome, which is a model based on infection, which can work. But even then, it's flawed because it depends on the biological terrain and why some people get sick and don't or why some people die and don't.

We see that with COVID, not everybody gets sick and sick or hospitalized or dies. People who are chronically ill or overweight or age and do because their systems don't work as well. So how do you address this? I think it's a really- I don't wanna get you in trouble with your garden. No, no, no.

It's a, I kind of chuckled as you were saying your garden analogy because I've used that exact analogy with people as well. And I think most athletes and coaches know this as well, that if you want to become an Olympic champion, it's not only about exercise, it's about exercise and diet and sleep and get rid of any toxins. That means no drinking, no drugging, no anything, because you are trying to get your body in prime condition.

It requires a multifaceted approach. Those things are all interconnected and they're all going to relate to whether you can grow your muscles, whether you can get faster, improve your cardiac health, all of those things. I completely agree with you. I think it's a huge challenge in our field. To me, the lowest hanging fruit is with the chronic severe mental disorders. I think that if, because right now, the prognosis is so abysmal for these disorders.

And the likelihood that any intervention, whether it's a single intervention or a complex intervention, the likelihood that anything will change the course of these disorders is extremely low in most academic psychiatrists' minds. It's like autism, right? Yes. extremely low in most academic psychiatrists' minds. It's like autism, right? Yes. So I actually am hopeful that we can get funding for studies like this using a quote unquote

treatment resistant population and maybe design a comprehensive treatment. You'll call it a functional medicine treatment. I'm trying to get mainstream medicine to buy into this. So I might just call it a comprehensive effective treatment. And I might call it a metabolic treatment or a mitochondrial treatment. At the end of the day, it's going to be the exact same thing as what you're doing. But sometimes language matters. And so I'm not sure. But I think that I think that we could probably get funding for such a study. I think we would want some of the best practitioners, maybe you included to really be be part of this protocol because we maybe get you know one or two shots and we don't have to cure everybody. But if we can even get

30% of those people dramatically improved, I think that would get the attention of a lot of people in the mental health field. And again, these disorders are the most disabling disorders. They are some of the most costly disorders to society. So it won't only get the attention of those in the mental health field, it will get the attention of insurance companies, the government because the government is providing disability. And so not only is the government because the government is providing disability.

And so not only is the government providing disability payments to these people, they are failing to get tax revenues from their employment. And I can be the first to say, having worked with these people for well over 25 years, these people are desperate to contribute to society. They want to work. There's this stereotype out there that, oh, depression is a leading cause of disability because everybody's lazy slackers and they're just looking for an excuse to be on disability. Let me just maybe disabuse some of the, if any of your listeners are thinking that and thinking, yeah, that's right. Let me disabuse, you have a few notions. Number one, they're not living the high life. You're living essentially in poverty on that lifestyle. But this notion

of self-respect and autonomy is huge. And I have had schizophrenic patients crying in my office because they just want to work and earn some money to be able to hold their head high and say, I earned some money. And I remember with one of these patients, I tried with her for six months to help her get a job bagging groceries at a grocery store. And at the end of the day, she couldn't do it.

She couldn't do it because her symptoms would get worse. She started thinking that the manager was stealing money. She got paranoid about the manager, started causing trouble, and it was a complex intervention like water, sunlight, and good soil, if it requires a complex intervention, that maybe we can get people to take this seriously. The relationship between mental health and metabolic disease is bidirectional, which means if you have a mental illness, you're more likely to have metabolic disease and vice versa. And if you have a metabolic disease, you're more likely to develop a mental illness. You're

more likely to have a heart attack, for example, if you have depression and you're more likely to develop depression after you have a heart attack. So these observations that I made really put questions in my mind as to there must be something more to what we're doing that needs further investigation. And I believe that there are metabolic issues that are not necessarily addressed within the field that I think needs to start occurring. We need to start including that in the way that we diagnose and treat and evaluate disease. Yeah, I was thinking you were talking earlier about this idea of comorbidities, which is a term we use in medicine to describe diseases that occur in the same patient. So if you have high blood pressure, diabetes, depression,

reflux, we call these comorbidities. But we were talking earlier about how they may not really be unrelated, that in fact, they may be very connected. And it sounds like from your observations, you made the conclusion that maybe it wasn't a coincidence that the fact that people who were overweight or unhealthy also had mental health issues. Maybe there was a relationship,

nutritional deficiencies, metabolic issues. You talk a lot about insulin resistance. So how did you come to sort of understand that that was really going on? That the biology of that was something that was real. So I originally started off with an interest in learning about nutrition and metabolic issues in obesity and I wanted to treat obesity and then I saw that in a lot of the patients there were

psychiatric conditions in those patients so I started to veer into the realm of psychiatry and got very interested in that. So what happened was that when I was treating metabolic dysfunction, not necessarily obesity, but metabolic dysfunction, which is problems with blood sugar or insulin resistance or high blood cholesterol, I saw improvements in quality of life, in mood and anxiety symptoms, in psychiatric symptoms essentially. And that really got me interested in what is this relationship, why is this occurring? And got me interested in treating these patients in a slightly different way than standard of care, really integrating the understanding

of what metabolic dysfunction is. And I then started a clinic and I started to do research and that's how my path started. And I started early on developing this clinic in residency training. Which is incredible because when you look at the level of mental illness in society, it's one of the biggest causes of disability and one of the biggest costs is depression and anxiety.

And I remember when I was seeing patients early on, treating them for insulin resistance and pre-diabetes and other issues or gut issues or other factors that were going on related to autoimmune disease or inflammation and we would get them healthy, they would sort of say, wait, my depression went away, my anxiety went away, my panic attacks are gone, my bipolar disease is better, my ADD is better and I'm like, well, how did that happen? And then you begin to go down the rabbit hole

and you begin to look at the biology of what's happening. And one of the, I think the greatest discoveries around mental health is that it's an inflammatory problem very often that the brain is inflamed, but the brain can't say ouch, like you have a sore throat or, you know, a swollen ankle it manifests as all these psychiatric symptoms so I'd love to be sort of take us down the road of how inflammation is connected to mental illness and what the approach is that you're using to help correct that. Sure so that's uh you know quite an important question. And, you know, when we talk about how nutrition affects the brain and specifically focusing on reducing that sugar and processed

foods and refined carbohydrates to improve mental and physical health, we know that consuming excessive amounts of sugar, processed foods, and refined carbohydrates lead to obesity, metabolic problems, fatty liver, heart disease, even cancer. There is evidence for this and the body is really one whole system and what happens in the body also affects the brain. The brain has a delicate balance of neurotransmitters or chemical messengers with more sugar and processed foods. These levels really become unbalanced and they're significantly off. So I'm talking about-

So wait, wait, so your brain chemistry gets screwed up when you eat processed food and sugar, is what you're saying. Yeah, yeah, and I'm talking about ultra processed food also in particular, because I do think that there's a difference between processed food and ultra processed food also in particular, because I do think that there's a difference between processed food and ultra processed food. Ultra processed food is like the real sugar, the cookies, the cakes, the chips, the potato chips,

it's kind of highly processed things versus minimally processed foods, maybe some oils, vegetables that are frozen, that's a little bit different than ultra processed food. And so the research is showing differences between those things in the brain. Yeah. And you need the right raw ingredients

for chemical reactions to occur in the brain and elsewhere like vitamins and minerals and nutrients, you need proper functioning, you know, of the brain, you need proper functioning of the brain, you need proper speed of transmitting signals. Your brain is composed of electrical cells and it's a complicated web of signaling molecules. Those cells need fat to develop and to function properly. So you need those omega-3s in your diet.

And if you eat sugar and ultra processed foods, the chances are that you're likely not getting those important nutrients, those vitamins and minerals for those important reactions that you need, nor are you absorbing them. The most people with metabolic dysfunction actually have nutritional deficiencies and are malnourished.

So you're saying it's people who are overweight and obese often are very malnourished and vitamin and nutrient deficient. Yes, that's right. That's sort of a paradox, right? Right, right. I think they're eating all this food, why are they nutritionally deficient? But they're actually among the most malnourished.

They are, unfortunately. They're looking at all the wrong places for the nutrients. They eat more and more food. I think a study from Kevin Hall and others showed that if you let people eat as much as they want and you give them ultra-processed food versus whole foods, they'll eat about 500 calories more a day of ultra-processed food because they'll keep eating and they're hungry and they keep driving. You talk a lot about it in your work about the biology of what these do to your brain

in terms of dopamine and the addiction reward pathways in the brain that make you literally become addicted to these compounds and how that affects you. Right, so the rates of obesity and binge eating and addictive like eating are rising alongside the increasing dominance of ultra processed foods in the modern food environment. And there are several mechanisms as to how this works, some which act directly on the

brain and some that indirectly act through hormonal signaling. So our body is very complicated and the brain is connected to the body. And we used to learn in medical school that you have this blood brain barrier that nothing can get across it. But that's not it's like the Berlin Wall but in reality it's it does leak right and there are things that do cross and it's more like a coffee filter you know it's a sip. Right yeah so so ultra processed food and sugar decrease our dopamine receptors and make us eat more compulsively. Much like addictive drugs, the highly processed foods, they trigger dopamine reward pathways

and they invoke addictive-like behaviors which have been well-documented and include intense cravings, includes feelings of withdrawal when cutting down on ultra-processed food, continuing to eat these things despite knowing the adverse consequences to it, and repeated attempts to try to quit. I'm describing addiction here, basically, and the consumption of larger quantities

over time than intended. People go, it's like emotional eating, it's not really biological true addiction. What you're saying is this is really a true biological addiction, just like heroin or cocaine or alcohol, that you get withdrawal, you get cravings, you get increased need for more and more of the substance

to receive the same pleasure, you down regulate the receptors for pleasure, so you have to take more of the stuff to actually stimulate that reward pathway, and it's really this vicious cycle that people get into, and then they blame themselves, and they feel guilty, you know, for doing it, and they think they just have no willpower, but you're saying it's much bigger than that. Yeah, that's exactly right. It's, so sugar is an addictive substance. It's not just something we say. It has a straightforward neurochemical basis in the brain, just like any other drug.

And I think of sugar as a, it's a recreational food. It's not a food that's essential for survival. We make sugar, you know, through the process of gluconeogenesis, through other foods that we consume. And so it's really about excess carbohydrates. It's not- I call sugar a recreational drug. I've never heard anybody say it,

but I'm probably, oh, he's right down in my book. Sugar is a recreational drug. It's like, if you like tequila, it's fine, but not breakfast, lunch, and dinner in the quantities we're having in America. Exactly, yeah. And we also, actually, I would like to share a story about this. Just during the era of COVID, since we're in it, just to give context as to why I wrote

about this and why I'm working on this as well and continuing to feel motivated to continue to do my work is the shelter in place order had come a couple of months back for my county and I'm in California, I live in Menlo Park. When it was announced, my husband, he's an infectious disease physician at Stanford and I'm a psychiatrist and a state medicine physician as you mentioned.

We both felt doubly invested in this pandemic. We went to our neighborhood Safeway grocery store and we saw many people loading up their carts with Pop Tarts, Hawaiian Punch, popcorn, anything ultra processed basically. And they weren't loading up their carts with fresh vegetables or, you know, they were out of cookies at the grocery store.

Yeah, they were using toilet paper. And toilet paper, exactly. And there were still, you know, produce left in the store. You know, it wasn't like they ran out of produce. No. So here I was. I wasn't gonna run on broccoli. No. Here I was at the checkout counter

and I was thinking to myself, you know, staring at the person's and I was thinking to myself, you know, staring at the person's car in front of me that is full of the recreational food, as I mentioned, the food that's not necessary for survival and detrimental to our health. I thought to myself, this is certainly not preparing them for the pandemic or helping their immune system and if anything, weakening it. And this is our local Safeway. This is the heart of Silicon Valley.

So in this context, it wasn't about affordability or access. That is what motivated me to kind of get that public message out on this topic. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman.

Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for

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