Mental Health - Transcript

Dr. Mark Hyman
Coming up on this episode of The Doctor Hyman Show.

Dr. Shebani Sethi
The relationship between mental health and metabolic disease is 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.

Dr. Mark Hyman
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's 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're in need of deepening your knowledge around your health journey, check out my membership community, the Hyman Hive. And if you're looking for curated and trusted supplements and health products for your health journey, visit my website at DoctorHyman.com for a summary of my favorite and thoroughly tested products.

We have a mental health crisis. Globally, three hundred million people are suffering from anxiety. Two hundred eighty million people are suffering from depression. Now, treating thousands of patients over the last thirty 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.

And 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 is this inflammation coming from?

Obviously our diet, but also from our microbiome. And I learned this early in my medical practice. In fact, on one of my early books called The Ultra Mind 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 going 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 intimately 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, 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, I guess like Chris Palmer, Uma Naidu, and psychiatrists from Stanford, and integrative psychiatrists, functional psychiatrists are all seeing this, and data is really exploding on this. When I wrote the book fifteen years ago, there was data, but it was limited. But I saw, 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.

And I, in fact, I did have chronic fatigue. And I started to deep dive into the literature. And I consulted with other doctors and scientists, people on the leading edge of medicine. And I started to do some experimentation. And 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. Was messing up my gut because mercury interferes with 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, just take out the bad stuff, put in the good 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 any fungal that was designed to kill that particular bugs. And literally overnight, her OCD went away, and she would 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 terrorizing her little sister, tearing up pictures of the family, just kind of a 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 antifungal, 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 gonna dive deep into the gut brain connection. We're gonna 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 a hundred billion neurons, brain cells, nerve cells. Right? 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 And this contains, get this, 500,000,000 neurons.

So there's five times as many neurons in your gut as in your brain. Now there's a bidirectional 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 their 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 whatever's 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 I had to run to the bathroom, right? This is the gut brain connection at work. There was a study that looked at more than 1,200,000 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 a 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 bidirectional. 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 micro 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.

It travels through the brainstem, to the gut, and it connects the gut 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 that is really important.

The vagus nerve connects to other things like your heart, 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 going move my arms. You move your arm. But you'll go, oh, I want to digest my food.

Can you please digest the food? Then 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-one. Right? You might have heard about this. This is Ozempic, Wegovy, and so forth. Lounjaro, these are drugs now, quote drugs, but they're not really drugs.

They're just mimicking your body's own GLP-one at a much higher concentration. This is also known as a satiety hormone, meaning 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 sends a 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 going talk about why they're important.

But these are made by your gut that 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 500,000,000 neurons that's embedded in the lining of the GI tract.

What's in them not only is nerve cells, but also hormonal cells, right? 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 that regulates appetite, and then make sure to fulfill 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.

And the microbiome consists of about a hundred trillion microbes, maybe about 5,000 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 another thing that's involved.

Right? You don't just have your brain brain and your second brain. You have your microbiome brain. Let's call it. Right?

It's really important. And it helps regulate everything in your body, and it regulates mood particularly a lot. You know, the composition of your gut microbiome, and I'm going into this because it's important to understand if you're going to 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 to 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, 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 that 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 b twelve, 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 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 this is 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, 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 could 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 complex network of things, nerve cells, endocrine cells, or hormone cells, immune pathways. It's the psycho neuroendocrine immune system, right? We talked about this a lot. It involves all sorts of activities, like the transport of neurotransmitters, metabolites, 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, pleasure, 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 altruism, by the way. By the way, there are certain bacteria that help increase dopamine. Things like lactobacillus plantarum, bacillus subtilis, bacillus cereus, 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 the secretions of your intestinal tract, peristalsis, 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, 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 the diet, actually help with improving serotonin. What about GABA? This is the relaxation neurotransmitter.

It's sort of the receptor upon which Valium and the benzos work. So GABA is sort of a relaxation neurotransmitter, and it helps reduce neuronal excitability, helps reduce anxiety and stress with sleep. And a lot of bacteria can help produce this in your gut, like bifidobacterium, lactobacillus plantarium, lactobacillus reuteri, lactobacillus rhamnosus, even things like achromanxia. We talked about the silhouette valine from Pendulum Therapeutics. She basically was growing achromanxia in this big vat to be a probiotic, and they started to analyze what was in over the metabolites that the achromanxia was producing.

And they actually found a big spike, and it turned out to be GABA. So this achromanxia bacteria, which is so important for so many reasons and have many podcasts and things we've written about it, I'll share it in the show notes. The achromanacea actually produces GABA, so it's like a natural value. Other bacteria can influence the levels of neurotransmitters by encoding genes for enzymes that produce 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 neuroplasticity, neurogenesis, meaning making new brain cells and the connections between brain cells. Also, can produce a 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. And 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.

Dr. Chris Palmer
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.

It it The majority of people with depression, bread and butter depression, are not getting better with our current treatments. And, 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, 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 Gets

Dr. Mark Hyman
people off gluten.

Dr. Chris Palmer
Yes. It gets people off gluten. It gets people off lots of other toxic, foods probably. It 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 gonna convince other mental health clinicians to use the ketogenic diet for serious mental disorders because nobody's gonna believe this. They're just not gonna believe it.

Unless I can present a clear and plausible mechanism of action based on science, nobody's gonna buy this. And this miraculous treatment that I am seeing in front of my eyes is gonna go wasted. And I so I kind of felt like I'm an academic

Dr. Mark Hyman
You might lose your job.

Dr. Chris Palmer
Yeah. That's I I did worry about that many times.

Dr. Mark Hyman
I wouldn't go to jail like Galileo, but you might lose your job.

Dr. Chris Palmer
I worried about that. The the good news now is that I have the full support and endorsement of McLean Hospital, actually.

Dr. Mark Hyman
Amazing. That's unbelievable.

Dr. Chris Palmer
They are very enthusiastic and supportive of this.

Dr. Mark Hyman
Oh, see, when I heard about what you're doing, I just said the happy dance. I was like and I've been telling everybody. I'm like, wow. Finally, somebody's getting it where it counts.

Dr. Chris Palmer
That's awesome. The 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. Mhmm. 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, 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, you know, Harvard position and, evidence based medicine.

Dr. Mark Hyman
So

Dr. Chris Palmer
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 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.

Dr. Mark Hyman
Mhmm. It's quite extraordinary and you know, I don't if you're aware of this, but right at Harvard there is Uma Naidu who has a whole department of nutritional psychiatry talking about the microbiome and the brain. And there's another physician who's been on my podcast at Stanford. They have a department of metabolic psychiatry. So 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. So when I when I look at sort of the mitochondria, it's really about, you know, metabolism and energy. And and and and it it's so I'd like you to sort of unpack how that actually connects to psychiatric diseases. Because, you know, I first heard this concept when I talked to Martha Herbert, who's a psychiatrist so neurologist, right? Neurologist.

And I think she's also was a psychiatrist, I might be wrong, who who was treating autism. And she was doing brain scans on these autistic kids. She saw their brains were swollen and inflamed on biopsies with these kids got killed in a crack or something. And see these brains are just full of inflammatory cells and immune cells, the white blood cells called the glia. And she also called what they have a metabolic encephalopathy.

She said that that autism is just not a brain disorder, it's a systemic disorder that affects the brain. And and it's what I hear you saying that psychiatric illness for the most part is a a systemic disorder that affects the brain. Now the causes can be many, like it could be like your diet, it could be your microbiome. But I I was with a gentleman this weekend whose family it's a Hungarian Jew whose family was killed in the Holocaust. He says, I remember I know a 50 members of my family were killed in the Holocaust and everybody's name.

And I lived in a constant state of trauma and stress my whole life. And you know, I was like, wow, this is the epigenetics of this. And Scientific American just came out with a paper, not a paper, but an article sort of documenting some of the research in New York after nine eleven where they saw women who were pregnant when nine eleven happened, their children were 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. And I was like, wow, this is the data is really coming along in this. So there's a lot of things that can affect it.

But often, you know, the psychiatric problems are so misdiagnosed and mistreated honestly. Creates so much suffering. And so, you know, what you're talking about is is really a revolution.

Dr. Chris Palmer
It is. It, 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 they actually are responsible for much more than just energy production. So most people know mitochondria is the powerhouse of the cell, and so they create ATP, which is our energy source.

But 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, and so in many ways, the reason that I became, like, 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, production, the release of neurotransmitters, the influence of neurotransmitters. They play a significant and powerful role in inflammation. But inflammation in turn affects mitochondria. And so it all, at least in my mind, once I started diving deeper, I was kind of flooded with all of these questions.

But wait, this can't it can't be this simple. Like, this this is too 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 Yeah. Yeah.

And and at the end of the day, everything in my mind seems to converge on these issues.

Dr. Mark Hyman
Yeah. Well, it's so true because, you know, I was reflecting on a I guess we had on a previous podcast who's a pediatric neurologist trained at Harvard, Oxford. She works at University of San Diego now. And she she did brain imaging, functional MRI imaging of the brain in autistic kids and finally had energy problems, that mitochondrial energy deficits were evident in the brain of autistic kids. And then by giving them mitochondrial nutrients, basically, the cofactors and helpers that actually help you turn food and oxygen and energy, like co q ten, for example, or in 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 deficient or mitochondrial issues. It's it's 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, you know, the neurologic lane is seeing this too and so is pretty much every other the other issue. I mean, 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.

So it's great. It's really amazing. And I think that that this is such a breakthrough and and and I think, you know, there's besides the the ketogenic diet are you approaching addressing mitochondrial function? Because for example, in autism, they're using these mitochondrial cocktails and and supplements to help.

Dr. Chris Palmer
So and that that's that's where when I read your book, I was a little embarrassed because because if you want the road map to if you want the the self help version of how can I fix my mitochondria, I feel like your book's Ultramind solution is that road map? It 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. And these can be wildly different in different people. And I think that's, you know, it's it's a point that you made in your book. It's a point that you make commonly. And so it's not that there is a one size fixed, you know, fits all solution for people.

So one person could have an autoimmune thyroid disorder and have, you know, a horrible, 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, you know, 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 and the treatment for that might be vitamin B12 injections because they can't absorb B12.

So very different treatments, but you're addressing the same root problem or the same root cause which is metabolic, in my mind, 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. And but there are hundreds of different inputs that that 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. Yeah. Others might have seizures, and others might have schizophrenia. And, and that probably depends on a variety of factors. What what are the different, you know, components or environmental factors that are contributing the

Dr. Mark Hyman
or, you know, other things we may not even understand. Yes. Right? Yeah. It's it's so true.

And I I 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 would treat this guy's weight loss and schizophrenia got better. And and I was like, wow, I call myself the accidental psychiatrist.

You know, I never intended to figure this stuff out, but I could not ignore what was in front of me whether and I had a I had a patient with ADD once who was so severe and he had, you know, really terrible inflammatory symptoms as well, asthma and allergies and gut issues and migraines. And, you know, of course, the doctor who's treating him, the psychiatrist just treated ADD with a stimulant and ignored the other things because, of course, they're not related.

Dr. Chris Palmer
Of course.

Dr. Mark Hyman
But I treated it I just cleaned up his diet. I gave him some vitamins. I cleaned up his gut. I you know, I 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. Their 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.

And it went from, like, severe dysgraphia to perfect penmanship in two months. And I'm like, holy crap. What is going on in the brain? How does it go from being chaotic and disorganized and asynchronous, dis synchronous to being completely coherent? And I I and it was really a mind blowing concept for me.

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.

Dr. Chris Palmer
I did not know that.

Dr. Mark Hyman
Yes. So I I'm gonna tell you this quick story, then I I don't wanna dive into 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 just sort of somehow got the idea that there was some abnormal molecules going on in the brain and that it was related to some kind of nutrient problem.

So he gave high dose of niacin and zinc and b six and magnesium. And many of these patients would improve or get better. And and so he began to write about this, talk about this, and and then he was friends with Linus Pauling. And they Linus Pauling is a two time Nobel Prize winner. He discovered the structure of proteins, and he almost discovered the well, he kinda did discover the double helix of the DNA and he told his son about it, then they went his son went to London and hang out with Watson and Crick and they kinda took it.

That's a whole another story. And then he wrote an article in Science Magazine, which I mean, which Science, which is a very prominent medical journal, which I don't know if you've actually seen, is called orthomolecular psychiatry written by Linus Pauling. Have you seen that?

Dr. Chris Palmer
I have. Actually,

Dr. Mark Hyman
yes. Yeah. Well, that that was the genesis of that. And essentially, the idea was that we could correct ortho means to straighten and molecules 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, and then Jeffrey Bland, who was really the father of functional medicine, was a student of Linus Pauling's.

Linus Pauling was kind of thought of as a crackpot later in his life. I mean, I don't know if you can recall anybody who won two Nobel Prize at CrackBot, but he was kinda dismissed for his ideas about vitamin c and and everything. But but he was onto something, and this is what we're seeing now. So I think your your work is so important and your ability to actually communicate this, to look at the science is so important. So so talk about how how we can think about some of the the 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's connected. How do I start to address that in myself?

Dr. Chris Palmer
It's a great question. And, you know, inflammation is, as you know, is a complicated topic because so 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 if you when a woman is pregnant, if she experiences a serious infection, sometimes even a mild infection like with 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.

And the mental disorders are not trivial disorders. It's not anxiety because you are hospitalized. It's the disorders include things like autism, schizophrenia, mental retardation, obsessive compulsive disorder and others. And these can become lifelong disorders. And so 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, you know, hypothesis right now is that inflammation takes a toll on your metabolism, plain and simple. And that it dramatically, we have very good direct evidence that inflammation takes a toll on mitochondrial function. Actually inhibits the function of mitochondria in some brain cells. We have direct evidence for that.

Dr. Mark Hyman
And by the way, the brain has got the most mitochondria per cell of any organ in the body. So it's really important.

Dr. Chris Palmer
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, you know, runny noses or hay fever are like eighty six percent more likely to have chronic depression, than people without So so in some cases, these things are unavoidable, I just have to say that. I mean, you know, a woman getting an infection while she's pregnant, there aren't a lot of things that she can do to necessary I mean, are some things she can do to avoid an infection, but it's not gonna be a hundred percent, and I don't wanna get into a situation where we're trying to blame pregnant women for getting an infection.

Dr. Mark Hyman
But you can do something about it when the baby's born and you can fix the baby afterwards.

Dr. Chris Palmer
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, making removing, as as you say, removing the bad stuff from your diet and putting in the good stuff.

Dr. Mark Hyman
So easy.

Dr. Chris Palmer
It it it 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? You know? If I remove fat from my diet, am I gonna be all good?

No. No. It's not that simple. And it's not as simple as carbohydrates, you know, as somebody who's, you know, using the ketogenic diet. Some will say, you just remove carbohydrates, that will solve all of the world's ills.

I don't believe that at all. No. No. 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, you know, to just prioritize self care for, you know, even a month or so after that and 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.

Dr. Mark Hyman
I mean, one of the best doorways to the mitochondria is exercise. Right? 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 and we know it's better that they equivalent to many drugs for depression if you just exercise regularly, vigorously. Right? And we know that diet also plays a role. And, you know, one of the challenges and I I wonder how how do you address this with your colleagues? Because this is something I've I've found even at, you know, Cleveland Clinic working with some of the researchers who are like, well, you know, we can't do everything at once.

We can't do diet and exercise and supplements and sleep. And I'm like, we can only do one thing at once because we don't know what's gonna And I'm like, wait a minute. If you wanna grow a nice garden, you don't just go, I'm gonna give the water the plant water only, but no soil or sunlight. And then I'm gonna give it sunlight, but no soil or water. And I just it it doesn't respect the laws of nature.

So so how do you kinda 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 is sick or hospitalized or dies. People who are chronically ill or overweight or age should do because their systems don't work as well. So how do you address this?

Dr. Chris Palmer
I think it's a really

Dr. Mark Hyman
wanna get you in trouble with

Dr. Chris Palmer
your No. No. No. It's I I I I kind of chuckled as you were saying your garden, analogy because I've used that exact analogy Oh, really? People as well.

And, you know, I think, you know, most most athletes and coaches know this as well, that if you wanna 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. And, and it requires a multifaceted approach. And 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, you know, cardiac health, all of those things.

And so I completely agree with you. And I think it's 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.

Dr. Mark Hyman
It's like autism, right?

Dr. Chris Palmer
Yes. So I actually am hopeful that we can get funding, for studies like this using a quote unquote treatment resistant population and 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 gonna 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 to really 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 thirty percent 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 it won't only get the attention of those in the mental health field. It will get the attention of insurance companies

Dr. Mark Hyman
Of course.

Dr. Chris Palmer
The the the government because, you know, 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 For sure. And I can be the first to say, working having worked with these people for well over twenty five years, these people are desperate to contribute to society. They want to work.

There's this stereotype out there that, oh, depression is the 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 of a few notions. Number one, they're not living the high life.

You're 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, couldn't do it.

And 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 nightmare, and she got fired. And Wow. And so, I think that if we can demonstrate that even if it requires 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.

Dr. Shebani Sethi
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. I mean, we need to start including that in the way that we diagnose and treat and evaluate disease.

Dr. Mark Hyman
Yeah. Was thinking you were talking earlier about 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 how did you come to sort of understand that that was really going on? That that that the the biology of that was something that was real?

Dr. Shebani Sethi
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, in 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, I started to do research. And that's how my path started. And I started early on developing this clinic in residency training.

Dr. Mark Hyman
Which is incredible because when 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. I remember when I was seeing patients early on treating them for insulin resistance and prediabetes 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, you know, my my depression went away. My anxiety went away. My 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 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.

Dr. Shebani Sethi
Sure. So that's quite an important question. And 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, 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

Dr. Mark Hyman
So wait. So your brain chemistry gets screwed up when you eat processed food and sugar, is what you're saying?

Dr. Shebani Sethi
Yeah. Yeah. And I'm talking about ultra processed food also in 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, these 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.

Dr. Mark Hyman
Yeah.

Dr. Shebani Sethi
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 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.

Dr. Mark Hyman
So you're saying it's people who are overweight and obese often are very malnourished and vitamin and nutrient deficient.

Dr. Shebani Sethi
Yes. That's right.

Dr. Mark Hyman
And sort of a paradox. Right?

Dr. Shebani Sethi
Right. Right.

Dr. Mark Hyman
They're eating all this food, why are they nutritionally deficient? But they're actually among the most malnourished.

Dr. Shebani Sethi
They are, unfortunately.

Dr. Mark Hyman
They're looking in all the wrong places for the nutrients, so they eat more and more food. And I think a study from, you know, 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. And you you talk a lot about it then 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.

Dr. Shebani Sethi
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

Dr. Mark Hyman
It's more like a coffee filter, you know, it's a sip. Right.

Dr. Shebani Sethi
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 and the consumption of larger quantities over time than intended.

Dr. Mark Hyman
So, you know, people go all the through, it's like emotional eating, and it's not really biological true addiction. But what you're saying is this 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 substances 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 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. They think they just have no willpower.

But you're saying it's much bigger than that.

Dr. Shebani Sethi
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 it's a recreational food. It's not a food that's essential for survival. We make sugar through the process of gluconeogenesis, through other foods that we consume. And so it's really about excess carbohydrates.

Dr. Mark Hyman
It's not I like how I call sugar a recreational drug. I've never heard anybody say it, but I've always I always write 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 quantities we're having in America.

Dr. Shebani Sethi
Exactly. Yeah. And we also actually, I would like to share a story about about this just during the era of COVID since we're in it.

Dr. Mark Hyman
Yeah.

Dr. Shebani Sethi
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 an STD 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 at the grocery store.

Dr. Mark Hyman
Yeah. Cookies and toilet paper.

Dr. Shebani Sethi
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.

Dr. Mark Hyman
Run on broccoli.

Dr. Shebani Sethi
No. And here I was at the checkout counter, and I was thinking to myself, you know, staring at the person's cart in front of me that is full of the recreational food, as I mentioned, is 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 and or helping their immune system and, if anything, weakening it. And 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.

Dr. Mark Hyman
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