Essentials - Diet & Nutrition for Mental Health - Dr. Chris Palmer.

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Chris Palmer. Chris, Dr. Palmer, thank you for being here. Thank you, Andrew, for having me. I have a lot of questions for you, and I'm really excited about this topic because I think most people know what mental illness is, or they have some idea what that is. Most people have some idea what nutrition is. Fewer people certainly know how closely those things can interact. I think everybody is familiar with the feeling of a food or the ingestion of a food making them feel good in the short term. But I believe that very few people understand or are familiar with the fact that nutrition and our mental health interact in this very intimate, maybe even causal way. And that is something that occurs over long periods of time, meaning what I ate yesterday, the day before, maybe even 10 years ago, could be impacting the way that my brain and body are making me feel now. So if you would, I'd love for you to just tell us about a little bit of the history, in particular your history, with exploring the relationship between nutrition and mental health. And then we can dive into some of the more particulars of ketogenic diets versus other diets, and some of the truly miraculous findings that you and others are coming up with based on real patients and real experiences of people who suffer and then find relief by altering their nutrition. Sure. This story really starts with my own personal story. I don't need to go into great detail, but to set the stage, when I was a kid, I definitely had mental illness. Started with OCD. I went on to have subsequent depression, suicidality, all sorts of things. Somehow or another, I pulled myself together and got through medical school, actually did quite well in medical school, and then was doing my internship and residency at Harvard. And at that point in time, I was diagnosed with metabolic syndrome. So I had high blood pressure, horrible lipids, and prediabetes. And I was doing everything right, supposedly. I was on a low-fat diet, and I was exercising regularly. And year after year, my doctor kept telling me, diet and exercise. I was doing everything he kept telling me to do. Everything was getting worse. My blood pressure kept going higher. And at some point, he said, you're gonna have to go on medication for your prediabetes, something for your cholesterol, and something for your blood pressure. So three pills. Basically, you're screwed. It's your genes. You're just gonna have to bite the bullet and take meds. As a physician, I knew what that meant. I knew that I'm in my 20s. If I'm already on three meds for metabolic syndrome, I'm gonna be screwed by the time I'm 40 or 50, and I'm probably gonna be having heart attacks. I'd heard through the rumor mill that the Atkins diet could somehow help people improve their cholesterol and prediabetes. I was highly skeptical. I believed everything I was taught in medical school. Why would my professors lie to me? They knew what they were talking about. Low-fat diet was the thing to do. And the Atkins diet was clearly dangerous and reckless. And I had been trying the medical dogma for years, and it wasn't working for me. And so for whatever reason, I decided this is gonna be my last attempt at something different. And then I'll just bite the bullet and go on meds. So I tried the Atkins diet. Within three months, my metabolic syndrome was completely gone. I probably lost about 10 pounds through this process, but everything got normal. And when I went back to my doctor, he was shocked. The thing that was the most striking to me after doing the diet for three months was not the fact that my metabolic syndrome was gone. That was my goal. And it was a seemingly miraculous achievement because I got rid of everything with one dietary change. But the thing that I noticed was dramatic improvement in my mood, energy, concentration, and sleep. For the first time in my life, I started waking up before my alarm went off and feeling rested. That never happened to me before. I was meticulous about planning when my alarm went off and how many times I could push the snooze button in order to be on time for wherever I needed to be, whether it was school or the hospital or whatever. Prior to the diet, I always felt like there are two types of people in the world. There are these happy peppy people who just are so positive and they've got energy and they have this saying, they like to work hard and play hard. But I never understood who the hell wants to play hard. Like who's got energy for that? Like, aren't you tired from working so hard? I assumed that they were just lucky and privileged. They either had good genetics or maybe they had good childhoods or good parents or something, something that I didn't have. What was the journey forward into the work that you're doing now? So within a few years, I'm, you know, an attending physician. I've got all these patients in my clinical practice with treatment resistant mental illness. I'm in a tertiary care hospital. So I almost never get somebody off the street with their first episode of depression. Out of the gate, as part of my career, I get treatment resistant mental disorders. So I get people who've already been to six plus psychiatrists, therapists. They've usually tried dozens of different medications. They've been in decades of psychotherapy. They've often had ECT and other things and nothing's working. And I'm thinking, you know, well, we're kind of out of options for these other people and this diet is having this really powerful antidepressant effect. I think I'm gonna try it and just see if any of my patients are game to try it, to see if it might help them. Sure enough, it did. Didn't help everyone and not everybody was interested and or able to do it. But some of the ones who were able to do it ended up having a remarkable and powerful antidepressant effect. One woman actually became hypomanic within a month and she had been depressed pretty much nonstop for over five years, chronically depressed, suicidal, in and out of hospitals. And I saw her become hypomanic and I'm thinking, wow, this really is a powerful antidepressant effect. Like this is amazing. This is like a medication but better because it actually is working for her. At that point, we didn't have many clinical trials of the safety or efficacy of the Atkins diet for even weight loss or diabetes, let alone any mental disorders. And so I really actually felt like I'm on the fringe here and this is not going to be met with praise by anyone. So I'm just gonna lay low, I'm gonna offer it to patients. And I went along that way up until 2016. So low carbohydrate diet, certainly low sugar. Yeah. I'm assuming you're not a nutritionist. So how did you prescribe a nutrition plan for your patients? The first few patients, it was try this Atkins diet. I wanna see ketosis. So I was strongly recommending that patients achieve urinary ketosis. And the interesting thing is I noticed a pattern that when they were trying the diet and not getting ketones, they often did not get a clinical benefit. It was once they got into ketosis that I began to notice the clinical benefit. The thing that completely upended everything that I knew as a psychiatrist though was when I helped a patient in 2016. 33 year old man with schizoaffective disorder. He had been my patient for eight years now. He had daily auditory hallucinations. He had paranoid delusions. He could not go out in public without being terrified. This man was tormented by his illness. It ruined his life. He had already tried 17 different medications and none of them stopped his symptoms. He weighs 340 pounds. And for whatever reason, he gets it in his head. I'm never gonna get a girlfriend if I don't lose some weight. He also recognizes I'm never gonna get a girlfriend cause I'm a loser. I'm schizophrenic. I live with my father. I have nothing going for me. For a variety of reasons, we ended up deciding to try the ketogenic diet. He decides to give it a try. Within two weeks, not only does he start losing weight, but I begin to notice this dramatic antidepressant effect. He's making better eye contact. He's smiling more. He's talking a lot more. I'm thinking like, what's gotten into you? Like you're coming to life. I've never heard you talk this much. I've never seen you so excited or present or alive. I haven't changed his meds at all. The thing that upended everything that I knew as a psychiatrist was six to eight weeks in, he spontaneously starts reporting, you know those voices that I hear all the time? They're going away. And he says, you know how I always thought that there were all these families who were controlling my thoughts and out to get me and they had targeted me and I'm thinking, oh yeah, we've been talking about that for eight years. We can talk about that again. He says, now that I think about it, I don't think that's true. And now that I say it, it sounds kind of crazy. It probably never was. I've probably had schizophrenia all along like everybody's been trying to tell me and I think it's going away. He's now lost 160 pounds and kept it off to this day. He was able to do things he had not been able to do since the time of his diagnosis. He was able to complete a certificate program. He was able to go out in public and not be paranoid. He performed improv in front of a live audience. At one point, he was able to move out of his father's home and live independently. Did he stay on any kind of antipsychotic or other medication? We have slowly but surely tried to taper him off his meds. He has been on meds for decades. He started medications when he was a young child. His brain is developed in response to all sorts of psychiatric medications and it has not been easy to try to get him off. And I just want to say for any listeners, getting off your meds is very difficult and dangerous and you need to do it with supervision with a mental health professional or a prescriber. To stay in ketosis, what sort of blood levels of ketones do you like to see in your patients? What is the range that you think most people could aspire to? So it really depends on the patient and what I'm treating, quite honestly. And I don't think every patient needs the ketogenic diet. For some patients, simply getting rid of junk food can make a huge difference in a mood disorder, for instance. So a junk food meaning highly processed food, food that could last on the shelf a very long time. Highly processed foods that are usually high in both sugar, carbohydrates, carbs, and fats. Those seem to be the worst foods. That combination, high sugar, high fat, seems to be the worst combination for metabolic health. And lo and behold, we've got emerging data that strongly suggests it's also bad for mental health. So to step back from that, so for some patients, I might just want to decrease glucose and insulin levels and I can do that by getting rid of sweets. For other patients, like patients with schizoaffective disorder or schizophrenia or bipolar disorder, especially if it's chronic, if I'm using it as a brain treatment, then I do want a ketogenic diet and I usually want reasonably high levels of blood ketones. For depression, I want to see at least greater than probably 0.8 millimole. For psychotic disorders and bipolar disorder, I usually want to see levels greater than 1.5. That's what I'm shooting for, if at all possible. I think that for a lot of listeners and people out there who are familiar with how changing your diet or changing your exercise can positively impact sleep and weight and all these things and it cascades into feeling better, that makes perfect sense. But for a lot of the world still, the idea that changing or using nutrition as a dissection tool or as a treatment tool to understand and treat mental illness is still a kind of heretical idea. That to them, it kind of falls in the, okay, well, that's like a woo science or something like that. They immediately think, didn't Atkins die of a heart attack? You know, I hear that a lot, which I do think is throwing the baby out with the bathwater but it's an interesting thing nonetheless. And then I think that the majority of people sit in the middle and just want to see science and medicine come up with treatments that work. And I have to say, I'm very relieved to hear what you said earlier, which was you never said that people should come off their medication and just become, go on a ketogenic diet and everything will be cured. You're certainly not saying that. And rather you're saying, if I understand correctly, that nutrition needs to be considered one of the major tools in the landscape of effective tools and that it can be very effective. Let's talk about epilepsy and how the ketogenic diet is not just used for epilepsy but is one of the oldest, if not the oldest examples of the use of nutrition to treat a condition of the nervous system that can be incredibly debilitating, even deadly. Yeah. The reality is that this literature and this clinical history and all of the research we have was the godsend that I needed to do the work that I'm doing. Otherwise I would have been discredited on day one. The ketogenic diet, unbeknownst to most people, was actually developed a hundred years ago, 1921. By a physician for one and only one purpose, to treat epilepsy. It wasn't developed as a weight loss diet. It wasn't developed as the diet that all human beings should follow. And the reason it was developed is because of this longstanding observation since the time of Hippocrates, that fasting can stop seizures. Most people think going without food is bad and they equate it with starvation. But in fact, when we go without food, it causes tremendous shifts in metabolism, both brain and body metabolism. And it puts the body into a mode of autophagy and conservation of resources and all sorts of things that are beneficial to human health. And this is why fasting has been used as a therapeutic intervention in almost every culture and almost every religion for millennia. But for the most part, that was all thought to be religious folklore. In 1921, one physician used intermittent fasting on a child with seizures and found that, oh, lo and behold, this religious folklore stuff has something to it, it actually worked. The problem with fasting is that you can only fast for so long before you starve to death and that's not a very effective treatment. As soon as people start eating a normal diet again, their seizures usually come right back, oftentimes with a vengeance. And so it can be a good short-term intervention. The fasting can take a few days because it can take a few days to get ketosis and then you can get some relief from chronic seizures, but it's not a good long-term treatment because again, people will starve to death as soon as they start eating, seizures come back. So it was actually Dr. Russell Wilder at the Mayo Clinic who developed the ketogenic diet with one and only one purpose. He wanted to see, can we mimic the fasting state using this special diet to see if it might stop seizures long-term? And lo and behold, it worked. Early results were extraordinarily positive. 50% of patients who used the ketogenic diet became seizure-free and another 35% had a 50% or greater reduction in their seizure frequency. So about 85% efficacy rate. By the 1950s, pharmaceuticals were coming out and we had many more anticonvulsant treatments. And there's no question, they work for a lot of people. That's great. And taking a pill is so much easier than doing this diet. But lo and behold, even to this day, people with epilepsy, about 30% don't respond to the current treatments that we have available. 30% will have treatment-resistant epilepsy, which means they continue to have seizures no matter how many anticonvulsants they're taking. Even if they've had brain surgery, it just doesn't stop their seizures. And so in the 1970s, the ketogenic diet was resurrected at Johns Hopkins for these treatment-resistant cases. And lo and behold, it works. Not for all of them, but it works. And about one third become seizure-free. And these are people who've tried everything and nothing's working. So one third becomes seizure-free. Another third get a clinical benefit, meaning a 50% or greater reduction in their seizure frequency. And the other third, it doesn't seem to work. And so the reality, the godsend for me is that we have decades of neuroscience research on the ketogenic diet and what it is doing to the brain. We know that the ketogenic diet is influencing neurotransmitter levels, in particular glutamate, GABA, adenosine. It changes calcium channel regulation and calcium levels, which is really important in the function of cells. It changes gene expression. It reduces brain inflammation. It changes the gut microbiome, and gut microbiome's a huge topic right now. And there are some researchers who argue that is the primary benefit of the ketogenic diet. It's changing the gut microbiome in beneficial ways. So it's doing a lot of things. It obviously improves insulin resistance, lowers glucose levels, lowers insulin levels, which improves insulin signaling. The key for my research that I've outlined, the real magic is that this diet stimulates two processes that relate to mitochondria. It stimulates a process called mitophagy, which is getting rid of old and defective mitochondria and replacing them with new ones. And it also stimulates a process called mitochondrial biogenesis, which means that after people have done the ketogenic diet for a while, months or years, many of their cells in their bodies and brains will have more mitochondria, and those mitochondria will be healthier. And I believe that is the reason the ketogenic diet is such a powerful treatment, not only for epilepsy, but also for people with chronic mental disorders. If you're looking for randomized controlled trials documenting efficacy in large numbers of patients with these disorders, we don't have them. They're underway now, but we don't have them yet. Maybe we could just talk about mitochondria for a moment and then talk about these two major effects. What are some of the other things that mitochondria are important for in neurons and maybe other cells of the brain? If you think of the cell as a computer, a lot of people think of mitochondria as the power cord to that computer because they're providing the power. And they are, in fact, the power cord to that computer. But actually their real function is the motherboard of that computer. So mitochondria are directing and allocating resources throughout a cell. That is their primary function. And then they happen to be powerhouses as well. To give some clear examples, mitochondria play a direct role in the production and release and regulation of some really key neurotransmitters, including serotonin, dopamine, glutamate, acetylcholine. Those are pretty powerful neurotransmitters. I would consider those the, I know you listed more than three, but the sort of primary colors of neurotransmission. Any one of those in excess or deficiency is going to have profound negative effects on a nervous system. Mitochondria are providing both some of the building blocks, if you will, for some of those molecules. They're part of the Krebs citric acid cycle. Some of the intermediate products actually go into making those neurotransmitters. Much more importantly, mitochondria provide the energy for the production of those neurotransmitters. And fascinatingly, mitochondria are directly related to the release of neurotransmitters. ATP alone is not enough. There've been some research studies that have actually found that mitochondria move along the membrane of the synapse to release batches of vesicles of neurotransmitters. And that if the mitochondria are removed from the synapse and researchers flood that cell with ATP, neurotransmitters usually are not getting released. Mitochondria are doing other things. We don't entirely even understand what all they're doing or how they're doing it, but they're doing other things than just providing the power. Mitochondria at least play a role in all of the aspects of the human stress response. So when humans are stressed, either physically or psychologically, there are several things that happen. Increased cortisol, increased adrenaline, inflammation, and gene expression, in particular in the hippocampus, occur with the stress response. And one group of researchers actually genetically modified mitochondria in four different ways and found that all those four buckets of stress response were impacted in one way or another, implying that mitochondria are somehow playing a role in those. In terms of their role in cortisol, we know that mitochondria actually have the enzyme required for the synthesis of steroid hormones. So that includes cortisol, estrogen, testosterone, and progesterone, some names that maybe everybody's heard of. So that means that if mitochondria are in short supply or dysfunctional, the production of those hormones may become dysregulated. Mitochondria play a direct role in inflammation and they turn the inflammatory system both on, or they at least play a role in turning the inflammatory system both on and off. One paper in Cell actually identified mitochondria as the key regulator in turning certain inflammatory cells off, and that when you inhibit mitochondrial function, those cells don't turn off. Mitochondrial levels of reactive oxygen species are a key signaling process to turn the inflammatory process off. Another study found that macrophages, so macrophages are an important immune cell that play a role in healing. So if you cut yourself, your body will send inflammation that way and send immune cells that way to try to heal your skin. And macrophages play an important role in that healing. One group of researchers tried to figure out how do macrophages know to switch between the different phases of wound healing? Because the macrophages do different things in the different phases of wound healing. And the conclusion of all of their research was that it's mitochondria. Mitochondria are sending the essential signals that change the state of the macrophages to induce these different phases of wound healing. So I've just talked about neurotransmitters, hormones, epigenetic expression, inflammation. For anybody familiar with the mental health field, they know these are like some of the key variables that researchers have been struggling with for decades, trying to figure out how do these fit together? We know that all of those buckets can be disrupted in people with mental disorders. And our field has struggled to understand but how do they fit together? How can we make sense of this disruption? I believe once you understand the science of mitochondria, you can actually connect all of the dots of the mental illness puzzle. What I'm hearing is that mitochondria, in addition to being important sources of energy production and output in cells, which of course they are, probably have other roles and that maybe someday what we call mitochondria will actually be two or three different little subcellular organelle. In the landscape of science education, oftentimes people think, okay, energy production, there'll be a picture or a cartoon of mitochondria like flexing its muscles. People go, okay, energy, mitochondria, mighty mitochondria. And then they'll think, oh, you know, they're just sort of like a dumb jock portion of the cell, right? They're not doing anything sophisticated. And everything you listed off is that they are doing many sophisticated, intricate things within cells. So now that everyone is well aware that mitochondria are doing a large number of very important things in a very regulated way, let's talk about mitophagy, which I have to presume is the intentional or not gobbling up of mitochondria, presumably to replace them with newer, healthier mitochondria, is that right? It is. So, and in many ways, mitophagy is a subset of autophagy, but it's got its own name because it is specific to mitochondria. There do appear to be some unique regulators of mitophagy compared to autophagy more broadly. Mitochondria actually are playing a role in autophagy itself and this makes sense because one of, so the global picture of autophagy is stimulated by fasting states or fasting mimicking states. So when your body senses that you don't have enough food, it actually hunkers down and starts to recycle dead old parts in this kind of carefully orchestrated way and it takes them to lysosomes, they get degraded, and then those degradation products get used for either energy or to build new things. Autophagy is always occurring at a low level, but you can really hyper-stimulate the process through fasting, calorie restriction, fasting mimicking diets, other things. And this is why fasting and calorie restriction is so kind of such hot topics in the medical field now is because they've been shown to induce longevity and we think it's probably through that process that you're stimulating the body to become lean and conservative in terms of its allocation of resources. And the body doesn't just destroy the healthiest tissue along with the old dead stuff. It has these processes that identify the old and defective parts first and they go first and that's what's beautiful about the whole thing and that's why fasting is so important. So mitophagy we know plays a really important role because there's this term called mitochondrial dysfunction, which some researchers are actually wanting to get rid of and move away from because, as you just said, mitochondria do so many different things and different mitochondria, even within the same cell, may very well be specializing in different tasks. And mitochondria from one cell to another are sometimes doing very different things. Like not all mitochondria can produce cortisol. That's specific to specific cells where those genes are getting turned on. So it's not like all mitochondria are producing cortisol, just the ones in your adrenal gland, for instance, are producing cortisol. And it has long been known for decades that mitochondrial dysfunction is associated with everything that ails us, essentially. So David Sinclair published a paper in one of the cell journals, I think, saying that, oh, mitochondria are actually the unifying link of everything that we know about aging. Defective mitochondria or defective mitochondrial function, mitochondrial dysfunction, is possibly the unifying cause of aging and all of the aging-related disorders. So mitophagy is trying to address all that, is trying to say, okay, this is bad, we don't want defective mitochondria, and how can we get rid of old ones or defective ones and replace them with new ones? And I think the most powerful signal and tool that we have right now is in fact related to diet. It's calorie restriction that is the oldest, truest, best proven way to prevent aging in a wide variety of animal species. Fasting and intermittent fasting, and again, you can only do those things for so long, and then fasting-mimicking diets can also stimulate this process of mitophagy. So what about the typical person who's an omnivore eating some rice, some pasta? Do you think that those people might feel far better or even a little bit better if they were in a lower-glucose state? I ask this because I think there are a lot of people out there who suffer from full-blown depression, but there are also a lot of people who suffer from moodiness and feeling not so great, subclinical depression. Yes, burnout is what I would call it. Yeah, and just feeling like some days are great and then other days they feel lousy for reasons they don't understand. I kind of break this field, and I'm probably getting too nerdy right now, but I kind of break this field into cause, what's the actual root cause, and what are effective treatments? And I really see them as two separate things. Calorie restriction, ketogenic diet, carbohydrate restriction are inducing metabolic changes in the brain and body, and regardless of what the person was eating, they are inducing metabolic changes that can be really beneficial to brain health. So going to your broader question about adults' modern day, if it's an average person who is not currently under psychiatric care, not taking prescription medicines, but is saying, I'm burned out, I'm exhausted, I want some of that brain energy that Andrew Huberman's talking about, he talks about feeling good, I want some of that, I'm probably actually gonna recommend, let's see if we can just carb restrict for a while, and see if that produces clinical benefit. I have one, he's not even a patient, just somebody who read my book, had chronic anxiety, was trying meditation, was trying all sorts of things. He was ready to go on prescription medicine. He read an early copy of the book. He took it upon himself without consulting with me to restrict carbohydrates alone. He did not go ketogenic. He is a vegetarian. He restricted carbs. Within three weeks said, I don't need prescription medicine. I can't believe how much better I feel. And all I did was cut out some of the high-carb foods in my diet. So I think for some people, it can be that simple. For people with serious mental disorders, if they are chronically depressed, if they're on lots of prescription meds, if they're disabled by their symptoms, and certainly if you're bipolar or have schizophrenia or something, those are the people I really do want them to work with a medical professional because meds may need to be adjusted. They really need a real shot at this diet. It's not like weight loss. Weight loss, everybody wins it. And either you're successful or you aren't. You look on the internet or you read a book and seeing whether it works or not. If you're using it to treat a serious disorder, I think you need serious help. On behalf of myself and the listeners and certainly just on behalf of everybody out there, because everyone does need to be concerned about mental health issues, whether or not they have them in their family themselves or otherwise, because they impact everybody. Just really want to thank you for doing the work that you're doing. You've given us a lot of hints into the underlying mechanisms that suggest as to why it would work. And you've given us examples as to how it has worked in patients that you've worked with. So thank you for being brave and for taking this on and doing it in such a structured way and for communicating it here today and with the general public through your book and your online presence. We will certainly point people in the direction of those valuable resources. Thanks so much. I really appreciate it. Thank you, Andrew, for being brave and having me on your show. It's been a pleasure. And for a great conversation.