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- [00:00]
Andrew Huberman
Welcome to the Huberman Lab podcast where.
- [00:02]
Chris Palmer
We discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Chris Palmer. Dr. Chris Palmer is a psychiatrist and researcher at Harvard University. He focuses on how metabolic health and mitochondrial health in particular, can be leveraged to treat and in some cases cure psychiatric disorders including schizophrenia, autism, depression, bipolar and adhd. Today we discuss how metabolic health, something we hear a lot about nowadays, is really about mitochondrial health and the specific lifestyle and other factors that you can use to improve mitochondrial number and function. We talk about things like exercise, sleep, sunlight, which you've heard about before, but we talk about those from a different perspective. And we discuss some things that have never been discussed before on this podcast, at least in light of mitochondrial health. Things such as creatine, methylene blue, nicotine. And we talk about the key role of specific B vitamins and iron in brain function. We also have a very direct discussion about vaccines and whether or not inflammation caused by vaccines can potentially damage mitochondria, which then leads to mental health challenges. And of course, in that context, we discuss the vaccine autism debate. We also discuss public health and what is needed to truly change the way people exercise and eat and the rapidly changing landscape of the National Institutes of health and the CDC. As you'll soon hear, Dr. Palmer gives us a masterclass on mitochondrial function and how to improve this vital aspect of our health. If you've heard about metabolic health, you've heard about the obesity crisis, that's important. But looking at all of that and approaching it through the lens of mitochondrial health, you'll soon learn, is absolutely the way to go. It's a new perspective that will change the way that you think about mental and physical health and that no doubt will impact your health practices in very positive ways. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, this episode does include sponsors. And now for my discussion with Dr. Chris Palmer.
- [02:16]
Andrew Huberman
Dr. Chris Palmer, welcome back.
- [02:18]
Chris Palmer
Thank you so much for having me back.
- [02:20]
Andrew Huberman
I credit you with leading the call to arms, the public awareness and the implementation of what some people call metabolic psychiatry, but what we could easily just call the relationship between mental and physical health and the use of nutrition supplementation and where appropriate, prescription drugs for the treatment of mental health. But what do you call this field that you've basically founded and that you're pioneering? There are others. Right, but that you're pioneering. And how should the general public think about the relationship between mitochondria and their mental health? For. For those that are not aware, educate us.
- [03:04]
Chris Palmer
I could talk for hours on this. So first of all, thank you for. I think you're actually giving me way too much credit, though.
- [03:13]
I don't know about that.
- [03:15]
I'm talking a lot about it. And I think I will accept that maybe I'm able to talk about it in a way that helps people understand it that other scientists haven't been able to. But, you know, one of the more important reasons I want to say this is because unbeknownst to a lot of people, this field has actually been around for about a century and a half. Researchers in the 1800s, around the turn of the century, well up into the 1960s, were hyper focused on the role of metabolism in severe mental illness, schizophrenia, bipolar disorder. They were actually measuring levels of lactate and glucose and other kind of metabolic biomarkers in people with schizophrenia and bipolar disorder. Documenting differences, really honing in on these metabolic disruptions is potentially the cause of mental illness. And then our field lost its way. We became focused on neurotransmitters and assumed that they were the primary cause of mental illness. While other fields were focused on psychological and social factors. You know, we got cognitive behavioral therapy. We still had psychodynamic psychotherapy, but people were doing research on adverse childhood experiences that was really taking off, documenting that that's related. And so, you know, the field kind of splintered into these biological, psychological, social camps, and people really hyper focused in all of these ways. To me, this field of integrating metabolism with mental health with physical health is about unifying that whole story. It's about unifying and building on what these researchers a hundred years ago were pursuing. It's about integrating the biological, psychological and social camps. It's about putting it all together and stop being so reductionistic and simplistic to suggest that it's all biological or it's all psychological or it's all social, and that if it's one, it can't be the other other, it can be all of them. And it's different combinations for different people. So in many ways, I'm just standing on the shoulders of giants who have done groundbreaking work to create the science that allows us to put this all together. With that said, I do firmly believe that we are on the Cusp of a revolutionary change in the paradigm of the mental health field of how we think about mental illness. You know, there are myriad biological things. The psychological and social things are all obvious and true. Yes. Stress, trauma, loneliness, adverse childhood experiences, all of those things come together. Our field has long known that all of those things play a role in mental illness. Exactly. Which mental illnesses? It's essentially all of them. Every one of the labels in DSM 5 can be impacted by biological, psychological and social factors. So trauma in childhood increases risk for post traumatic stress disorder. Duh. Everybody knows that Trauma in childhood also increases risk for neurodevelopmental disorders. If it occurs early enough, it increases risk for substance use disorders, personality disorders, psychotic disorders, mood disorders, anxiety disorders, dementia later in life, and everything else, every label. What else do adverse childhood experiences, increased risk for all of the metabolic disorders, obesity, type 2 diabetes, cardiovascular disease, autoimmune disorders, premature mortality. You know, we have statistics that, just sticking with that theme, adverse childhood experiences. If you have six or more adverse childhood experiences compared to somebody who has no adverse childhood experiences, now that's a rare group, granted, but for the people who have six or more, on average, they live 20 years shorter. They lose 20 years of life because of those adverse childhood experiences. And so is that a mental health issue? I would say it's a physical health issue. It's both. It's both a mental health issue and a physical health issue. And so how can we understand that? How can we understand that trauma and childhood increases risk for heart disease and obesity and diabetes and dementia and PTSD and ADHD and substance use disorders? And the only way to connect it is through metabolism and ultimately through mitochondria. Unfortunately, people like simple answers and they're like, so diet will fix everything? I'm like, no, I never said diet will fix everything.
- [08:46]
Andrew Huberman
But it can help.
- [08:47]
Chris Palmer
It can help and it can be life changing and life saving. I don't want to minimize or step back from my work with dietary interventions. There is no doubt in my mind it can dramatically change people's lives. But it's not just diet. It's lots of other things. And so it's putting it together and trying to make sense of the science. For what does cardiovascular disease have to do with depression or ptsd? On the surface, a lot of people scratch their heads and they really don't know. They assume that, well, one's a brain disorder and one's a heart disorder. And it's like, no, we need to integrate that because all of the risk factors essentially the same biopsychosocial risk factors that increase risk for heart disease also increase risk for brain disease. And we just, we need to start putting it together. We need to be more sophisticated. We have computers, we have AI. It's 2025. We can do better.
- [09:55]
Andrew Huberman
Yes. Well, first of all, I, and I'm sure the listeners really appreciate your humility regarding who's responsible for the big surge in the interest in this field. So thanks for crediting your predecessors and the others in the field. At the same time, I credit you with really popularizing a lot of these terms, being willing to go public facing and share about metabolic psychiatry, for lack of a better way to put it, metabolic psychiatry, and really championing these ideas and being open to being part of a medical and science and public discourse community. So I'd be remiss if I didn't say that. So hopefully you'll take that in and if you won't, then I very much.
- [10:40]
Chris Palmer
Appreciate it and thank you.
- [10:41]
Andrew Huberman
Well, it's true.
- [10:42]
Chris Palmer
Thank you very much.
- [10:43]
Andrew Huberman
It's true. And I'm not alone in that sentiment.
- [10:46]
Chris Palmer
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- [13:45]
Andrew Huberman
If I think about a mental health condition like depression, let's take depression to start off. I can just broadly create two columns of things or approaches that one might take. One is this mental model of sort of a molecule deficiency. I'm not saying this, but there are many who at one point thought depression is related to a deficiency in serotonin or depression is related to a deficiency in dopamine. Either levels regulation, enzymatic control, whatever the level of control. Just this idea that these molecules are somehow lacking. If you put them back, you can relieve some symptoms of depression. The other column that comes to mind for me, having Looked at the data on cognitive behavioral therapy, on the data on psychedelics in the clinical setting for the treatment of depression, SSRIs and other so called antidepressants. Is this notion of neuroplasticity, the idea that neural circuits can change and that neural circuits control our sense of well being, our perception of self, perception of others, feelings of agency, et cetera. And it's now very clear that if you change levels of neuromodulators, like dopamine, like serotonin, you don't necessarily cure depression, but you open a window for plasticity. And then perhaps the therapy that you're doing can modify brain circuits more robustly. So I think in terms of molecule deficiency, maybe it's a vitamin deficiency, a neuromodulator deficiency, and then I also think about plasticity, that these treatments are just allowing for more brain change, more rapidly. What other columns would you add to that picture? And perhaps first, do you think that picture is woefully inadequate or just partially inadequate? Because I think this is the way most people think about the treatment of mental health. They think, oh, there's something missing. You take a drug and you get that thing back and then like adhd, you don't have enough dopamine or you.
- [15:54]
Chris Palmer
Put it in and then all of.
- [15:55]
Andrew Huberman
A sudden attentional circuits work better. This kind of thing versus plasticity, which is the modification of those circuits. And the two things are not mutually exclusive. But I think until now there really hasn't been a clear understanding that there are other columns for mechanistic change in mental health.
- [16:15]
Chris Palmer
I would say the concept of metabolism, metabolic regulation, mitochondrial function, mitochondrial health actually is an umbrella concept for everything you've just said. It's an umbrella concept for, well, how do we create neurotransmitters? Where do these neurotransmitters come from? What regulates their production? Release from cells. And then even to go further, what impact do those neurotransmitters have on other cells? They are largely regulating brain metabolism. And the way we usually think about it is they are regulating brain activity. But if you ask the question, well, what is brain activity? Brain activity is either is fueled by metabolism, that a neuron cannot be active unless it has the capacity to increase its ATP kind of production. And then when you suppress a neuron, when you inhibit its function, the ATP production goes down. So whether you want to think of metabolism as just a consequence of neural activity, I actually think about it as an integral part of neural activity. It's kind of like your car can't go without the engine. A cell can't go without mitochondria. A cell can't do what it's supposed to do without mitochondria. The other concept that you mentioned, neuroplasticity. Neuroplasticity is all about energy and metabolic resources to create new connections, new neural connections between axons, dendrites, somas, other things, other aspects of neurons and cells and other types of cells, astrocytes, oligodendrocytes. But in order to get neuroplasticity, neuroplasticity implies growth and modulation and even pruning. But it involves change. And in order for a living organism to change that requires this foundational concept of metabolism. Now, on the surface, to a lot of people, that sounds too abstract, and it sounds like, well, that's ridiculous then if you're. You're saying that metabolism is everything in biology, and I kind of am. Of course it is. You. You can't talk about biology without talking about metabolism. But when you talk about metabolic health, it becomes much more concrete, pragmatic and real, with real tools that you talk about all of the time on this podcast. Exercise promotes metabolic health. Exercise promotes neuroplasticity. They are inseparable. You can't improve your metabolic health without also at least opening up the opportunity for neuroplasticity. Improving your diet does the same thing. Sleep, or lack thereof, can impact this. Substance use can impact this. And so, you know, in a way, it. It basically says, let's connect all of the dots. Let's not hyper focus on serotonin and a serotonin imbalance or deficiency as the singular cause of depression. Because for those of you who don't know, that is ridiculously reductionistic and it is absolutely not true. We know that. We know that with certainty. Now, you know, the. The whole serotonin hypothesis of depression came about not because researchers identified serotonin deficits in the brain. That entire concept came from the observation that medications that modulate serotonin activity or inhibit its reuptake into neurons, those medications, SSRIs, other types of antidepressants, those medications can reduce the symptoms of depression in some people. That was just a purely serendipitous finding. It was serendipity. The first antidepressant was actually a tuberculosis treatment. They were giving it to patients on a tuberculosis ward. And an astute infectious disease doctor noticed some of these patients are really depressed. But when I give them this tuberculosis treatment, they perk up. Like, within a few weeks, they start looking a lot less depressed. And I Don't think it's a coincidence. I think it's the medication I'm giving them.
- [21:34]
Andrew Huberman
Do you recall what the drug was?
- [21:35]
Chris Palmer
Aproniazide. It's the first MAO inhibitor. And I could be saying the name wrong, but it's first MAO inhibitor and that became the first antidepressant, which makes sense.
- [21:51]
Andrew Huberman
MAO inhibitors inhibit the enzymes that break down, or let's just speak about these enzymes broadly, either. I think most antidepressant drugs or treatments for adhd, typical prescription treatments, either reduce the breakdown of neuromodulators like serotonin, dopamine, acetylcholine, depending on which one we're talking about, or they reduce the reuptake so that there's just more neuromodulator around for longer.
- [22:19]
Chris Palmer
Yes.
- [22:20]
Andrew Huberman
Tell us about mitochondria in the framework of mental health.
- [22:25]
Chris Palmer
So most people know mitochondria as the powerhouse of the cell, if they know it at all. So these tiny little organelles and the powerhouse of the cell reference means that mitochondria take the breakdown products of the food that we're eating. They are the primary thing. Using the oxygen that we're breathing in, they are creating the carbon dioxide that we're breathing out and that they are turning food into ATP, which is the energy currency of the cell. So they're taking food and oxygen and lots of other things. But let's just simplify food and oxygen, converting it into ATP. And that is what the powerhouse of the cell kind of refers to. There is no doubt they do that. There is no doubt that when that process stops, humans have about six minutes or so and then we're dead. That process is critical to life. There is no other process in the human body that you can disrupt that will kill the organism faster. It is central to living organisms, this production of ATP. So I don't at all mean to take away or minimize that function, but research over the last 25 years has completely upended that simplistic notion of what mitochondria are doing. They are actually doing so much more. Some people have created the reference that mitochondria are like the workers inside a cell, that in order for a cell to work, you need a workforce because there's so much that needs to be done, signals need to be sent, like all this work, all of these different things need to be functioning. And mitochondria are absolutely providing the energy for those things to happen, but they're also orchestrating a lot of it. So, for example, they play a direct role in converting food into some of the substrates for the production of neurotransmitters. But they also go further. They store, like, some neurotransmitters like gaba within themselves, and that plays a role in gaba's release from a neuron. They actually go to the cell membrane and move along the membrane, dispensing vesicles of neurotransmitters. And when you take the mitochondria away from the synapse, but provide that synapse with ATP, vesicles don't get released. Neurotransmitters aren't getting released. The mitochondria are doing more. We don't exactly know what, but they're doing more than just providing the energy. They. They play a role in turning inflammation and immune cells both on and off. They help start the process, but they also help coordinate the cessation of that process. They play an instrumental role in both the first and the last step in the synthesis of cortisol. And they play a role in the first step in the synthesis of all of the steroid hormones, which include estrogen, testosterone, progesterone. So that if you have dysregulation of cortisol, or if you have dysregulation of testosterone or estrogen or progesterone, you must understand the role of mitochondria in that dysregulation, because they are critical in the production and release of these hormones. They are the primary regulator of epigenetics. So epigenetics are the expression of genes from the cell nucleus, and researchers have long known that that's related to levels of reactive oxygen species. It's related to levels of cal related to other cell signals. Those cell signals are mostly originating within mitochondria during the development of any cell mitochondria, they are like a universe unto themselves, and there's so much we don't know about them. But what. What researchers have found is that mitochondria actually line up, literally line up in an organized fashion around the cell nucleus and take on different confirmations. And that is somehow sending signals to the genes to result in the expression or the suppression of different genes from the nucleus. And that when researchers take these mitochondria and, like, mess them up or something, the cell doesn't develop normally. You know, they've been implicated in all of the phases of the human stress response to psychological stress. So that includes cortisol release, noradrenaline release, it includes inflammation, and it includes epigenetic changes. So those are kind of the four buckets of the human stress response, cortisol, adrenaline, inflammation, and epigenetic changes. And researchers actually manipulated mitochondrial genes. Two genes in the cell nucleus that control for mitochondrial proteins, and two genes in mitochondria themselves. And by manipulating these four different genes, one at a time in mice, they could impact all of the four aspects of the stress response. And so what that means is that mitochondria are somehow involved in regulating the human stress response. And so the way that I think about it is that, and the way that many researchers actually think about it now is that mitochondria, you know, there are hundreds, sometimes thousands of them in our cells. In each of our cells, most neurons have thousands of mitochondria. The mitochondria are actually moving around. They use the cytoskeleton to move around the cell. They fuse with each other. It's called mitochondrial dynamics. They change shape, they do all sorts of things. And again, that impacts all of these signaling processes. But that's just within one little cell. So you can think of one cell as almost a village of mitochondria, that they're all just doing different things and working together to help that cell function. But in fact, when you think about hormones like cortisol, you can think about it as a way for mitochondria in one cell to produce cortisol that they can get sent to mitochondria in another cell to make that other cell do something to either increase its activity or decrease its activity. Some people actually think about human cells as just a network of mitochondria. All kind of mitochondria throughout the body and brain are just doing all sorts of things. And at the end of the day, we come back to just common sense. At the end of the day, it's about helping the organism adapt and survive. Ultimately, organisms rule number one, they need to survive. Rule number two, they need to reproduce. And rule number three, they need to adapt. And mitochondria are playing a foundational role in all of those basic aspects of organismal survival. And again, to some people, well, that's so high level. That's like what you're saying. It's everything. I'm like, yeah, it kind of is. And mental health falls under it. How could we think about mental health without thinking about the big picture? Like, let's start with the big picture and then let's put health into it, and let's put the lack of adaptation or the lack of survival or the these other things.
- [31:09]
I'd like to take a quick break and thank our sponsor, AG1. AG1 is an all in one vitamin, mineral probiotic drink with adaptogens. I've been taking AG1 daily since 2012, so I'm delighted that they're sponsoring this podcast. The reason I started taking AG1 and the reason I still take AG1 is because it is the highest quality and most complete foundational nutritional supplement. What that means is that AG1 ensures that you're getting all the necessary vitamins, minerals and other micronutrients to form a strong foundation for your daily health. AG1 also has probiotics and prebiotics that support a healthy gut microbiome. Your gut microbiome consists of trillions of microorganisms that line your digestive tract and impact things such as your immune system status, your metabolic health, your hormone health, and much more. So I've consistently found that when I take AG1 daily, my digestion is improved, my immune system is more robust, and my mood and mental focus are at their best. In fact, if I could take just one supplement, that supplement would be AG1. If you'd like to try AG1, you can go to drinkag1.comhuberman to claim a special offer. They'll give you five free travel packs plus a year supply of vitamin D3K2 with your order of AG1. Again, go to drinkag1.com Huberman to claim this special offer. Today's episode is also brought to us by eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating and sleep tracking capacity. Now, I've spoken before on this podcast about the critical need for us to get adequate amounts of quality sleep each and every night. Now, one of the best ways to ensure a great night's sleep is to ensure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop about 1 to 3 degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about 1 to 3 degrees. 8 Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. Now, I find that extremely useful because I like to make the bed really cool at the beginning of the night, even colder in the middle of the night, and warm as I wake up. That's what gives me the most slow wave sleep and rapid eye movement sleep. And I know that because eight Sleep has a great sleep tracker that tells me how well I've slept and the types of sleep that I'm getting. Throughout the night. I've been sleeping on an eight Sleep mattress cover for four years now. And it has completely transformed and improved the quality of my sleep. Their latest model, the Pod 4 Ultra, also has snoring detection that will automatically lift your head a few degrees in order to improve your airflow and stop you from snor. If you decide to try 8 sleep, you have 30 days to try it at home and you can return it if you don't like it. No questions asked, but I'm sure that you'll love it. Go to eightsleep.com huberman to save up to 350 off your Pod 4 Ultra. Eight sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com huberMan to save up to $350 off your Pod 4 Ultra.
- [34:00]
Andrew Huberman
What are some of the things that we know can improve mitochondrial health, either number, function or otherwise? And maybe we can talk about the basics first and get a little bit granular, if you could, about, you know, what are the prescriptions for keeping your mitochondria healthy or improving your mitochondrial number and improving their function. And then we can transition from there to the more, let's just say the more advanced ways of doing that. Is there a role for supplementation? Is there a role for drugs? Is there, you know, these days where I hear about Urlithin A I because I'm a little bit of an adventurer these days, I and I'm turning 50 later this year, I decided to experiment with a peptide that is SR31, which is specifically to improve mitochondrial function. I'm doing this with the full understanding. It may do nothing or it may kill me, I don't know, but we'll find out. But someone had to do it. And I'm a one variable at a time kind of guy. So it was important for me to stay with my current regimen and only change that, do blood work, et cetera. Because a lot of people, some people out there are more in the mode of trying to do a bunch of things. And I don't think that's as helpful to me. It's also just not. It's not in keeping with my nature, my scientist.
- [35:16]
Chris Palmer
One variable that is great.
- [35:18]
Andrew Huberman
That's right. I'm monogamous with respect to variables. Right. So what can we do at a basic level to keep and improve our mitochondrial number and function? And if we have to hit on some of the usual suspects, fine. But if you could tell us how, how we can do this.
- [35:35]
Chris Palmer
So I'm really going to start with the basics and they're going to sound cliche and they're going to sound too basic to most people. And I just want to set the stage for, even for severe mental illness. We can talk about strategies that will work. And these strategies that I'm going to describe are not really appropriate. Like when, when somebody becomes severely ill, these strategies may not be sufficient, but the basics are what we call the field of lifestyle medicine. So there are six pillars of lifestyle medicine. They include diet, nutrition, exercise or movement, sleep, managing substance use, ideally reducing it or minimizing it or eliminating it, stress reduction practices, mindfulness meditation, yoga, and the last one is relationships. I throw in the word purpose into relationships because I think even if you don't have a lot of friends or family, you can still have a very full, thriving life if you have a purpose. So those are the six pillars. Unfortunately, this is where the cliches and the worthless advice begin, especially in the diet nutrition camp, because people will say, eat more plants, eat some broccoli, have some good blueberries. Blueberries, have antioxidants. Have some blueberries on whatever else you're eating and everything will be fine. If you just add a couple of servings of blueberries a week, you'll improve your health.
- [37:17]
Andrew Huberman
Brain food.
- [37:18]
Chris Palmer
And that is such worthless advice. It is not at all that simple. And so. So I think diet nutrition gets complicated fast. The other things are actually pretty straightforward. Should you move your body? Yes. Should you stress your body intermittently, allowing for full recovery? Yes. That's what most people call exercise. And what are you doing when you exercise? You're actually. If we look at like the muscles, for example, muscle tissue, what exactly does exercise do? Whether it's isometric exercise to increase the size of the muscle, or whether it's endurance capacity, which actually does not change the size of the muscle at all, but allows for somebody to run longer, faster, harder. So marathon runners, for example, can be quite thin. You can look at a marathon runner and think you're not even an athlete. They don't look all that different. Yet they can run sometimes a hundred miles. And what makes their muscles different than my muscles? Because I can't run 100 miles.
- [38:35]
Andrew Huberman
Me either.
- [38:36]
Chris Palmer
What makes their muscles different than mine, even if the size isn't different? There is one and only one thing that makes their muscles different, and it's called mitochondria. The number, the number of mitochondria and, and almost certainly the health of mitochondria. You can actually take a biopsy of their muscle and you will see a much higher density of mitochondria in their muscle tissue than you will in mine. If you actually then did a, a more thorough assessment of ATP capacity, they, their muscles or their mitochondria would be much healthier than mine. They, their mitochondria would have greater capacity for ATP production than my mitochondria would. So that's exercise. There are lots of things you can do with exercise for people who don't exercise at all. Yes. Get out and just walk. Just do something. Maybe get some sunlight in morning while you're. While you're at it.
- [39:28]
Andrew Huberman
Sounds like a good idea.
- [39:33]
Chris Palmer
The substance use is obvious. It's the thing. You've been talking about it. I've been talking about it.
- [39:39]
Andrew Huberman
Which substances deplete mitochondria? I've been very interested in this. I'm a big lover of certain genres of music and whenever the topic of music comes up, the name Rick Rubin comes up because he's been on this podcast twice. The famous Rick Rubin, amazing producer. And I'm blessed to have him as a close friend. And I often ask Rick, I'm like, why are so many of these folks in music dead? There seems to be a history of people who did stimulants, took a lot of stimulants, cocaine and amphetamine in particular. Musicians that did that in the 70s and 80s and 90s seemed to drop dead of heart attacks later when they were not currently using. As far as we know, those stimulants. Is it the case that stimulants like cocaine and amphetamine deplete cells of mitochondria? Do we know that to be true?
- [40:37]
Chris Palmer
We do know, and it's slightly more complex story. So it's all about the dose. So stimulants are used to treat adhd, and we know that people we've known for decades, people who have adhd, who have symptoms of adhd, have glucose hypometabolism in their brains. So their brains are not producing enough ATP from glucose. What is one way to increase that? Dopamine. Dopamine will increase that. So you can give people stimulants to improve their brain metabolism enough so that they now no longer have symptoms or at least have a reduction in their symptoms. That story is unequivocally true. We have lots of animal data, human neuroimaging data, clinical research studies documenting that appropriate doses of stimulants, so that's usually lowish doses, can improve brain metabolism. And what that means is that is they're actually stimulating mitochondria to produce more ATP. However, metabolism is all about balance. You can underdo it and you can overdo it. And when you overdo it, what happens is that if you hyper stimulate mitochondria with high doses of stimulants, the mitochondria are essentially running on all cylinders and electrons start leaking out of the electron transport chain. And what happens is that that creates reactive oxygen species which then damage the mitochondria themselves and damage other aspects of the cell. And it can lead to chronic mitochondrial dysfunction, chronic metabolic dysfunction. It's challenging with stimulants because people are looking for a yes or no answer. So, Dr. Palmer, do you think stimulants are good or bad? I don't have an answer to that. It depends on the person, it depends on the dose of stimulants, it depends on the type of stimulant, it depends on what impact it's having on that person. But we need to open our minds to the possibility that, yes, maybe some people do benefit from stimulants, and maybe at the same time, other people are harmed in catastrophic ways by stimulants and can all be linked through mitochondrial mechanisms. It can certainly be linked through dopamine. But again, we have to ask, well, what is that dopamine doing to the target cells? That when dopamine gets released and connects with a dopamine receptor, what happens to that target cell? It changes the metabolism of that target cell. It increases the activity of that target cell. So stimulants are one Back to this bigger kind of lifestyle medicine picture. Stimulants are definitely one high dose stimulants, very harmful to human health.
- [43:55]
Andrew Huberman
What are some others?
- [43:56]
Chris Palmer
Alcohol we've known since the 1960s. In the 1960s, researchers were trying to figure out how the hell does alcohol cause cirrhosis. We knew that, We've known that. We've known that for a long time. Alcoholics develop liver failure, they develop cirrhosis of the liver, and they can die from it. How exactly does that happen? In the 1960s, researchers figured out it's mitochondrial toxicity, interesting in the liver cells. That is what's making the liver cells die. That alcohol gets converted into this molecule called acetaldehyde, which is very toxic to lots of cell parts, but in particular to mitochondria. Mitochondria are processing this alcohol and other enzymes and kind of other things are trying to detoxify the alcohol. But at the end of the day, mitochondrial toxicity seems to be a clear route. So when, you know, when I was doing research on mitochondria for the book, There were over 10,000 published research articles of alcohol and mitochondria. And I was initially shocked by that. And I wondered, like, what's that about? Like, how. That's how I know this 1960s story and everything else is because research has been looking at how. How is it that alcohol can be so toxic. And the two organs that are most effective are the liver, because that's the primary organ trying to detoxify it, and then the brain. And why the brain? Because the brain is highly sensitive to metabolic disruption. Other substances of abuse. Tobacco. The carcinogens in tobacco.
- [45:54]
Andrew Huberman
So not nicotine per se. Do we know if nicotine is depleting mitochondria?
- [45:59]
Chris Palmer
Nicotine is a stimulant for mitochondria. So again, similar story. Low doses can be great. High doses may in fact be toxic.
- [46:09]
Andrew Huberman
Oh, good.
- [46:10]
Chris Palmer
You've got to get. You gotta. You gotta find the right balance.
- [46:13]
Andrew Huberman
I'm not a big nicotine guy, but lately I started chewing half of a piece of nicotine gum a few times a week. So 2 milligrams to 4 milligrams, which is very low dose. Couple of, I would say maybe three, four days a week. I'll do that. And I'm doing it specifically for brain health reasons. And I have no relationship to any nicotine pouch or gum or anything like that. So I want to be really like company. So I'm doing a little experiment. And you know, it's an interesting stimulant because it relaxes you a little bit too. But I wouldn't want kids to start doing this or people in their 20s or 30s. Like I said, I'm approaching the fifth floor. I'm going to be 50 and September, and I want to do everything I can to hold onto the neurons I've got. So I think low level stimulation of perhaps the mitochondria and other. Certainly the acetylcholine system with nicotine is a good idea. But what I see is a lot of people who are taking these pouches that range from anywhere from 3 milligrams on the low end dose side all the way up to 8 milligrams. And it is very habit forming. People start with one pouch or two pouches a day, and pretty soon they're doing a canister every day or two. So even the cost, it starts to be a big deal. But it's pretty incredible. I was on the Berkeley campus and I went to a little convenience store near the Berkeley campus recently. This kid came in and we started chatting. He was a podcast fan. We were Chatting. And he was there to buy nicotine pouches. I said, how many of those do you go through a week? And he's like 7 or 8. I was like, really? He's an engineering student. But in my years in college, it was always just, you know, some coffee or something? Yeah, some coffee we didn't really have.
- [47:54]
Chris Palmer
Stick with coffee for the young.
- [47:56]
For young folks.
- [47:57]
Andrew Huberman
Yeah, for the young. A little bit. A little bit of coffee.
- [48:00]
Chris Palmer
And again, it's about. It's about dose and it's about look. So most things that enhance metabolism quickly can be addictive. And I think that's the challenge for a lot of people is that you get that energy right away. At some point, you acclimate to that substance somewhat and then you want more, you want that same increase that you got before. So it's just important to kind of be mindful that you can overstimulate metabolism, mitochondrial function, and then you start depleting mitochondria. And then. Yeah, and then you actually, the mitochondria begin producing more reactive oxygen species, which ends up being detrimental. So it's like driving your car again, if you think about mitochondria like an engine. It's like an engine of your car. When you're driving your car on the highway, you don't want to go too slow and you don't want to go too fast.
- [49:18]
Andrew Huberman
And acceleration is costly. And acceleration is costly. Right. I mean, transmission systems create this incredible efficiency of being able to travel at speed with more efficiency. But accelerating is a different thing altogether.
- [49:32]
Chris Palmer
I mean, that's the way that I think about it. And so somebody who's addicted to drugs and alcohol, for example, they're on a roller coaster ride of hyper stimulating their metabolic rate and then trying to suppress that hyperstimulation with sedatives so that they can sleep or calm down. And then they're just. But they're destroying their metabolic health. And does that really play out like. And is that. You know, some will say, well, Chris, that's just one of myriad things that they're doing to their cells. Sure. But does it play out in diseases that we think of as metabolic diseases? Absolutely. Type 2 diabetes? Yes. Cardiovascular disease? A hundred percent. Like premature mortality. Yeah. Like, it, there's. It's kind of like the elephant in the room that we have just failed to look at because we've been so splintered with. No, it's biological. No, it's psychological. No, it's social. It's like it's all of them. Let's look at the elephant that comprises all of them.
- [50:40]
Andrew Huberman
One of the beautiful things about science is that you isolate variables. You can get very reductionist. We know that there are these things called mitochondria that they move around. I mean, these discoveries are truly incredible that have been made in the last hundred years or so. But there's been this kind of obsession, I, I think in, in the, the public discussion around health that, you know, around things that are obviously related to the thing that you're trying to cure. So serotonin and brain health, it's like, oh, okay, it makes sense. You know, the Listening to Prozac book came out. We increase serotonin. Some people are feeling better. Maybe it's through neuroplasticity, maybe it's direct effects of serotonin and. But it makes sense. Serotonin, brain, right? You know, it's. But if we zoom out from that and we accept, because it's true that essentially all cells are dependent on mitochondria for their function, why wouldn't we go to this fundamental layer first in order to try and improve mental and physical health simultaneously?
- [51:42]
Chris Palmer
Right.
- [51:42]
Andrew Huberman
It's a very different way of approaching medicine in general. Normally we go, okay, well, the issue is right here. That's where the tumor is. That's where the circuit deficit is. This is where the, the lesion is or the growth. And we're going to go there, right? But to avoid the pathologic state in the first place. These six pillars are wonderful, by the way. A diet, exercise, sleep, substance overuse or abuse, stress, mitigation, and relationship, slash, purpose. So we're going to keep returning to this theme of mitochondria's foundational throughout today's discussion, because I think people need to frame their health in that context. I really do. Also, years ago, my postdoc advisor, the late Ben Barris, he died unfortunately of pancreatic cancer. But you're seeing incredible scientist, MD and scientists who really popularized the study of glia. Prior to that, they were seen as kind of like backwater science. Everyone thought it was just glue for the brain. He used to stop us in the hallways late at night and he used to. We called it getting bend because you'd want to leave and he would like. He was a night owl. It was awful. And you'd get stuck there. But I'll never forget he stopped and.
- [52:52]
Chris Palmer
He called me Andy.
- [52:53]
Andrew Huberman
And he said, he did this numerous times, but he said, andy, why? No one calls me that, by the way, anymore. He said, andy, why is it that as we get older, we have less energy. And I'm like, I don't know, Ben. He's like, someone needs to. He's like, why don't you work on that? Why are you working on these retinal cells? Like, you, you should work on that. And he said, why is it that we. That our brain is less plastic? Like, well, I don't know. I think it's the glia. Right. And there is some evidence that it has something to do with the glia, among other things. But there's a fundamentally interesting question. You look at kids and they're just full of energy. And we. There's the NAD hypothesis and there's these. But it always seems to circle back to mitochondria.
- [53:33]
Chris Palmer
Yes.
- [53:34]
Over and over.
- [53:34]
Andrew Huberman
So I think the answer is very clear. It's, it's. We have a ton of mitochondria early in life and over time it gets depleted. Is it that simple? I mean, there are other things too.
- [53:46]
Chris Palmer
There are other things. But I actually do think that's a. It's not just the number and density of mitochondria, but it's the health of mitochondria. Because unfortunately, you know, our cells have a process for getting rid of defective mitochondria. It's part of autophagy. There's a sub kind of category called mitophagy in which defective mitochondria should be shuttled to lysosomes or shuttled out of cells. Recent paper actually found that microglia in the brain again send out these nanotunnels to astrocytes and collect defective mitochondria from the neuron.
- [54:31]
Andrew Huberman
Amazing.
- [54:31]
Chris Palmer
And then take care of the disposal process for that neuron.
- [54:34]
Andrew Huberman
We are so cool.
- [54:35]
Chris Palmer
And that when you inhibit that, it appears to increase and accelerate neurodegeneration. And when you enhance that, it appears to improve or reduce neurodegeneration. But I think it is, I think children have more energy because they have healthier metabolism, healthier mitochondrial function. And when we look at like, again, like, is there evidence for that? There's overwhelming evidence for that. There are thousands of peer reviewed published articles in leading journals, Nature, Cell, like all sorts of journals over the last several decades just to again try to bring this back to just common sense. So we have these things called diseases of aging. What are the diseases of aging? The diseases of aging are obesity, type 2 diabetes, cardiovascular disease, cancer, neurodegenerative disorders. Those are universally thought of as diseases of aging. Interestingly, what often gets left off of that category are the mental disorders. Especially today, a lot of people think of mental disorders as primarily a youth problem. But in fact, mental disorders, depression, anxiety, psychosis are actually diseases of aging. So the center for disease control has put out kind of charts of any age group. What is the probability, if you are, you know, a youth in America today that you will be prescribed an antidepressant, an SSRI antidepressant? If you're between 20 and 40, what's the probability among the remaining people who are still 20 to 40? Among all the people that age, as people get older, the risk for antidepressants prescription goes up. The highest category of people prescribed antidepressants are 65 and older.
- [57:01]
Andrew Huberman
Really? Well, I guess some sense. That makes sense. Although I would have thought it would be the younger population.
- [57:08]
Chris Palmer
Most people do. And that's why I'm saying this, because it's shocking to most people. It was actually surprising to me. But I'm. I was thinking, wait, if my theory is correct, then mental disorders should be a disease of aging. And in fact, they are antipsychotic prescriptions. What age group is the most likely to be prescribed an antipsychotic over age 80?
- [57:31]
Andrew Huberman
Really?
- [57:31]
Chris Palmer
Oh, it goes through the roof because dementia is associated with 40 to 50% of the people with dementia will have psychotic symptoms, hallucinations and delusions. They'll have agitation, benzodiazepines. The prescription rate goes up. Now with them. With benzos, there is a dip starting at age 65. And that is really because physicians are explicitly told, do not prescribe benzos to people over 65. So the rate starts going down. But with antidepressants, it's almost linear. The older you are, the more likely you are to be receiving a prescription for an antidepressant. Antipsychotics, there are some waves and shifts. Women, for example, around the time of menopause, get a peak. So you get a peak around the age of 20, which is new onset schizophrenia. And then it kind of comes down a little. And then women, around time, menopause, higher peak. And then it kind of comes down a little. And then late in life goes through the roof, Goes through the roof again because of what we call dementia. So the diseases of aging anyway are all of the metabolic disorders and, oh, by the way, the mental disorders. And in my mind, we need to tie that together. That is not a serotonin problem.
- [59:03]
Andrew Huberman
Right.
- [59:04]
Chris Palmer
We need to tie that science together. And the only way to tie that science together is to look at the bigger picture that we call metabolism. And ultimately you have to look at mitochondria and mitochondrial biology. To understand it, I'd like to take.
- [59:20]
A quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins such as bpa, exposure from harmful plastics, and tests for pfas or forever chemicals. Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas. For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood. Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption. I'd been eating a lot of tuna while also making an effort to eat more leafy greens and supplementing with NAC and acetylcysteine, both of which can support glutathione production and detoxification. And I should say by taking a second function test. That approach worked. Comprehensive blood testing is vitally important. There's so many things related to your mental and physical health that can only be detected in a blood test. The problem is, blood testing has always been very expensive and complicated. In contrast, I've been super impressed by function simplicity and at the level of cost, it is very affordable. As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com Huberman Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman podcast listeners. Again, that's functionhealth.com huberman to get early access to function, let's talk about diet.
- [61:08]
Andrew Huberman
And nutrition for a moment. In recent years, you've talked a lot about the clinical use of the ketogenic diet for various mental health disorders and cited some spectacular results. Um, and this has had a huge impact on everybody's thinking about what ketogenic diets originally were for. It was developed as a medical treatment for epilepsy, is my understanding. Only later did it become popular as a potential avenue for losing body fat, et cetera. But what are some of the ways that people can use diet and nutrition to improve metabolic health generally? But let's be more specific. Mitochondrial health number turnover, all the good stuff that happens in mitochondria. How can nutrition be used to improve that? And why would it be that the ketogenic diet would improve mitochondrial function? Or is it that the ketogenic diet bypasses the need for standard cellular metabolism by pulling on some other cellular metabolism mechanisms? I'm just trying to draw the link here between ketogenic diet and mitochondria because we've, you've well established that mitochondria are central to this whole picture of mental and physical health.
- [62:25]
Chris Palmer
I'll throw in a plug before I go deep into the ketogenic diet story. But you, you also threw a question in there about other dietary interventions or how can diet impact. There is no question diet plays a profound, profound and central role to human metabolism and all of the consequences of human metabolism. And you very eloquently laid out the case for early life. A woman who's breastfeeding her infant, that breast milk has a profound impact on whether that baby's brain develops normally or not. That has dire consequences potentially for the outcome and the health of that child. And it's all about nutrition. We've known that for decades that if women are malnourished during pregnancy, it impacts that infants the fetus's lifespan. Really, it increases risk for mental disorders and metabolic disorders. Increases risk. If your mother is starving while she's pregnant or has to fast or has to go without nutrients, it increases that child's risk for metabolic disorders. Obesity, diabetes, cardiovascular disease. We've known that. And that is, you know, there are lots of theories about obesity around that. It also surprisingly increases risk for schizophrenia and bipolar disorder and antisocial personality disorder and all sorts of other mental disorders in terms of other dietary patterns. I, I just wanna, and we can do a deep dive into any of these if you want and then I'll go on to ketogenic diets. But ultra processed foods really bad for your physical health and your mental health. We have just growing body of evidence for that.
- [64:25]
Andrew Huberman
Is that because of the increased calorie consumption. There's this really nice paper that was published a few years ago showing that people who eat above a certain threshold of processed foods tend to consume on average about 500 calories more than they require per day, which might not seem like much, but over time that compounds and they gain a lot of adipose tissue. And then the adipose tissue is secreting a lot of things into the bloodstream that make the whole situation even worse. Both brain and bodily but aside from the caloric load, I mean, is there any evidence that these food dyes and other things that are included in these foods are detrimental to mitochondrial health? This is a somewhat controversial thing these days because some of these dyes were banned recently, which I saw as a good thing. But then some of the die hards in the scientific community like oh, those dosages represent like 6,000 fold what you'd have to what most people eat, the dosages used in mice. But, but the FDA still pulled those dies and the FDA is a pretty conservative body. So I don't know. Not every chemical is bad, of course, but are these additives really that bad?
- [65:41]
Chris Palmer
So to try to answer your question, are the chemicals and additives harmful? The real answer is we don't actually have adequate scientific evidence one way or another. And why don't we have adequate scientific evidence? Because we're not spending money to research it. So right now the rules to this day are that there's this concept called grass general, regarded as safe. That food companies can develop new molecules that will preserve a food, make a food hyper palatable, make it tastier, make it more shelf stable, whatever, whatever they want to claim it does. But they can develop molecules, they can put these molecules into our food and they can get away with just saying, well, this is just generally regarded as safe, safe without any adequate safety testing whatsoever. And the FDA allows that. Now the new administration, RFK Jr. Just recently said he's going to try to change that rule and I welcome that change. I think that will be a phenomenal change. So the reality is that testing hasn't been done on all of these molecules. There are tens of thousands of molecules and like new chemicals, new additives, things that sometimes aren't even on the label that are added to food. And we really don't know for sure for each and every one of them whether this one is safe or not safe. What we do know overall, and this unfortunately comes down to epidemiological studies where they just look at hundreds of thousands if not millions of people and they assess like how much ultra processed food is this person eating? And is that associated? If we look at large populations of people and we stratify them by these, these people are eating mo mostly ultra processed foods and these people are hardly eating any. Are there differences in their health outcomes? And the answer to that is unequivocal. And it is perfectly clear, the more ultra processed foods you eat, the worse your physical and mental health both it's cardiovascular disease, it's obesity, it's Diabetes, it's mortality, it's cancer. It's also a broad range of mental disorders. And so we know that we, we've got more granular data that's hyper focuses on the mental health story. You know, One study, over 300,000 people, the more ultra processed foods you eat, a direct linear relationship. It was shocking how linear it was. The more ultra processed foods you eat, the worse your mental health. And it was so striking. It was not a subtle difference. It wasn't like, you know, oh, it was a 3% difference between the lowest. It was a threefold difference. The people who consumed ultra processed foods every day, multiple times a day, 58% of them had poor mental health compared to only 18% of the people who rarely or never consumed ultra processed foods.
- [69:29]
Andrew Huberman
Wow. So this would be even just like somebody has like a bag of chips and some, you know, just pour in water type premade soup or something like that. Those are ultra processed. This would be somebody orders a sandwich at the deli for lunch, which can be done in a relatively healthy way, depending on what's in that sandwich, and then does soda and bag of chips on the side. Like I mean you're, that's a lot of, in my opinion, highly processed food. But people, I think sometimes people don't think of it that way. Yes, One of the, I was surprised and somewhat delighted to learn that one of the ways that the, you know, the public health folks got kids to smoke fewer cigarettes because when I was growing up, like smoking was cool. Like if you smoke cigarettes, it was cool. People thought it was cool. It definitely is reinforcing because of the nicotine, the dopamine increases and it was considered cool. You had your like marble man image from the preceding decades. But then it was really the, the, the 90s kind of. It was the actors and models and stuff that made it cool. Like people smoked and it was supposed to be cool. And one of the ways that.
- [70:42]
Chris Palmer
We.
- [70:43]
Andrew Huberman
Ended up with people smoking far less was not just to ban it on campuses because that just makes teens want to do it more. Right. In college you wanna do it more was to have these commercials of these. It was all to be direct. It was just like these rich white guys in a room that was portraying like the boardroom of a tobacco company. And they were like cackling and talking about like hahaha, they think we're gonna, they don't think it causes cancer and this kind of thing. Basically pitting youth against adults so that the youth felt like their money was being taken by the. By the establishment. So is there a world where, you know, kids are going to be like, you know, forgive me, but, you know, like, f. That I'm not eating Doritos, you know, like, I'm not going to be manipulated by highly processed foods, or I'm going to hold on to my mental health by making healthy choices in terms of food. It's tricky, but it has a lot of the same parallels to cigarette use or alcohol use. But I feel like the only way to really get Americans to change their behavior besides scaring them fundamentally. But even if you do that is to incentivize it. And one of the best incentives historically for public health change has been to pit the. Make the public feel like they're pitted against the people that are trying to take their money unfairly and make them unhealthy at the same time? You got to activate that kind of rebellious spirit. Not going to do it. Just telling people this is bad for you. Doesn't work. Right. We know that. How do we incentivize people?
- [72:13]
Chris Palmer
Yeah, I'm not going to give a cliche answer because this is the trillion dollar question that everybody's asking. And, and it, it really, you know, the. The health of our country really kind of depends on it. With billions of dollars that this industry has in revenue annually, they can spend a lot of that money on really impactful marketing campaigns, getting people to believe that it's not as unhealthy as Chris Palmer and Andrew Huberman are saying. It's fine. Everybody deserves a treat. Within the last couple of weeks, the American Heart association was actively lobbying against a Texas bill that was trying to restrict spending food stamp money on junk food.
- [73:17]
Andrew Huberman
I saw that clip. It's so disturbing to see someone from the American Heart association actively lobbying to keep tax dollars directed towards including sugary soda. Not even diet soda, but sugary soda in lunches and food for people who are low income.
- [73:38]
Chris Palmer
And he went on record as saying, this junk food, this ultra processed food is not the root cause of obesity or diabetes or any of these health conditions, which is an absolute abject lie. And when you have supposedly respected organizations being bought by industry promoting misinformation, I. It's really hard. You know, everybody's all upset that, like, oh, people don't trust the science. They're not respecting the respected organizations. Well, the respected organizations need to step up and start behaving in a respectable manner. They need to stop. The American Heart association should not be taking a dime from any industry that plays a role in heart disease. Like they. It would be like, it would be like the American Heart association taking money from tobacco companies and then coming out and say, smoking doesn't really cause heart disease. People, everybody calm down there. There's still a lot that we don't know. We need more research. We need more research. Smoking doesn't cause heart disease. People, this is just scare mongering. This is just paranoid conspiracy theories. That is exactly what's happening now. They're taking money from food companies that have no vested interest in the human, in the health of the population that they are feeding. They know perfectly well that these foods are highly palatable. And what does that mean? It means addictive. And again, if I was selling food, I would want people to be addicted to the food I was selling. Why? Because you sell more, higher margins. If you sell food that people aren't addicted to, they'll just move on to the other food that is addictive and then you'll be out of business. So it's not an easy problem to solve. I don't mean to imply it's easy because if one or two companies steps up and does the right thing, they'll just go out of business.
- [76:03]
Andrew Huberman
Well, I feel like the smoking parallel is critical. And maybe the trans fat, the history of entire cities banning the use of trans fats, for instance, or the use of styrofoam containers, right? I mean, it's very different, very different issue. It doesn't directly get to human health of the Styrofoam.
- [76:21]
Chris Palmer
It's not good.
- [76:21]
Andrew Huberman
But it's about, it's about waste and environment. But I feel like there has to be a top down ban. And Americans also don't like bans, right? We don't like things, we like choice, but we don't like the consequences of those of choice. And then we want people to fix the consequences of those choices with treatments that don't have side effects. And then this is like kind of the cycle that I've observed in my lifetime over and over again. You know, I think it's the rebellion piece. It's when people realize they're being manipulated. Once people realize they're being manipulated, I feel like that's when they're willing to intervene and stop otherwise reinforcing activity, reinforced addictive activity. Save money and like take a different direction. Like that's, that's inherent to the American spirit. As much as we love freedom, we also, we have this like, no, you're not gonna, you're not gonna do this to me kind of spirit. We see it everywhere. This is my Belief. But then again, I was kind of a rebellious teen. But, but if it's in service to.
- [77:31]
Chris Palmer
Health, I'm, I'm hopeful. I mean my, my understanding, by no means am I an expert, but my understanding of what really drove the reduction in tobacco use was the taxes and the ban on advertising, the ban on television advertisements. Interesting that when you get rid of the advertisements, you're no longer tempting people with it, you're no longer able to spread misinformation. And when you make the product so expensive, people just, even if they want to try it, even if they're already addicted to try, already addicted to it now, they are highly motivated to get off of it. Why? Because it's costing them an arm and a leg.
- [78:18]
Andrew Huberman
Money hurts.
- [78:18]
Chris Palmer
And they, and they realize that I just don't want this. We could do similar things with ultra processed foods. If rebellion, education, whatever. I, I don't care what works. But we're all of the above. We're, we're, we're really fighting an uphill battle. So ultra processed foods, that's just one story. Vitamin nutrient deficiencies. Do you want to go to ketogenic diet? You asked me about that and I got sidetracked.
- [78:45]
Andrew Huberman
Yeah, we went into a public health discourse. We're weaving back and forth. That's what we do here. I think it's, look, it's very timely, right? I don't care if you're the staunchest Democrat or the staunchest Republican or somewhere in between. Like these issues affect everybody. And anyone who just wants to view Maha as a Republican thing, it's fine that I'm not affiliated with Maha. I am in favor of improved public health from whatever angles that can meaningfully be done. So tell us about ketogenic diet and then I'd like to ask about things that we can do to improve mitochondrial function in these other bins. But does ketogenic diet improve mitochondrial function? And if so, how does that work?
- [79:29]
Chris Palmer
The quick summary story for people who don't know ketogenic. So ketogenic Diet is a 100-year-old evidence based treatment for epilepsy. It can stop seizures even when medications fail to. We have over a dozen controlled trials of ketogenic diets in children in particular with treatment resistant epilepsy. We have two Cochrane reviews that came out positive. So Cochrane reviews are the gold standard in the medical field for meta analyses. Very rigorous. And they analyzed the data that exists and came to the conclusion that ketogenic diet, if somebody has treatment resistant epilepsy compared to treatment as usual which is try another antiepileptic medication. The ketogenic diet is six times more likely to result in seizure freedom.
- [80:20]
Andrew Huberman
Wow.
- [80:21]
Chris Palmer
Than just trying yet another epilepsy pill. So the ketogenic diet is a powerful anticonvulsant treatment. We use anticonvulsant treatments in psychiatry every day in tens of millions of people. Lots of these medications are used. So at this point we now have over 50 published pilot trials, case series, case reports, other lines of evidence of the ketogenic diet for psychiatric disorders, schizophrenia, bipolar disorder, depression, anxiety, anorexia or Nervosa. Surprisingly, these 50 reports represent over 1900 people. And on balance, the ketogenic diet appears to be an effective treatment, sometimes an extraordinarily effective treatment like in able to induce remission of schizophrenia or bipolar in people who otherwise had treatment resistant disorders.
- [81:30]
Andrew Huberman
And they're going off medication simultaneously.
- [81:33]
Chris Palmer
Some of them are. So there are. You know, I have heard probably from thousands of people around the world since my work has become more public and actually our first podcast together, hands down, the most cited reason people know who.
- [81:54]
Andrew Huberman
I am, as they should.
- [81:57]
Chris Palmer
Well, I know about you, but it's Huberman, Huber. That Huberman Lab podcast.
- [82:01]
Andrew Huberman
I'm just, I'm just a Runway for people to incredible messages to take off.
- [82:07]
Chris Palmer
Thank you again for the opportunity to disseminate this word and because at the end of the day, I'm hearing from thousands of people who simply listened to that podcast, made changes, started a ketogenic diet for their schizophrenia or other treatment resistant mental disorder. Reach out to me. You saved my life. I can't tell you how many times I've gotten handwritten notes, emails, messages from people who use those words. You saved my life. I never met this person. All I did was share this knowledge. And then they saved their own lives with knowledge. Coming back to your question now, in roundabout way, does ketogenic diet impact mitochondrial health? We, we have strong evidence that it does, and so it appears. So the ketogenic diet is mimicking the fasting state. And I just want to say that again, the ketogenic diet mimics the fasting state. What does that mean? It means the ketogenic diet is mimicking no food consumption. So is the ketogenic diet the healthiest diet that everybody should follow? No, that's not the way I think about it. The ketogenic diet is an intervention. It is shifting metabolism. It is shifting countless kind of systems, signaling, pathways, other things, gene expression in the human body and brain. And that results in effects. And the good news is these Effects appear to be life changing and life saving sometimes. So they're highly beneficial effects. Again, dose and the way you do it matter, because fasting, the extreme version of fasting is starvation and that results in death. So that is not at all a good thing. So let's make sure that if you're gonna do a ketogenic diet or a fasting regimen, that you're not depriving yourself of essential nutrition, that you're getting enough calories, you're getting enough nutrients, that you're doing it in a medically sound way so that you're optimizing your health and not hurting your health. But we have, you know, it's, it's hard to measure this in humans in vitro because we can't like do an intervention to a human and then dissect their brain and like biopsy it and look at the mitochondria under the microscope. So we mostly have animal data that supports this, but animal data strongly supports that ketogenic interventions improve mitophagy. So getting rid of these old and defective mitochondria, so you're kind of cleaning house, you're getting rid of the bad, and then you're replacing them with new, fresh ones, mitochondrial biogenesis, so that at the end of the day, the cell will have more healthy mitochondria. Now some researchers have really hyper focused on the ketogenic diet, might be working through the gut microbiome, this gut brain connection. And we have some evidence that that is true. So researchers actually took feces from human children with epilepsy before starting a ketogenic diet and then afterward while they were stable on a ketogenic diet. And then they transferred these fecal samples to mice who were predisposed to epilepsy or predisposed to seizures when they took the feces from the children while the children still had or seizing. The mice were more likely to seize when they took the feces from the children doing the ketogenic diet and transferred it to the mice. The mice were less likely to have seizures.
- [86:29]
Andrew Huberman
Interesting.
- [86:30]
Chris Palmer
Even though the mice were not on ketogenic diets. So there's something in the feces of children with epilepsy doing ketogenic diets that has an anti seizure effect. What could that something be? It could be the gut microbiome, but it could be molecules, neurotransmitters, neuropeptides, other things that those microbes are producing, or it could be neuropeptides and other factors that the gut cells are producing. So we really don't know for sure. What exactly is it? So on the surface, there's something in the feces, there's a gut microbiome, a gut brain connection thing. What does that have to do with mitochondria? So another research group did that same model, got mice to have an anti seizure effect from a ketogenic diet and then dissected their brains looking for what changed in the brain. How exactly is a ketogenic diet having an anti seizure effect in the brain? Because the pathology, the pathological finding, seizure is occurring in the brain. And when they analyzed genetic changes, upregulation, downregulation, it all centered on mitochondria that the changes in the gut were resulting in mitochondrial changes in the brain, which means brain energy metabolism in the brain. And so again, it's an umbrella theory. Doesn't replace what we know. It's not gut microbiome or serotonin, it's not gut microbiome or mitochondria. It's both. Both of them are true and it's all interconnected. So I, I do think we've got more than enough data that ketogenic therapies impact brain metabolism, which then impacts neurotransmitters. Really, what I hope will become one of many really important studies published by Ian Campbell and colleagues in the UK that they just did a pilot trial. 20 patients with bipolar disorder put on ketogenic diets and they found wide ranging improvements in metabolic health biomarkers like weight, blood pressure, other things. But they also found a reduction in brain glutamate activity which is often associated with bipolar disorder and hyperexcitability and seizures. And so that helps us understand, again, it's not metabolic or glutamate, a neurotransmitter, it's both. It's putting it together.
- [89:38]
Andrew Huberman
Yeah, the Campbell study is really interesting. We will link to that in the show. Note captions. And incidentally, we will also link to this American Heart association appalling quote, unquote testimony.
- [89:51]
Chris Palmer
Sorry. Aha.
- [89:53]
Andrew Huberman
I'm not, I'm not sorry. I'm not not sorry. But then again, I'm not a physician, so I don't have to worry about that. Well, maybe I do. Anyway, I'm not a cardiologist. Is there any rationale for people who don't have epilepsy or don't suffer from bipolar schizophrenia, but like myself, would like to keep our mitochondrial function as, as strong as possible and for doing a brief ketogenic intervention?
- [90:25]
Chris Palmer
Yes, the answer is yes. Can intermittent and I'm so. I'M going to lump ketogenic with other fasting mimicking diets and fasting itself. So can intermittent fasting or can cycles of fasting have health improving qualities or health improving effects? Absolutely. So interestingly, before I talk about even some of the science on this, and it's not super robust. Why? Because again, we don't fund diet studies. There's no money to be made from dietary interventions. Really, there's no patent on it. Nobody cares about dietary interventions.
- [91:10]
Andrew Huberman
But there are a lot of studies on exercise interventions.
- [91:13]
Chris Palmer
But even those are, they're not huge randomized controlled trials with 10,000 participants. They're not, you know, like even the federal government will fund large scale medication trials, statin studies and others. But they often don't. I mean there have been a few. The Women's Health Initiative funded a massive dietary intervention study and unfortunately that was a huge disappointment to the field because it was negative. They randomized women to just keep doing the diet you're eating or go on a low fat diet. And the low fat diet didn't do anything for their heart health or other objective kind of outcome measures. And put another way, just to just to really close this for people, it means a low fat diet is no better than the standard American diet. A low fat diet is equivalent. You get equivalent health effects from a low fat diet to a standard American diet. That's really bad. So low fat diets need to go away. And people who promote low fat diets need to stop promoting. They need to get, come up to speed with the science and just like move on. Like at least acknowledge there are healthy fats even though fat has more calories. Don't worry about those calories, worry about the health effects, the long term health effects.
- [92:47]
Andrew Huberman
Yeah, you gotta get those monounsaturated fats and you gotta eat your omega 3s and you have to, you know. And I'm a believer in some butter here and there.
- [92:55]
Chris Palmer
You were asking me about intermittent, yeah, ketogenic diets or intermittent fasting.
- [92:59]
Andrew Huberman
Intermittent fasting.
- [93:00]
Chris Palmer
So I'll just say that we have a long history in multiple cultures on earth. For thousands of years, fasting has been part of healing rituals. India, China, Christian fasting has been a part of rituals. And you know, most people just assume it's religious folklore, just silliness or whatever. But I actually think millennia of humans, we're not all stupid idiots. And that some people along the way actually noticed this seems to do something useful. And that's probably why it found its way in every culture and persisted for thousands of years because there was actually something meaningful happening. So what we have now in terms of more controlled trials, I'm gonna cite Valter Longo, who he doesn't call his diet a ketogenic diet, although it is a ketogenic diet. He calls his diet a fasting mimicking diet. And it's primarily a plant based 600 calorie a day diet.
- [94:16]
Andrew Huberman
Some people are going to hear that and just gasp.
- [94:20]
Chris Palmer
It is proprietary to him. I have no relationship with him. I'm not promoting his product. But he has a proprietary product called Prolon. You can get the benefits by just not eating anything or by eating 600 calories a day. I mean, you don't need to buy that proprietary product. But because he is selling this product, I believe he's using most or all of the funds that from most or all of the proceeds from the sale of that to fund research on it. They've done a series of studies that five day cycles, several times a year seem to be fine and improve a wide range of health biomarkers.
- [95:06]
Andrew Huberman
Interesting.
- [95:07]
Chris Palmer
And there's reason to believe that it may help improve metabolic health and longevity. So he's primarily a longevity aging researcher. He is promoting that. Could ketogenic diets also produce similar effects? I believe they can. Again, it gets really controversial fast because ketogenic diets can sometimes include red meat. And then we got the American Heart association telling us that red meat's bad for you and don't eat that red meat nonsense. And well, that we. So. And we get these splintering groups and we've got the vegan group saying that's awful for you. And unfortunately it just leaves people confused about like what, what are we supposed to do? Do we eat red meat? Do we not eat red meat? Do we like in moderation.
- [96:00]
Andrew Huberman
Yeah, I, but in moderation from healthy sources, not the processed stuff. But you know, I, I get it. People have animal reasons or environmental reasons, they don't do it. You know, the debate goes on and on.
- [96:11]
Chris Palmer
I've observed some people who are vegan.
- [96:13]
Andrew Huberman
Who seem very healthy, very robust aesthetically. They, they present well, if I'm just going to be direct about it. And then I've seen some people who go vegan and, and it's the exact opposite. And then I've seen, I think the strict carnivore thing seems to work for very few people, but the ones who love it, really love it. But even the folks like Paul Saladino who are the so called, you know, carnivore diet are now, then it became Animal based. And it now includes fruits and cucumbers and tomatoes and some dairy and you know, and so, you know, and honey and, and I like Paul. I get along well with Paul. I also get along with Lane Norton and they don't get along. But you know, I think it's teach their own within the context of the correct number of calories for a given person and their activity levels. But this idea of doing a, periodically doing a, perhaps a fast along the lines of the longo prolonged thing or, or, or total fast or water fast I guess it's called, or perhaps intermittent fasting on a, on a more reasonable schedule. Are there any data on that? Like eating only between the hours of say 11am and 7pm which is I, which is what I happen to do reflexively unless I wake up very hungry, which is really rare. I don't know why. Maybe it's a function of getting older. But is there any evidence that intermittent fasting that doesn't involve entire day and night fasts but more of the, you know, time restricted feeding to eight hours or six hours that it can be beneficial for mitochondrial function if it's done for short bouts of two to four weeks?
- [97:47]
Chris Palmer
My understanding of the literature is that it's a mixed bag when it comes to time restricted eating and intermittent fasting because more often than not they don't control what people are eating when they're eating.
- [98:04]
Andrew Huberman
Oh well that's no good.
- [98:06]
Chris Palmer
So they just, those studies mostly are designed to just say don't eat, only eat between 11am and 7pm because eat whatever you want, but it doesn't matter like, and as though it doesn't matter what they're eating. And some people are binging on ultra processed foods and others are eating like an adult. And, and then you've got everything in between as though that doesn't play a role. And, and so you get these studies that say it doesn't do anything useful. You get other studies that say maybe it does something useful. So I think, I mean at the end of the day I will say this. You know, I'm, you know, I've been talking a while with a really seasoned, established expert in the nutritional space, in the conservative nutritional space. He's held several government positions, he's helped presidents and others with campaigns and he has made a very strong case to me that, you know, less than 5% of the research budget from the NIH is spent on nutritional research. The NIH has an Office called the Office of Nutritional Research focused on organizing collaborations among different NIH institutes. And centers and their annual budget for a major government organization, Their annual budget is 1.3 million with an M dollars.
- [99:49]
Andrew Huberman
Oh, my goodness. That's.
- [99:51]
Chris Palmer
Which is a joke. It is a laughable joke.
- [99:54]
Andrew Huberman
Can't do much with that.
- [99:55]
Chris Palmer
And without trying to make this political, there have been people who've tried to increase the funding for nutrition research. Recently was proposed to increase that funding to $130 million and it was cut. That idea was killed by the lobbyists of the food companies.
- [100:21]
Andrew Huberman
I'm going to get really vocal about this lobbying through the American Heart association thing because I was just shocked. Right. For all the obvious reasons, American Heart association, you assume that they are all about healthy hearts. And we know metabolism is. And healthy weight and activity and all that is healthy for hearts. And it was so clear that they were on the take from these food companies and that's why they sent. Even just the timing and the delivery. Again, I'll post to the link because it's just like jaw dropping. Like, I can't believe this is like. It's like the old commercials of the people from the cigarette industry saying, yeah, the cigarettes don't cause cancer, and they know it does. And this is happening now in real time. And this conversation will certainly assist in drawing attention to this. I'll probably do a social media post on it as well. But there's this thing that happens in medicine and public health where the thing that's so obviously the problem is it's not even staring us in the face, it's slapping us in the face. And we take 20 to 30 years, relying largely on messaging through Hollywood kind of what actors are doing, what athletes are doing. Then people are like, oh, yeah, maybe this is a thing. And then think the battleship just slow, like, eventually just pivots. But there's been decades of horrible misfortune and loss in mental health and physical health. People thinking that there's something wrong with them or, you know, et cetera, et cetera. I mean, it's asinine. It's crazy. And so I'm excited about Maha, even though I don't have any affiliation to it, because it's the first time in my lifetime that anyone said, like, hey, let's actually just talk about and think about how to really get healthy. What do we know right now? And so I'm not a political person, but I think it's really important that we get focused on what's literally slapping us right in the face with, like, this is absurd. Forgive me for editorializing here, but we keep coming back to this. We know what, what we need to do.
- [102:17]
Chris Palmer
We know what we need to do. But yeah, we have not had the political will to do it. I think the hope is that one hopefully of many good things that could come out of Maha is separating industry interests from the health and welfare of the American population. I think if we can do that and we can begin doing unbiased research to really determine what is it about ultra processed foods that results in harm? We know they result in harm. Is it just that they're so delicious that people consume extra calories and it's still just as simple as calories? Or is it that there's something in those chemicals that makes the foods addictive? Or is it that there's something in those chemicals that actually impairs mitochondrial function? I think we have evidence to support all three of those hypotheses. Do people consume extra calories? Yes. You cited one of now many studies documenting that. Are they addictive? Yes, unequivocally they are. I mean, the most common eating disorder diagnosed today in the United States is called binge eating disorder. What are the criteria for binge eating disorder? Basically, addiction to ultra processed foods is really, if you look at the criteria and if you look at the behaviors, when people engage in binges, they're not binging on steak and broccoli ever. Like, never, never are they binging on steak and broccoli. They're binging almost exclusively on ultra processed foods. And then they go through these cycles where they binge on them and then they beat themselves up and they feel disgusting and they're, they're ashamed and they're humiliated and, and then they try their best, they white knuckle it to avoid those foods. And then something bad happens in their life. They get stressed, somebody cuts them off in traffic, they've had a hard day at work, their boss came down on them, whatever, and, and then they go home and they're like, you know, screw it. I hate my life, I hate myself. I don't. Health doesn't even matter for me. I'm addiction cycle and I may as well just enjoy myself. And just like an alcoholic would, just like a cocaine addict would. It's not that people are using every single day. You know, they go through cycles and it's really tragic. Harvard Medical School just literally two days ago, came out with an article, is sugar addictive? And their conclusion, no, no, because sugar is found in fruit, so it can't be addictive. I'm like, really? Is that. And they, they actually went, they went out of their way to say, well, you know, like, it's not like addictive like alcohol and nicotine, because people sometimes have trouble stopping those completely. And I'm thinking, and what do you think is different about sugar? Do you really don't understand that some people can't stop consuming ultra processed, high sugar foods? You really don't understand that? Like, are you living in an ivory tower?
- [105:54]
Andrew Huberman
Yes, I'm not, but I'm certainly not, not any longer. And it's also, I think, important that the highly processed foods and the palatability and the accessibility and the low cost. Right. We're not talking about eliminating pie and pastries. I think sometimes people think, oh, like, I'll never have a muffin again. I'll never have a chocolate croissant. That's not really what we're talking about. We're not talking about a homemade cake, we're not talking about cupcakes. We're talking about things that are easily purchased at low cost, unpackaged, eaten in transit. What we're doing, I realize, is painting this picture of a little bit of the past, the recent past. But what you do so beautifully is you're really orienting us where we are now and that the fact that we need more science, but we, we know an awful lot and there's so much that we can do. And these six pillars of diet, exercise, sleep, avoiding excessive substance, abuse, use or abuse, excuse me, stress, mitigation, relationships and purpose, which center back on mitochondrial health. Could we talk about some of the other things that we can do for mitochondrial health, things we can take these days? We're hearing a lot about creatine. What are the data on creatine and mitochondrial function or brain function? I'm not familiar with these data. I should be.
- [107:11]
Chris Palmer
So creatine is a molecule that is foundational to energy transformation in cells. So creatine goes into the mitochondria and there it gets combined with ATP to become phosphocreatine. And then it leaves the mitochondrion and goes to places in the cell where energy is needed, like a synapse or a ribosome that's trying to make some new proteins or something else. It goes to places in the cell where energy is needed and it can combine with ADP to be converted back into ATP. So it's basically a phosphate shuttle. Creatine is a phosphate shuttle that is foundational to energy metabolism. It is foundational to mitochondrial function. Our bodies can produce creatine on their, on its own, as long as we have the essential vitamins and nutrients that make it up, and there are several of those. Or we can consume creatine. Creatine is found only in animal based products, animal sourced foods. It is not found in plant sourced foods. So what we know is that from, because creatine is found in large quantities in the brain, so we can actually measure it using mass spec kind of scans. And we know that there's a range. Some people have low levels of creatine and some people have higher levels of creatine. People who consume less animal sourced foods, like vegans and vegetarians, on average, tend to have lower levels of creatine in their brain and muscles and other tissues. People with neuropsychiatric disorders, schizophrenia, Alzheimer's disease, depression, have been found to have lower levels of creatine than people who do not have those disorders. So we have reason to believe that creatine, from studies like that, that there is an association, meaning a correlation between low levels of creatine and brain disorders that we call neurological or psychiatric disorders. So the next question, logical question from a scientist should be, well, if we supplement with creatine, can that improve symptoms of neuropsychiatric disorders? And we do have evidence to support that. Not huge randomized controlled trials in tens of thousands of people. Because again, that would require government funding because creatine is off patent. Nobody's going to make a lot of money from doing a creatine study because anybody can sell creatine, anybody can make it and market it. It's off patent. So. But we do have randomized controlled trial data with creatine showing that it can improve symptoms of major depression, it can augment antidepressants, it can improve symptoms of bipolar disorder, it can improve symptoms of neurodegenerative disorders like cognition in Alzheimer's disease or mild cognitive impairment. But again, the studies are on the smaller side. They're not super robust quality. But unless the government steps up, unless the NIH steps up and funds a large, well done, well controlled, randomized, controlled trial of creatine versus placebo for any of these conditions, the skeptics and the hardcore scientists are always going to say, well, we don't have good quality data. Well, we're never going to have good quality data because there's no product. That's where we're at as a field.
- [111:40]
Andrew Huberman
Do you recommend it to your patients?
- [111:43]
Chris Palmer
Not right away. You know, there's more research coming out and there's more reason to believe that maybe I should be recommending it to patients more often than I Currently do. It certainly lines up with a metabolic, kind of mitochondrial. Improve metabolic health, improve brain health simultaneously. It lines up perfectly with that. And I just want to remind people, before you focus on what to take, focus on what you should be doing with your lifestyle. What is your diet, nutrition? Are you getting adequate sleep? Are you getting some bright light in the morning? Do you have relationships and purpose in life? Are you overusing harmful substances? Because I want to be the first to say, if you're not doing those things, creatine doesn't stand a chance in hell of helping your health. It just does not stand a chance to improve your health. There is no supplement that you can take that will undo the damage that a harmful lifestyle will have on you and your health. And, and the reality is the statistics are abysmal. I mean, one third of American adults are not getting adequate sleep. 60% of the foods that Americans are consuming are ultra processed foods. You know, the real money is not in the question, what should I take? The real money is in what should I do? How can I change my life and my lifestyle to improve my health? And so I just, yeah, I just want to drill that home for people, for better or worse.
- [113:34]
Andrew Huberman
I first learned about methylene blue from owning fish tanks. You clean fish tanks with them or it's a thing you use now? There's a lot of interest in methylene blue ever since a video of Robert Kennedy putting methylene blue in his water on a plane kind of went viral. Methylene blue has been around a very long time. What are your thoughts on it? What does it do? Is it going to help mitochondria? Is it for everybody? I don't take it.
- [114:04]
Chris Palmer
I don't take it either. And I've not used it in any patients so far. But I'm very interested in possibly starting to use it in controlled ways and patients who clearly need something more. We're doing all of the right things, we're doing the lifestyle things, we're doing ketogenic interventions or other things, and they still are not. Well, there's still room for improvement. So methylene blue, as you said, has been around for a long time. It's relatively cheap as a, as a fish tank cleaner. Methylene blue, fascinatingly, is primarily exclusively a mitochondrial agent. So it is an electron acceptor and donor. So that is what methylene blue does. It can accept electrons and it can donate electrons. So it's an electron shuttle, if you will. And how does that relate to mitochondria? Mitochondria as they are producing ATP electrons are flowing down the electron transport chain. And that is what results in the production of ATP. If it gets shuttled through the uncoupling protein, it results in heat production. And when electrons flow out of that system, when they leak out of that system, it creates reactive oxygen species, which again, are very harmful to both mitochondria and cells cells. So if you have dysfunctional mitochondria that don't seem to be able to contain the electrons appropriately, electrons are leaking out. So these would be mitochondria that are producing more reactive oxygen species than they should. Does that ever happen in biology? 100%. We've got decades of evidence that aging, neurodegeneration, Even obesity, type 2 diabetes, and a wide range of neuropsychiatric disorders are associated with that process, that increased levels of reactive oxygen species, often referred to as oxidative stress. So we got decades of evidence strongly supporting that. Can methylene blue play a role in that? Absolutely, because methylene blue can come in and take some of these wayward electrons and prevent them from creating reactive oxygen species, which might help calm things down. One of the challenges with methylene blue, as we discussed before, you can have too little and too much. Same with methylene blue. You can have too little and too much. You don't want to accept too many electrons. These electrons need to be flowing to the places they should be flowing, as opposed to oxidative stress. The polar opposite of that is called reductive stress. And that too has been found in people with schizophrenia and bipolar disorder and some other disorders. So it's really about dysregulated kind of balance between oxidative and reductive stress. And methylene blue, if you take it in overdose, could become a reductive stressor. So you don't want too much, but. So we do have pilot trials, again, small, not super well done pilot trials in a wide range of neuropsychiatric disorders. Depression, bipolar disorder, schizophrenia, Alzheimer's disease, others, many of them suggesting a benefit.
- [118:13]
Andrew Huberman
Do you know what the doses range?
- [118:16]
Chris Palmer
I don't know off the top of my head.
- [118:18]
Andrew Huberman
Yeah. Because methylene blue, as I understand, has some MAO activity. The can adjust some of the enzymes that in turn adjust levels of serotonin, which is why I haven't taken it. I've just been cautious about. I don't really want to boost my serotonin. There's this recent study out of a lab at Stanford showing that the rewarding properties of various things, as we know, increase dopamine in anticipation of a reward. But also Important. It seems these are mouse studies, but. But serotonin drops as dopamine goes up. And that drop in serotonin is at least as important as the increase in dopamine for the reinforcing properties of certain behaviors and substances. And I'm very reluctant to tamper with anything that would raise serotonin, because in these studies or these experiments, or in these experiments, I should say increasing serotonin offset some of the rewarding aspects of otherwise rewarding things. So I want things that are rewarding to feel rewarding. And so this. This difference between dopamine and serotonin seems pretty vital. I mean, that's not to say I'm, like, terrified of anything that increases serotonin, but to do it pharmacologically just seems a little sketchy, given I don't have a clinical need that I'm. At least not that I'm aware of.
- [119:42]
Chris Palmer
No. Well, and that's actually one of the warnings with. With methylene blue, is that if you. If taken in too, have a dose, you can actually get serotonin syndrome.
- [119:51]
Andrew Huberman
Could you explain what serotonin syndrome is?
- [119:53]
Chris Palmer
So serotonin syndrome is just like really excessive deluge of serotonin in the system. More often than not, it's completely unrecognized.
- [120:06]
Andrew Huberman
Really.
- [120:07]
Chris Palmer
It gets mistaken for psychiatric symptoms. So people can have anxiety, they can have panic. In extreme cases, you can get nausea, you can get fevers, you can get. I mean, in extreme cases, it can be fatal. So it's a serious thing. But more often than not, it gets dismissed. Because serotonin syndrome is most commonly experienced by people taking SSRIs. And by definition, they are psychiatric patients where they have a mental health condition. And so when they come in and say, I'm feeling nauseous, I feel anxious, I feel jittery, I feel I don't feel right. They get written off more often than.
- [120:52]
Andrew Huberman
Not, or given more medication.
- [120:54]
Chris Palmer
Yeah, let's say increase your dose. Let's increase your dose or whatever. So it's actually really tragic. I mean, one woman actually reached out to me who, after learning about my work, reading my book, she talked to her psychiatrist, tapered off all her meds, and it became clear that she probably had serotonin syndrome for a long time. Wow. To both her and her psychiatrist.
- [121:19]
Andrew Huberman
So the meds were causing the problem.
- [121:20]
Chris Palmer
And the meds were causing the problem, and nobody really recognized it.
- [121:25]
Andrew Huberman
Goodness gracious.
- [121:27]
Chris Palmer
Again. So it's. So anyway, methylene blue can cause serotonin syndrome. So I think if people are gonna. If people Wanna consider using it? I would. Number one, make sure you get a very reputable source of it. Make sure you're consuming it in a way that makes sense. I mean, it can stain your teeth blue and all sorts of stuff.
- [121:48]
Andrew Huberman
So make sure you're in blue, your tongue blue.
- [121:51]
Chris Palmer
But people will do IV infusions of methylene blue. So yeah, no, that's. I've seen people kind of hooked up to IVs with a methyl, a bag of methylene blue.
- [122:04]
Andrew Huberman
Do they turn blue?
- [122:05]
Chris Palmer
And I hope not.
- [122:08]
Andrew Huberman
Smurf smurf.
- [122:10]
Chris Palmer
But it is a medically approved treatment and I think it can be done in safe ways. Again, it's off patent. Nobody's going to stand to make any money off of doing large, well designed trials of methylene blue. But I'm really interested in it as this has these properties in addition to just being this electron acceptor and donor. There's some evidence that it may improve mitochondrial biogenesis, that it has anti inflammatory effects and that it can do other things that, that, that may be beneficial.
- [122:54]
Andrew Huberman
Interesting, very interesting. In fact, before moving on to some more clinical questions, we've been going deep into the science and some public health thoughts and reflections and ideas. There's a supplement called urolithin A that people seem really excited about for improving mitochondrial function. I'm not super familiar with the literature, but coenzyme Q12, urolithin A, we're starting to hear more about these sorts of things sold over the counter. Do you have any thoughts on those?
- [123:29]
Chris Palmer
There's a company timeline that puts out this product and to their credit, they have actually done some pretty well designed, robust, randomized controlled trials of urolithin A. They've primarily focused on muscle health and aging. And so they actually have reasonably good data published in reasonably good journals documenting that urolithin A, when given to elderly people, people, you know, people over 55, 65, that it can improve muscle mass and performance within I think like eight weeks and that that has overarching metabolic benefits that have, you know, in terms of biomarkers that have been associated with slowing of the aging process. So, so urolithin A, I think is definitely a supplement if among all of the supplements that should be considered if people are looking for something to take. I'm gonna repeat myself before you take urolithin A, I've said this to the chief scientific officer of the company when I was talking with him about this and I said, but you know that diet and exercise are much more. He said, yeah, yeah, yeah, of course.
- [125:05]
Andrew Huberman
Like, harder to sell.
- [125:07]
Chris Palmer
People have to do the diet and exercise and everything else, but then this could give them an advantage. And I don't deny that at all. I think it, it may very well give people an advantage. And again, the way that I think about it, it's not that diet and exercise are going to cure everybody, because they won't cure everybody. Some people are really ill. And the way that I think about that is that their mitochondria, their metabolic processes are really disrupted, they are severely dysregulated. And that a quote unquote healthy diet and good exercise and good sleep and good relationships are a phenomenal prevention strategy for some people. They can be a phenomenal treatment strategy. But I think on average that applies to people with mild to moderate mental health or metabolic health conditions that once, once people get into the severe category, severe heart failure, severe, you know, mental health condition like schizophrenia, bipolar disorder, crippling depression. My sense is just a clean diet and good sleep and good exercise is not going to be sufficient. And then we do need to start thinking about can we use this supplement or this methylene blue infusion or even neurostimulation, which is, can stimulate mitochondria and stimulate neuroplasticity.
- [126:46]
Andrew Huberman
Things like transcranial magnetic stimulation.
- [126:48]
Chris Palmer
Yes.
- [126:49]
Andrew Huberman
Which is done non invasively, right?
- [126:50]
Chris Palmer
It is non invasive. And so can we use those types of strategies to try to improve someone's mental health? And we've got plenty of evidence that, you know, especially with tms, that it can be very helpful for some people. But again, is not a panacea. None of these things are a panacea. And although I just said that none of these things are a panacea. So if you're, you know, people. One of the biggest criticisms I get is, Dr. Palmer, you have not given me the recipe to cure my crippling X disorder. And it's like, well, I, I'm trying to teach you the strategies and the science so that you can put together your own treatment plan. I am not here to sell any one thing as this is the panacea to cure all mental illness, the ketogenic diet. It can be life changing, life saving, it can be nothing short of miraculous for some people, but it is not a panacea. I've seen people do ketogenic diets and not get cured, not get remission. And so I'm always looking for what else, what else can we do? How else can we use this model to further enhance mitochondrial function, metabolic health? And the reason I think the Reason I'm getting traction is because when you come back to it, we just keep coming back to these like pillars of common sense for the most part. Yeah, like diet might actually make a difference to your brain health.
- [128:38]
Andrew Huberman
I don't think it's just Americans. I think our species needs to run up against the guardrails at the edge of the cliff six times and sadly see a good number of people go over to their demise. Before we go, wait a second, we need to think about how fast we're taking these turns. We need to pull back. I mean, there's something weird about our species that we love to develop technology and then find the destructive aspects of those technologies and pull back. And a lot of our, you know, it's like two steps forward, one step back type evolution, it seems inherent to Homo sapiens. Forgive me for getting so macroscopic here, but when you look through, there's a wonderful book, the Prince of Medicine, there's a history of medicine, Galen and like, it starts there and all the way forward and you read like the, what is it? The Emperor of all maladies about cancer and you just realize like we're stumbling forward and making miraculous progress and at the same time we are seemingly deliberately overlooking a lot of the stuff that's just obvious. It's like the old advice as we exit this conversation about supplements, the old advice that if you just eat a balanced diet, you're good, doesn't work anymore. I noticed that because quote unquote, balanced diet. First of all, no one can agree on that. And people get caught up in the vegetarian versus carnivore debates, which are really like. Or vegan versus car, which are really at the extremes. So we, we've lost our, our bearings. We're kind of like, like true north is so clear what true north is. It's mostly non processed, minimally processed foods getting adequate quality protein. You could do that vegetarian, you could do that with some animal based products if you, if you choose. It's doing that for 90% or 80% of one's nutrition. It's exercise. We know what forms are like, all the information's there, as you're pointing out. But somehow we're just going to have to keep putting it back in our faces or see enough unfortunate stuff that we, oh, wait a second, like this is time for a course correction. But hey, that's what we're trying to do here, right? And we have colleagues to do it as well. And I'll just throw in, as long as we're editorializing a lot today, I think in the last five years, the discourse around public health, from the mental health side, from the cardiology side, from the cancer side, from the longevity, has really transformed in no small part thanks to social media and podcasts. So things are evolving.
- [131:10]
Chris Palmer
Thank you, Dr. Huberman.
- [131:11]
Andrew Huberman
Well, and thank you. And thank you. Vitamin deficiencies and mental health. It almost sounds like we're headed deeper into supplements, and we might touch on that. But a few years ago, I went to a McKnight meeting and somebody presented some proteomics data where they were sequencing spinal fluid from depressed patients and finding that certain depressed patients had deficiencies in certain vitamins that could easily be replaced through supplementation. And lo and behold, their depressions were, in these particular patients were being cured, literally reversed, going into remission by virtue of taking the appropriate vitamins. But the issue was they had to use spinal taps. So it was not in order to know what these patients needed, but it was really striking. I thought, goodness, we're talking about B vitamins and depression. So could you tell us about B12 and other B vitamins and methylation and folate? There's a little cluster of topics here that I think is super interesting and that people really should know about vis a vis depression and other CNS challenges.
- [132:14]
Chris Palmer
Before I get into the complex part of the story, let me just start with basics. So, and this relates to nutrition, that a lot of these basic vitamins and minerals like vitamin B12, folate, and iron. Let me. I'll just stop there. B12, folate, and Iron, these are all essential to mitochondrial function. They play a role in numerous enzymes and other cellular reactions outside of mitochondria, but they are all central to mitochondrial function. And so if you are deficient in these vitamins, your mitochondria will not function properly. So it's. At least it doesn't prove the mitochondrial theory of neuropsychiatric disorders, but it's consistent with the mitochondrial theory. And the reality is, a lot of Americans are, you know, a lot of different populations within America and then certainly in other countries can be highly deficient in some of these. So iron. You know, there's a study in JAMA just last year, 40% of females age 12 to 21 in the United States are iron deficient.
- [133:37]
Andrew Huberman
Wow.
- [133:38]
Chris Palmer
It really depends on the definition of iron deficient. But their overarching conclusion, based on what they thought was a reasonable definition that the journal JAMA went ahead and published was 40% of young. Of girls and young women, 12. So this is menstruation, obviously, it's Menstruation. They are losing blood. They are losing blood and they are not consuming enough iron or there's something wrong with the way they're processing iron. So let me just stick with that. And what does that have to do with neuropsychiatric disorders? Well, boys and girls pre puberty have the same rates of mental illness. If anything, boys are maybe a little more. Because they're more likely to have autism and they're more likely to be diagnosed with adhd. So but for, for the most part, we'll say like depression and anxiety. Exact same rates. Puberty hits and girls just skyrocket. The rates of mental illness skyrocket in girls. Now, are there psychological and social causes of that? Yes. We can talk about you're becoming an attractive sexual mate and maybe people are, you know, being mean to you or people are, you know, making you uncomfortable or you are becoming a victim of sexual trauma. Do those things happen? Of course those things are happening. Could that contribute to depression and anxiety? Of course that could contribute to depression and anxiety. Again, it's not either or. So, yes, let's stay with the psychological and social causes, but let's also go into the biological causes. If these girls and women are now iron deficient, that affects their brain function, it affects their whole body health. Most people don't think of that as a metabolic problem, but I do. These girls and women can be thin. They can be absolutely beautiful and thin and iron deficient. And that means they've got a metabolic mitochondrial problem that could be affecting their brain and that could be playing a role in their depression, anxiety, their, you know, eating disorder or whatever else they've got. Vitamin B12, folate. We know that low levels of those vitamins are associated with all sorts of neuropsychiatric disorders. B12 deficiency, for example, is very common among vegetarians and vegans. In India, for example, where most people are vegetarian or vegan, 50%, 5 0% of their population is B12 deficient.
- [136:32]
Whoa.
- [136:32]
Andrew Huberman
What are some food sources of B12? Is it. Would.
- [136:35]
Chris Palmer
Is animal sources red? Red meat, basically, animal source foods, again, eggs, red meat, other types of meat. Yeah. Be it you need animal source foods for the most part, or if you're going to be a vegan or vegetarian, please take appropriate supplementation. You can get this in a vitamin, but please make sure you're doing it correctly and maybe get your levels measured every now and then. At least once a year, your annual physical, make sure that your doctor knows I'm vegan. Please do a full assessment of vitamin and nutrient levels for me because I am at a high risk. So B12 is impacted by other medications, B12 absorption. And interestingly, oral contraceptives can reduce absorption of or impair absorption of vitamin B12.
- [137:28]
Andrew Huberman
Interesting.
- [137:29]
Chris Palmer
Metformin can impair absorption of vitamin B12. So just picture a woman who's overweight, who's following a vegetarian or vegan diet, who's also on metformin for her diabetes, who's also on birth control just because she's at very high risk of being B12 deficient. And what does B12 deficiency do in terms of neuropsychiatric disorders? Everything. It has been associated with higher rates of depression, anxiety, psychosis, bipolar symptoms. But people can be hallucinating and delusional from B12 deficiency. And the challenge with B12 deficiency is that the neurological damage can become permanent. So if this is not recognized and identified early enough, people can be permanently injured. So that's the simple story. Some people just aren't consuming enough or they're taking metformin or they're taking oral contraceptives or whatever. They're menstruating, and they haven't really figured out an appropriate diet to compensate for the loss of blood. So all of those things can interfere with vitamin absorption or whatever and can result in neuropsychiatric symptoms. Unfortunately, this story gets a lot more complicated. So we've long known that there's an autoimmune form of vitamin B12 deficiency called pernicious anemia, in which antibodies to something called intrinsic factor prevent vitamin B12 from being absorbed in the digestive tract. So you could be eating all the meat in the world, you can't absorb it, and you can become B12 deficient. That autoimmune disorder increases with age. So you could have been living, living a happy, healthy life. And then at age 65, you develop pernicious anemia. You can no longer absorb B12. And this is actually one of the treatable forms of dementia that we know of. The cardinal symptoms are look like dementia. And the only way to help these people is if some astute healthcare clinician measures a B12 level, identifies and recognizes the problem, and then does further testing for pernicious anemia, this autoimmune form of B12 deficiency. And then you correct it, and the treatment is vitamin B12 injections. Taking a pill won't work because you can't absorb it. So you've just got to inject people with vitamin B12 and it can restore everything for most people.
- [140:19]
Andrew Huberman
Will a B12 oral supplement work like a methylate B12 capsule.
- [140:24]
Chris Palmer
As long as they don't have this autoimmune form, yes. Okay, it'll be fine. And again, if you're eating lots of meat, you may not need any supplement at all. So over the last year, there have been a couple of publications that have just come out that have now recognized a brand new form of autoimmune B12 deficiency. And it targets a protein called CD320, which transports vitamin B12 across the blood brain barrier. The researchers essentially identified this and people in people who are having pretty severe neuropsychiatric symptoms. So symptoms of either neurological disorders or other kinds of disorders, but mostly focusing on neurology because it's neurologists who have been doing all this work. When they first identified this antibody, they took blood from these people's veins, just like you would if you were going into a doctor for blood draw. The B12 levels are normal. Everything's normal in the periphery because the person may be consuming enough B12 and it may be getting absorbed fine. So they're not anemic. They show no signs of B12 deficiency. But when the researchers tested their cerebrospinal fluid, they had almost no B12 in their central nervous system.
- [141:59]
Andrew Huberman
So that requires a spinal tap, right?
- [142:01]
Chris Palmer
This is not in order to diagnose it. It required a spinal tap. And they ended up treating some of these people with immunosuppressive agents to reduce this autoimmune condition and high dose vitamin B12. And some of the people had reversal of symptoms, meaning their neuropsychiatric symptoms went away. The research is still in preliminary stages, but the researchers have looked at how common is this? Because at first glance it sounds like, well, that's just a really rare condition that can't be relevant to human health. They sampled just a general healthy control and about 6% of those people had this antibody.
- [142:51]
Andrew Huberman
Wow, it's really high.
- [142:52]
Chris Palmer
They then sampled people with neuropsychiatric lupus. So these are people who have an autoimmune disorder already lupus, and they have neuropsychiatric symptoms. 20% of them had this antibody. And then they just recently. This is unpublished data, but they have looked at people who have a demyelinating condition of unknown etiology. And about 50% of them had this ant 5, 0%.
- [143:27]
Andrew Huberman
So this is like an Ms. Like.
- [143:28]
Chris Palmer
Condition, had this antibody.
- [143:30]
Andrew Huberman
And what's the solution? B12.
- [143:32]
Chris Palmer
The reason this is of interest to me and we're hoping to do some research on this in patients with psychiatric disorders. Is because there is a treatment, immune suppressive kind of treatments to either reduce this autoimmune condition and, or high dose vitamin B12 injections. So you want to flood their system with vitamin B12 so that some of it can get across the blood brain barrier.
- [144:02]
Andrew Huberman
And again, oral B12 won't work in this case. Right?
- [144:05]
Chris Palmer
Oral B12 may very well work in that case. But I would actually, I mean, in these situations, what we know is that these people's brains are being damaged from severe B12 deficiency. So I would probably just go for the definitive massive injection and try to try to rescue those brain cells.
- [144:29]
Andrew Huberman
This is very interesting. I think people should get their B12 levels measured. A standard blood test, right?
- [144:36]
Chris Palmer
It is unfortunately for this new autoimmune central B12 deficiency. They're working on a commercial test, but you can't get this, this blood test right now. Okay, so perhaps to come. Stay tuned. But I guess the point of it is this, that I think for the majority of people, 60 to 80% of people who are suffering from neuropsychiatric disorders, I actually think using interventions that are easily available today will help them heal and recover. I really believe that I, I stand nothing, I don't get any money from lifestyle interventions. I don't get a commission for everybody who does a ketogenic diet.
- [145:19]
Andrew Huberman
In theory you'd have fewer patients to treat. In theory, you lose money because you have fewer patients to treat.
- [145:24]
Chris Palmer
Money by, by getting people better and then they move on and don't need me anymore. I honestly believe that. But I also believe there will be 20%, maybe up to 40%, who have severe disorders for whom those strategies just won't work. And so I'm really interested in, well, what else could it be? And this is just one of many examples of what else it could be. They could have an autoimmune form of central B12 deficiency. And why does that matter? Because we can test for that and if they have that, we can treat it. There's a clear, unequivocal treatment. And you know, at the end of the day, I think one of the biggest themes of my work is that right now in the mental health field, we assign these diagnostic labels to people and for many of them they become life sentences. You have schizophrenia, that's a lifetime sentence. It's probably never going to get better. You certainly always have to take medicines for the rest of your life. You have bipolar disorder, it's for life. You have chronic depression, sorry, we just don't know how to treat it. Depression should Go away. But it's not going away for you. We don't know what to do. Sorry. So sorry. I know that, you know, on the surface it may sound like, well, those are just rare people, Chris. They're not rare people. Hundreds of millions of people on our planet are given these life sentences and we assume that we now know the cause. The cause is you have schizophrenia. That's the cause. And in fact, schizophrenia is only a label of symptoms. Schizophrenia means a person who has chronic psychotic symptoms of unknown etiology. Of unknown etiology. Because if we know the etiology, you don't call them schizophrenic anymore. You say they have vitamin B12 deficiency and psychosis, or you say they have an autoimmune disorder like lupus and psychosis. And why is, why is that so important? Because there's a treatment for these other things other than just antipsychotic medicines. And what I really hope and implore our field will do is we will come into the 21st century and begin to recognize that there is a cause of schizophrenia, there is a cause of bipolar symptoms, there is a cause for chronic depression, and that we will begin to look for those causes and we will begin to treat those causes. As opposed to just putting people on antipsychotics or antidepressants or mood stabilizers and telling them, well, we're really sorry. We know these medicines don't cure your illness. We know these are not disease modifying treatments. We're really sorry we can't do better. You're just going to have to suffer for life like, we can do better.
- [148:48]
Andrew Huberman
And I applaud your efforts to bring about that change. I mean, I think people realizing that often, not always, but often mitochondrial dysfunction is at the heart of these things is critical. Speaking of which, I have to ask, and feel free to pass on this question if you like, but. But I've become very interested in vaccine biology and the debate about vaccines, about the adjuvants that are used to deliver the vaccines. Obviously, it's a very contentious topic. I just want to know, without being, I'm not trying to be provocative here. Is there any evidence that vaccines, or the adjuvants for vaccines or anything about vaccines in their delivery can disrupt mitochondrial function? You know, so often we think that it's like the vaccine having a specific effect on what the vaccine was designed to target that could potentially cause side effects or something like that. That's what many of the theories hold, but given the key role of mitochondria in all aspects of brain functioning, and given that some people are convinced, I'm not saying I believe this, but are convinced that vaccines are tied to these mental health challenges or to autism. Let's be direct about this. Is there any evidence that vaccines can, of any kind, can disrupt mitochondrial function or support mitochondrial function for that matter?
- [150:15]
Chris Palmer
It is a contentious.
- [150:18]
Andrew Huberman
Maybe it's a different.
- [150:19]
Chris Palmer
No, no, no, no, no, no. And I definitely, I'm definitely going to answer it, but I'm going to give a long winded answer if that's okay. Because. Because I want, I want to give credible information.
- [150:27]
Andrew Huberman
Yeah.
- [150:27]
Chris Palmer
And I don't.
- [150:28]
It's the only information we're interested in.
- [150:29]
And I don't want to come down on one side that vaccines are 100% safe. There's no question passionate about it or yes, vaccines cause autism and that's why we've got skyrocketing rates of autism, because I don't think either of those extreme positions is true. So I want to first back up and just ask a slightly different question. Is there any evidence that high levels of inflammation impair mitochondrial function? The answer to that is unequivocally, yes. High levels of inflammation, inflammatory cytokines like, like TNF alpha, interleukin 6 and others impair mitochondrial function. We know that it is clear and unequivocal and there are physiological reasons for it. The organism has to adapt. So when you have the flu, do you have neuropsychiatric symptoms? Yes, you do. You're going to feel exhausted, you're going to be less risk taking. You are not going to want to reproduce. More than likely you're going to completely lose your libido, completely lose it. Like zero interest. And what are you going to want to do? You're going to want to hide in bed and pull the covers over you and just retreat from the world for safety. Those are all effects on your mood, your motivation, rewarding behaviors, all sorts of things. The inflammation, the infection is doing that to you. And we know that it's inflammation because this happens with cancer. It happens with treatments that cause inflammation. If we give treatments that cause high levels of inflammation, people experience these symptoms acutely. If we give interferon, for example, which can be a treatment for some disorders, people will acutely develop all of these symptoms. So we know that interferon itself will produce all of these neuropsychiatric symptoms. We also know from basic cell biology interferon interferes with mitochondrial function. We know that it is unequivocal. Now let's go to autism. Is there any evidence that inflammation can lead to autism. We have decades of evidence for this. We know that over the course of the last century, as there were kind of outbreaks of bacterial or viral infections in the population, we saw higher rates of neuropsychiatric neurodevelopmental disorders in the offspring of the pregnant women. So we've long known that, and that evidence is pretty well established.
- [153:31]
Andrew Huberman
For instance, forgive me, but the one that I'm aware of is that flu in pregnant mothers at the first to second trimester transition is correlated with statistically higher incidence of schizophrenia in the offspring. Do I have that right?
- [153:47]
Chris Palmer
That's correct.
- [153:48]
Andrew Huberman
Okay.
- [153:49]
Chris Palmer
But then there was a rubella outbreak that resulted in much higher rates of autism in the offspring. I think that was in the 1960s. And now we have really decades of animal models. So they take mice and they inject them with lipopolysaccharide, which causes an inflammatory reaction. And when they do this to pregnant mice, the mice that are born to those women, those female mice are at much higher risk for showing signs or symptoms of what looks like a neurodevelopmental disorder. It different diagnosing or whatever. A neurodevelopmental condition in a mouse, is it 100%? No, it's just we increase the risk. So if you inject a pregnant mouse with lipopolysaccharide, can she. Can that mouse still have a normal appearing mouse? Yes, but can't. But the probability that the offspring will have a neurodevelopmental. Symptoms of a neurodevelopmental condition increase. That is where so much of the autism research has been focused, is trying to understand this, trying to understand what is happening with inflammation. How does that impact neurodevelopment? We know that. So now back to the question that you posed. Is there any possibility that vaccines could contribute to that process? Do vaccines increase inflammation? I think the answer to that is yes. Is there variation in the inflammatory response between different people? I think the answer to that is yes. Can some people have a hyperexaggerated inflammatory response in response to a vaccine? I think the answer to that is yes in that condition. So in that rare, less common condition where somebody is having a hyperexaggerated inflammatory response to a vaccination, could that impact neurodevelopment? The science right now says yes. We have no reason to think it wouldn't. There's one case of a young child who already had an existing mitochondrial disorder. It was already known she got vaccines. And I think within days or weeks of getting the vaccinations she developed profound neurodevelopmental symptoms. That case won a lawsuit that went to court. It was tried in court and she won. And the court ruled that the vaccine did in fact contribute to this girl's neurodevelopmental condition. Now, they assumed it was because she had a pre existing mitochondrial disorder. And I would support that. It lines up perfectly with what I've been talking about all along, that people who have vulnerabilities with mitochondria or metabolism, you can only absorb so many hits. And when you get that final hit, that tips kind of the balance to impact neurodevelopment, you can get that when? Now coming back to the bigger question. So should people get vaccinated or not? We do have reasonably good evidence that unvaccinated people are more likely to develop autism than vaccinated people.
- [158:17]
Andrew Huberman
Is that right?
- [158:18]
Chris Palmer
The problem with that study is that it's a retrospective cohort, epidemiological study. And the biggest critique that I have of that type of research is that the researchers decide what they control for and what they don't control for. But the existing research, right now, as published and as designed, suggests that if you don't get a vaccine, you're more likely to develop autism than if you do get a vaccine. And how would I understand that? I just talked about infections themselves can cause neurodevelopmental disorders. So if a child gets measles, they're not only at risk of dying of measles, they're also at risk of impacting their mitochondrial function and developing a neurodevelopmental disorder as a result of getting a severe infection.
- [159:17]
Andrew Huberman
Assuming there's choice, there's a risk benefit analysis. Do you want the potential inflammation from the vaccine or lack of inflammation? You run the gamble. It's hard to predict who's going to have a big inflammatory response and who's not. Although I'm thinking in the back of my mind about these lifestyle factors, even though it's a young child or a, or an adolescent in some cases, but young children, typically there are things that you can do to bolster the health of that kid going into a vaccine. If you're choosing to vaccinate your kids, right, like proper sleep, proper nutrition, proper everything, you wouldn't want them even slightly sleep deprived because that would increase the risk of inflammation, right? I mean, these things compound, as I understand it. So I think what most all parents really want is a sense of control over what are inevitably a mixture of controllable and uncontrollable Factors. And this is what I hear when I really listen to this debate about vaccines. I hear my science colleagues inevitably saying, okay, the Wakefield data were bs, et cetera. Like, no, no, no, there's no possibility. And then I hear parents who are having kids, whose kids are due for vaccines, and they're like, I don't know what to do. They're terrified. And these are smart people, and they don't know what to believe anymore. That's the challenge.
- [160:42]
Chris Palmer
I mean, the science that I just laid out is true. It's clear. And again, we've got decades of research to support most of what I've just said. All of what I've just said. I think if you understand the biology, when a child begins to show symptoms of a neurodevelopmental disorder, instead of assigning a label, this is autism. It's a life sentence. Good luck, we should be intervening. And what could we do to intervene? What you just said, in terms of prevention strategies? Absolutely. Let's make sure that even before you're going to the doctor, even before you're exposing yourself to any of these vaccines, that you're healthy. Why? Because we want you to be healthy. Why wouldn't you want to be healthy? So let's just be healthy. But I would actually go much further and say as soon as a child begins to show signs or symptoms, especially when it's an abrupt change when they were developing in a neurotypical way, and then all of a sudden they got an infection or they got a vaccine or something happened, and now they are falling off the trajectory. And that's what we hear from these parents who are saying, no, this is real. That's why they believe vaccines cause it. Do I think it was just the vaccine on its own? I suspect a lot of them have had other hits. They probably had other vulnerabilities going into that vaccination, and that the vaccination. If we even entertain the possibility that that vaccine did contribute to their autism, I'm doubtful that it was the sole only cause. I'm doubtful that it was the sole cause. But regardless, once the kid starts showing signs or symptoms, we should be doing a full workup. We should be looking for vitamin and nutrient deficiencies. We should be looking for this central B12 deficiency. Did the vaccine somehow cause an autoimmune reaction to CD320 so that now this kid has central B12 deficiency and that is why this kid is falling off the chart? Should we entertain a ketogenic diet for this child? I would say yes, we should that should be on the table of options. We might want to put this child on a ketogenic diet. Does that ever happen? It happens all the time in kids with epilepsy. So why not do it for neurodevelopmental conditions? But again, it's not just keto diet is gonna save the day. And we don't have to think about Central B12 deficiency or any of these other things. Like, let's put it all together, and especially with AI, now we can do this. This is a solvable puzzle. It is a complex puzzle, no doubt, but it is a solvable puzzle and we should start to solve it. But right now, the state of the field is that we assign a label autism, and we tell the parents to just prepare for a disabled child. Just prepare yourself to take care of a disabled child for life. We're really sorry, we don't have anything more to offer. We can do some ABA training, we can do some basic, you know, we'll try to teach them some social skills. The real outcome data on that is pretty bad. If your brain's not working right, it's hard to teach people how to do the skills that the brain is designed to do. And that's the challenge, is that it's all well and good to recognize a problem, but now we need to come up with effective treatments. And we know that a lot of the, you know, people talk about early intervention with autism as though early intervention is going to save the day. I don't mean to bash the people doing that work. Let's do anything we can. It might help a little, but when you look at the outcome data, it's not helping much. And when you look at the statistics of the prevalence of autism, it's going through the roof. So those strategies are just not working. They're not working for prevention, they're not working to improve long term outcomes. They're not. I mean, we have a lot of work to do.
- [165:30]
Andrew Huberman
So I appreciate the thoroughness of your answer. I can promise you that anything we put out about that will include the full context. We're not, we're not.
- [165:41]
Chris Palmer
People will take the sound bite and.
- [165:42]
Andrew Huberman
Yeah, well, if they do, I'm gonna get, I'm gonna get rabid by posting the preamble because it's very important that people hear the full context. And I really appreciate you embracing that topic with the depth and rigor and sensitivity also that you do, because I don't think we can duck this vaccine question anymore. I never thought in my lifetime that vaccines would be a thing it's like when I was a kid, everyone got the polio vaccine, the measles vaccine, and kind of went about our way. I do understand the number of vaccines that kids are getting now. Like, the vaccine schedule has expanded. Yeah. I've been kind of thrown into the middle of this as different guests have come on this podcast who've said they do get the flu vaccine, others who say they don't. And, you know, gosh, if ever there was a separator besides Democrat versus Republican, it's this vaccine thing. It's really like v. Separator. It's so closely tied to believes in science, doesn't believe in science. Those are the stereotypes. Right. Or suspicious of science, NIH and cdc. Or believes in science, NIH and the CDC wholeheartedly. Like, the divide is very stark. And this needs to stop. Like, the divide needs to stop. We need to start filling in with answers. And I think there's soon to be a exploration, a scientific exploration of the relationship between vaccines and autism. I read this someplace on X, which means. But I think that's the idea. And I think some people are kind of upset that this, that resources were going to be devoted to this because they felt like it was. It was a done deal. And then others are very excited because they feel like, hey, listen, if. If you don't think there's a link, then here's an opportunity to, to establish that with. With real rigor. And I think everyone's just really interested in the studies being done properly. Look, I think more data is always great.
- [167:41]
Chris Palmer
I don't disagree. I've. And I've. I've actually talked to some former NIMH directors about this and some other leading people in this field, and there's no doubt that this topic has been brought up multiple times at the nih. So there's this interagency coordinating committee on autism within. Among all of the NIH kind of centers and institutes that's existed for decades. They have looked into this issue. I've talked to some autism advocates who've said, like, I was hoping that vaccines might. Might be the cause. Like, I was really hoping to see that vaccines are the cause because that would then give us a cause and it would lead us to interventions to make vaccines safer or whatever. And she said, but it's just not there. It's just not there. And this former NIMH director that I spoke with, it's just not there, Chris. It's not there. We looked. We looked high and low. Again, I'm not sure that everybody Looked with the same degree of scrutiny again. The study that I saw looked at people who are unvaccinated by choice. So these are rebellious people who are defying state laws, who are risking not getting their children into schools because they're not getting vaccinations. That's the cohort of unvaccinated people. And then they're comparing them to the cohort of vaccinated people and they only controlled for like two or three variables. They did not control for obesity, they didn't control for diabetes. And we know that obesity and diabetes play a role in risk for autism. And we know that people who have existing health conditions might actually be more likely to be worried about vaccines and then not get vaccines. Perfectly happy, healthy, thriving people usually just go along with status quo. They usually don't refuse vaccines. So people who are refusing vaccines probably had some pre existing health condition. They didn't control for that. Did that pre existing health condition increase risk for autism? Probably.
- [170:23]
Andrew Huberman
Well, if there's an inflammation link, then yes.
- [170:25]
Chris Palmer
Like, like, probably. I mean, you look at any pre existing health condition and does it increase risk for other health conditions? Usually the answer is yes. Yes. So we know that like women with obesity, much more likely, twice as likely to have an autistic child, is that right? Yeah. Meta analysis, over 3 million people, women with obesity have double the risk of having an autistic child. Have rates of obesity been skyrocketing in our population? The answer is yes. Are pregnant women also in that camp of obese women? Yes. Well, that accounts for a doubling of autism. Same deal with diabetes. Women who have diabetes twice as likely to have autistic children as women who don't have diabetes. When you put the two together, obese and diabetic, quadruple the rate of autism in the offspring.
- [171:24]
Andrew Huberman
What about dad? You know, there are these theories about the statistically significant increases in rates of autism for offspring of men who are 50 or older. My read of the data is that it's still a very small increase. It's not like the kind of increases you're describing here for diabetes.
- [171:44]
Chris Palmer
It is so men with obesity twice as likely to have an autistic child as men who are not obese, which.
- [171:51]
Andrew Huberman
Is, which is something like 25 times greater than the increase due to age of the male. So this is so important because people hear, oh, you know, older sperm equals higher probability of autism. But yes, still a very low probability of autism compared to dad is obese, but in his 20s or 30s.
- [172:12]
Chris Palmer
Yes.
- [172:13]
And so, you know, a lot of people are Hyper focused on vaccines cause autism and they come back to rates of autism are skyrocketing. There has to be a reason. Well, I agree. Rates of autism are skyrocketing. I agree there does have to be a reason. Maybe we're missing the elephant in the room. Rates of metabolic poor health are skyrocketing in our population. Rates of obesity and diabetes are skyrocketing. But rates of poor metabolic health. So metabolic syndrome has five biomarkers. You know, abdominal obesity, blood pressure, glucose, high levels of glucose, and then high triglycerides and low HDL cholesterol. Those are the five biomarkers of metabolic syndrome. Only 7% of Americans are healthy in all five biomarkers.
- [173:12]
Andrew Huberman
Yikes.
- [173:13]
Chris Palmer
Only 7%. Poor metabolic health influences neurodevelopment and offspring. We know that. So we see skyrocketing rates of autism. It's not just autism. We see skyrocketing rates of ADHD as well, simultaneously. And everybody's scratching their heads trying to figure out where's all this autism coming from? Where is all this ADHD coming from? Well, look around, people. As the metabolic health of the United States population declines, we are going to see more neurodevelopmental disorders.
- [173:55]
Andrew Huberman
Such a critical message, but also reassuring in the sense that we can do something about it.
- [174:02]
Chris Palmer
We can.
- [174:03]
Andrew Huberman
Yeah, because what you're talking about is metabolic dysfunction, mitochondrial dysfunction of the parents. Right. So, you know, trying to control the, the behavior of still unborn or yet to be conceived children is pretty tough to do. And, and yet anyone thinking of conceiving should really pay close attention to their metabolic health is clearly the message. I think obesity becomes a little bit of a, of a, of a critical factor, yet a distractor. That wasn't meant to rhyme for when we hear metabolic health, I think a number of people hearing this will say, well, I'm not overweight, so my mitochondria are probably healthy. But what you listed off included high triglycerides. You said blood pressure, which, you know, there's some thin people or, you know, non apparently obese people. I say apparently obese because a lot of people are carrying a higher body fat percentage than they realize, even though they're, they're not, you know, taking up a lot of space. So I think, you know, it's not always and low hdl. So sometimes, you know, we're shocked to see, like, oh, this person is like, apparently healthy, but has, you know, low HDL and has got their apobs through the roof and they're, they're not well, but Just because they're not obese doesn't mean they're metabolically healthy, correct?
- [175:31]
Chris Palmer
That is absolutely correct. And I go back to some of our prior conversation. So a 14 year old girl who is severely iron deficient is metabolically unhealthy. Why? Because her mitochondria can't function properly without iron. She can be thin, she can otherwise look like a healthy attractive girl, but she can be metabolically unhealthy because she doesn't have all of the essential vitamins and nutrients that she needs to have properly functioning mitochondria and metabolism. And why would that matter? It matters because she might develop an anxiety disorder or she might develop depression, or she might develop symptoms of an eating disorder and then we're all scratching our heads, giving those labels, oh, you've got depression, you've got anxiety, you need Prozac, and maybe she really needs iron.
- [176:38]
Andrew Huberman
Right? I mean, what I realized and, and this was really where I wanted to bring us to, is a question for you. I have an idea, but let's also pose the question as an idea and feel free to bat it down. I'm beginning to think that in order to get out of this health rut that we're in, that clearly relates to mitochondrial dysfunction and at the same time there are tools, the lifestyle tools that you described. Yes, there are supplements and maybe methylene blue will be advantageous and methyl A B12 perhaps, but certainly the lifestyle factors. Most people, again, when they hear metabolic health, they just think, okay, metabolism, obesity, thinness or fatness and it sort of becomes a gravitational pull towards that. Do you think it's possible to create a metric? I don't want to say BMI as an example because that's controversial for some people. But is it possible to create a metric of all around metabolic health that would be incentivized so that people can live better lives, their offspring can be healthier as well and we can unburden the healthcare system and potentially avoid millions and millions of people having these so called incurable mental health disorders in air quotes.
- [177:55]
Chris Palmer
You know, what you're describing is kind of in my mind a really important next step. And the great news is that there are, are several research groups that I know of that are working on exactly that. One is a commercial company, I'm not going to name any names, but one is a commercial company that has a product of a series of biomarkers, blood biomarkers, that they believe represent ultimately mitochondrial dysfunction. All of the different cellular pathways that can result in mitochondrial dysfunction and, or can reflect mitochondrial dysfunction. And they believe that their test might be able to predict the development of autism, that every child at age one should get this blood biomarker and it will tell us who's at high risk of developing a neurodevelopmental disorder. The test itself doesn't tell us what's wrong, it just tells us something's wrong. And then the clinicians need to go to work and try to figure out what is going on, what is causing this metabolic mitochondrial dysregulation so that we could potentially intervene. I've talked with one of the leading mitochondrial researchers really in the world. He's got a set of 20 biomarkers that he believes represent mitochondrial dysfunction broadly. And then there's another research group that is, has actually narrowed it down to just five different biomarkers in men and five slightly different. There's some overlap, but slight differences in women. And those five biomarkers alone were able to distinguish people with chronic severe suicidal depression from healthy controls with over 90% sensitivity and specificity.
- [179:49]
Andrew Huberman
Wow.
- [179:50]
Chris Palmer
So I think that is one of the directions we need to go, is we need to establish tests with all of these groups. I want to just state clearly and plainly, because one of the common questions I get is what's the blood test I can get for my mitochondrial health? There isn't one. That's the answer. There is not one. There are lots of different biomarkers that can suggest dysregulation of metabolism and mitochondrial function. And again, these three research groups are all working on it. You know, in order to get those five biomarkers for men and women, they, I think they measured 400 different biomarkers. So we need to make sure that that gets replicated, that it's, you know, prospectively, it can identify people. I'm, I'm less concerned about kind of the incentivizing and let's give insurance discounts and other things. I actually think the majority of human beings that I know authentically want to be healthy and they authentically, they really want to have healthy children. They will do anything to have healthy children. So I don't think we necessarily need to come up with some incentives right now. I think if we develop evidence based tools that prospective parents can use to assess their own metabolic mitochondrial health and more and maybe, maybe more importantly, assess their prospective children's health and then we pair that with evidence based strategies to help them improve their metabolic health so that it will improve the outcomes for those children. I mean, that's the holy grail, what I just said. Probably represents decades of research. The sooner we get started, the better. And some of it's already underway, as I've mentioned. So it's not like we start from ground zero. People have been on this trail for a while, so. But it is going to require a concerted effort. It's going to require massive NIH funding to support that type of research. We have a new administration that is talking about massive disruption in the way things are done. They're talking about massive changes at the nih. I am really hoping and praying that we're going to see that type of research as opposed to the current model of research which focuses on, well, here's your diagnosis, schizophrenia or hypertension. And what, what new pills can we develop to treat this condition or how can we understand this condition? Like, I, I think we have enough evidence to be able to really start with more effective, to be able to really aggressively pursue more effective treatment and prevention strategies.
- [183:00]
Andrew Huberman
Fantastic. What role do you see yourself in going forward? I mean, clearly public education about these issues related to metabolic and mitochondrial health is a wonderful home for you. In addition to all your clinical work and everything else, you're doing this, you're clearly very passionate about it. If I may ask, do you have plans to get involved in helping the new nih, new health and human services folks steer in the right direction?
- [183:31]
Chris Palmer
I am more than happy to serve as a consultant if asked. And I have had some conversations with a wide range of people. So I'm more than happy to do my part. I think for the immediate future, honestly, I'm focused on some of these lines of research through McLean Hospital and Harvard Medical School. I'm really aggressively working on setting up a healthcare system practice to start where we will treat people with these severe chronic mental health health conditions. That I started a wait list about a year ago and I have over 5,300 people on my waiting list. I can't treat 5,300 people, but I have the privilege of a lot of brilliant clinicians are reaching out, wanting to work with me. What I'm hoping to do is to put into practice, into real world practice everything that we've talked about and more with real human beings to demonstrate. This really does work. It really does work. And I've been doing this work as a solo clinician for 30 years now. And I welcome the opportunity to begin to develop protocols and processes and use artificial intelligence to really try to create algorithms. If we can do that, then, yeah, we hold the potential to help millions, if not billions of people. And, and I, you know, the theory is great and I'm really a big fan of the theory. I it, it continues to line up new evidence. Since I've published the book, new evidence has come out just completely supporting it and if anything bolstering it, putting it into actual clinical practice is really where the rubber meets road. And as we've just talked about, there are so many things we can do for people who are suffering today. And I'm probably, it's not even probably. I'm most excited about that. I'm most excited about training other clinicians and demonstrating for the world that this really works, that people can get better from severe treatment resistant mental illnesses.
- [186:16]
Andrew Huberman
Fantastic. Well, I and everyone else are super grateful for your real enthusiasm and like clear devotion to that last statement. And you know, I'll finish today's discussion with where we started, which is to say thank you for being such a pioneer for this clearly new direction for mental health and for bridging the gap between mental health and physical health and clarifying for all of us today what you mean, what people mean when they say metabolic health. We really have to think about mitochondria, what they do, the many, many roles they play in cells and are everywhere in the body and the paths to improving mitochondrial health, lifestyle supplement, in some cases drug based and the preventative care that we can take. Especially for people that are thinking of conceiving children to get their metabolic health right, but also of children regardless of age and also for your public health work. I mean you really put yourself out there. You were willing to embrace this vaccine question and did it with incredible care to all sides and at the same time staying really close to the data in hand and offering new questions. So that just is emblematic of everything you do, Chris. And it's such a pleasure and an honor to have you back again. And if people want to reach you, we'll provide portals for that. I know there's a lot of outreach toward you. I really also appreciate seeing you on social media, on X and on Instagram. It is really important that people hear from you. And then what's lovely also is that as new studies come out that agree or disagree with some of the things that have been said today, you're always one to put those out there and address considerations and get people excited but appropriately excited or cautious but appropriately cautious. So, so thanks for everything you're doing far too much to list again right now. Hope to have you back again because the progress is happening so rapidly. In the meantime, thanks for this incredible voyage and education for Me and everyone listening. You're doing God's work. Thank you.
- [188:28]
Chris Palmer
Thank you, Andrew. And thank you for doing everything you're doing. You're also doing God's work and I know that. Yeah. What you do is not always easy. And trying to give actual practical protocols, so to speak, is really important. And you're probably doing more for the mental health field. I don't know. I'm struggling to think of who's doing more for the mental health field in the mental health of millions of people around the world than you. Right now. I'm hard pressed to think of someone.
- [189:07]
Andrew Huberman
It's a collective effort, folks like you and the people that come on here, you know. So I consider you a colleague and a comrade, for lack of a better word. We had a Russian on here recently, so comrade in that effort. Yeah, thanks. I know how much you care and I care too. So thanks for those words.
- [189:26]
Chris Palmer
Thank you.
- [189:27]
Thank you for joining me for Today's discussion with Dr. Chris Palmer. To learn more about Dr. Palmer's work, including his research and his clinical practice, and his absolutely spectacular book, Brain Energy.
- [189:37]
Andrew Huberman
Please see the show Note Captions if.
- [189:39]
Chris Palmer
You'Re learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five star review and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcasts or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comment section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols An Operating Manual for the Human Body. This is a book that I've been working on for more than five years and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course I provide the scientific substantiation for the protocols that are included. The book is now available by pre sale@protographsbook.com there you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols, an operating manual for the human body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms. So that's Instagram, X threads, Facebook and LinkedIn. And on all those platforms I discuss science and science related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast. Again, it's Huberman Lab on all social media platforms and if you haven't already subscribed to our Neural Network Newsletter. The Neural Network Newsletter is a zero cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one to three page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You Simply go to hubermanlab.com, go to the menu tab in the top right corner, scroll down to newsletter and enter your email. And I should emphasize that we do not share your email with anybody. Thank you for joining me for Today's discussion with Dr. Chris Palmer. And last but certainly not least, thank you for your interest in science.