Transform Your Mental Health With Diet & Lifestyle | Dr. Chris Palmer

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33:53Again that's 8sleep .com slash Huberman to save up to $350 off your Pod 4 Ultra. 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 mitochondrial 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?

34:32Is there, you know, these days, why are you about your Othenei? Because I'm a little bit of an adventure these days, I, and I'm turning 50 later this year, I decided to experiment with a peptide that is SR -31, which is specifically to improve monocondrial function. I'm doing this with the full understanding. It may do nothing or make you me. I don't know. But I will find out. But someone had to do it. And 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, etc. Because a lot of people, some people out there are more in the mode of trying to do a bunch of things.

35:11And I don't think that's as helpful to me. It's as also just not in, not in keeping with my nature. Massage is one variable. That is great. That's right. A 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 we can do this. 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.

35:53Like 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 producing 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.

36:47So those are the six pillars. Unfortunately, this is where the clichés 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 thing will be fine. If you just add a couple of servings of blueberries a week, you'll improve your health, brain food. And that it 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.

37:33Should 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 It 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.

38:23They don't look all that different yet. They can run sometimes a hundred miles. And what makes their muscles different than my muscles? Cause I can't run 100 miles. Me either. Um, 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 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 more thorough assessment of ATP capacity, their muscles or their mitochondria would be much healthier than mine.

39:09Their 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. I've been mourning while you're while you're at it. Sounds like a good idea.

39:32The substance use is obvious. It's the thing you've been talking about. I've been talking about it. What substance is 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, an 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. It took a lot of stimulants, cocaine and emphetamine in particular.

40:15Musicians that did that in the 70s and 80s and 90s seem 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? 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?

41:10Dopamine, 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 or imaging data, clinical research studies, documenting that appropriate doses of stimulants, so that's usually low -ish doses, can improve brain metabolism. And what that means is that they're actually stimulating mitochondria to produce more ATP. However, metabolism is all about balance. You can underdo it and you can overdo it.

42:02And when you overdo it, What happens is that if you hyperstimulate 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?

42:47I 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 it 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.

43:41It increases the activity of that target cell. So stimulants are one back to this bigger kind of lifestyle, medicine picture. Stimulus are definitely one, high -dose stimulants very harmful to human health. What are some other 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.

44:27Interesting. 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. Yeah. 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 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.

45:17And I wondered, like, what's that about? Like how? That's how I know this 1960 store and everything else is, because researchers have 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, so not nicotine per se. Do we know if nicotine is depleting mitochondria? Nicotine is a stimulant for mitochondria. So again, similar story.

46:04low doses can be great. High doses may in fact be toxic. Oh good. You've got to get you got to you got to find the right balance. 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 two milligrams to four milligrams which is very low dose. A couple 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 interesting stimulant because it relaxes you a little bit too.

46:47But I wouldn't want kids to start doing this. There are people in their 20s or 30s. Like I said, I'm approaching the fifth floor. I'm gonna be 50 in September. And I wanna do everything I can to hold on to the neurons I've got. So I think low level stimulation of perhaps might have contraed, and other, certainly the state of calling system with nicotine is good idea. But what I see is a lot of people who are taking these pouches that range from anywhere from three milligrams on the low and dose side all the way up to eight 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.

47:23So even the cost starts to be a big deal, but it's pretty incredible. It 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. It 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? He's like seven or eight. 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. I'd stick with coffee. Yeah. It's for the young folks.

47:56Yeah. for the young. For the young. And a little bit of coffee you're going to need. And again, 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.

49:01So 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 wanna go too slow, and you don't wanna go too fast. And acceleration is costly. And acceleration is costly, right? I mean, that transmission system, so you know, create this incredible efficiency of being able to travel at speed with more efficiency, you know, but accelerating is a different thing altogether. 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 rollercoaster ride of hyperstimulating their metabolic rate and then trying to suppress that hyperstimulation with sedatives so that they can sleep or calm down.

49:51And 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 two diabetes, yes. cardiovascular disease, 100%, like premature mortality, yeah. Like it, 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.

50:37Let's look at the elephant that comprises all of them. 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 100 years or so. But there's been this kind of obsession, I think in the public discussion around health, that around things that are obviously related to the thing that you're trying to cure. So serotonin and brain health, it's like, go, okay, make sense. You know, the listening to Prozac what came out, we increased serotonin, some people are feeling better.

51:16Maybe it's through neuroplasticity, maybe it's direct effects of serotonin. And but it makes sense. Serotonin brain, right? You know, it, um, 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, uh, first in order to try and improve mental and physical health simultaneously? It's a very different way of approaching medicine in general. Normally, we go, okay, what the issue is right here. That's where the tumor is. That's where the circuit deficit is. This is where the lesion is or the growth.

51:53And 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. us. 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 Barras, he died on the unfortunate pancreatic cancer, but you see incredible scientist MD and scientist who really popularized this study of Gleea, prior to that, they were seeing this kind of like back, water science, no one ever thought it was just glue for the brain.

52:41He 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 was like, he was a night owl, it was awful and you get stuck there. But I'll never forget, he stopped and he called me Andy 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 should work on that. And you say, why is it that our brain is less plastic?

53:15I'm like, well, I don't know. I think it's the glia, right? And there are 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 there's the NAD hypothesis, but it always seems to circle back to mitochondria. Yes. Over and over. So I think the answer is very clear. 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. 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.

53:55Because unfortunately, you know, our cells have a process for getting rid of defective mitochondria. It's part of autophagy. There's a sub -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 nianotennels to astrocytes and collect defective mitochondria from the neuron, amazing. And then take care of the disposal process for that neuron, we are so cool. 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.

54:46But 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, 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.

55:39Those 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 anti -depressant, an SSRI anti -depressant? 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 at that age, as people get older, the risk for antidepressant prescription goes up.

56:55The highest category of people prescribed antidepressants are 65 and older. Really? Well, I guess some sense that makes sense, although I would have thought it would be the younger population. 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 was thinking, wait, if my theory's correct, then mental disorder should be a disease of aging. And in fact, they are. Antisecotic prescriptions. What age group is the most likely to be prescribed in antipsychotic? Over age 80. Really? 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.

57:44They'll have agitation. The benzodiazepines, the prescription rate goes up. Now, with that, 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. Interesting. So, with antidepressants, it's almost linear. The older you are, the more likely you are to be receiving a prescription for an antidepressant. Antisecotics, 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 nuanced as schizophrenia.

58:28And 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 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. 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.

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1:00:34The 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 slash huberman. Function currently has a weight list of over 250 ,000 people, but they're offering early access to huberman podcast listeners. Again, that's functionhealth .com slash huberman to get early access to function. Let's talk about diet and nutrition for a moment.

1:01:10In 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. 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, etc. 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.

1:01:54How 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 a ketogenic diet and mitochondria because we've well established that mitochondria are central to this whole picture of mental and physical health. I'll throw in a plug before I go deep into the ketogenic diet story, but you also threw a question in there about other dietary interventions or how can diet impact.

1:02:37There 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 breastmilk 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.

1:03:33Increases 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 anti -social personality disorder and all sorts of other mental disorders. In terms of other dietary patterns, I just want to, and we can do a deep dive into any of these we want, and then I'll go on to ketogenic diets, but ultra -process foods really bad for your physical health and your mental health.

1:04:22We have just growing body of evidence for that. Is that because of the increased calorie consumption?

1:04:33There's this and 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 dies and 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.

1:05:13But then some of the diehards in the scientific community like oh, those dosages are represent like 6 ,000 fold what you'd have to eat. What most people eat, the dosages used in mice. But the FDA still pulled those dyes 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? 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?

1:06:00So right now, the rules to this day are that, you know, there's this concept called grass, general regard 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 shelves, 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 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.

1:07:00I think that will be a phenomenal change. But the reality is that testing hasn't been done on all of these molecules. There are tens of thousands of molecules and new chemicals, new to 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 people are eating mostly ultra processed foods and these people are hardly eating any are there differences in their health outcomes.

1:08:06And 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've got more granular data that's hyperfocuses on the mental health story. You know, one study over 300 ,000 people, the more ultra -process foods you eat, a direct linear relationship. It was shocking how linear it was. The more ultra -process foods you eat the worst of your mental health.

1:08:56And 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 three -fold difference. The people who consumed ultra -process 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. 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.

1:09:50And 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. I was surprised and somewhat delighted to learn that one of the ways that the public health folks got kids to smoke fewer cigarettes because when I was growing up, 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 marble man image from the preceding decades, but then it was really the 90s kind of, it was the actors and models and stuff that made it cool.

1:10:37People smoked and I was supposed to be cool. And one of the ways that we 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? And Colleen want to 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 the board room of a tobacco company and they were like cackling and talking about like, ha, ha, 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 establishment.

1:11:20So is there a world where, you know, kids are gonna be like, forgive me, but like, F that, I'm not eating Doritos. You know, like, I'm not gonna be manipulated by highly processed foods or I'm gonna hold onto 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 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.

1:12:02You have to activate that rebellious spirit. Uh -uh, not gonna do it. Just telling people it's bad for you, it doesn't work, right? We know that. How do we incentivize people? Yeah, I'm not gonna give a cliche answer because this is the trillion dollar question and that everybody's asking. And it really, the health of our country really kind of depends on it. With billions of dollars, 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 Huerman are saying, it's fine.

1:12:55Everybody 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. 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. 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.

1:13:54And when you have supposedly respected organizations being bought by industry,

1:14:08promoting misinformation.

1:14:13It'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, 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's still a lot that we don't know.

1:14:57We need more research. We need more research. Smoking doesn't cause heart disease people. This is just scare mongering. And that's it. 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.

1:15:43If 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 if one or two companies steps up and does the right thing They'll just go out of business. 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 a styrofoam container is right I was very different Very different issue. This doesn't Directly get the human health of the styrofoam.

1:16:21It's not good but 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 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. And 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 take a different direction.

1:17:15Like 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 team But if it's in service to health. 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 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.

1:17:57You'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 it, now they are highly motivated to get off of it. why because it's costing them an arm and a leg. Money hurts. And they realize that I just don't want this. We could do similar things with ultra -process foods. If rebellion, education, whatever, I don't care what works. But where all of the above, we're really fighting an uphill battle. So ultra -process foods, that's just one story. Vitamin nutrient deficiencies. Do you want to go to ketogenic diet?

1:18:43You asked me about that and I got sidetracked. Yeah, we went into the public health discourse we're weaving back and forth. That's what we do here. I think it's, I mean, 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. 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?

1:19:27And if so, how does that work? 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 treat merresist and 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 analyze the data that exists and came to the conclusion that ketogenic diet, if somebody has treatmasers and epilepsy compared to treatment as usual, which is try another anti -apolptic medication.

1:20:16The ketogenic diet is six times more likely to result in seizure freedom than just trying yet another epilepsy pill. So the ketogenic diet is a powerful anti -convulsive treatment. We use anti -convulsive treatments in psychiatry every day in tens of millions of people. Lots of these medications are used. So, 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 by polar disorder, depression, anxiety, anorexia and an aboso, surprisingly. These 50 reports represent over 1900 people and on balance, the ketogenic diet appears to be an effective treatment sometimes and extraordinarily effective treatment like in able to induce remission of schizophrenia or bipolar and people who otherwise had treatment resistant disorders and they're going off medication simultaneously.

1:21:32Some of them are. So there are, you know, I've 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 I am as they should. Well, I know about you, but it's human. That human lab podcast. Well, I'm just a runway for people to incredible messages to take off. 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.

1:22:30I 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 and roundabout way, does ketogenic diet impact mitochondrial health? 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.

1:23:27So 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.

1:24:16So let's make sure that if you're going to 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 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.

1:25:13So 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 We 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.

1:26:07When 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. Interesting. Even though the mice were not on ketogenic diets. So there's something in the feces of children with epilepsy doing ketogenic diets that result 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 neuropapdides and other factors that the gut cells are producing.

1:27:05So 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.

1:27:23What does got mice to have an anti -seasure 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 -seasure effect in the brain? Because that's the pathology, the pathological finding. Seasure is occurring in the brain and when When they analyzed genetic changes, up -regulation, down -regulation, 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.

1:28:22It's not got microbiome or serotonin. It's not got microbiome or mitochondria. It's both. Both of them are true and it's all interconnected. So I do think we've got more than enough data that ketogenic therapies impact brain metabolism. which then impacts neurotransmitters. That's 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 and 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 hyperaccedability and seizures.

1:29:28And so that helps us understand, again, it's not metabolic or glutamate and neurotransmitter, it's both. It's putting it together. Yeah, the Campbell study is really interesting. We will link to that in the show no captions. And incidentally, we will also link to this American Heart Association appalling, quote unquote, testimony. Sorry, I'm not, I'm not sorry. I'm 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 a from bipolar schizophrenia, but like myself, would like to keep our mitochondrial function as strong as possible. And for doing a brief ketogenic intervention?

1:30:25Yes, the answer is yes, can intermittent, and so I'm gonna 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, but there are a lot of studies on exercise interventions. But even those are, they're not huge randomized controlled trials with 10 ,000 participants.

1:31:21They'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 of 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 it didn't do anything for their heart health or other objective kind of outcome measures and put another way just to really close this for people. It means a low fat diet is no better than the standard American diet.

1:32:13A 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 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 facts. Yeah, you gotta get those mono and saturated 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.

1:32:54You were asking me about intermittent. Yeah. He's that guy's intermittent fasting. 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.

1:33:16India, China, Christian, fasting has been a part of rituals. And most people just assume it's religious folklore or just silliness or whatever. But I actually think millennia of humans were not all stupid idiots. And that some people along the way actually notice is 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 Walter Longo, who he doesn't call his diet a ketogenic diet, although it is a ketogenic diet.

1:34:07He calls his diet a fasting, mimicking diet, and it's primarily a plant -based 600 calorie a day diet. Some people were gonna hear that. Just... It is proprietary to him. You 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 can, you don't need to buy that proprietary product. But because he is selling this product, I believe he's using most of all of the funds that from, that most are all of the proceeds from the sale of that to fund research on it.

1:34:52They'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. Interesting. 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.

1:35:40Well, that we, so then 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 are we supposed to do? Do we eat red meat? Do we not eat red meat? Do we eat like moderation? and sound healthy sources. Yeah, I feel like, but in moderation from healthy sources, not the process stuff, but I get it. People have animal reasons or environmental reasons. They don't do it. The debate goes on and on. I've observed some people who are vegan who seem very healthy, very robust. Esthetically, they present well, if I'm just gonna be direct about it.

1:36:18And then I've seen some people who go vegan 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 were the so -called Carnivore diet are now, then it became animal -based and now includes fruits and cucumbers and tomatoes and some dairy and, you know, and so it's funny. And I like Paul. I get along well with Paul. I also get along with Ling Norton and they don't get along. But I think it's teach their own within the context of the correct number of calories for a given person in their activity levels.

1:36:58But this idea of doing a periodically doing a, perhaps a fast along the lines of the long go, pro long thing or total fast or water fast, I guess it's called, or perhaps intermittent fasting on a more reasonable schedule. Are there any data on that? Like eating only between the hours of say 11 a .m. and 7 p .m. 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 fast, but more of the time restricted feeding to eight hours or six hours that it can be beneficial for mitochondrial function?

1:37:43If it's done for short bouts of two to four weeks. My understanding of 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. Oh, that's no good. So those studies mostly are designed to just say, don't eat. Only eat between 11 a .m. and 7 p .m. Because it eats 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 then you've got everything in between, as though that doesn't play a role.

1:38:32And so you get these studies to say it doesn't do anything useful. You get other studies to say maybe it does something useful. So I think, I mean, at the end of the day, I will say this. I've been talking a while with a really seasoned, established expert in the nutritional space, in the conservative nutritional space. He's helped 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.

1:39:36And their annual budget for a major government organization, their annual budget is 1 .3 million within M dollars. That's a joke. Which is a joke. It is a laughable joke. Can't do much with that. And without trying to make this political, there have been people who have tried to increase the funding for nutrition research. Recently was proposed to increase that funding to $130 million. And it was cut. But that idea was killed by the lobbyists of the food companies. I'm going to get really vocal about this lobbying through the American Heart Association thing because I was just shocked. 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.

1:40:37And it was so clear that they were on the take from these food companies and that's why they send, 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. It's like, there's like the old commercials of the people from the cigarette industry saying that the cigarettes don't cause cancer and they know it does and we're just, 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, this thing that happens in medicine and public health where the thing that's so obviously the problem is like it's not even staring us in the face.

1:41:13It's like 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 look 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, it's, it's, it's a sign. It's crazy. And so I'm excited about Maha, even though I don't have any affiliation to it, because it, it's, 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.

1:41:59What do we know right now? And so I'm, 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. For, for, for, for, give me for editorializing here, but we keep coming back to this. We know what, what we need to do. 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 many good things that could come out of Maha is separating industry interests from the health and welfare of the American population. I think we can do that and we can begin doing unbiased research to really determine what is it about ultra -process foods that results in harm.

1:42:55We 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 the, 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.

1:43:40What are the criteria for binge eating disorder? It's basically addiction to ultra -positive foods. It's, really, if you look at the criteria and if you look at the behaviors, you're When people engage in benches, 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 ashamed and they're humiliated. And then they try their best, they whitenuckle it, 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.

1:44:35And 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 more of a 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's found in fruit, so it can't be addictive. I'm like, really? Is that, and they actually...

1:45:20They actually... They actually... They actually 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? Like, do you really... understand that some people can't stop consuming ultra -processed high -shurger foods. You really don't understand that. Like, are you living in an ivory tower? Yes, and 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.

1:46:04We're not talking about eliminating pie and pastries. I think sometimes people think, oh, 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 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 this painting, this picture of a little bit of the past, the recent past. But what you do so beautifully is you're really orientating us where we are now. And that the fact that We need more science, but we know an awful lot, and there's so much that we can do.

1:46:42And these six pillars of, you know, diet exercise, sleep, avoiding excessive substance abuse, or 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. 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.

1:47:36And 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 be combined 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 its own as long as we have the essential vitamins and nutrients that make it up. And there are several of those.

1:48:31Or 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.

1:49:45So, 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.

1:50:39Anybody can make it and market it. It's off patent. 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 disease. disorders like cognition in Alzheimer's disease or mild cognitive impairment. But again, 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.

1:51:34Well, we're never going to have good quality data because there's no product. That's where we're out as a field. Do you recommend it to your patients? 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, improved metabolic health, improved 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.

1:52:20What is your diet nutrition? Are you getting adequate sleep? Are you getting some bright light in the morning. Are you, 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 the reality is the statistics are abysmal. I mean, one third of American adults are not getting adequate sleep.

1:53:10Sixty percent 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. 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 glue ever since a video of Robert Kennedy putting methylene glue in his water on a plane, kind of went viral.

1:53:54Methylene glue has been around all 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. I don't take it either, and I've not used it in any patients so far, but I'm very interested and 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. They're still room for improvement. So, methylene blue, as you said, has been around for a long time.

1:54:35It's relatively cheap 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.

1:55:42So 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 percent? 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?

1:56:37Absolutely, 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.

1:57:28So 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 by polar disorders, because if any Alzheimer's disease, others, many of them suggesting a benefit. Do you know what the dose is? Range. I don't. I don't need it. I don't need it. I don't need it. I don't need it. Yeah, because methylene blue, as I understand, has some MAO activity.

1:58:22The 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 But I don't really want to boost my serotonin. There's this recent study out of the lab at Stanford showing that the rewarding properties of various things as we know increased dopamine in anticipation of a reward, but also important it seems. These are mouth studies, 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, I should say, increasing serotonin offset some of the rewarding aspects of otherwise rewarding things.

1:59:24So I want things that are rewarding to feel rewarding. And so this difference between dopamine and serotonin seems pretty vital. I mean, that's not to say I'm 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. Well, then that's actually one of the warnings with methylene blue is that if you've taken in two have a dose, you can actually get serotonin syndrome. Could you explain what serotonin syndrome is? So serotonin syndrome is just like really excessive deluge of serotonin in the system.

2:00:01More often than not, it's completely unrecognized. Really. 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 feverish, 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, or 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.

2:00:50They get written off more often than not. We're given more medication. Yeah, let's increase your dose. I think he's 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. To both her and her psychiatrist, so the meds were causing the problem. And the meds were causing the problem, and nobody really recognized it. Again, so it's, so anyway, methylene blue can cause serotonin syndrome.

2:01:32So I think if people or get a, if people want to 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, to constrain your teeth blue and all sorts of stuff. So like sure, you're in blue, you're tongue blue. But people do IV infusions of methylene blue. So yeah, no, that's, I've seen people kind of hooked up to IVs with a bag of methylene blue. Do they turn blue? And they hope not. Smurfing was smurfing. But it is a medically approved treatment. And I think it can be done in safe ways. Again, it's off patent.

2:02:20Nobody's gonna stand to make any money off of doing large, well -designed trials of methylene blue. But I'm really interested in it as these properties. In addition to just being this electron, excepter 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 may be beneficial. 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 EuroLith and A that people seem really excited about for improving mitochondrial function.

2:03:16I'm not super familiar with the literature. But co -ensime Q12, EuroLith and A, we're starting to hear more about these sorts of things sold over the counter. Do you have any thoughts on those? 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 uralithin 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 uralithin 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.

2:04:19And that that has overarching metabolic benefits that have, in terms of biomarkers that have been associated with slowing of the aging process. So your Lithuanan A, I think, is definitely a supplement among all of the supplements that should be considered if people are looking for something to take. I'm going to repeat myself before you take your Lithuanan 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 like harder to sell people have to do right the diet and exercise them being else But then this could give them an advantage And I don't deny that at all.

2:05:16I think it may very well give people an advantage and 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 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.

2:06:07That once people get into the severe category, severe heart failure, severe, 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 neuro stimulation, which is, can stimulate mitochondria and stimulate neuroplasticity. Things like trinitranium magnetic stimulation. Yes, which is done noninvasively, right? It is noninvasive. And so, can we use those types of strategies to try to improve someone's mental health?

2:07:00And 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 ex -disorder. And it's like, well, 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.

2:07:47The ketogenic diet 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 it, 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. Like for the most part, yeah. Like diet might actually make a difference to your brain health.

2:08:38I 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 technology then 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. I'm a, forgive me for getting so macroscopic here, but when you look through, I, 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.

2:09:26and 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 balance 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, which are really at the extremes.

2:10:07So we've lost our bearings. We're kind of like true north is so clear what true north is. It's mostly non -process, minimally processed foods, getting adequate quality protein. you could do that, vegetarian, you could do that with some animal -based products. 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 owe away a second. Like this is time for a course correction. But hey, that's what we're trying to do here, right?

2:10:45Absolutely. 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 launcher, has really transformed in no small part, thanks to social media and podcasts. So things are evolving. Thank you, Dr. Huber. Well, and thank you. And thank you. So 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 midnight meeting and somebody presented some proteomics data where they were sequencing a spinal fluid from depressed patients and finding that certain depressed patients had deficiencies in certain vitamins that could easily be replaced through supplementation and low and behold, their depressions were in these particular patients were being cured, literally reversed, going into remission by virtue of taking the appropriate vitamins.

2:11:49But 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. 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 these of e -depression and other CNS challenges. Before I get into the complex part of the story, let me just start with basic. So, and this relates to nutrition, that a lot of these basic vitamins and minerals, like vitamin B12, folate, and iron.

2:12:34I'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 mitochondrial will not function properly. So 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.

2:13:21So, iron, you know, there's study in JAMA just last year, 40 % of females, age 12 to 21 in the United States are iron deficient. Wow. 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 girls and young women, 12, so this is menstruation, obviously. It's menstruation. They are losing blood. They're 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.

2:14:12What 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 the most part, we'll say depression and anxiety, exact same rates. Puberty hits and girls just skyrocket. the rates of mental illness, skyrocketing girls. Now, are there psychological and social causes of that? Yes, we can talk about your becoming an attractive, sexual mate, and maybe people are being mean to you or people are making you uncomfortable or you are becoming a victim of sexual trauma.

2:15:07Do 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.

2:15:57And that could be playing a role in their depression, anxiety, their eating disorder, or whatever else they've got. Vitamin B12 fully, 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 %, 50 % of their population is B12 deficient. Whoa. What are some food sources of B12? Is animal sources red red meat? animal source foods again eggs red meat other types of meat. Yep. 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.

2:16:51You 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 MnB12. Interesting. 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.

2:17:55And 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.

2:18:45So 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 perniscusenemia 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 a happy, healthy life. And then at age 65, you develop pernicious anemia.

2:19:36You can no longer absorb B12. And this is actually one of the treatable forms of dementia that we have. 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, will a B12 oral supplement work?

2:20:22Like a methyl A B12 capsule? As long as they don't have this autoimmune form, yes, 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 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 neurologist who have been doing all this work.

2:21:22When 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 beginning 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. So that requires a spinal tap, right? This is not the standard. 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.

2:22:21And 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. Wow, it's really high. They then sampled people with neuropsychiatric lupus. So these are people who have an autoimmune disorder already, lupus, and they have neuropsychiatric symptoms.

2:23:0420 % of them had this antibody. And then they just recently, this is unpublished data, but they have looked at people who have a demilinating condition of unbiased. unknown ideology, and about 50 % of them had this antifibzero percent. This is like an MS -like condition. Had this antibody. And what's the solution? B12. 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 wanna flood their system with vitamin B12 so that some of it can get across the blood brain barrier.

2:24:02And again, oral B12 won't work in this case, right? 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 rescue those brain cells. This is very interesting. I think people should get their B12 levels measured. It's standard blood test, right? It is, unfortunately, for this new autoimmune central B12 deficiency, they're working on a commercial test, but you can't get this blood test right now.

2:24:44Okay. Um, so, uh, perhaps to call it 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. In theory, you'd have to take your vacation to the street. In theory, you lose money because you have fewer passions to choose. You lose money by getting people better and then they move on and don't need me anymore.

2:25:30I honestly believe that, but I also believe there will be 20 % maybe up to 40 % who have 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 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.

2:26:34It'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.

2:27:17That'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 schizophrenia 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 that so important? Because there's a treatment for these other things other than just anti -psychotic 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.

2:28:14There 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 gonna have to suffer for life. Like we can do better. And I applaud your efforts to bring about that change. I think people realizing that often not always, but often might a condrial dysfunction is at the heart of these things is critical.

2:29:03Speaking of which, I have to ask and feel free to pass on this question if you like, but I've become very interested in vaccine biology and the debate about vaccines, about the adjuvants that are used to deliver the vaccines. is it obviously there'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? 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.

2:29:46That'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? It is a content. It's maybe it's a different episode. No, no, no, no, no, no, no. And I definitely, I'm definitely going to answer it, but I'm going to give a long windowed answer if that's okay because I, because I want, whatever I want to give credible information.

2:30:26Yeah. And I don't, the only information we're interested in. And I don't want to come down on one side that vaccines are 100 % safe. There's no question about it. Or yes, vaccines cause autism. And that's why we've got skyrocketing invasive 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 TNF alpha, interleukin six, and others impair mitochondrial function.

2:31:09We 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.

2:32:01The 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.

2:32:46Now 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 outbreaks of bacterial or viral infections in the population, we saw higher rates of in the offspring of the pregnant women. So we've long known that, and that evidence is pretty well established. 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?

2:33:47That's correct. Okay. But then there 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 lipopoly saccharide which causes an inflammatory reaction and 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's different diagnosing or whatever, a developmental condition in a mouse. is it 100 %?

2:34:47No, 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. It's 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?

2:35:41Do 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. Yes. Can some people have a hyper exaggerated 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 hyper -exaggerated 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.

2:36:49It 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 blinds 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.

2:37:54When 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. Is that right? 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.

2:38:53And 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. 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 is not. Although I'm thinking in the back of my mind about these lifestyle factors, even though it's a young child 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?

2:39:50Like proper sleep, proper nutrition, proper, proper everything. You wouldn't want them even slightly sleep deprived because is that would increase the risk of inflammation. I mean, these things compound as I understand it.

2:40:05So, 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 or BS, et cetera, are 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. I mean, the science that I just laid out is true.

2:40:45It'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.

2:40:59If you understand the biology,

2:41:05when 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, It is soon as a child begins to show signs or symptoms, especially when it's in a abrupt change.

2:41:59When 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. This is, that's why they believe vaccines cause it. But 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.

2:42:46I'm doubtful. 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?

2:43:31It 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 a disabled child, just prepare yourself to take care of a disabled child for life.

2:44:16We'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 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 out of, 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.

2:45:07I don't It might help a little, but when you look at the outcome data, it's not helping much. 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. I mean, we have a lot of work to do. So I appreciate the thoroughness of your answer. or I can promise you that anything we put out about that will include the full context. We're not, we're not, we're not, people will take the sound bite and 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 is.

2:45:51And I really appreciate you embracing that topic with the depth and rigor and sensitivity also So 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 they kind of went about our way. I do understand the number of vaccines that kids are getting now. Like the vaccine schedule has expanded.

2:46:24I've been kind of thrown into the middle of this as different guests have come on this podcast. You'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 over. It's so closely tied to believes in science, doesn't believe in science. Like 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.

2:47:03We 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 were kind of upset that this, that resources were going to be devoted to this because they felt like it was a done deal and then others are very excited because they feel like, hey, listen, if you don't think there's a link then here's an opportunity to establish that with real rigor. And I think everyone's just really interested in the study being done properly.

2:47:38Look, I think more data is always great. I don't disagree. And I've actually talked to some former NAMH 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 be the cause. 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 vaccine safer or whatever.

2:48:39And 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.

2:49:37They 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. Like, well, if there's an inflammation link then yes.

2:50:24Yes. 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. So we know that like women with obesity, much more likely, twice as likely, to have an autistic child. Is that right? Yeah. Metatanalysis, 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. Our 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.

2:51:15when you put the two together, obese and diabetic, quadruple the rate of autism in the offspring. What about dad? You know, they're the series 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. It is. So men with obesity, twice as likely to have an autistic child as men who are not obese. Which is something like 25 times greater than the increase due to age of the male. So this is so important because people here, older sperm equals higher probability of autism, but yes, still a very low probability of autism compared to that is obese, but in his 20s or 30s.

2:52:12Yes. And so, you know, a lot of people are hyper focused on vaccines, cause autism. And they come back to rates of autism or 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. It reads a poor metabolic health. So metabolic syndrome has five biomarkers, abdominal obesity, blood pressure, glucose, high levels of glucose, and then high triglycerides and low HDL cholesterol.

2:53:00This is the five biomarkers of metabolic syndrome. only 7 % of Americans are healthy in all five biomarkers. Only 7 % poor metabolic health influences neurodevelopment and offspring. We know that. So we see skyrocketing rates of autism, it's not autism, we see skyrocketing rates of ADHD as well, simultaneously. And everybody's scratching their heads trying to figure out where is 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. Such a critical message, but also reassuring in the sense that we can do something about it.

2:54:02We can. Because what you're talking about is metabolic dysfunction, mitochondrial dysfunction of the parents. So, you know, trying to control the behavior of still unborn or yet to be conceived. Children is pretty tough to do. 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 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 -no apparently obese people.

2:55:01I say apparently obese because a lot of people are carrying a higher body fat percentage than they realize even though they're not, you know, taking up a lot of space. So I think, you know, it's not always in 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 apobies through the roof and they're not well. But just because they're not obese doesn't mean they're metabolically healthy, correct? That is absolutely correct. And I go back to some of our prior conversation. So a 14 year old girl who is severely ironed deficient is metabolically unhealthy.

2:55:46Why? 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 you really need iron.

2:56:38Right. I mean, what I realized, and this was really where I wanted to bring us to Is a question for you. I have an idea, but I it's also opposed the question as an idea and feel free to bat it down. And 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. There, yes, there are supplements and maybe methylene blue will be advantageous and methylene 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.

2:57:24Do 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. Yeah, what you're describing is kind of, in my mind, a really important next step. And the great news is that there are several research groups that I know of that are working on exactly that.

2:58:10One 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.

2:59:08I'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 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. So I think that is one of the directions we need to go.

2:59:53is we need to establish tests with all of these groups. I wanna just stay 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 it 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.

3:00:37I'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 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.

3:01:41I 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.

3:02:34is schizophrenia or hypertension and what new pills can we develop to treat this condition or how can we understand this condition? I think we have enough evidence to be able to really start with more effective to be able to really aggressively pursue more effective of treatment and prevention strategies. 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.

3:03:19If 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? I'm 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 am 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 where we will treat people with these severe chronic mental health conditions that I started a wait list about a year ago and I have over 5 ,300 people on my waiting list.

3:04:22I 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.

3:05:21And I, you know, the theory is great. And I'm really a big fan of the theory. It continues to line up new evidence since I've published the book. New evidence has come out just completely supporting it.

3:05:44And He's really where the rubber meets road and we've just talked about there are so many things we can do for people who are suffering today. 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. 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 today.

3:06:35Thank 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, 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, you know, 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.

3:07:14And 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 an incredible care to all sides. And at the same time, staying really close to the data in hand and offering new questions. So that's just as 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 will 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.

3:07:54And then what's lovely also is that as new studies come out, 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 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. time. Thanks for this incredible voyage and education for me and everyone listening. You're doing God's work. Thank you. Thank you, Andrew. And thank you for doing everything you're doing.

3:08:32You're also doing God's work. And I know that 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 and the mental health of millions of people around the world than you right now. I'm hard -pressed to think of someone. It's a collective effort, folks like you, and the people that come on here. 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.

3:09:21I think I know how much you care and I care too, so thanks for those words. Thank you. 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, please see the show note captions. If you're learning from Endor and join 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.

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