How to Get The Most From Your Sleep Cycle | Dan Pardi on Health Theory

You know, you think of weight, you think of food, but it's very possible that even things like light might be having a very large input here. Well, you can then look at epidemiological research and shows that people that chronically get less sleep are much more likely to develop diabetes. And we used to think that poor sleep was just a very common and early symptom of Alzheimer's disease, but we now know that it might actually be directly involved in its pathogenesis. Hey, welcome to Health Theory. Today's guest is Dan Pardi. He's a sleep researcher at Stanford who received his doctorate from Leiden University, one of the oldest and most prestigious universities in the world. He's got a very holistic approach to wellness and his areas of expertise include sleep, optimizing cognitive performance and high performance in general, as well as the role of diet, exercise and fasting on our overall health and well-being. Additionally, he's the CEO of Human OS, a company aimed at giving people an optimized operating system for healthy living. Now, the place I want to start, this whole idea of the OS for healthy living is really interesting to me, but the thing I'm most fascinated by is that it started with your dad's battle for cancer. Yeah. So, walk us through that. How did that inform what you're doing now? Yeah, that's a It's one of the points that caused a refocusing, remotivation and dedication to this field of health. At the time I was doing research with somebody named Dean Ornish who was looking at a multifactorial lifestyle program. So, all different aspects of lifestyle and how that, if brought together, could affect the progression of prostate cancer. Interesting. My dad was then diagnosed with cancer. So, I thought I'm in a unique position to help him a bit. And so, what I would do is go and just give him all sorts of information and it was overwhelming to him and he wasn't able to then make change that I thought could affect his condition. Mhm. I When he didn't make the change, I'd get frustrated. And when he passed away, it really made me think about if I'm in this field wanting to actually influence how people live and their health, you need to understand behavior. You need to understand what is going to help somebody pick up some of this knowledge that's out there and make it a part of their life. So, that was one of those aha moments. And then from there, I dedicated some serious time to understanding behavior. Created a model called the Loop Model to sustain health behaviors. And that was really the basis of Human OS. Did you read the book Change or Die? I haven't. So, the the concept is pretty straightforward. You tell people to change and most people don't. So, even if the outcome is, "Hey, if you don't take this pill." And I think it was that simple. It's like you have to take a pill once a day, every day. And compliance after like 3 months or something drops to like 5%. Yeah. Which is crazy. But what I love is that you didn't hit that and go, "Oh well, that's just a thing." You dive into human behavior. What did you learn in that discovery process about human behavior? What's working against us? How do we begin to take hold of it? And then maybe most interestingly, what is the Loop Method? Sure. The idea is in order for somebody to adopt and sustain a health behavior for a long term, not just a 30-day trial or 60-day period, so this becomes a part of their pattern of living, they should know why they are doing something, how to do it, if they're doing it, and if it's working. Mhm. And you can see that each one of those four components independently will reinforce somebody's ability to pick something up and take and and go with it. So, often times what you'll see is that if somebody doesn't, let's say, change their behavior when information is given to them, you might just lob more information provisions at them, right? Oh, here's more information. But maybe they just didn't have the skills to implement that good idea. Or they tried it for a little bit and then their old behaviors were swept back up. They didn't have any feedback or to say this is actually are you living in accordance with your own goals? Or maybe they just didn't know if it was actually working or not. And because one, you know, insidiously challenging aspect of our health is that a lot of things that are good for us might be what I call the meaningful but invisible. They matter, but we don't get that feedback to make us immediately detect if it's having a presence. And it might be, right? You might have a significant improvement in let's say memory performance over a 12-week period, but you're but you might not recognize it by the time you get there. It might actually feel like you're just performing as you've always been. And that actually can go up and down, improvements and decrements. So, is there a way to then use technology to then make people more informed about things that can help them, more informed about their own patterns of living, and then empowered to put all that into practice? And I actually think that we need technology in this world to help us take care of our health well. I found this so interesting in some of your talks. Define health. Yes. So, that question was posed to me a while ago, and I totally stumbled on it. It's one of those broad questions that is hard to define. I think probably the explanation that I like the most is that it is a the ability to maintain balance or homeostasis within the body. So, if you are challenged by some sort of, you know, infection or arm break, it your ability to get back to a place of balance is a marker of health. But it is also more than that. It is it is something that can we can use as a currency to realize our goals and aspirations in our life. And I think if you take that if you drink that in and you believe it, then all these things that can feel like friction might actually just be opportunities to live in accord to the the fullest version of yourself. I love that definition. So, now let's say that I have that, but I'm still struggling to implement. What are the behaviors and like what are the behavior modification tools that people can put in place to comply? I think the first aspect of this is to clearly understand the problem at hand. Right? If you don't really know what your your challenge is, your own efforts will be either inefficient or you won't really know if you're headed in the right direction, even though you're spinning your wheels. We're born into a time where the default settings around us and the expectations of our environment and the pressures of culture and work and even the built environment will predictably lead to issues with our health, chronic disease. We have to be a little bit weird. We have to make a daily effort to counteract those forces to affect our pattern of living so that we actually are being good stewards of our health. It's not something that is just there until it's gone. It's something that you need to cultivate and nurture. Then next, you want to be a lifetime learner because 15, 20 years ago, circadian rhythms, the the microbiota, things like that were not a part of any model that was used to predict or describe health. We know information is changing regularly. So, I love that saying um have strong opinions, hold loosely. Which means to me that you take the time to form an understanding now, but you don't defend that at all at in the face of new information. So, you need to be have the ability to upgrade that, to up-level that. And then you have to be able to take big concepts that you learn about and personalize it into the fabric of your life, your family, your kids, whatever that is. How can you take this idea that you think is going to benefit you and make it real for you? Because if it's too if it there's too much friction and conflict, you don't personalize it, you follow rules, you might be able to do that for 2 weeks, 3 weeks, but then you'll you're really likely to go back to whatever patterns you had previously. What else? I think your response to failure. Right? Failure is a part of the process, a regular part of the process. Can you address failure with compassion for yourself and also with resilience where you're like, "Oh, what can I learn about the fact that I wanted to go to the gym four times this week, but I went twice? What was it about the week? Constant assessment uh to then just know how you can do better next week." So interesting that as you're talking about how to get people to comply with health stuff, that you're talking about mindset. In the beginning, so when I first started this film uh everything journey and talk through all these problems, it was why is the protein bar guy talking about mindset? And then when I exited Quest and started Impact Theory and did all this mindset stuff. And then I said, "Guys, we're going to do a show called Health Theory." Everyone's like, "Why is the mindset guy talking about health?" And it's been like this constant frustration for me for people to understand, if you want to optimize for your health, you have to optimize your mindset. If you want to optimize for your mindset, you have to take care of your health. Yeah. And because I talk a lot about working hard and busting ass and all that and what greatness demands, people think that I don't sleep. They think that I just grind my way to success. Yep. The reality is that if and you've talked really powerfully about this, if you want to even have good decision-making abilities, you've got to sleep. Run us through like a sleep 101, why it's so foundational to your work and what people should be doing. Yeah. I left a company that I loved at a job that I loved to start a startup and my PhD. And I thought it could all implode. It would be too much for me to handle. And so I thought, "If I am going to upregulate my ability to show up every day, I need to then basically take care of the machinery that is doing the work." So what is it that makes me feel sharp every day? And sleep then is of course one component of that. And what I've realized it's so it's funny, we kind of encapsulate sleep as it's this packaged thing, but it's almost like, "Tell me about daytime, right?" That's a big window, you know? And what sleep ends up being is a very great window into your soul, you know, and into the into the workings of the brain and how like what is happening physiologically. So, you really understand um it gives you a window to like narrow the field a little bit to then understand how our physiology works in general. If you had to make a hypothesis about two or three reasons why we sleep, what do you think are the two or three most important things that happen while people are sleeping? Yeah, it's a good question because it's been almost like definition of health under what is the solitary unitary purpose of sleep has been notably hard to define. We know very important things can happen. It's purging of energetic byproducts, it's purging of potentially neurotoxic products that are a result of that, it is plasticity that's forming. It is reregulation of our immune system. There's a lot going on and I think there has not yet been one, I think, model that explains everything, but we do know that incredibly important things occur. So, what are people doing that messes up their sleep? Yeah, so that's a it's a really good question and the the common question that you get is how much sleep do you need? Right? How much time should I be in bed? It's easy. But the things that matter for sleep are are timing, intensity, and duration. So, duration is sort of the easy one, it's that what I tell people is spend enough time in bed so that you wake naturally. That means you're not waking by an alarm. And so, what I like to get what I call complete sleep is aim to spend half an hour more in bed than what you think you'll need so that if your body needs it on that night, you'll get it. Now, you might not ever need it or you might not need it or you might need it rarely, but allow for complete sleep to happen. You also want the timing of your sleep to be regular. So, if for instance, you go to bed usually from midnight and wake up at 8:00, but tonight you go to bed at 4:00 a.m. and you wake up at noon, it's 8 hours, but the sleep will not be as restorative as it was if you were sleeping in that same window every night because we now are introducing concept of circadian rhythms which are repeatable 24-hour processes. So, when you're getting REM sleep at 4:00 a.m., your body, because of your past experience over the last several weeks, knows do REM-like activities at that time. And so, it'll be more efficient. Sleep itself will be more efficient at doing what it wants to do if you regularize the timing of your sleep. Mhm. And then, you have intensity and that is really not something that you can take action on directly. Right. Go sleep hard. Do it. But, you can do things during the day that then will facilitate depth. And you can also create an environment that is less disruptive. Okay, so talk to me. What can I do during the day to make sure that I'm sleeping hard? Yeah. So, if you look at people that undergo bed rest because they have a broken leg or in studies that put people on bed under bed rest to then see what their sleep is like, you notice they end up having a fragmentation of their sleep. So, they have more naps during the day and they have more periods at night where they are up. Without an adequate amounts of physical activity, there is a fragmentation of your sleep. You don't need a ton to then get better sleep, but then where does that sensitivity sort of drop off? You uh use running as an example because we can just define it by time. You go regularly for a 20-minute run. Today, you go for a 4-hour run. You've now overloaded your system to a degree that might actually impair the amount of sleep that you get. There's a bidirectional relationship there where a little bit of the stimulus aids in the depth of sleep and too much can overwhelm it. Now, it doesn't automatically mean you will sleep poorly, but you have a higher risk of doing so. You might sleep like a rock. And then, there's temperature fluctuation. So, this is actually a newer area, but we live in a very insulated world, right? Even if we go outside and there's not much variation in the temperature, we can layer ourselves so that our what we're being exposed to is very narrow. We also know that signals from a wider breadth of temperature within the day can might actually feed into that what's called a homeostat. These things that are collecting the signals of daytime usage that then help you sleep deeply. And then a big important one is is light. So, light coming into your eye will communicate with receptors at the back of the eye that are not actually communicating with the visual cortex that help us see, but they are communicating with the master clock. And it we spend 90% of our time indoors now. So, if you we are not getting as much light as we used to. So, if you go outside, don't wear glasses. Get outside for at least a half an hour. Get some glasses. Sunglasses yeah. Sunglasses yes. Yeah, thanks. And then in the evening, you really just want to have whatever internal light environment is reflect what's going on outside. So, as the sun goes down, dim the lights. Uh and then also change the tone so you're getting less blue light cuz that is the the blue is the major signal to these retinal ganglion cells that says to the master clock, it's daytime. Yeah, speaking of which, I was listening to one of your talks and you talk about how the fact the fact that fat has photoreceptors or light receptors? How is that possible? Probably like one of the coolest discoveries of last year. But those same receptors that are in the back of our eye, they're called opsin receptors and all opsin receptors, and there are many, over 100, they have the ability to transduce a light signal into a nerve signal of some sort. So, Peter Light in Alberta, researcher, Professor Peter Light You have to be joking. [laughter] I know, isn't that I mean he's that is that his Hilarious. Yeah. I don't know if I rolled right over that one. Peter Light who studies light Uh I don't think there was a name change there. I think that's his his given name. He did a screen to see are these receptors anywhere else in the body? And he's found them in fat tissue. Wow. And he's like, this has to be an artifact. This can't be this can't be a thing. Mhm. And so, he was able to test if light hitting fat tissue had an effect. Mhm. And he put his hand over the light and the signal went away, he took his hand away from the light and the signal reappeared. So he thought, "Wow, this there's something here." And that made him investigate it more thoroughly and what he found is that fat tissue has light receptors, the same ones in our eye, and they respond to light and it makes the fat cells shrink, become less inflammatory, and they release a whole different uh profile of hormones. And we might actually have a light deficiency, not just for vitamin D, but for our regulation of fat. What we the conversation around fats regulation is often times fairly uninformed. We regulate fat tissue like we do temperature. It is a it is something that is not simply just a matter of did we, you know, the calories in calories out. Your body is making a lot of adjustments. Now those calories do matter, but it is making a ton of adjustments to those calories to then say, "Do I want that fat storage to shrink or to expand?" And you And it's trying to regulate it similar to how a thermostat would regulate uh temperature in a home. You set it at 72. This is super interesting. So we can say that that the fat in our body works as a gland. Is that fair? Yeah, you could say that. It's a yeah. But is there logic to like the the hypothalamus, that um thermostat you've talked about fat trying to stay in a range, um that it goes up and down sort of regularly, uh but it but it stays in that tight band. Like this is so interesting to think of it as uh secreting hormones and being a gland. Walk us through the details of that. Yeah, so we now know that fat releases, I think over 50 different what are called adipokines. Adipo fat, kines like a cytokine, which is like a hormone. And so um as triglycerides enter into our fat tissue then leptin is produced continuously. so that flux of fats fat tissue fat leaving and entering the fat tissue will then cause leptin be to be made proportional to that. Then that signal goes into the blood and there's various receptors for it. So one in the brain in the brainstem, you actually have one in your pancreas as well, but then in the hypothalamus. So the brain is then detecting how much fat is circulating. Ah, you've lost a little bit of weight. Less fat storage, less leptin release. Be hungry, get that fat stores back up. And you have neurons in the brain in the hypothalamus and these and a lot of the hypothalamic centers will connect. So you have these discrete groups of cells that communicate with one another that then affect things like motivation, temperature, uh even sleep. And so there's a balance of different cell types within an area called the arcuate nucleus and depending on the signals that are present will then initiate this cascading effects that will affect hunger, that will affect energy expenditure, all to try to keep your fat levels in a constant level. Now it doesn't have to be the exact same level, but within a range. Now, why do we then get fatter? It's thought that this homeostat this fat homeostat is much better at defending weight loss than weight gain. Makes sense. Evolutionarily it was probably much more of a concern. And there's also some thinking that those neurons actually get damaged by our environment our internal environment from the types of foods that we eat and challenges to them from even things like poor sleep. So nutrient inadequacies, things like that, all these things can affect the health of that tissue and it's one of the reasons why I am favorable towards a ketogenic diet because beta hydroxybutyrate is one of the ketones and it can cause those those tissues within the brain to actually start to remodel and regenerate. And so somebody that has diet-induced obesity they they have a very hard time losing weight because even if they lose weight, their body wants to get back to that set point. And if you look at people that are on a ketogenic diet, for a lot of them, they just start eating to satiety, they eat normally, and yet they they the weight comes off naturally. Now, is there's no guarantee that that weight will stay off, but I think you put yourself in a much better position, you know, if you lose weight on other ways, not all other ways, but other ways. If you look at somebody's physiology once they're 50 lb lighter, for a lot of people, it looks like their body's desperately trying to get back up in weight. Their brain will stay active seeking food. So if you do fMRI and there's food on the table, they will stay seeking even even if they're full, right? Everything is engineered all the different processes are engineered to get you back up to that weight. What are some of those processes? That's so interesting. Like So I I've had a lot of these symptoms. So I used to be 60 lb heavier. I lost that and I did it so stupidly, you can't imagine. I did it in a rapid starvation diet and just insane amounts of cardio. So my calories were probably between 1,200 and 1,500 a day. As much as I could make it just pure protein as possible. I was inflamed. It was crazy. My joints hurt, my knees, my wrists, my elbows, I mean it was gnarly. But unfortunately, I wasn't thinking, "Hey, listen to your body." I was just thinking, "You're getting leaner, you're getting leaner, you're getting leaner." But you want to talk about seeking food at all times. Like all I could think about was when my next meal was. But I never thought of that as like anything other than, "Well, your calories are crazy low." But what are the mechanisms that like trap people? Cuz there are some people who will swear that they can't, no matter what, they can't lose weight. And I've always, if I'm honest, I've always really discounted the, "Well, it makes me hungrier." Yeah. So interestingly, a ketogenic diet, I'm very interested in the mechanisms by which it might be working. And it and there, the ketone beta-hydroxybutyrate might actually be turning on genes that help to reset those tissues that are controlling body fat, effectively lowering your set point to a place that's healthier. That's a possibility. The other diet that can do that is very low energy diets that actually have very low energy. People say that's starvation. calorie? Low calorie. Yeah, cuz you don't have to actually be on a ketogenic diet to produce ketones. If you are in a state of fasting or in hypocaloric intake, then you're going to produce ketones. So give me the order in which the body burns calories and and include alcohol as the fourth macro, which some people will say. Yes. So, preferentially the body will burn glucose and that is thought because the brain is a very very glucose hungry. It is only 4% of our body weight and yet it consumes 25% of the calories we eat. It's a very metabolic metabolically active tissue. Do macros always go in an order? So here's what I heard, this could be total Uh number one that if there's alcohol in the system it will be metabolized first Yeah. followed by glucose It depends Yeah, so actually it depends on your relative status. What type of macros have you been eating over the last couple of weeks and then what enzymes have been generated in response to that exposure? Okay, so it's not like there's some set it's always going to burn them in this order. See, most studies are always looking at what is under this normal condition, which is our standard diet. It's not looking at under all conditions and under things like fasting or what might be evolutionarily more regular in terms of like you know, not having breakfast until maybe noon. We have what's called metabolic flexibility, which is thought to be something that is a good state to try to achieve, which means that you can readily burn different types of fuel sources. So, you know, it's it's extraordinarily complex. People give simple explanations for it, but you know, this is actually one of the biggest public health needs in our world because the amount of comorbidities that associate with obesity, it will bankrupt our society. You know, you think of weight, you think of food, but it's very possible that even things like light might be having a a very large input here. And like like sunlight even, right? We're talking about that. So, if fat is a regulated tissue, and we are living fully clothed, um I wouldn't say that there's any silver bullet, but there's a lot of different inputs. And so, I think overall one sort of perspective of mine is to try to live more naturally, but in a way that is actually going to work within the the modern world. Mhm. One thing you said that I found so interesting is, all right, fat's a regulated tissue. It is um creating all these hormones. It's responding to the environment. It actually has light sensitivity, which still freaks me out. And hey, by the way, boys and girls, you're staying inside all day. You're clothed up when you go outside. Guess what signal you're giving your body. It's wintertime. Guess what the body does in winter. It stores more fat. Yeah. I wanted to literally stop my research at that point, strip, and run outside and just to like shred up a little bit. Yeah. Uh of course, it's not going to work quite like that. Yeah. So, you've got fat as a gland, as a regulated tissue. Yeah. Um do I understand it correctly to say that it's it's breaking something. As you get obese, you're more likely to get more obese. And there's something that breaks that cuz like when you look at people, their set point is riding with them as they're getting heavier and heavier, which is already terrifying. And then it's also secreting things that make you more hungry, that delay your um where you're still searching for food longer. Um One, is all of that true? Like did I just explain that accurately? Yes, but we're missing a very important part to the model. Which is that it's not the only thing that explains our food-seeking behavior. We also will eat food because it tastes good. Mhm. Independent of our hunger, right? We know that where for instance, somebody, you know, you eat a full meal and you're out and you're full. But your appetite is renewed when the dessert cart is brought over and you're like, "Oh, I I can eat that. Yeah, let's get four of those." Mhm. That is another driver of food intake. And we live in an environment that is really designed for overconsumption. So it it's very easy to overeat in our world because the palatability of food is one that will then promote overeating. And it the design of food, processed foods, it also will make you feel less full per calorie. So there's a delay before you even feel fullness. All right, we got to talk about that cuz you showed a visual in one of your talks. It was so powerful and I've been in this a long time, but for some reason that visual really hit me. But when you showed the raspberry tart, which is like a little raspberry pie, it looks so innocent and delicious. And then you showed the equivalent amount of calories in bowls of raspberries. It was like seven or eight bowls of raspberries. It was crazy that just like That actually is a lot of work from Barbara Rolls and her book Volumetrics, which is It is stunning when we think about the how we can dense calories into modern food products. And that's what I want to talk about. When people say processed food, what they're talking about is making it hyperpalatable so I want to overeat anyway. And then secondarily, it it has a lot of calories per physical volume. Yes. So our central nervous system preferences are designed to detect and prefer caloric density. So it is different than eating the the tart versus the raspberries, right? We have now the ability to design food to make us want to seek it. It's a very disadvantage environment. But, the good news is that eating raspberries is also perfectly satisfying, but the more of that highly palatable calorically dense food that you eat, the more that it'll drive food seeking behavior. So, there is a behavioral element to this, how it messes with your neural circuitry. going on mechanistically though? So, is it is it through that mechanism that it's it triggers the release of ghrelin instead of leptin? Like There's so many different molecules that are at play. Metabolically, you're right. Ghrelin is released from what are called oxyntic cells within the gut, and it's very low after a meal, and it'll rise. And as it's rising between your meals, it makes you hungry. It's the only gut-derived peptide that actually promotes feeding versus fullness. Leptin is this what's called a tonic signal. It's sort of operating in the background. We call it a fullness signal. It's not quite. It's actually setting the tone of how full you'll even be from a meal. So, if you have low leptin, you'll naturally be less sensitive to the fullness signals of a meal. So, satiety and long-term fat regulation will work together. Now, independent of that, you have this brain circuitry that's going on that can Think of it almost like addiction to a rewarding signal. The more exposure you get to it, that will then drive seeking food seeking behavior. So, you're not really hungry, and yet you're craving. A lot of people experience this in the afternoon. You're bored, and you're like, I just want to eat something. Right? We know it in our lives. It we we can detect it instantaneously. The easy example is when you bring something that is very calorically dense at the end of a meal, and you're full, but you now want to eat more. It is not the homeostat that is evaluating calories and fullness that's saying, "Oh, you should eat more." It is pleasure, and the pleasure that derives from caloric density. Well, now let's really freak people out. Talk to me about the impact on um [snorts] willpower maybe a cheesy way to say it, but a decision-making if I slept poorly. Yeah, what we see is that not only do hormones change in response to getting inadequate sleep, but our brain changes, too. So, there's something called the neuro-competitive model of decision-making, which means that if you look at that thing that tastes delicious, this reward part of your brain will light up first. It'll It'll respond to it before the executive control self-control area kicks in that says, "Yeah, you might love how that tastes, but it's not good for you." Right? So, you can see that competition taking place. It happens all the time. That process of looking at the the donut that you love, but ordinarily don't want to eat, then that is biased towards eat this now, and it ends up creating a behavior we call effort discounting. You then are this much less likely to work at this thing that ordinarily you totally say, "I care about this, so I'm going to make an effort to just not have donuts in my life." And you're like, "Okay, you know, eff it." I'm like "Tomorrow. I'll just have it now." And that can actually translate to like whether it's going to the gym and the food that you eat. And people live in that in that state where I I I care 95% of the day I'm thinking about eating well, and in that moment of hunger and potentially compared with sleep loss, you make a decision that you're then disappointed in yourself in. And you've talked pretty powerfully about like how much time do you have to lose a night before you start to see some of this stuff going on. Yeah. What I found is that reliably people that miss out an hour or two of sleep have impairments in vigilance, as you'd imagine. So, they're less objectively alert the next day, and they feel sleepier. So, subjective alertness is apparent, too. And interestingly, independently, so I'll will you about the study cuz it's quite cool. I had people come in and what I cared about was what they ate. So, we created a baseline and they had, by the way, eight different choices that ranged from like clearly unhealthy gummy bears to, you know, ostensibly healthy, right? So, things like you know, just cut apple slices or something. And what's another criticism I've had of previous research is that the decisions of the healthiness of the food were made by the investigators, but everybody has their own opinion about food. Yeah, yeah. Right? If you think there's four different types of decisions, there's I like it and it's healthy, easy. Right? I don't like it and it's not healthy, easy. The two in the middle are the most interesting. It's really healthy and I don't really like it, which is sort of characteristic of health choices that we have to make sometimes. And the more most interesting one is I love it and it's totally not healthy. Right? How do people respond to food that they recognize as or they think, "This isn't good for me, but I love this." And what we saw is that when people were subjectively sleepy, they were much more likely to eat foods that they rated as high like low health. So, they were defecting from their own personal health standards, you could say. And now, just to compound things, you've got, all right, you miss an hour or two on sleep and now all of the sudden you're leaning towards the things that you have high like low health, yeah. But also losing sleep makes you look at a blood level like a pre-diabetic. And so, you get this double whammy. Walk us through that, like what's going on metabolically um when you don't get enough sleep? Yes, so that is still being investigated, but it was one of the very first things that was discovered in response to sleep loss. So, they did sleep sleep deprivation studies and found that healthy young subjects ended up basically looking diabetic after either one night of total sleep deprivation or a couple nights of partial sleep restriction, where you're not getting as much sleep as your body wants. What's going on there? So, then that stimulated it some more investigation into that. Now, maybe that is because of altered circadian timing. It was hard to parse that because we know melatonin, a darkness hormone, will actually cause insulin resistance. You want it because over the course of the night, you don't want insulin taking blood glucose out of the bloodstream and storing it cuz then you'd go hypoglycemic and you'd wake up. So, rather the body it's a it's a there's beautiful dance. When darkness falls, melatonin is released. Melatonin travels to the pancreas and it prevents insulin from being released and you keep blood glucose levels stable at the across the night. So, I think when some people that are waking up in the morning and they're looking diabetic, they might still have high levels of melatonin at night uh from the night. We also see that our fat tissue simply becomes less sensitive to the effects of of insulin. And so, it's just not reading the signal of insulin and helping it to store glucose as well. And so, therefore blood glucose levels elevate and then, you know, whether or not that is pathogenic, like does that cause diabetes? Well, you can then look at epidemiological research and shows that people that chronically get less sleep are much more likely to develop diabetes. So, you have to look at acutely what's a mechanism and then epidemiologically what happens when people generally do this and then you have to just try to figure out what's going on in between, but clearly there's an issue going on there and there's no part of the body that goes untouched when we don't sleep get the sleep that we need. All right. So, if I want to get into rad shape, I know that I need to sleep. I know that I need to both get the right kind of light exposure at the right time and I need to um watch my cognitive impact on what I choose for food and then just overall what I choose for food. Yeah. What's the role of of exercise? Um you've talked about how exercise may um like on the surface, it has some counterintuitive impact on weight loss, which I thought was pretty interesting. Yeah, it makes sense if you're burning more calories, you'll just lose weight. And for a lot of people, that actually feels true. Um, probably 12 years ago at the Society for Neuroscience meeting, I saw a very interesting abstract or poster where it was 6 months of of chronic, which that kind of sounds bad, but regular exercise. So, three to five times a week, at least 50 minutes. And what they were looking at actually was the brain and the brain's ability to make, um, to have willpower, essentially. And what they found is that your ability to kind of traverse the world rife with many bad options for us becomes strengthened, uh, when we exercise regularly. You have stronger willpower when you exercise regularly. And we know that to be true. Do Do we know what the mechanism is? Yeah, so there's a couple of different mechanisms. So, one of the mechanisms is acute and it has to do with blood flow to the brain. And when you exercise regularly, the signals that are generated by the demands of creating blood flow throughout the body end up supporting, uh, more blood flow access throughout your body. So, you can perfuse your tissues more easily, including the brain. Exercise that's at sufficient intensity, so at least 80% most studies show, so 80% 80% of max effort will then stimulate, uh, in a variety of ways, something called brain-derived neurotrophic factor. And this is essentially a fertilizer to grow new neurons. So, yeah, it helps us with weight loss, but in a way that is not quite what we expect. It's not just through energy expenditure, but it is through the, signals that are generated from exercise that then keep our body functioning well. There also might be some bimodality here where certain amounts of exercise generate more hunger, but it's not exceeded by what you actually take in. And that has a lot to do with individual susceptibility. Like there's what are different types of eater eating patterns, too. Some people are uncontrolled eaters, so once they start, they just keep going. Some people are really good at just stopping when they're full. They'll leave food on their plate. I don't understand those people. So, um it is it is enormously complex. The the simple message, I think we should seek that in a way. But at the same time, those who promote it as though it encompasses everything that matters, um you know, I think that they're not adequately informed. They're not adequately informed. All right, if you had 90 seconds to tell somebody who's 100 lb overweight what they need to do to lose that weight, Yeah. what would you tell them? So, I think there's two great strategies that I've seen be very effective. One is to go on a packaged food diet. One that is designed for weight loss. So, it's giving you an adequacy of nutrients in its design, and it is a black box. You're only eating what's on the food. I see. I see. So, it Is this somewhere that you can actually get Yeah. There's medically assisted weight loss facilities across the United States that do this. Are there not compliance problems? Actually, I mean, once people get into a rhythm, they do quite well. Okay. They do quite well. 100 lb is a lot. I wouldn't necessarily recommend that for people that needed to lose that, but that is at a level where the excess adiposity or body fat is really health impairing. Now, that's one strategy, and it is effective. Another strategy is a ketogenic diet. I've seen people lose hundreds of pounds with that style of diet. And when I Now that I've explored the mechanisms more, I think it's my preferred style because you can actually have whole foods, and you can eat to fullness and you can lose quite a bit of weight. But at the same side, I mean, I've seen people that have gone on that diet and haven't lost much weight at all. Um but I think with you if you can construct a diet that makes it easier for the body to take in fewer calories comfortably and there are more ways to do it. But if I'm trying to have people lose 100 lb, the simplicity of the keto diet is a great tool. What do you think about um cold exposure, heat exposure? Yeah. Does it have a role in health, longevity, anything? I think it does. I don't exactly know its role, but the bigger window in which cold and heat exposures fit into is exposure to stressors. Mhm. Both cold and hot will elicit what are considered heat shock and cold shock proteins, which are actually shat They're called chaperone proteins and they do multiple jobs within a cell. One, they will find misfolded proteins and they will magnetically bind to the misfolding parts of the protein and can sometimes move them back into a confirmation where those proteins now remain effective. They It's like a key in the lock. Woah. If they're too broken, then they will help to aggregate those proteins. They bring them together and they can deliver them to the lysosome for breakdown into um it's part of the autophagy process. You were at that. So, autophagy vacuums up all of the different broken-down proteins and it delivers them to the lysosome, which then is the incinerator. Okay? Once they it goes to the incinerator, these proteins that have gunked up and are impairing the cell the function of the cell, you now just have created new substrates for new proteins to be built. And so they can support health in that way. Uh and so that's quite interesting and it has neurological effects. So, there seems to be some and improve in mood. Um it's very It actually is very similar to the effects of exercise on the body. Uh, I interviewed a guy, Jari Laukkanen, and he's out of Finland. So, culturally, people sauna there regularly. And they have now been releasing paper after paper. It's a 20-year cardiovascular study of 2,000 men. And what they're looking at is how did How did these men fare depending on a variety of factors, but in this case, how do they fare depending on their regular usage of sauna exposure? So, men that sauna four to seven times a week compared to men who only sauna once a week, cuz that's how common it is there. They will have really a 65% reduction in their risk for all forms of dementia, for myocardial infarction, other forms of cardiovascular disease, and for hypertension. It's all like 64 to 66% reduction compared to men who sauna less frequently. And I think that those effects are very similar to what you'd see if those people didn't sauna, but just did exercise. So, for me, how that's changed is I've been exposed to this information, I sort of think, well, I'm pretty tired today, so I'm not going to exercise, I'm going to sauna, but it's I'm doing one or the other. And so, I'm getting regular exposure to that form of a stressor. And then every morning I take a cold shower, too. Um, so. Yeah. Really interesting. And that your talk on exercise is what made me think about the cold and heat exposure because And this is soft, it's not like the science-based cool stuff that you've been giving us, but there is something to when you exercise every day, your your toughening your mind. Like, you're just practicing doing something hard. And so, I'll say there's I take a cold shower every morning. There probably is something I'll believe you that there's something going on biologically. Um, but just from a I'm doing something hard every day, my psychology, I can feel adjusting. My willingness to step into that cold shower, even though I don't want to, um, and having to do something to my mind to do it to either focus on this is my identity. It's who I want to be. These are the actions that I need to be to be congruent with myself. You know, doing all of that stuff is incredibly powerful and and then because I've practiced that when I get in front of food that I don't want to eat it's the same thing. Eating that would be a violation of my identity which I've spent every day either in the gym or in the cold shower or both sharpening so that I'm always living in accordance with the things that I tell myself about who I am. Yes. Um so I find that really really interesting and I I do want to ask one quick question about GHB. Mhm. For anybody who thinks it sounds familiar, it is the compound that was part of the date rape drug but it has some pretty fascinating effects and you said if looking at this compound it seems tailor-made to be effective against Alzheimer's. Why is that and if that's true, why isn't anybody talking about it? Yes, I'm I'm I'm conflicted with this. And let's get into it. So gamma GHB stands for gamma hydroxybutyrate and I'll give you a little bit of background. In the 90s you can get it from GNC. Say what? Yeah, you could Really? Yep, it was available in every health food store. It wasn't regulated. And people would take it to sleep better. Bodybuilders got word of it because there's research behind it that it actually will stimulate the release of growth hormone. Oh, great. But it does so because it elicits a form of sleep, slow wave sleep that is when most of your growth hormone is released. Ah, but these Italian research just got researchers discovered that it's also released even if it doesn't cause sleep. So then bodybuilders started to take it every couple of hours and that frequency of exposure can cause down regulation of the neural systems that it's activating and that can then develop a very serious withdrawal syndrome. So we had multiple lines of stories that were developing around this drug. One, it can get you very lean, and it helps with sleep. Others it started to be used in the capacity for date rape, but that is a story in itself. Rohypnol or roofies are a very long-acting benzodiazepine drug, and those can be slipped into a drink, and then somebody would have retrograde amnesia, which means they couldn't remember the 15 hours before that event. That was heavily banned. GHB came GHB became the next because it was broadly available. It became the next thing people that were looking to do that used, and it absorbed a lot of the notoriety of Rohypnol. Um but simultaneously, narcoleptics had been put on it to affect how their sleep, how awake they felt the next day, and another symptom that they have, which is called cataplexy, which is a a loss of muscle tone, when they experience emotion. Which is so weird. Yeah. What? Yes, it has to do with the fact that narcolepsy is narcoleptics are missing a protein in their brain, and the circuitry with which that neural system, hypocretin, is attached to happens to connect with our amygdala and emotion. And so when people were about to tell a joke or the anticipation of laughter could make them go into a cataplectic attack, and they could have sagging of their limbs or jaw or completely fall to the ground. It's very interesting model to understand sleep, too, because it you know, a thousand a hundred years ago, you know, you would do lesion studies. You'd like block out some part of the brain and see what broke, and it would then you'd go, "Oh, this might be in this part of my brain might be important for this function." Well, this happens naturally in narcoleptics where probably due to autoimmunity, this group of cells is attacked. So, anyway, these people do not have a good therapy for cataplexy. And why is is so interesting? Because most hypnotics will put you to sleep. They will prevent deep sleep from occurring. So, they get you to sleep faster and they might help with sleep continuity, but you're not getting this deep deep sleep. Can be great in the short term, but it's we're now discovering very problematic if you take that chronically. So, things like Ambien and Sonata. Uh why is deep sleep important? It is during that time that physiological state where we purge those neurotoxic substances. And one of the two hallmark features of Alzheimer's disease is neurofibrillary tangles and the accumulation of beta amyloid, this gummy substances substance that accumulates when we use our with high energy usage. And if we're not purging that, then that could gunk up the the functioning of cells. So, this vicious cycle ends up happening where there's an area of the brain called the medial prefrontal cortex. That area of the brain high energy usage during the day, and it is also responsible for then generating deep sleep at night. It's also part of the brain that ends up accumulating beta beta amyloid first. And so, your ability to purge that has everything to do with how much slow wave sleep that you get. And then this accumulates there, preventing slow wave sleep from occurring. So, it's this feed forward cycle. And we used to think that poor sleep was just a very common and early symptom of Alzheimer's disease, but we now know that it might actually be directly involved in its pathogenesis. So, why is GHB good? Not only does it help very uniquely generate the sleep the type of sleep that's needed to purge that. And how much can we rescue somebody that's already developed it? Well, it certainly might be preventative. But it also, because butyrates, if you think GHB is gamma hydroxybutyrate, and I've been we've been talking a lot about beta hydroxybutyrate. Those molecules are very very similar. And butyrates will actually turn on they do what's called epigenetic modulation to modification. They will turn they will turn on genes that have been silenced. Um [snorts] and so in the brain you'll see that a brain protease called neprilysin is now upregulated when you take GHB and that can go to the beta amyloid and digest it. So I mean, perfectly uniquely suited. And there's one more thing. GHB can also be utilized by neurons as a fuel. It can enter directly into mitochondria. And one of the problems with this whole system is as you start to the mitochondria become impaired in their ability to generate enough energy to then satisfy all the cellular needs and it's this downward spiral spiral because the mitochondria can't maintain enough energy production to maintain cellular integrity, those cells turn into senescence, more inflammation, more disorder, faster faster pathology. And so GHB can clear the clear the proteins, it can generate the sleep, it can also serve as a fuel to keep our mitochondria functioning. You know, a big part of my own PhD thesis focused on this and I think that the argument is compelling. I think that they have a ethical there's an ethical uh consideration for them to pursue this cuz we don't have good therapies for Alzheimer's disease. Wow, man, I'll be very interested to see where that goes. I know. Dude, you've got so much interesting stuff. Tell these guys where they can find you. Tell them how they can find HumanOS. I think it's all amazing and worth pursuing. Thank you. Yeah, so humanos.me We roll out podcast every week, a newsletter. We're constantly creating little short courses that are 20 minutes in length. Um we call them micro courses and we have them all peer-reviewed. We're constantly rolling out how-to guides that just make it easier, workouts, recipes. So it's meant to support your lifestyle in a variety of ways. So make you smarter over time, help to make today easier. And uh all of our thinking goes in there. Love that. All right, what's one change people could make that would have the biggest impact on their health? [sighs] Boy, I probably should say something about light. [laughter] No, what's the what's the truth or the most interesting thing even? I I love the idea of fresh, familiar, fluent. Mhm. Be a positive force in your own community. Learn and I'll explain what I mean there. So, at this model that I've developed for information, we love the fresh. That's like the tweet that came out today. What's what's new? But we live in the familiar, which means we don't spend enough time understanding something so that we can explain it to a friend. We are not the only person in our lives that is responsible for our health, but we have a huge responsibility. We can't outsource that. It's not our doctor's responsibility, although they are part of our care team, but we are too. So, we need to upregulate our knowledge and we need to try, test different things, explore different things. What I would say is when you learn something, try to learn it well enough to explain it to a friend. So, go to coffee, have your little health crew. Whether it's family or friends, go to coffee with them, go to tea, go for a walk, and try to explain something. And you might fail, but that's an opportunity to go back, tighten up your learning, then try again. And that I think will bring you to the place where you have strong opinions held loosely, cuz you'll know why you think about something until it's modified by new info. And I think you're much more likely to be able to exploit valuable information for your own benefit when you get to that place. Uh makes total sense. All right, guys. This is one of the more fascinating people I've come across. You're going to definitely want to dive into his world and check it out. You will be richly rewarded. And I cannot thank you enough for coming on the show. Thank you so much. If you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. [applause] Amazing, dude. Thank you guys so much for watching and being a part of this community. If you haven't already, be sure to subscribe. You're going to get weekly videos on building a growth mindset, cultivating grit, and unlocking your full potential.