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Dan Pardi – Full Interview


I’m Dan Pardi. I do sleep research, and I am also very interested in the question of how do we be healthy and all the different ways that we can understand what that looks like and how to implement it in our lives right now. I think there’s a lot of theories about what makes us healthy and live long, and I think it’s always important to look at the examples of the world where that’s actually a reality and whether or not we want to implement what they do in these different zones prescriptively is another question, but I think understanding those populations as well as possible is a really smart thing to have at our disposal. It’s such a good question, and I don’t really have the answer in my mind, at least in terms of I like the idea of have strong opinions and hold them loosely, but can we just reproduce what they’re doing and expect the same result? We live in a very different world. I think what we can do now is we can test and see how we feel, and that sometimes can be misleading and sometimes it can be really informative. We’re trying to read the tea leaves, and it’s understanding what’s known in the world, understanding ourselves better, understanding ourselves now and then having things that we want to test and try to see does this meaningfully augment my day-by-day experience? Do I feel better? Do I think better? I think having a very tight relationship with how you think and perform is one of the smartest things we can do.

We are products of our environment in so many ways, and the world in modern life is different than it’s ever been in all of human history. Not only that. If you’re born this year, life is different than it was 10 years ago, and that trajectory is not going to change. It’s going to accelerate. We’re born into a world that is really different than what our biology expects. We have the ability to live at all different parts of the world within a lifetime. We have modern forces that are shaping what we do and what we should be aspiring and driving towards, and so a lot of people aren’t thinking necessarily about their health every day as much as people that are more geeked on the subject, and so they are really subject to the pressures of their job, pressures of their family and then ways that we can manipulate interests and behavior to use an app a lot, to spend less time with people and more time inside, to seek conveniences so in the limited amount of time we have, we get more personal time. There’s a lot of things that shape how we live, and we definitely need ways to take charge of that so that how we are living is not entirely affected by those pressures, those modern pressures and forces. There are many organizations, companies, VCs investing in technologies, the point of which is to entirely take control of how the person is living. We’re going to tell you what to eat, when, when to go to sleep. That I think is the misappropriation of potentially useful technology. Technology is better when it helps us become more in touch with ourselves, not less in touch. I don’t think that we need something that always is telling us this is how you live right now. I do understand that there are probably use cases where that might be useful. It can get people better, but I think we should… We have this relationship with ourselves. We should aim to understand ourselves better in the world. What is health? It’s proper biological functioning. That’s how I think of it, a good general description. What the World Health Organization says health is the ability to withstand insults and challenges and maintain homeostasis or an internal balance, but I think probably one of the most important aspects of health is their second aspect of their definition, which is health as an attribute to helping you realize your aspirations and to live a high-quality life.

We know that delayed discounting is something where if you don’t eat this cheeseburger now, then how much health benefit will you get in the future? That tends to be intangible, and it’s not a very powerful motivator. While most people are… recognize that they don’t want a chronic disease, we don’t do anything healthy usually so that you prevent peripheral arterial disease, right? You do it because of culture, and it feels good, and you do have a recognition that it’s good for the body. I think one of the best ways to implement health in your life, to be healthy, to do those things that are hard or at least different than what everybody else is doing is to focus on performance. Am I thinking well? Am I going to perform well in my life, in my social relationships, in the things that I care about. My performing well at a meeting tomorrow in a presentation. I think if you can harness that understanding and potential, then it can really fuel your ability to do the right things or things you want to do to be healthy. It is a tighter feedback loop and that we know from a behavioral perspective that that really does matter. On one hand, technology can completely distract us from our health. It can lead us astray. You could spend all your time engaged in theoretical health behaviors of testing and diagnosis and reading without a lot of doing. I have this saying that knowledge itself does not immunize you from living a healthy lifestyle. Right. You could have theoretically be the most knowledgeable professor on a certain topic, and they are not protected by their knowledge if they don’t implement that into their lives. Conversely, you could have this teenager that has a very natural lifestyle, is out waking up early and surfing and eats good food with their family and has low social stress in a good community. They might not know any of the theory or benefits of why the things that they’re doing are good, and they’re going to get all the benefits from it. I do think that knowledge matters because in our world, again, as we were talking about earlier, our behaviors are often shaped by what’s convenient and what is everybody else doing, so knowledge on something can help us make choices that are different than what everybody else is doing around you. I think that to a degree, having fluency around certain subjects can help, and I think technology can facilitate that. I also think having more knowledge about yourself can potentially be useful, but it can also potentially lead you down some rabbit holes that aren’t that helpful.

Right now, we see that with things like Fitbit. You see reports that some people are trying to do it for weight loss, and it actually made them gain more weight. There is again potential for these things to be useful, but you have to understand how to use them, that it’s not a silver bullet. It’s a part of more of a whole ecology of health behaviors that we need to engage with ,and if it is again reinforcing a lifestyle pattern, that itself is good, then I think technology can help us live more naturally. When it helps us live more like a technocrat and disconnected from our natural behaviors, then I think we get into trouble. For a long time, I’ve been compelled by the idea of ancestral patterns of living, and I think that some people put all of the answers into trying to replicate and understand what do hunters, gathers, modern day or ancestral estimates tell us about how much potassium we should be getting, what’s our movement patterns like. I think is another valuable, informative source, so we combined ancestral understanding; we combined modern-day science; and we combined an understanding of behavioral science and then technology to facilitate all that. I think we have a nice ecosystem in the realities of modern life to help us say, “Okay, I’m going to try to live more naturally, and what does that mean? It means that you’re not over-indexing one behavior, you’re not trying to say, “All of my health efforts are going to go toward exercising more.” It’s a linear… The more I exercise, the healthier I get. But rather that there’s a lot of different factors. There’s sleep; there’s food; there’s stress both dealing with handling psychological stress and also seeking out stressors so that we have different exposures. Exposure to the sun, exposure to cold and hot. Those are all stressors, but those actually will facilitate our important biochemical signals that are a part of our health. We sometimes think that we’re perfectly healthy as these free-standing units, and the reality is that our health is in relation to the environment around us, so the exposures and how we live. That means that we probably instead of trying to just run more miles per week, that we want to just get more of a variety of exposure types. I think that ancestral patterns can provide a nice template to say there’s a heuristic, like what do they do? How can that guide me in the type of behavior now? A good example would be do I want to just get up in the morning, run a couple of miles, and then sit at my desk all day in a low-lit room at a computer? Probably not.

On the other hand, do I want to get some morning light exposure? Do I want to be up and have different types of movement throughout the day, so more low-intensity exposure, more high intensity? Do I want to also rest and nap?That can all be informed by thinking, “How do our ancestors live?” Then using that as a guide to try to help us do better across more of those domains. I think that that’s some really informative heuristics. Yeah, so if you look at equatorial regions, the band of temperature that they experienced across a year was somewhere between maybe 50 degrees to 90 and then sometimes beyond that, depending on where you live. That is actually a relatively narrow band for what a lot of people are exposed to, but we have a way to use institutionalized shielding, so we control our environments when we’re inside a room. We control our environments when we’re outside by putting on multiple layers of clothes. That all adds to more comfort, less stress. What happens though is then the body becomes less comfortable in different heat ranges. We have a harder time controlling with heat, although you can have air conditioning when it’s really hot, but it’s a lot easier to manage cold. Now why is that potentially important? Well, if that was over millennia, the natural exposures that humans got, then there might be, there might be important signals that are derived from those types of exposures. There might be benefits to specific exposures in temperature, particularly cold and also hot, that facilitate something important in our health ecosystem of our body. For example, we do know cold exposures will trigger something called heat shock proteins and also cold shock proteins. What these do, these are chaperone proteins that will help to prevent protein aggregates. We know Alzheimer’s disease built up a protein aggregate called beta amyloid. We also know that they will add to stress resistance, so the old idea that don’t go outside when it’s cold, and you’re going to catch a cold, that’s probably true if you don’t get cold exposure often, but if you do get cold exposure often, then you’re actually building resistance. You’re building resilience.

That’s a part of our health is to build resilience, so a great example is sunshine on your skin. If you have not been getting much sunshine over the winter, and you step outside, and you want to let’s say get a tan, don’t go spend seven hours in the sun. You’re going to burn, but if you get a little bit of exposure, that stress, that hormetic stress will cause an adaptive response causing melanin to produce a dark pigment in your skin, which makes you more resistant to more sun exposure, and you build your resistance. We can do that with cold. We can do that with heat as well. We do it with exercise. Adding stressors into our life is actually an important part of our health. It is that stress that facilitates and adaptive response. That adaptive response ends up being health promoting and keeping our body functioning as we want it to. How can you add more cold to your environment and to your life, and how do you do that? Well, an easy way to do that is to take a cold shower in the morning. I think that there’s additional benefit of having a strong sympathetic response from that cold exposure, which will then help with circadian alignment, so you have better circadian rhythm alignment. If you think about what are circadian rhythms, I’ll introduce that. These are repeatable, 24-hour processes that help keep our body in rhythm. We know that there are certain times of day where we have what are called phase relationships where one hormone might be high, another one is low, and that’s going to then create almost like a lock and a key in terms of the cellular response that’s being instigated. There are different activities that the body does at different times of day that are, again, part of our health process. Yeah, so circadian rhythms are a really fundamental part to our health. Only in the last 10 or 15 years have an understanding of circadian rhythm that’s now been derived by science, has it become a part of the equation of our health. Same with gut microbiota, same with epigenetics. Before that, it was diet and exercise, right? Now we know that there’s these other things that are really fundamental that are at play, and so what circadian rhythms do is they help to look at past behavior to then try to predict a physiologic response for that time of day. That’s why we don’t want… The body doesn’t try to have you get up seven times during the night while you’re sleeping to go to the bathroom.

You feel hungry during the day. You feel like going to the bathroom during the day, and at night, there’s a whole other set of physiological activities that take place that are suited for that time of day. Now, when we have light exposure, which is the main synchronizer of circadian rhythms at times when your body usually would be getting darkness, so having artificial light at night, that’s going to tell the brain that it is daytime. It’s going to act naturally to that signal, which is then going to create an unnatural or potentially pathogenic response in the body. Another signal there is getting cold exposure early in the morning, and so you have this robust catecholamine response from epinephrine, and that is going to make you feel more alert. It’s going to help to align your circadian rhythms, so it’s going to contribute to that panoply of signals that helps your body understand this is daytime,and that’s going to keep a lot of your rhythms in line. Let me stress the importance of this. We know that people who do shift work or that have chronically misaligned circadian rhythms, they have fourfold increases in cancer rates. They have multifold increases in cardiovascular disease and risk. It is a clear indication that the body is not functioning as it should because it doesn’t understand what time it should be doing things, and so you have this misalignment that is affecting our health and our performance. We know that it impacts memory. We know it impacts cognitive functioning and physiological processes too.That’s one thing that’s talked about less is the cold exposure-induced catecholamine response, but that’s one thing that I’ve noticed that helps me have more robust alertness during the day, which then actually will facilitate deeper sleep at night. Circadian rhythms are again trying to anticipate what the needs are of the body based off of past experiences and exposures so that, for example, if you typically eat at every morning at 8 a.m., the body is going to prepare enzymes that are going to help to process that meal. If you are eating a certain type of food every single day at that time of day, those enzymes are going to be suited for breaking down that type of food at that time of day. In a recent podcast of mine, we talked about breakfast skipping, and I think if you have high variability in your meal times, that is a condition that is less favored for proper metabolic responsiveness to the meals that you take in, which could lead to poor regulation of blood glucose and could also lead to things like obesity.

That’s one indication and an example. Now does that always mean that breakfast skipping is a bad thing? Actually, I don’t know because maybe if you always skip breakfast, and your first meal is let’s say at noon, that could be favorable. There’s more research that needs to be done to understand these things more closely, but another good example is just for example how blood glucose is regulated at night. When the body releases melatonin, which it does in response to something called dim light melatonin onset, which means that the certain tone and intensity of light is coming into the eye, it’s affecting something called intrinsically photosensitive retinal ganglion cells, which are types of photosensitive cells in the retina that will communicate not to the primary visual cortex, but back to an area of the brain called the master clock. That master clock then is then saying okay this is the time of day that it is, therefore, initiate these programs. Again, how does the body maintain stable blood glucose levels over the course of the night? Well, one thing that dim light does it stimulates melatonin. Melatonin will directly affect pancreatic beta cells to suppress insulin release. Insulin, as we know, will store glucose, right? If you’re suppressing insulin, it’s going to actually help to keep blood glucose available in your bloodstream for longer, right? You’re going over a seven-hour fast. Now,that’s not the only thing that happens. You also see a buffering of blood glucose by a growth hormone response in response to slow-wave sleep. That will also will cause insulin insensitivity, which typically is thought of being a bad thing, but it’s actually an adaptive physiological response to maintain blood glucose. Then during the night, it changes, so as you go through your slow-wave sleep and then into more REM sleep, you see towards the end ofthe night more cortisol being released. That then helps to then produce more gluconeogenesis in the liver and also to release some glucose from your cells. Altogether, you have different mechanisms, all circadian controlled, that then help keep stable blood glucose levels while you’re fasting. That’s a really nice explanation to see how this orchestration of your physiology is all being timed so that you end up having good, stable energy levels, and you’re not waking up in the middle of the night because you’re starving or because something is alerting to you because of poor bioenergetics. That’s a nice example then.

Biomarkers are theoretically these things that we can rely upon that indicate current or future health. If you get, for example, a measurement of inflammatory marker, that can tell you that there’s something going on or that you’re healthy. A lot of the establishment of our biomarker ranges were within a context that has already shifted greatly from a more ancestral natural living condition. How much we can rely upon those markers, all ofthem, is variable. Some of them are more productive, and I think we’re going to learn a lot as we enter into the space of big data, where we’re able to collect a lot more data on a lot more people and also during what we’ll consider more natural healthy times versus just trying to predict a disease oryou may already have it.You have already had a heart attack, and so now we’re actually trying toprevent the second one, and we’re going to measure these certain markers. Do I think that we’re going to enter into a period where we’re going to be able to collect a lot of data on ourselves? People are going to be making decisions off of that data that is going to lead them down some wrong paths potentially, but through it all and through a period of sort of awkward teenage years of big data, eventually, we’re going to arrive at a place where we understand populations and subpopulations and perhaps even somethings that are uniform for all humans that are predictive and indicative ofhealth. I have higher confidence that if we manage two of those markers will indeed will be driving towards health, will help an individual get towards health. That’s I think the reality of the situation. How soon we’ll get there, I don’t know.We know that we live in a much more sterile environment than we have in the past, and children that grew up with dogs and grew up on farms, they have more diverse ecology in their microbiota. That seems to correlate with future health outcomes, positive ones. Less cardiovascular disease, less cancer. We also know that for example children that are born in the ICU, the NICU, so if they’re born prematurely, what did they use to do? They wouldkeep them under 24-hour light exposure because the nurses will want to monitor the health of the child. Well, it turns out that their circadian system doesn’t fully develop until for six months after the child is born, so they’re getting circadian cues from their environment and also from the mother.

If the mother is up late at night reading a book or gets up to feed the child late at night and turns on a light and that alters their circadian rhythm, those signals are being passed to the child and that’s having an influence on the child’s future for the rest of their lives because it’s affecting the health of the circadian development. Excuse me, it’s affecting the development of the health of the circadian system. Those are some interesting exposures, but we also know that who we’re surrounded by, life purpose, there’s a lot of things that can lead to subconscious psychological stress, whether you’re aware of it or not. One very interesting thing about people is that we will acclimate to our stressors in our lives. If things are improving, and it takes eight weeks forthem to improve, it can be meaningful but invisible. The same meaningful but invisible trajectory can happen in the other direction where you’re performing better at one point, things have gotten worse over eight weeks, and you don’t see it. You don’t really see it. We don’t have that objective feedback that’s constantly telling us. Sometimes you can. It’s not unseeable, but it’s easy to overlook, and how do we address that? I think, again, really understanding ourselves and checking in and yeah, are there some things some objective measures perhaps that you can… a battery of life health and quality of life? Those things are all I do believe in the power for objective technological measurements to inform us and help us have that ah-ha moment. Ah, thereis something here. But I think that subjectively just having that really good relationship and taking a moment for some metacognitive processes of saying stepping back and then thinking about your life, like how am I doing? How do I feel? How are my behaviors aligned with my goals for how I want to be living? All of that really matters, and so yes, I’m super excited about technology. I think that eventually it’ll help us in our own efforts, but we have a lot of power right now, and I don’t think we should be looking for one silver bullet that’s going to explain everything or waiting for the future tohave all of our problems solved. We don’t know what’s going to actually happen, and we have a lot of information right now that resides within you, but the problem with listening to yourself is that we have confirmation bias. We can see things that aren’t there, so just try to be very accurate with what you see. Hold your opinions loosely, and realize that you might be doing something right nowthat you think is good for you, and it might not be.

Be open to modifying your approach to find something better if it’s not serving you as much asyou think it is. So many aspects of our health and how we live are dependent on one another, so the food we eat will impact the sleep we get at night. The sleep we get at night will impact our desire to be physically active the next day. The physical activity types, modes, and modalities that we actually engage in will affect what we choose to eat and how we sleep, so they’re all interconnected. We think of them in silos, but the reality is is that … and that’s okay to try to understand individual contributors with better fidelity, but ultimately, they’re all interrelated, and so we have 24 hours to affect how we’re living, the exposures that we’re under, the behaviors that we engage in. That is our template, right? That’s what we have to work with, so all the knowledge that you have, all the technology needs to be coalescing in this period of a day to guide to then hopefully have you have these right types ofexposures and to including exposures to friends and including exposures tothe right microbes and foods. Now we do know that light during the day have a very important impact on light at night … or excuse me sleep at night. Part of that is hormonal signaling. Part of it the entrainment or the anchoring of our circadian rhythm. Let’s say you get eight hours of sleep,and you typically sleep from midnight to eight. That’s your usual pattern, and one night you go to bed and you go to bed at 4 a.m., and you wake up at noon. Eight hours of sleep, right? That sleep willnot be as restorative, and the reason why is because your body … sleep itself is a circadian rhythm, and your body is used to getting slow-wave sleep at acertain time and REM sleep at a certain time. Consistency of schedule ingeneral is a valuable thing. Now we also know examples where cultures will stay up way past their typical bedtime and dance late in the evening, and that’s one thing that I’ve always noticed is that dancing was a big part of ancestral communities. It was a way to bond. It was a way to be physically active, and so this concept of orthorexia is an important one, which is I do think we need to be mindful and drive the right behaviors against this backdrop of common lifestyle patterns that we know lead predictably to disease. At the same time, we have to have the ability to just embrace the opportunity to go out late one night with friends and live life in that regard as well. That’s the art of health.