Dhru Purohit Show - The Cancer & Dementia Link Nobody Warned You About and How to Reset Your Circadian Clock to Lower Your Disease Risk with Dr. Satchin Panda

Episode Date: February 25, 2026

This episode is brought to you by Puori, Cozy Earth, Fatty15, and Birch Living. Circadian rhythm is one of the most overlooked drivers of long-term health. It influences when we sleep, how we metabolize food, how our brain repairs itself, and even how our immune system functions. When this internal clock falls out of sync, the effects ripple through every system in the body. Today on The Dhru Purohit Show, Dhru sits down with circadian biology expert Dr. Satchin Panda to explore the four pillars of circadian health and how losing alignment can contribute to cognitive decline and Alzheimer’s disease. Dr. Panda shares key strategies to reduce your risk and breaks down the science behind why protecting your master clock is critical for preventing chronic disease. He also explains the importance of time-restricted eating, how timing influences the effectiveness of medications and cancer immunotherapy, and the role exercise plays in detoxification.  Dr. Satchin Panda is a world-renowned pioneer in circadian biology and a Professor at the Salk Institute for Biological Studies, where he holds the Rita and Richard Atkinson Chair. Recently named a semifinalist in the XPRIZE Healthspan competition, Dr. Panda leads "Team Circadian" in groundbreaking research to reverse biological aging through rhythmic optimization. His discovery of the blue-light sensitive protein melanopsin and his extensive research on time-restricted eating have reshaped global health guidelines, leading to featured presentations at premier international forums including the American Diabetes Association and the professional diabetes societies of Europe and Australia. In this episode, Dhru and Dr. Panda dive into: (0:00) Intro (00:59) The Circadian–Alzheimer’s Connection (3:00) Why Light Controls Your Health (26:36) Sleep as Brain Defense  (34:01) Inside Your Master Clock  (38:17) Why Meal Timing Matters  (49:33) Time-Restricted Eating Explained  (57:12) Timing Your Medications  (1:01:27) Circadian Biology & Cancer Treatment  (1:09:25) Exercise as Cancer Insurance  (1:16:01) What Exercise Does at the Cellular Level  (1:26:23) Minimum Effective Dose of Movement  (1:57:47) The Circadian Challenge  (2:06:21) Circadian Rhythm as Your Operating System  (2:11:20) Final Takeaways  Also mentioned in this episode: OnTime Health App  Human Performance Alliance  For more on Dr. Satchin Panda, follow him on X/Twitter, Instagram, Ontime Health’s Instagram, YouTube, LinkedIn, or visit his Website. This episode is brought to you by Puori, Cozy Earth, Fatty15, and Birch Living. Quality protein matters. Get 32% off Puori Grass-Fed Whey Protein and a free shaker when you start a subscription at puori.com/DHRU and use code DHRU at checkout.  Right now, get 20% off your Cozy Earth sheets and sleepwear. Just head over to cozyearth.com/dhru and use code DHRUP. Fatty15 is offering an additional 15% off its 90-day subscription Starter Kit. Go to fatty15.com/dhru and use code DHRU to replenish your C15 levels for long-term health. Birch is exclusively offering my community 27% off their Birch Living mattress—just head to birchliving.com/dhru today. Sign up for Dhru’s Try This Newsletter Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Suchin Panda, world's leading expert on circadian biology, ton of research inside of the space. Professor at the Salk Institute, welcome back to the podcast. You know, our last interview together, largely because of you, I had nothing to do with it, has over a half a million views on YouTube, hundreds of thousands of downloads on audio. And we have you back on the show today to remind us that your body has a master, clock and that almost everything about how long and how well you live depends on whether or not

you're working with it or against it. And so we're excited to dive deep into a whole bunch of new topics and one of the top ones that we want to get into is tell us what we know now in 2026 when it comes to the intersection of cognitive decline, Alzheimer's, and circadian biology. So what do we know now? So what do you think of cognitive decline? The only sign of cognitive decline is actually depression. In many people, there is loss of interest in regular day-to-day life. And people usually close themselves.

They're not mingling with other people anymore. So let's break it down to depression is one aspect. Then the other aspect is the sleep may be disturbed. And we are actually seeing both in humans and also laboratory models that years before the onset of dementia or mild cognitive disorder, there is sleep disruption. These people cannot fall asleep easily or if they fall asleep, then they wake up quite a few times or during daytime they have excessive sleepiness. So now we have depression and then sleep disruption. The third thing that is emerging slowly, and now there is a lot of human studies pointing to,

and you mention that now the physicians are saying that you should maintain a healthy body weight. Because what we now know is some people are describing dementia as type 3 diabetes. So that means when your blood glucose control is disrupted, when you have high blood glucose, or if you have cholesterols and lipids are elevated, then that also increases your risk for dementia. The reason that we think is the supply of nutrient to the brain is affected,

and maybe there is plaque somewhere along the arteries, so that also reduces blood flow to the brain. So now we have at least three components, sleep disruption, depression, depression, and then this metabolic disorders. So from circadian part of view, what we know is people who get enough daylight. And when I said enough daylight, then that's a very weird term because actually our visual system kind of mimics and hides how much light we get. Because, for example, when I walked into this studio, initially my reaction was, wow, this is so bright.

And then within few seconds, I got adopted. And now I'm like, huh, maybe there should be more light on Drew's face. So the point is, our visual system actually doesn't tell our brand how much light is actually present. So we always continuously adopt just like our smartphone. You don't see an overexposed picture and you don't see under-exposed picture. So when we objectively measure light by putting light sensors on people, even in Southern California, in Sunnis San Diego and LA, what we're finding is more than 70% of people, adults,

who even have a regular job, all those are kids who are going to UCLA, UCST, and all these colleges, 70% of them don't even get one hour of daylight. And we know that daylight has wonders because it has actually three very powerful effect. First is the bright light acts as anti-depression. So it reduces your risk of depression. And even in San Diego and California, there are a lot of people with depression.

Second thing it does is it increases alertness and executive function. So light actually has that positive effect. And the third thing that we are just slowly learning is it has a weird effect that daytime light exposure increases your nighttime melatonin production. And we know that melatonin is a hormone that's produced from the pineal, and it actually helps us to fall asleep by relaxing, by dilating our blood vessels, etc. So one thing I would say is most people should actually get outdoor for at least an hour during daytime to get some daylight. And in many places in the world, the weather may be okay to go outdoor, but if you cannot go out of the way, for example, if it is snowing or if it is too hot,

then even under a canopy outside, or even sitting right next to a large window in a sunny day, will also give you enough amount of light. So that's one thing that we are understanding that this is very important. And now there are many researches where people are actually putting bright daylight simulating light,

because most of the light that we see indoor is actually not as good as daylight, because daylight has a very nice balance of blue and green, yellow, red, all this full spectrum of light that we don't have in many of the lights. But in all these interventional studies, when people with mild cognitive decline or all the stages of Alzheimer's disease, when they're given this daylight simulating light, even indoor, they actually have much better management of the disease.

Like, for example, they feel less agitated during daytime, their sleep improves. So at least there we do have some proof that light during daytime improves mood, reduces depression, increases alertness, and may help better sleep at night. The reason why I use the word may help, this has not been done in people with early cognitive decline,

but it's mostly with younger individuals and middle-laced adults. Now, the second thing, so this takes care of kind of sleep and mood deserters. Can I mention one thing about the mood disorders based on something that you were sharing earlier is that, you know, you published research in 2024 on time-restricted eating, and you also talked about this connection between circadian rhythm and how it plays into depression, anxiety, and so the point that I really want to drive home and mood instability is that really circadian rhythm might not just be a symptom of those conditions, but could be a central cause of them. And because daylight seems like such a light intervention, right, not a heavy

intervention, it's not a prescription, it's not a medication, it's not a supplement. It's so easily overlooked. And because most of us are indoors, we don't realize, unless if you're using like a Lux reader, you think it's so bright inside. And yet I regularly am in a broad room that isn't more than 500 lux. Yeah. As you mentioned, it's raining outside in LA. We go outside right now, it's probably at least 5,000 lux on a cloudy day that's there. So we are only beginning to understand how so much of our biology is related to these things

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Just head over to cozyEarth.com and use the code D-H-R-U-P, Drew P, for up to 20% off. And if you get a post-purch survey, please mention you heard about Cozy Earth right here. It really helps support the show. Because comfort isn't just nice. It's how we take care of each other. Yeah, so you brought up a very important point. light, we think that it's a very mild intervention. But if you think about it, our ancestors

means up to, say, 1850, 1850. So 150,000 or 200,000 years before that when our ancestors were on this planet, the one predictable chance that happens every single day was in the evening, there was no electricity, there was no light switch, there was no rectangular pieces of glowing objects. So in the evening, as soon as the sun went down, it was really dark.

And the only source of light was maybe firelight or maybe a candlelight. And one candle light, the light that comes from a single candle in a dark room, and if you're sitting one yard away, so that's one locks of light. So our ancestors were getting one locks of light if they're lucky, because not everybody could afford to have this. at nighttime. Between sunset and 9.30 or 10, because we have measured now circadian rhythm and populations who have no access to electricity, and that's what we see.

Like less one or two locks until they go to bed. And when that candle is put out, then it's so pitch dark, you can't even see your hand right in front of your face. So it's zero locks. And then just before sunrise, the light goes from zero to 500. And then within an hour of sunrise, when our ancestors went outdoor, because, you know, there is no incentive to stay indoor because there was no refrigerator.

There is nothing to eat. And they have to get out. And it was so largey with birds and animals, they have to get out. And within an hour of sunrise, the light would hit 10,000 or maybe 50,000. If it is a sunny day. So just imagine our life evolved on this planet with this strong contrast between zero locks at midnight and tens of thousands of locks during daytime. There is no other environmental factor that changes 10,000 fold every single day in our entire life. So that's the driving force that has already designed our body and brain to adopt.

to anticipate that darkness at night, and also to anticipate that light during the daytime. And for a long time, we thought that this is just metaphysical, this is just in your mind, but I think they discovered that there is circadian rhythm, and there are specialized type of light sensors that sense this light, and all of these are encoded in our DNA, and there is no escape from this.

Modern medicine can change your appearance, you can change an organ, We can have dental implant or kidney. We can change our kidney and many things. But we still cannot escape from this very 24-hour rhythm in our sleep-wake cycle. So we take this for granted, but this light is so powerful that we forget that.

So during daytime, we don't get enough light, and at nighttime, we light up. So in the evening, in a typical home, you know, we also have the tendency that we'll go and buy the brightest light to get the best bang from up for a buck. But then in the evening, we're exposed to 300 to 500 locks of light. And if you're going to a store, like a grocery store or a drugstore, it means a lot of people go line up for the medicine in the evening, the drugstores have 1,000 locks of light. So bright. So bright. It's almost like twilight.

And LED and usually just a very narrow spectrum. Yeah. And I think that that's the biggest polytent that we ignore, that this light in the evening is such a strong, I'll say hormone disruptor, endocrine disruptor because it disrupts our melatonin. So, you know, at 1,000 lux, if you're in that store for half an hour,

then your melatonin is slammed down. to almost undetectable level, and then it takes you some time to build up that, and it also increases stress. So we have to remind ourselves that our body was designed to live in a very rhythmic, very predictable light, dark cycle, and that's why this light during day time is so much important,

and also having a dark room improves your sleep. And a lot of us, we actually don't have darkness anymore. Would it be fair to say that evening, light is another form of almost like a toxin that we're all living with, that too much evening light with a narrow spectrum over years, we have to think of it no differently than, yeah, it may not have immediate implications like secondhand smoke, but it is a form of a toxin that we're all being slowly exposed to over a period of time. Yeah, so it is actually a secondhand smoke because, you know, if I smell secondhand smoke, it may not affect me next day, but if I keep on having that secondhand smoke,

So evening light is almost like secondhand smoke. Yeah. And in fact, we are seeing that now, you know, we cannot do these experiments in humans, but in animal models, if you take an animal that is predisposed to dementia, algeous disease, and then put that animal in continuous light or extend the day with extra hours of light, then or disturb the sleep, then those animals actually get dementia much earlier. than animals that have strong light dark cycle. So there is this causal relationship

between circadian disruption because of light and dementia. So this is something that everybody can do. So that's why I always tell these are this small investment everybody can do when you're going to buy a light bulb, particularly for your bedroom, living room, kitchen, etc., then don't go for the biggest bank for your buck, actually go for modest amount of light so that you have 20 to 30 locks or 40 locks of light. And there are quite a few apps that can measure light.

And then one of the apps that we have on time health, so that also has a light meter. So, and the second thing that people can do is instead of having light switches, it's better to have dimmers because during daytime, you can crank up the light and then nighttime you can crank it down. And many years ago, I replaced most of my light switches with dimmers. And these days, when I walk into somebody else's house, like Trent's house, when I see switches, it almost cringes me because I know that I'll be sitting in the living room with bright light and then I cannot sleep that evening. So these are small changes that people can have, people can do that will have huge impact. Yeah. So let's just recap a couple of those before, you know, you were going through your list as it relates to coffee. cognitive decline. We talked about the depression aspect of it, its relationship to circadian biology,

in particular, the light aspect. And then we have sleep and we have the metabolic side. So we'll continue down those. But just to go through some of your action items that you share here, especially as it's related to light, making sure that at night we're dimming in the lights in the evening, not over exposing ourselves to super bright light. There's this whole movement now of people going out of their way to find incandescent light bulbs, I definitely am participating inside of that or getting in some, especially the bedrooms, getting more like red spectrum light bulbs that are there

so that they're not getting as much blue light that's there. Using dimmer switches, especially on the overhead lighting that's there. And if you can use lamps that are there instead of overhead lighting, those things play usual. Are you a fan of blue light blockers? Are you not a fan of those?

Well, actually, you know, when you're talking about incandescent light, you're essentially reducing blue light at the source. For many people, blue light blocking glasses in the evening works because when they have no control over the source, if they cannot change the light bulb in the room, at least they can put the blue light blocker. Yeah. And I have seen quite a few people who use blue light blockers

and then they say they fall asleep much easier. Yeah. And I can relate to that because when you block blue light and enough blue light, then you actually allow melatonin to rise. And typically, a melatonin, this sleep promoting hormone melatonin, begins to rise two to three hours before our habitual bedtime. So that means, suppose you are going to bed at 10 o'clock, then from 7 p.m. onwards, melator is slowly creeping up. And if you have a lot of blue light, then melatonin will not go up. And if you block that.

So now the question is, which ones are real blue light blocking glasses? Yeah, there's a whole variation in terms of product quality and things like that. So many different types of blue light blockers. We buy different types, all these different types, and then when we use a spectrometer to really see the spectra that's coming out of them, which spectra is blocked, The rule of thumb is if the glass is looking yellow and red, then that's a true blue light blocker

because it reduces at least 50 or more percentage of blue light. And that's why these glasses are looking yellow or red. And we do give them to many of our study participants who want to improve their sleep. And in many cases, we do see they improve. But as I say, you know, there are many causes for sleep disrupt. Sure. And this is just one of them. It's one.

And this is just like having a toolbox in your house. It's not like you can have only one screwdriver that will fix everything, but you need a bunch of toolbox, tools in the toolbox and this is one of the tools. That's one of the tools. Okay, great. So zooming out big picture, we started off with cognitive decline. Yeah. And you're not a physician, but you are a researcher.

You're one of the world's most foremost researchers inside of the space of circadian biology. And there's all this emerging science that's out there that so many of the things that people are worried about because they look out into the world and we see increasing rates of Alzheimer's, which also disproportionately impacts women. Yep. Right? We know that through a lot of the research that's out there. People are also worried about things like cancer, which we'll talk about in the future. So many of those things are connected back to circadian biology, but we're not paying enough attention to it because a lot of this in the history. history of medicine is considered emerging science that hasn't made its way down to the practicality

where your physician is writing your prescription for an incandescent light bulb or for dimmer switches. You have to become the CEO of your health to say, hey, there's things that I can do every single day that could potentially lower my risk of getting these disease. And even if they don't, because these diseases are multifactorial, they're still going to help you with so many other aspects, including feeling good. So we talked about the dimmer switch. We talked about the light. We talked about at least one hour of daylight outside, which most people, even in Southern California, are not getting. So those are related both to depression, but they're also related to sleep. Is there anything else that you want to say about circadian biology and sleep as connected to

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and a lifetime warranty so there's super little downside to giving it a shot. I want all my listeners to enjoy a deep restful night's sleep with a new mattress from Birch. So if you're If you're interested, go to birchliving.com slash Drew for 27% off. That's Birch, B-I-R-C-H-L-I-V-I-N-G-G-com slash D-H-R-U. That's me for 27. 27% off exclusively for my community today. Yes, so I mentioned that very early on, we do see sleep disruption that precedes cognitive decline. It's an early indicator.

It's a very early indicator. And then the question was going back to circadian biology. I'll just say one or two very foundational things. So one is we know that we have circadian clock. So when I say circadian clock, these are essentially nearly a dozen different genes. They talk to each other and then they turn on and turn off each other in a way that we produce. The cells produce a 24-hour rhythm. cellular function and energy production, cleaning, and all that stuff.

But the bottom line is not all clocks are, although we have clocks all over our body in the brain, there are only 20,000 nerve cells. They are sitting at the base of our brain, the base of the, we call it hypothalamus. It's called supra-chaismatic nucleus. It's a mouthful. but then the bottom line is this is the timekeeper of our entire body. And these 20,000 neurons has so tiny and so clustered together that most neurobiologists actually ignore that.

But the question for us was, well, is the clock disrupted very early on in dementia? So we cannot do that in humans for obvious reason because we cannot take out the SCN and look at them. But what we're finding, this is even unpublished because we just had this in Society for Neuroscience, and then they actually selected this finding to be a press release. What I'm finding is these master circadian clock neurons actually show early sign of deterioration in the brand

way, way before even the part of the brand, like the hippocampus, which is implicated in algymos, disease, and dementia are affected. Just to make sure I understand, and the audience does too. So this supercosmatic nucleus, which we learned about the last time you're on the podcast. I love that word, by the way. We're seeing evidence that it's being disrupt. When it's disrupted early, that could be some of the first indication well before somebody ends up with any kind of diagnosis that's there.

Yeah, at least in laboratory mouse model. Yeah. And then what is important now is when we come up. compare that in humans. What we're finding is even in humans, though now there are many sophisticated blood testing and other types of testing for predicting dementia. And there also what we're seeing is people show

early sign of sleep disruption way before, sometimes even a decade before the clinical onset of dementia or mild cognitive decline. The question is people will say, how do they know my SCN is getting sick? right? It's part of the brand that we cannot access. But ACN has different signals that we can measure with wearables and other stuff. So, for example, the first thing is our body temperature rhythm may also deteriorate. That's what we see in mice and lab animals. Our eating pattern

may also change because we also see these mice may eat slightly more in the middle of the day because mice sleep during the daytime. And their metabolism, changes. So it's so all these signs if we put them together maybe this is where we have some idea that okay so these are little prediction or these are the signs of sleep disruption circadian rhythm disruption because you can have temperature body temperature rhythm disruption but may not have sleep disruption or you may have sleep disruption but your core body temperature may still cycle. But if we come up with new algorithms where these can be combined to see hey, some things are not looking good.

And now let's go back and get that good sleep and good circadian rhythm. And maybe we can delay that dementia or even reduce the severity by a decade. And, you know, in my family, one of my grandfather actually had dementia and I have seen it firsthand. If I have the knowledge that I have now,

if I go back in time and say, okay, can we implement those to delay that onset or reduce the severity just by implementing few things. So we talked about light and sleep, but then I'll also talk about metabolism. Then it's a huge thing. Just imagine when we lose our identity,

we cannot recall names. We cannot recall where we are. That's the end of our identity as a human. And if we can delay that, then that will be really good. So this is what we are seeing, that the circadian clock is affected. It means it's not that when we go into the SCN, we are not seeing that there is plaques

because plaques are outside this. What you are seeing is these cells now have more gunk. So what we call lysosome, which actually takes all these waste, this is the waste basket of the cell. That waste basket is full, completely full, and is overflowing. And actually the cells should remove that waste

or recycle that waste, but it's not happening. So we see that early size. of, you can say, disrupted autophagy maybe in the SCN. So the recycling of waste is not happening properly. And that affects the clock. And then the clock gets disrupted. It's almost like throwing sand into the clock. And then things progress from there.

Yeah, you have this master clock inside of you that's so beautifully designed by, you know, nature, the universe, God that was intended to orchestrate so many things in your body. but through use and abuse or lack of use when it comes to something like sunlight, getting sunlight during the day, we have all this gunk inside of it, and then it becomes a situation where then you're not sleeping as well because of it. And those sleep disruptions as one core component can be something that builds up even more gunk. And now you have this downward spiral. So it may seem like such a soft intervention, but we know, do a lot of the research that you've highlighted, that even just getting out outside, dimming the lights a little bit at night, protecting

this master clock is so important. And then even because sleep disruption is so multifaceted, sleep apnea, so many things play into it, if you're not sleeping well, taking it seriously, taking it seriously and saying, hey, okay, I'm not going to be anxious about that because anxiety drives worse sleep but i'm going to take it seriously and i'm going to start going down the rabbit hole of seeing what could be things that i could do do i have sleep apnea do i need a sleep study uh do am i grinding my teeth at night and i need an appliance to help out with that am i drinking caffeine a little bit too late which is disrupting my circadian rhythm many of the things you talked about in our first episode together so whatever it is taking sleep seriously

to protect this master clock, which ultimately protects the brain and the body. Yeah. So sleep is one aspect of the master clock. And actually, what is interesting is the master clock tells the sleep center when to sleep. And the master clock also tells the stress system or our adrenal gland when to wake up.

And when you have that master clock is disrupted, it's not only sleep that's disrupted. It's also not telling our adrenal gland to crank up the cortisol or the stress hormone at the right time. So you may have high cortisol at the wrong time of the day or you may not have high cortisol in the beginning of the day. So all of these are interlinked. I just said, this is a master clock.

So that means it's almost like a conductor of an orchestra. The conductor never plays any instrument. Yeah. Right? So it's almost like as passive as that. It doesn't, means if we really try to connect, it doesn't directly control stress hormone. It doesn't directly control melatonin.

It doesn't directly control when you feel hungry. But it's the conductor. It doesn't have to play anything. But it just tells all the orchestra player, which note to play at what time. So coming back to this, as I said, you know, we have clocks in every cell. So one of the analogy that when you're talking,

it came to mind is it's almost like you are in an nice neighborhood and there is a nice elementary school that just popped up. It's a nice building, beautiful gardens and then there are this well-tren teachers who are eager to teach children. So now the teachers are the clocks in different parts of our body. And now just having the clock and just having a beautiful and strong body when you're born is not enough because just having elementary school in a nice neighborhood doesn't ensure that the kids will be well educated. They have to have the discipline to show up and the school at, say, 8 o'clock or 8.30 a.m. And then go through different classes, whether it's physical education, science, and biology, or arts.

So similarly, in our body, we have clocks. But we have to show up for when to eat, when to get light, when to exercise. These are the basic elements. So just imagine in that elementary school, even if the kids are showing up in the school, but they're not going to the respective class at the right time and they're just wandering the hallway.

Then after a while, the teachers will also get frustrated. And even if the kids start going back to the classroom, they may not be motivated to actually tease the kids. So you might say that, well, what becomes very important is, just like training these kids that will form the foundation for the rest of their life, and there is no replacement for that. You cannot have a pop, you cannot pop a pill with kids that will make him or her smarter.

So just like that, we cannot imagine that is that a replacement for sleep? No. None. Is that a replacement for exercise? No. Is that a replacement for light? None. So just like disciplining your kids so that they go to the right class at the right time

so that they form a strong foundation, we also have to take this circadian rhythm, this four or five pillars of circadian rhythm seriously. And if we take them seriously, then you build a strong foundation for the rest of your life. And those four are light, nutrition, physical activity, and sleep. And we talked about light, and we talked a little bit about sleep, and then physical activity and nutrition are the other two pillars of circadian with it. Well, let's talk about, especially in the context of cognitive decline, right? Let's talk about the nutrition and the metabolic health side,

because both of those things deeply are connected to circadian biology. You know, one of the biggest thing about circadian biology, we always forget is, yes, it makes our body to sleep. So that means it actually defines a time when we should feel sleepy and fall asleep. So that's the night part of this story. But during daytime, the circadian rhythm or circadian clock also primes when we should feel hungry.

And now people have done these experiments in humans. They will isolate them. and then they have no sense of time, and then if they ask them repeatedly, when are you feeling hungry, then the bottom line is circadian clock actually makes us hungry within a very short window of eight to 12 hours.

So that means we feel hungry, or slightly hungry to more hungry or whatever scale you can put, somewhere between, say, a couple of hours after waking up until a couple of hours before we go to bed. So if we're in bed for eight hours, you add two hours in the morning and then add two hours before going to bed, roughly 12 hours. And within that, we think that this circadian clock makes our hunger hormone rise and be above baseline for 8 to 12 hours.

So that means we are designed to eat during that time. And it's not only hunger hormone. Actually, it bookends that interval with two hormones. One is in the morning there is rise of cortisol that is produced from our adrenal gland and cortisol peaks within an hour after waking up. People always relate cortisol to stress and people think that, well, I'm feeling stressed in the late afternoon. I'm feeling stressed at work. My cortisol may be high. But whatever stress level we might have, nothing beats the morning cortisol serves that happens right after waking up.

So for one hour after waking up, that's when we have the highest cortisol. Which is a good thing. Our body's trying to get us ready for the day. Yeah, I mean, we're going from zero to 100 in like an hour. It has to prepare. But that cortisol also is not good for managing our glucose. So in that way, not only our hunger hormone begins afterwards, it actually ensures that you are not hungry.

You are not designed to be hungry right after you wake up because there is cortisol search. You have to wake up. You have to go look for food because the food was not there. The caveman just didn't wake up. And then there was a banana or something next to it. The animals already ate that. So that's how we are designed.

And it's not only that. In the evening, there is rise of melatonin. And melatonin, just like it prepares our body to sleep, it also makes your pancreas to sleep. So that means pancreas is the organ that produces insulin. And insulin is the hormone that helps us to observe all that glucose from any meal into our muscle. And in the evening, that rising melatonin will inhibit pancreas to produce enough insulin. So if we eat very close to our bedtime, then blood glucose remains high for longer time.

So in that way, the clock does now three things. Morning hormone, that is not good for our digestion. evening hormone, that's also not good for our glucose control, and in between, it increases hunger hormone so that we can eat. And then as we eat, it's a very complex phenomenon. Just imagine that we haven't produced, humans haven't produced, even a single machine that will take all the food that we eat. You just put that into that blender or whatever,

and on the other side, we have ATP coming out, energy coming out. It's a very complex process. It has to digest all this food. within four to five hours. Just imagine even if you leave that food in a waste basket, that will take five to ten days to decompose. And we are decomposing literally, like within a couple of hours. A huge amount of acid that's produced,

all the digestive enzymes have to break down that food. And then all of these have to be extracted and then send to liver. Liver has to sort it and take it to different places. At the same time, we have food color and then many things that are in natural food that our body doesn't need. So it sorts them out.

Those toxins have to be removed. So it's a very complex process. So the circadian clock actually primes thousands of genes in our gut lining, in our stomach, in the blood circulation to absorb all of this from the intestine, take it to the liver, liver has to sort it. So it's a very complex, very elaborate process that happens during this window.

So then what happens is if we disobey that, it's like wandering in the hall and then going to the wrong class. So, for example, if you go to, if you now eat very close to your bedtime, there are many things that are happening. One is your insulin production is impaired, so your glucose will remain high. But not only that, your stomach is not ready. It is already has said, okay, I'm going to sleep. And so your food remains undigested and it doesn't move inside the intestine and then the next day you feel groggy

and you feel like you have a food hangover. So now coming back to metabolism, then what happens is if we eat within that prescribed, the SCN or circadian prescribed during the up 8 to 10 or maximum 12 hours. The natural sort of time that we were designed to be eating within. Yeah.

There's eight to 12 hours. Eight to 12 hours. It's better to target eight than you land at 10. So that means that from the time that you eat your first meal to the time that you're ended, it's within that eight-hour window. Yeah. Eight, but then it's okay to go to 10 because in most of our studies we try 10. People can stick to 10 for a long time.

Yeah. But the point is when we eat within that time, then few things happen. Our nutrient absorption is much better. our liver is much better in sorting those nutrients so that, you know, the toxins or unwanted chemicals that are in the almost in every food. Even natural food has many unwanted chemicals. Those things are cleared properly. And then when we go through that fasting period, overnight fasting, that's when our fat cells

and even liver breaks down some of the fat and produces ketone bodies, and that's the craze about ketogenic diet because these ketone bodies that are produced by our body at the right time, they make, they have a lot of different functions. One is actually brain seems to use ketone bodies. Previously, we thought that the brain doesn't use, actually does use. And then our heart also uses ketone bodies and our immune system actually benefits a lot from ketone bodies. So that's one. And then during fasting, we also produce high, amount of growth hormone. And you might think that, okay, only the kids need growth hormone, but actually we forget

that we are almost like kids because we are recycling almost one-tenth to one-fifteenth of our body except the bone almost every single day. So that means you are a new person in every 15 days too. Hopefully our brain is not going through that reason. We are not making new neurons, but the rest of the body does. And when we don't produce that growth hormone enough, then our gut lining doesn't repair well. And our skin doesn't repair well.

And then that way you have almost like leaky guts. You know, undigested food or bacterial components from the food or even bacterial dead bacteria from the food can get into the blood circulation and can cause inflammation. And sometimes that inflammation, if it's affects the brain that also increases your risk for dementia. So the bottom line is this eating and fasting,

that cycle that our ancestors went through was also designed in a way to protect our brain so that it's not continuously bathed in high glucose coming from our food because after our food means, our blood glucose can go up by 30, 40%, because we go from 100 or actually ideally, should be 90 milligram per deciliter, but I say 100 is a good number

because 100 milligram of sugar in 100 milliliter of blood. If you drain all of my blood through, you'll find only 5 liters of bloods. That means you'll get only 5 gram of sugar from my blood. So that means when people say, well, this is just half a teaspoon of sugar. Just, I'll take just one bite of that cake. actually taking almost the amount of sugar

that's stored more than the amount of sugar that's in their blood. So that high amount of sugar, when it goes, it actually disturbs a lot of organs, including our brain, and that's the reason why we have a strong control mechanism to produce insulin to get that sugar out of our blood as soon as possible. And when we eat outside that window, a blood sugar surge is too high.

that's also, you know, it's almost like you're driving a car and you're getting a dent then and there. And then after seven years, you know that your car doesn't actually look like a car. It's almost like a tin part. Yeah, it seems so innocent, but all this late night eating. Yes, not one late night of eating is going to immediately, you know, end up with a cognitive decline. But we're talking about this chronic exposure.

You look around this world, the Western world, today, even in places like, you know, India or visit Argentina a few years ago. People regularly start dinner at like 10 p.m. at night. Yeah. You know, so there's regular chronic late night eating and often eating things that are highly refined carbohydrates. You have this excess sugar that's floating around the system at a time that your body was not optimally designed to process all this.

Even if it's great food that you're eating, then super-house. healthy food and years, days of that turns into weeks, weeks turns into months, turns into years. We understand now this is abuse on our body. And then we wonder, why are we ending up with these systems that are malfunctioning? We're breaking the natural rhythms that our body was designed to follow. And one of those is this window of eating. And then if you ask most people, people, they will say that, oh, well, I eat within 12 hours or 10 hours because I eat three meals. And this is so ingrained in people's mind. And even our 150 years of nutrition research is based on one simple idea, which we call 24

hours dietary recall. So that means, I'll ask you, through, what did you eat yesterday for breakfast, for lunch, for dinner, and snacks. And then to help you recall, I'll say, well, Well, remember, what time did you wake up? Six o'clock? Did you eat something at nine? And then I was, oh, yes, I forgot.

I had a cup of coffee or something like that. So that's the way nutrition science has been collecting data, and they always assume that one day of data is predictive of what did you have it every single day, which is not true. We know that. The way I eat in the weekday, we can, maybe very different. There's a lot of variants. A lot of variants, but nobody had measured that.

So many years ago, almost Now, 11 years ago, we met this app called My Cicadian Clock, which is still available, and we asked people, 150 people from San Diego, who are going to their regular work, 9 to 5 work, or they're staying at home, we ask them, log everything that you eat. Just open the app one click. Take a picture of your food, second click, and press a third click. That's all. You don't have to tell us what you ate, how much you ate.

We'll look at your picture and figure out. If it is a black coffee, then maybe we'll not count it as food. because it has less than 5 kilo-kilk. When we did that from 150 people over two to three weeks, we were shocked because what we found was on an average, people are they're likely to eat within an interval of 14 hours, 45 minutes. So that means 50% of adults in our study were eating for 14 hours, 45 minutes or longer.

So that means if they walk up at 6am and they're like, I'm not feeling very alert. So I'll have some coffee. I'll just put a little bit of cream and sugar. That's counted because, as I said, just half a teaspoon of sugar will increase your blood sugar to 150 if your fancreas is not working. And then if they walk up at six,

how did you have their first coffee at 6.30 or some cracker or biscuit or whatever it is? And then at the end of the day, when they're going to bed, if they have a nightcap or a glass of milk or something else to have a bite before they're going to bed at 10 o'clock, that's already 15 plus hours. We found less than 10% out of 150 people,

only 10 people who are eating regularly within a 12 hours window. And no one has a 10 hours at that time. So now we have been continuously collecting this data, and now we have data from 20,000 people for two weeks. And what we find is that's roughly true. And, you know, over last 12, 13 years, we have been talking about what is called

time-restricted eating in scientific violence, and then this is one form of intermittent fasting where the popular form is eight hours eating, 16 hours fast, but it can be 10 hours eating, 14 hours fast. And now what we're finding is nearly 10% of adults are actually eating within 10 hours or less out of this large cohort. now, like in 2024, 25.

So that means we went from less than 10% eating under 12 hours to now 10% eating within 10 hours or shorter. That is very gratifying because we didn't have to, we didn't tell them anything. But they are getting all this information from media like yours, podcast, and there are many influencers who have been breaching this to a lot of people. But at the same time, 90% of people are still eating over 12 hours or longer. So there is still scope for 80% of people to change their behavior and try to eat within a sort of time so that they can improve their health. A huge part of that is helping them understand how so many of these things that we're all afraid of.

I have a grandfather, my mom's dad, who was diagnosed with cognitive decline and dementia. and, you know, you see it firsthand, and so many people can relate to this. If you've had a family member, somebody that you love, there's a group of our friends just not too far away from this studio here in Los Angeles. There's a memory care center that a group of our friends volunteered at. And it's most well known that I believe it was when President Ronald Reagan was dealing with his own diagnosis of dementia. He had spent some time over there as well in this facility.

And a group of our friends went to go volunteer. And, you know, we all left feeling like so much empathy for the people that are there navigating was number one. Number two, you can't help but to see how it's an unfortunate cycle how so many of the individuals there. And the nurses are doing their best that they can. But the entire facility runs on sugar. Yeah. And they literally asked us to bring cake, cupcakes, sugar, because it's the only time that the people there. feel like they have any sense of feeling like a little bit happy,

but that's obviously a whole other thing that's there. But number three, so many of my friends that went to go volunteer together was, wow, this is something that we wouldn't want anybody to experience. And so if there's anything that we can do that could even slightly reduce our risk of this, we should be paying attention to it now. And that's why we're talking about this now.

Because sometimes if you say circadian biology, the supercosmatic nucleus, you know, these things goes over people's head. Yeah. But if all of a sudden you say, hey, do you want to minimize your risk potentially of cognitive decline in Alzheimer's? All of a sudden, people are paying attention. Yeah. And so now we have to unravel all these areas of circadian biology and help them understand because nobody taught them, you know? Yeah. We were learning trigonometry in high school. Nobody taught us to do our taxes or how to eat in a way that actually would make sense and work for our biology. So first and foremost, I want to acknowledge you for coming back on the podcast to take this.

very important topic and go piece by piece by piece to help people connect the dots because I'm not a clinician. I'm not a researcher. I don't have any background in this. And I know that I'm very worried about this. And I know that my audience is very worried about this. And if we can put these pieces of the puzzle together, all of a sudden light bulbs go off. And just like that audience space that was part of your app, which we have a link to in the show notes that people can check out. Naturally, you hear this more and more, you try it, and you're like, wow, if I stick to 10 hours of an eating window, I notice that I sleep better. I notice that I feel better. I have more energy. And that's not even changing necessarily what you're eating during

that time period. So all these interventions, we can propose them. You share the research. People can try them. There's great apps, which we'll talk about some of your apps that can help them support them on that journey. And then culture now starts to change. And people realize they don't have to wait for a randomized placebo control trial that's showing the exact thing that's there. They get to do an end of one case study and see, wow, I'm genuinely sleeping better. I feel better. And I'm actually doing a better job in weight management as well too. So when we do, going back to the time rest of eating or eating within eight hours or nine hours or ten hours. We talked about metabolism and how it affects.

One is we know that people with uncontrolled type two diabetes or diabetes in general whose blood sugar is pretty high, they cannot manage it. They're at a high risk for dementia. Super high risk. Super high risk. So what we are saying is this time restitution eating, this pattern in animal models, of course it reduces blood glucose, but then in humans, at least now we have three randomized clinical trial, control trial, where we find people who are on the borderline

pre-diabetes, they improve their blood sugar. People who are in type 2 diabetes, they also improve their blood sugar, whether they are already are taking medication or not. And this is very important because there are many people who are on metformin or maybe GLP1 receptor agonist, like Ozympic, or maybe other drugs. But that drug is not working for some people. And they may be still having a hemoglobin A1C of 7.0 or higher. And when we have those people, they don't have to change their medication on top of the medication when they're trying time resusciting. They're still seeing more improvement. So that means it can even help people who are taking medication.

The reason being circadian rhythm not only maintains our health, it also maintains some. some critical aspect of treatments, particularly drugs and other stuff, because the drugs are designed that are administered in a way that our bodies should absorb and metabolize them correctly and should send it to the right target.

Like, for example, if I'm taking a medication for diabetes, it should actually fix my appetite and insulin production. So it should go and act on the target. And at the end of the day, when the drug has done its job, and it has broken down, it should also clear from our system. So these three processes, the absorption, action, and clearance, all these three are also circadianly regulated.

So that means when our circadian rhythm is disrupted, not only we are predisposed to many diseases because it weakens our body, it also weakens the efficacy of the drugs that are designed to treat our body and mind. the drugs can't do their job because they're not within the proper circadian biology. Yeah.

Or they can't do their job as well as their potential. Yeah. And this is, again, this is another emerging field because most people are thinking, well, I'm already taking this medication. How is this circadian rhythm going to help me? You're talking about maybe I should get light and all that stuff before I took the drug.

No, the point is we are seeing it again and again and, you know, cancer. is a great example because there are a lot of cancer drugs. Now they're showing that at what time the drug is administered, even immunotherapy drugs, which are the latest ones. There are many, many papers coming out in humans that there is a better time. The reason is this. The drug absorption, its action, and elimination,

a strongly influenced by circadian rhythm. So if you put a good drug at the right time in the platform that has a lot of cancer, then that drug is not going to work. So even if people are on different medication to manage different conditions, having a strong circadian rhythm improves their chance of getting the benefit from that drug.

And just because you mentioned it, just one question, because I know my audience will kill me if I don't ask you right now. You talked about cancer, and I've seen you post about it on X, by the way, everybody follow Dr. Pand on X with a link in the show notes.

But generally speaking, I've seen you write about that And is it largely that if you're on chemotherapy or if you're on these immunotherapies, largely doing those earlier in the day tend to work better for our circadian biology? Is that too simplistic? Yeah, it's roughly true because immunotherapies are the best drugs right now. But of course, there are many cancers for which immunotherapy doesn't work. But immunotherapy does work for melanoma, non-small cell, long.

cancer and certain forms of head and neck cancer and even kidney renal cell casinoma and if we look at all the literature now there are at least 25 or more clinical trials that are showing that earlier in the day the same immunotherapy delivered has much better overall survival and progression free survival all these two are very important, then the same immunotherapy delivered in the later part of the day, like after 3 o'clock or 4 o'clock. Now the question is, how much is the benefit, right? So is it 1% or 2% or whatever it is?

So now if you think of, if you ask, what is the efficacy of an immunotherapy drop, like even for any X type of cancer where it is prescribed, the efficacy is 20%. So that means out of five people who are taking the drug, immunotherapy, one person may see benefit. What we're seeing with timed therapy, that number in some cases jumping to two out of five. So we are doubling. That's crazy.

That's like hazard ratio, HR, the hazard ratio that's usually reported. It's 0.46 to 0.6, 0.65, something. along that line. And why this is important is now, if you look at drug industry, all the researchers who actually work on cancer, they are trying to figure out how to improve this efficacy from 20% to 25% or 30%.

But actually delivering the drug at the right time is already improving what they're targeting now. And this is not in the general knowledge and also it creates a lot of challenge for the oncologist. because, you know, there are so many cancer patients, they cannot do justice by putting all of them in the morning. Sure, everybody will want the morning.

Everybody would want the morning. So then the question is, can we do something so that people can actually, suppose, say, if time restating and lighting is actually improving their circadian clock, can we change that circadian clock so that they go to bed at a slightly different time and then eat at a slightly different time so that they can still go in the afternoon when the appointment is

and can still get the same benefit as in the morning. Because the point is, it's circadian rhythms are not tired to really how the planet rotates, which time zone you are. So for example, if you are waking up, I know that you're a new dad, so you're working up at five or six. And my daughter is already 20 year plus. I don't have that.

I don't have to drop her. been there, you've done that. Yeah. So I was say, I wake up at 9am, and you wake up at 5m. And if we do it regularly every single day, then actually my circadian clock is four hours delayed related to years. Sure, no different than if you were in another time zone. Yeah, it's almost like I'm in a different time zone.

So that means if you're going to see your duck at 8am, so that's three hours after waking up, the same as me going to my duck. at noon. So this is now another idea. How can we implement in humans by tweaking the circadian rhythm, by changing light, dark cycle, or sleepwalk cycle, or even eating fasting cycle, so that we can still have the same benefit, even if your appointment is at a different time. It's such an important topic. You know, every single recent president, I believe, since like even Clinton, maybe Clinton, Obama, Biden, Trump, every one of them has talked about this cancer moonshot.

Yeah. And how important it is to, you know, put resources and research and anything. If there was a drug company that came out and said, hey, we can go from 20% to potentially, you know, now it's right. Yeah. They, this would be front page news. Yeah. And what you're saying right now is we know through multiple trials that are out there

that just simply timing that with your natural circadian rhythm, which we know has scalability issues, which could be solved by personalized medicine that's there. But at least right now, if you know and you can advocate for yourself or you can advocate for a family member and you could talk to your oncologist, you know, you could talk to your doctors and say, hey, listen, if there's any way that I could do this early in the day, you would double your chances of beating that cancer. That should be front page news. Yeah, that should be.

And then another thing that I forget is, you know, these people, they're in clinical trial. They were not asked, or there is no report when they went to bed, how was their sleep, whether they were getting enough light. And if they're eating late at night. Eating late at night, nothing. My guess is if we even optimize that, just like the elementary school, now they have to, you know, if I'm a cancer patient, I would listen to all kinds of discipline that I can do to improve my chance of survival. Now suppose say we bring all all those disciplines together, can we even crank up their survival to 50% from 20 to 40

and now 50 or 60%? So I guess what we're trying to say here is the circadian biology has already the wisdom and the means because it's not only that we just know Secaadian, we know how to shape it with light nutrition, sleep and also exercise. then we can put all this together in a program that will improve survival not only from cancer, actually in dementia also we are finding in mouse model or animal models of dementia, if we just do time-restuted feeding or eight hours or nine hours of eating, we also make this mice resilient against dementia.

So there is huge potential for both cancer and dementia by strengthening circadian rhythm. But the first thing that anyone, anywhere can do is to pay attention to what time they're getting the immunotherapy or what time they're getting different drugs for managing their metabolic health that can also benefit from time receiving and fewer the circadian intervention. The more that you learn about circadian biology, the more that you understand, it's tied to everything. It's tied to everything inside of the body. And just because we're on the topic of cancer, you know, one of the favorite posts that you made on X, formerly known as Twitter, that I've shared with so many people,

and unfortunately shared with friends whose parents are navigating cancer, people who are worried about it. My mom, I've spoken very publicly on the podcast, had breast cancer now probably got a diagnosis maybe 15 years ago. Knock on wood, it was caught very early, which is a huge part of beating cancer. It was caught very early.

We addressed it from multiple standpoint. She had a traditional oncology. She had a functional medicine doctor who personalized a lot of different treatments for her. And it was a combination of multiple different things and knock on wood again, she beat it very early. So even people who have cancer in their family history, you had this fantastic post. We'll link to it and we'll put it on the screen on YouTube talking about, and this is again, directly connected to circadian biology is that exercise is the best insurance again.

Against cancer, the premium is only 30 minutes of exercise a day. And the post, basically, for those who are listening on audio, is this branch that's out there. You know which post I'm talking about. I'm not connected to the monitor, otherwise I'll bring it up over here. But people can see it on the screen right now on Spotify and YouTube. In a middle, you have exercise effects on cancer. And then all these things that branch out, its impact on gallbladder,

gastric, kidney, liver, ovarian, thyroid, breast. cancer, it reduces, you know, the disease, it increases disease-free survival, all these tentacles. Yeah. So Thai exercise, which relates to movement, which is one of the key things as it's connected to circadian biology, just flush that out for us a little bit. First, talk about cancer, and then also it's a huge part of cognitive decline, dementia, and Alzheimer's. Yeah, so exercise, when we think of exercise, we also have to go back to our ancestors because I always think of, I always compare that because, you know, this is how our body was built. We actually put this Fitbit-like device, actually I'm wearing a whoop, but then on Argentinian tovas.

Not me, it's Horatio Dele Iglesia from Seattle. He has a large, long, ongoing study in Argentina where these people did not have access to electricity. They were almost like hunter-gatherers. They're like a modern nomadic tribe or modern day sort of tribe. Yeah. So there are very few pockets of population all over the world now. You rarely find this population who have no access to electricity. Yeah.

And then you ask, how is their lifestyle? What do they do throughout the day? And when I say that we are designed for this circadian rhythm, we go through four distinct phases throughout the day, 24 hours. We go from pitch dark sleep to early morning prep when we are going to look for food and all that stuff and throughout the day we're staying with a lot of light and then in the evening as the illumination goes down,

we have to run back because I don't know how many listeners here have ever stayed, gone camping and have lost their way and cannot get back to that tent and how do they feel? So that was the feeling, like people had to run back home. So when we look at their daily step counts, the daily step counts roughly equals to 17,000 steps. And out of that 17,000 steps, nearly four to five thousand steps is within that twilight zone. Because they're running back, there is a lot of activity before it becomes dark.

people who are staying at home, they're also trying to prepare food or get the kids back or whatever they're doing. So there is a big spike in the late afternoon. And then we ask, okay, so what happens when we exercise?

Actually, throughout the day when we engage our muscle, muscles are the largest part of our body. Although we always think of muscles as, you know, if you're muscular then you saw your six-pack or your biceps or something, but actually nearly 70% of her body

is muscle, different types of muscle. Let's see in the intestine also there is muscle that are contracting. And these muscles have broad control of our metabolism. And when they're not contracting or when we're not engaging these muscles, then essentially we have this powerful machine

at our disposal, it's like buying a Ferrari and keeping in a garage for the rest of its life. It's going to deteriorate. It's going to deteriorate. So one thing is, when we're not using muscle, we're actually not using the metabolism and other stuff that it does. Another thing is, when we exercise, we know that as soon as I stand up from here and start walking, my heart rate will go up.

My breathing will go up. So it's not only my muscles are exercising, my heart is exercising. It's actually contracting much faster. It's pumping blood much more. much more frequently. Lungs are also contracting and expanding to supply oxygen. And this oxygenated blood,

it's not only going to muscle, it's also going to my brain. It's going to my kidney, going to liver. And it's almost like, you know, I suppose say you have a clogged brain and the first thing that you want to do or if you call the plumber,

then the first thing they want to do is just flush it with a lot of water. And that's one aspect. of exercise is it actually irrigates the entire system with enough oxygen attenade and nutrient-riched blood so that all your tissues cells are well-fed. And the second thing that it does is, of course, the arteries are supplying all this nutrient-trace oxygen-rich stuff. But then the veins are also draining all the waste product.

So exercise itself is also a cleansing. If you're thinking about cleansing, then exercise is the best clenger because it opens up all these clogged arteries, clogged drains, supply chains, and also it drens. It's the best detox. Forget all those detoxes that are out there that people are talking about.

Yeah. Exercise is the best detox. And this is, you know, I was not, you know, for most of my life, I was not an exercise buff because I was always thinking exercise. means you go to gym and then get a gym membership and do all this stuff. But then almost six years ago,

Clara Wu and Joe Sy, they came up with a very simple idea that is everything that we know about health comes from learning from people who are sick. So we actually barely know anything about what makes us healthy. So that's why they started this alliance called Usai Human Performance Alliance, and our goal is to study what makes a person perform

at its peak physical, emotional, and intellectual performance. And when you think of that, then athletes actually are at peak physical, emotional, and intellectual performance. And then if we think of athletes, the athletes normally have to build muscles and endurance. They also have to think clearly, strategize well, to win the gain. And they also have to be emotionally strong

that one loss is not going to pull them down. So that actually made me really think about exercise and then I went back to circadian rhythm and I realized that, well, we're designed to be active throughout the day and mostly even more towards the end of the day.

And as part of this Usai Human Performance Alliance, first thing we wanted to know is what does actually exercise do? to our body. And it's interesting that last 50 years of biomedical research with molecular biology, we have gone back to studying genes and different disease and all that stuff. We did not have a foundational molecular atlas of what does exercise do to different parts

of our body. So then as part of this, we now collect at least 20 to 30 different organs and brain regions from laboratory animals who are going through regular physical activity. They're not actually trained on treadmill or they're not lifting weights. This is just like being physically active. It's like a new mom playing with the kids

or running around, doing the regular chores, something along that line. And what we're finding is, as starting nearly 80% of our genes respond to exercise in at least one or two organs. So that means, you know, we are just looking at 30 different tissues, but actually our body is composed of at least 200 different cell types,

different types of cells. So I think exercise rewheres our entire genome, every single gene responds to exercise. And when we do this on a large scale, and we ask, okay, so what are those genes that are affected by exercise and how they relate to cancer? What we're finding is they relate to everything that actually supports or prevents cancer.

So, for example, they improve mitochondria function that we know. A lot of people know that mitochondria function is important for healthy life. And then in cancer, the mitochondria producing too much reactive oxygen species, which is essentially a toxic byproduct of metabolism or they're not fully active.

And sometimes the dead mitochondria are not cleared. So one thing from exercise we're finding is almost everywhere. in the body and brain, this affects mitochondria function. It also affects many of the forms of DNA damage repair, our DNA gets damaged every single day. And exercise also improves that damage repair. It also improves our immune function.

So all of these are now coming back together that, yes, exercise not only has benefits that we heard from our grandparents or my gym bodies, actually molecularly, now we know which changes are happening. And what is also interesting was exercise, for example, these mice are exercising in nighttime because they're active during nighttime, they sleep during daytime. And you can ask a simple question,

is exercising, benefiting all of this stuff only when they exercise or even after exercise when they're going to sleep? Lingering effects. Lingering effects. And what we're finding is, yes, the biggest effect of exercise, during the sleep phase actually comes

or it's effect on kidney and lungs. And this is interesting because we know that many people with kidney disease, they actually benefit from exercise. But at the same time, we know that when you're exercising, you're producing a lot of toxic byproduct that has to be cleared by kidney. And people thought that you should not exercise if you have a kidney disease because it will pressure your kidney.

But what you're seeing is, no, it actually explains why exercising improves your kidney function at night time. You may not have a kidney disease, but a lot of people have hypertension, high blood pressure. And high blood pressure, kidney plays a big role in maintaining our blood pressure. And this may explain why exercise also helps reduce or better maintain blood pressure.

And why you are talking about blood pressure when you're talking about cognitive decline in cancer because blood pressure also affects our brain function because the pressure in our blood also affects how this pressure is transmitted to the blood vessels that go through our brain. If the pressure is too high, it might rupture a blood vessel in the brain.

And you may not get a stroke, but these micro blood vessels that are busting in our brain that slowly accumulate over long period of time before we have telltale sign of dementia. So this is one way that, you know, exercise, its impact on kidney and then blood pressure regulation, and that might affect how we are predisposed to or we are prevented from dementia. And for cancer, we think that this exercise, we know what are the changes and how they relate.

But we still have to go back and ask why this changes. What advantage is the cells are getting by changing that way in response to exercise. But the bottom line is, yes, now we have a molecular handle on why exercise is beneficial, and then we can also go back. So this molecular atlas will help us in many different ways. One is explaining why exercise is preventative for many types of cancers and even for dementia and many other diseases. Second is we're finding how exercise affects the genes that are involved in again, drug absorption, metabolism, drug action, and elimination.

So this is also explaining why exercise may improve the efficacy of certain drugs or may reduce the side effect of certain drugs because this toxic toxic byproducts of drugs are also cleared much better when we exercise. So this is an exciting aspect of my newly found love with exercise. And that also means when you see this data, I remember like 15 years ago or 12 years ago when I saw the impact of time restricted eating, then it was a no brainer to adopt that. And then I lost like 15 pounds and I feel much better. And when I saw this impact of exercise on multiple organs and also in the brain region, And actually the best, the part of the brain that most response to exercise in both male and female animals is the hippocampus. And that's foundational for memory and cognition.

Which directly ties into cognitive decline, dementia, Alzheimer's. Yeah. And my colleague at Salk Institute, Rusty Gaze, almost 25, 26 years ago, he had made the seminal discovery showing that Exercise in animals can increase neurogenesis, adult neurogenesis. So that means that new neurons, new nerve cells that are born in the brain. And that has led to this idea, which is again and again proven in many different labs, is exercise actually improves cognition and neurogenesis. And now the reason why we're surprised about hippocampus is this.

We know that there are different parts of the brain that are involved in nutrient management. or smallity or how thick is our blood, and then they also regulate how much we exercise, there are motor control, neurons, and all that stuff. We thought that exercise will affect those grand reasons the most. But it's not true. It's the hippocampus that was affected, and that was the big surprise.

And now within hippocampus, now we know, or we are beginning to know, with cell types. So there is the neurons or the nurturing cells around the neurons or the blood vessels that supply blood and drain the waste product, those are affected. So this is opening a completely new chapter in my lab, and also I'm getting into, now I run more and I pay attention to exercise. Well, zooming out for a second, right?

Because exercise is connected to circadian biology, and circadian biology is core to both of these two disease states we're talking about. Cognin, Alzheimer's, dementia, and also cancer. We're just picking two. Those are also two of the four main drivers and killers of most people that are out there, including, again, also heart disease and all the metabolic diseases that are out there. So just like you were saying, time restricted eating, you know, eight to ten hours is we're trying to narrow that window.

Is there a minimum that we know that exercise, especially related to cancer, cognitive decline, is there a minimum for the people that are listening today? Because the challenge that a lot of people do is they go to their doctor and again, all well-meaning. I have many physicians, you know, with us being Indian, half of our families are doctors that are out there. The other half is engineers. They all engineers, a couple lawyers in there too.

They all mean well. And they'll often say if they're not fully educated in this space and they also have very little time with their patients, lose weight, exercise more, right? Eat a little bit better, lose weight, exercise more. But people are listening today and are saying, well, I thought I moved around a lot, but then maybe I start tracking my steps and I'm getting, you know, only 5,000 steps a day. And by the way, 4,000 and less is considered sedentary by the CDC, right? Yeah.

So what is the minimum viable dose that is supportive for people who are like, hey, I want to reduce my risk. And exercise could be a part of that. If we go back to ancestral population saying 17,000 steps, so 20,000 steps, that's almost impossible to do in a regular basis for most people. And then also there is not much incentive to do it. Who is going to walk roughly 17 kilometers or 10 miles every single day? Yeah.

So this is where I think going back to even the CDC guideline of 30 minutes of physical exercise, physical activity doing every single day, 150 minutes, or 200 minutes, that itself is pretty good. But then if you go back to step counts as a unit, then I think there are some studies showing that 7,000 steps are higher on an average. Like, that doesn't mean that. Because when we say 7,000 steps,

people will target 7,000 steps, but they'll end up with 5,000 steps. So my personal goal has been 10,000 steps. and then I end up on an average 7,000 steps. And then the question is, is that 10,000 steps like walking in the park or actually you're running when actually your breathing and heart rate and all that stuff goes up. So this is where I think we have to figure out whether you are in, it comes to Joan training, June 2, June 3, Joan 4, Zone 5 in your heart rate,

and then are you zone 2 or higher? because that's when your heart is really pumping more than at baseline. So it's not like walking in the park and going to a museum. A little bit more vigorous. A little bit more vigorous. Your lungs are working much better. And you can have a conversation, but then not too long. You are still feeling the conversation.

So that's the kind of exercise at least everybody should be engaged in. And of course, then the question is whether you have the motor. control and the muscle strength to maintain that physical activity. And this is where strength training comes in. And I guess even in your podcast, you have talked a lot about strength training and how our lifestyle has become such that, you know, when I was a kid, I remember going to the farmer's market and walking back with two bags full of vegetables. I don't remember even walking from the growing.

restore to my car with two bags of vegetables these days. You put that in a cart and then push it, right? So even in everyday life, the point is in everyday life, you don't have to go to the gym. You still can do a lot of activities at home or in your daily life where you can lift weight in many different ways. You can still, for example, if you're in a building

at Salt Institute, we have like six floors. and we have 24 stairwells. So in my lab, I challenge everybody that can you do a stair challenge and walk up and down up every 24 stairs? And we have gone up to say 12 stairwells. So that means you go up six floors 12 times and go down six times. There's a lot of physical activity with enough climbing and coming down.

So the point is most people these days, either live or work in a place that has stairwells. Most of us actually have a lot of opportunity to incorporate physical activity in our daily life. And we should pay attention to that. And on top of that, almost most people nowadays, even your smartphone is counting steps. So, you know, these step counters are almost like mirrors

because they're reflecting back our behavior, or how much steps you are taking. So if you have a mirror at home and you don't even bother to look at the mirror to see how you look, then what else we can do? So I guess people have to kind of pay attention to beginning with steps

and then going to physical activity and getting into a gym, getting some exercise, but this is where another important point that came in, this is very important. Because starting from, you know, weekend exercise enthusiast to Olympic level athletes, we know that nearly 40% of athletes actually exercise more than the amount of food they eat. And for a long time, this is called relative energy

deficit in sports because it was first kind of really started in athletes because, you know, the athletes and their coaches, they're always trying to figure out how to get that gold medal, in LA, in a couple of years, there will be a lot of anxiety about that gold medal, and then they want to do everything. So that's how I think it was detected that many athletes eat less than what they are spending.

And some people might think that, okay, so this is a good strategy for weight loss, and why not to do it if you're not an athlete? And this is where my colleague, Dr. Laura Van Rasmai, and she came up with this idea that, well, this has been in the folklore kind of stuff. And because physicians and athletes and coaches, they think that, well, you have to plow through, brave through this, and then don't worry about that. Even now, many women think that if they're running regularly and their kind of training

for marathon or half a marathon, it's okay to have irregular menstrual cycle or become completely a menoric because it's so common that people think. it's normal, but we have to distinguish between what is common and what is normal. Being common is not normal. For example, if there are 60% of people over the word, that's not normal. So similarly, if 60% of athletes are going in or irregular menstrual cycle, that's not normal. And people initially thought this is the stress and the anxiety of winning the game or the

depression from losing a game and all the stuff is playing in and they've been. don't have good sleep. They're more irritable. They lose sexual drive also both male and females. And they also have bones that are more brittle, so they're more prone to bone fracture. The joints and ligaments also might give up in some time. And for a long time, even there is no medical code, ICD code for relative energy deficit. And for a long time, people thought, this is just in the mind and we have to brave through

and maybe they have to just eat, and it's not a big deal. And Laura, what she did was she said, well, if we want to show there is a cause and effect, then we have to do that intervention to see, can we take a bunch of people, ask them to exercise, and then we reduce their food intake? No, you cannot do that. This is on ethical.

So this is where she went back to the lab and brought a bunch of lab animals and put them on exercise so that they're doing enough exercise that we know has good health benefits. This is important that these animals are doing the exercise that is known to benefit our health. So they are supposed to be healthy,

but then she slowly reduces their food intake by giving them slightly less food, less food in every single week to mimic what happens in humans because some of the athletes they actually eat even 20 to 30% less than what their body needs. And when she does that, the first thing that comes, that pops up is this mice are sleeping at the wrong time. And they have very fragmented sleep. And we know that many athletes do have fragmented sleep.

And the thing that this is the stress of competing. Then when you look at the cortisol level, the cortisol levels are high. So they are stress. Of course, the cortisol is high. And the blood glucose is pretty low. So no wonder some of the athletes might feel lightheaded even when they're not exercising. And then the powerful thing about mouse experiment

is now we can look at every organ. And what we found, surprisingly, was in female mice, the uterus was shrunk by almost 50% or more. Wow. And you don't see that from outside. And most athletes will not go and sleep under a MRI machine to see, or to do a CT scan or MRI scan, to see what is happening inside the body.

So these female mice, they were training a lot, under-eating, and their uterus shrunk 40%. Did it get back or it was just permanently strong? So this is the next experiment that we have to do. And then almost the entire brain completely rewires itself. And we know that this part of the brain, and we are surprised that the part of the brain that is involved in severe depression,

And it's called Habanola, but you don't have to remember the name, but this is right in the center of the brain that gets a lot of connection from many parts of the brain and also instructs different parts of the brand on when to eat, what to eat, or many things it regulates. It also right next to the CSF ventricles that have the cerebral spinal fluid. This is the fluid in which our brain slosses around

so that it has enough cushion, and also this is how the brain also detoxifies and gets nutrient. So that part was the most affected one. And here is the contrast. We just talked about how exercise affects hippocampus the most. But when you are doing exercise with less nutrient, it's not the hippocampus. That's benefiting. It's actually part of the brain that's involved in severe depression, that lights up.

And that might explain why many of these athletes also have severe depression. So over-training. Overtraining. Undereating. Under-fueling. Under-fueling. Yeah. It can have all sorts of cascading effects on the body.

Yeah. And you have so many young people especially that are in, even if they're not competing at an Olympic level, high school sports these days is intense. Yeah. Even at like your standard high school, you know, football players, volleyball players, you look at the routine that a lot of these kids are following, it's as if they're training at a collegiate level now compared to even when I was in high school, you know, 20 years ago or 25 years ago, whatever. And it's so much more intense. Yeah. You know, we could be, if we're not

paying attention to this, we could be, you know, there's so many benefits and so many beautiful things that come from exercise and leadership skills and being part of team sports and weight training and wrestling and all these different things. But we could be having all. ongoing damaging effects for a lot of these kids that could be very difficult to recover from if you're in this prolonged state of training a lot and under-fueling. That's what I'm hearing from you. That's exactly. And then it's, you know, it's not only one organ or one part of the body.

It's actually affecting even the big chunk of the brand, and particularly the part of the brand that coordinates different functions in the brand. And it's not benefiting the hippocampus that's supposed to benefit and increase our cognitive reserve and cognition and all. that stuff, it's actually affecting part of the brain that's involved in stress and depression, anxiety, all this. And then when we take the blood out of these mice and look for what is in this blood, are there metabolized like small molecules and proteins that are floating around that will give us some hint. What else is going on? What we find is there are telltale sign that

that some of the neurons or the insulation for the neurons, that insulation is actually deteriorating. So we have myelin basic protein, which is the insulin. It's almost like. The fatty insulation. Fatty insulation, like the electrical wires, they have insulation.

So those proteins are floating around in the blood. And that's also worrisome because we need that insulation in the brain to be healthy so that our brain, our neurons can talk to each other without crossing wire. Right after the paper came out, we had another interesting paper from a completely different lab. They were looking at what happens to ultra-marathoners who are running for many, many hours

because they're also going through relative energy deficit for a relatively short period of time. But, you know, for example, I cannot run a marathon because I felt too stressed or my... But then these people are running ultramarathon. they're not stopping to eat a big meal and they're burning a huge amount of calories. And in their blood also,

this damage, this telltale sign of damage to their brain also shows up. So we think that, you know, we have to be careful about this. And then around the same time, one of our colleagues who is also part of the USA Human Performance Alliance, Kate Ackerman, who at Boston Children and now, she has her own women, health clinic in Boston, she actually treats many elite athletes.

She was even the team doctor for the US Olympics, sorry, the US Olympics team for the last round. And her group tracked Boston marathons. You know, the Boston running in the Boston Marathon, you have to qualify. You really have to be good. You have to be good. That was one of my in the bucket list, maybe in my next life.

But anyway, so out of these thousands of people who are running in Boston Marathon, their group did a very simple survey, even going back to the simple 24-hour dietary recall, how much you typically eat, and from there, you get a good estimate of whether they're under fueling or fueling enough. So they have the data on how much they typically eat,

and they know how much they're going to run that day. And in every marathon, there are some, Some injuries and people, you know, the injuries can go from mild muscle leg to severe muscle pain or somebody breaking a tendon or rupturing something. And when they looked at the injuries from Boston marathoners, the injuries are more among people who are under fueling. This is another telltale sign that most people think that they have to lose weight to run a marathon. And this is such a general knowledge that most people who want to.

run a marathon, the first thing they do is, well, I have one kilo less to carry, so I should lose weight, I should eat less, and then run a marathon. So this is how, you know, you might have good intention to do exercise, but when you take it to too extreme, then it can backfire. And now it's become even more alarming because GLP1 drugs are used by a lot of people, millions of people. So ubiquitous. So ubiquitous.

and then at the same time, people are saying that, yes, you have to build muscle mass, so do exercise. So you're losing your body mass very quickly. Sometimes 20, 30% of your weight in a very short period of time. Very short period of time. At the same time, the doctors and, you know, regular vibe now is you should actually take the Olympic,

go to the gym to maintain or build up that muscle mass. So this is where I think Laura's research also comes into place. So the next thing we want to try is also to see whether these people who are going through rapid weight loss and exercise, are they experiencing some of the telltale sign of relative benazate deficit, which may not affect. For example, if somebody is a post-monopausal women, she may not be concerned about the uterus size. but then it also affects bone health. Yeah, there's so many things that are playing into it.

So the bone might become more brittle and the brain might get affected so that they actually may lose the pleasure of living because it affects the depression center and the depression, the total sign of depression, molecular sign of depression actually goes up. So that's why, you know, I had never thought that I will study exercise and also exercise in the presence of energy deficit,

But this is an example where, you know, someone bright comes into the lab and says, okay, so I'll try to prove that in animal models. And then it opens a completely new frontier because now not only athletes, GLP1 users, and then new mothers, there are a lot of new moms who are trying to lose that weight that began during pregnancy. At the same time, they're breastfeeding. you know, when you're breastfeeding, even 100 ml of milk production

requires another 400 to 500 kilo-Cal. So we are not calculating how much that milk production is almost equivalent to somebody doing exercise because that needs a lot of energy. And how do we balance that? Do we know how much they should be eating and what kind of nutrition?

And then you're stressed, your circadian rhythm is off, you're running around, you're barely, you're trying to feed your baby. wife is in this standpoint. You're trying to feed your baby. And the last person you think about is yourself.

And now you understand why, like so many traditional cultures, Asian cultures, you know, different cultures around the world. So much emphasis was focused on how do we support the mom in this first 100 day period and making sure that she's already exercising by producing breast milk. Yeah. We need to limit, you know. Other stress. Other stress that's there. making sure she gets food. In Korea, they have these Korean postpartum facilities where women go.

And they're sort of recreating a lot of what happened, you know, in traditional living where you'd have, you know, aunts and your mother or your grandmother all there feeding you things, making sure you're okay, making sure that you provide enough help and support. And largely today, I feel for so many moms that are out there, new mothers, because we don't have that same sort of family infrastructure and a lot of the work, even if dads are very involved, which I am. I like to think that I'm very involved. Still so much falls on the mother.

And what I'm hearing from you is that this is another example of a lot of energy demands in a very unique state of life and a classic time where people who are either trying to lose weight or are just under fueling based off of what those demands are in their life and how that opens them up for all sorts of challenges. We've had many of the world's leaders that have part of the meno revolution, talking about perimenopause, menopause, bone density, and the unique challenge that women have. People like Dr. Lisa Mascone, Dr. Sarah Godfrey, who've been on this podcast, Dr. Mary Claire Haver, and they've all talked about how, you know, we think of this thing as starting later in life,

but so much of it even happens based off of how are you fueling, exercising, in terms of having some level of, you know, just light walking and not being like completely sedentary after pregnancy because you, your bone density is greatly impacted after pregnancy. Yeah. So that's why this is a wide open area that, you know, after getting into this human performance alliance, then thinking about, yes, everybody is starting disease, but how can we study people who are thriving? How can we actually come up with plants? and what do we know about what is actually good health? And frankly, this idea about pregnancy,

sorry, the postpartum lactation and energy deficit, this was not my idea, this was actually loudest idea because she also went through, she had a baby, and then we had, one day, we're trying to make a slide of how this relative energy deficit relates to other conditions. And it's like, yeah, you know, yeah, in postpartum, there are so many people that are trying to lose weight.

And now it also triggered, it kind of one, another light bulb went on. And that is, we talk about postpartum depression. Is it because of two things. That is, these women now are so sleep deprived at night that they just want to catch up on their sleep during daytime. So they don't have enough time to go outdoor to get the best antidepressant and the broad daylight. And the second thing is,

Are they actually under fueling that's activating part of the brain that's involved in triggering depression? My wife is going to literally think that I paid you to talk about this right now because this is what we're dealing with right now. And my heart goes out to her because she's doing the best that she can and she needs a lot of support. I'm there to support her other things. It's more the system, the environment that's around so many mothers,

new mothers like my wife, that it's very difficult to do these things and do them consistently in the modern day world that we live in. And it's a problem that doesn't get talked about enough. Yeah. So that's another big aspect of this human performance alliance is we're putting a lot of emphasis on women's health because women athletes, female athletes, are also understudied. And at the same time, now we are seeing that in US Olympic team

and many Olympic team, in some Olympic team, more than 50% of athletes are women. And if we look at college-eat athlete, and also everywhere, they're more, women athletes and we have so little idea about how women's body is adapting to exercise, sleep, nutrition, et cetera. So that's why I think this is just the right time that I got into this. You teed us up perfectly.

That's going to be your third appearance. You're going to bring your colleague. We're all going to get a chance to talk about this work because it's definitely something that needs attention. But I'm glad you gave our audience a little bit of a preview of Laura's work, your work, group, again, does it have a website that people can follow? It does have. So, Human Performance Alliance, and I'll send you that website.

This is the, I think in my last 25 years of research career, this is the best team to be involved in because we have team in Stanford, Stanford Biomechanics. They are actually figuring out from just general video field, can you figure out whether somebody is at a high risk for ACL injury or how much is the ground reaction force? whether that person should be jumping this way versus that way to actually improve. So there is a lot of biomechanics and mechanobiology kind of stuff going on there.

And then it also goes to people in University of Oregon redesigning the shoes, athletic shoes for women. Just imagine all these shoes are actually designed based on male physical form. But women's forms are very different, and when they're on, it's very different. So even that is also being discussed, and it's kind of interesting to see how these innovations are coming through. And then we have Kate Ackerman, who is talking about real challenges of Olympic athletes. And then we just have a new center who is also dealing with elite athletes who are an NBA kind of players, what they're dealing with.

And I had the fortune of even kind of ride along with a NBA team for seven days. And then I realized, gosh, even if you give me $10 million, I'm not going to do this. Because we forget that the athletes are the most severely affected shift workers. Because a typical NBA player doesn't sleep in the same city for seven days in a row. They're constantly on the go. They're constantly on the go. And then most of the games are in the evening. So there is a lot of disruption to their sleep.

Yeah. And they don't get enough time to recover and refill. So in that way, I think I'm fortunate that I'm part of this group that works on all these aspects of how to build an athlete. Because at the end of the day, everybody's an athlete. Yeah. Because if you're thinking about it, we always want and aspire to be that athlete in our age group, we always talk about like, okay, so if I'm in the 50s age group,

can I be equivalent to those top 10 players in my age group? Sure, sure. And that is the impetus to be in that to improve our human performance. And this also brought a lot of talent into the lab, like, for example, all the exercise studies that I talked about taking different tissues and blood and checking that. So that was driven by another talented postdoc staff scientist, Cheryl D. Meyer, a German who had a strong foundation of exercise physiology, but she brought that knowledge.

And then now we have a much better molecular atlas. So all of these are really exciting thing that are going on. And also these are the things that everybody can do. We are not talking about drugs or supplements to improve certain things. It's what, how to leverage, what we are designed to do. You're designed to sleep. We are designed to get light. We're designed to exercise.

And we are designed to eat healthy. By the same time, all these things interact in such a intricate, delicate way that we also have to figure out the balance. Just like we figured out that you can eat the same number of calories, over 15 hours, over 10 hours, but 10 hours is better. Similarly, you can have the exercise. But now we've got to figure out what is that. optimum nutrition, that will help.

Your question was whether they will gain back that uterus size. Sure. And that's the next experiment, set of experiments that we're doing to see is that a specific nutrient combination that will improve that. Because we know from some other studies that Serald and Meyer did, that if we change just the macronutrient composition and when this mice are fed, we can improve the endurance capacity by 500%. So this is in mice, of course, in humans it will be less,

but then we give the same number of calories from different source. We just change the protein, fat, and carbohydrate composition. One group of mice will run maybe 400 meters and the other group eating slightly different macronutrient, micronutrient composition within certain time, eight or nine hours, they will run 4,500 meters.

So five-fold chains. So similarly, we think that when we come back to this relative energy deficit, we may find a diet composition that will benefit, that will accelerate that recovery back to normal. Well, I mean, that's a whole topic that I look forward to exploring with you guys in the future. But I think one practical takeaway from that

for our audience right now, beyond the idea that it's so fascinating, and has all these implications, not just with moms, but all the people that are on GLP's, you know, just as you were sharing before, is that so much of my audience has gotten the strength training and exercise bug because many researchers and doctors

and different influencers have been on this podcast, talking about it. And along with that, just make sure you do an audit and look at your life and make sure you're not under-fueling for your activity level. Yeah. Do a little bit of research that's there. Make sure you're not eating too little.

You might have weight loss goals. You might have different ideas of where you should be. But if you're underfueling, you're putting a different level of stress, especially it seems like if you're a woman in particular, you can have a lot of impact on your body. So just be paying attention to that if you're somebody who's training at a higher level than you were before. And, you know, it's not something that you've audited recently. take a look at it and make you sure you're not under fueling yourself.

Yeah. And then the first sign among men and women is that sleep might... Your sleep is off. Sleep is up. Irregular sleep or your sleep is disrupted. You may be waking up a few times a night or you may have difficulty falling asleep. So that might be a good sign that look at your exercise routine and how much you should be eating. Or another thing is if you're exercising too close to your bedtime.

Again, this is a large start. done by Hoop, they published it last year that if you're exercising too close to the bedtime, then your sleep may be disrupted. And this was somewhat known from, you know, laboratory studies in small number, but then when Hope did a study with tens of thousands of people, then now we know that it's actually happening in the real world. Coming back now to some of the topics that we were talking about in the beginning, you know, we've been recording now for over two hours. Time has flown by and I think it's a great opportunity as we're winding down over here to do a little bit of

a recap about how some of these things that from the outside look very soft and you can think, do I really need to be getting an hour of sunlight every day or daylight every day? Do I really need to be, you know, squeezing my eating window to, you know, this eight to ten hour period? And you've laid out the evidence that for at least two of the big killers that are out there, two of the scariest diseases, I would argue, Alzheimer's, cognitive decline, dementia, and also cancer, circadian biology is so core to minimizing our risk of these. Now, before we do a little bit of a recap on some of the key pillars of circadian biology and things that people can do today to start reducing their risk, I want to give a little bit of a plug. Your team has put together a fantastic

circadian challenge that anybody can do. Yeah. And it's a very good. And it's a little bit of a plug. I want to give a little bit of a plug. You know, It's part of your app that is also available for folks that are out there. Can you mention the app and a little bit about it? Yeah. So this one is the on-time health half. So we talked about four foundations, light, exercise, nutrition, and sleep. Just following these four. Again, going back to my elementary school analogy that not only you have to so off to the school,

you also have to do all this go to these classes at the right time. So that's the idea. And then to test whether it's actually working, we just had the good fortune of being selected as semi-finalist for XPRIZE health span. So the XPRIZE is now doing a challenge all over the world. They selected 40 teams from around the world as semi-finalist to come up with a simple idea or even can be injectable stem cell, whatever it is. Can you show that these, your idea is working in a small set of people and then if it is

working, then you go to final and they will select 10 teams to see whether by incorporating whatever you are testing, can we reverse aging in the sense that your biological markers, whether it's heart disease marker or strength and cognition and immune function, they look much younger. Not like I'll get rid of my gray hair or I'll get rid of my wrinkles in the face, but internally, am I looking much younger? So that's the whole idea.

And this is where we put together these four pillars, light, exercise, nutrition timing, and sleep. Of course, nutrition timing, we also made sure that these people get enough nutrition and also healthy nutrition. So a Mediterranean diet within nine hours. And you talked about four killers, two killers. You described heart disease and metabolic diseases are the other ones.

And actually, the inclusion criteria was the metabolic or cardiometabolic disease. So we also wanted to make sure that this works because cardiometabolic disease is everywhere. More than 70% of people have it. Number one killer. So the idea was very simple that for every person, we screened them very thoroughly over two days. And then based on their lifestyle, based on their numbers and how much exercise capacity they have, based on V-O-2 max, stress test, muscle strength,

isometric strength. We come up with a personalized plan. And the plan is very simple. You have to be in bed for eight hours to get enough sleep. And then we give all the toolbox full-up tools to improve their sleep they can adopt. Second is morning fast or morning preparation. so that they fast for at least two hours after waking up. And then the third one was they have to eat within somewhere between 8 to 10 hours.

Some people can eat within 8 hours. Some people need 10 hours because of their work or lifestyle. And then during that daytime, we made sure that they exercise. But the exercise is most likely in the late afternoon is better because there are a lot of studies now. more than 25 clinical trials have shown that late afternoon is much better in regulating blood sugar and blood pressure than the same exercise in the morning. And this is among people who have metabolic disease. It's not that well established in healthy people because in healthy people, these parameters are all healthy. And then the last thing they had to do was the evening preparation.

So there is no food within three hours before going to bed. There is no strain of exercise and there is no bright light. We even gave them actually blue filtering glasses that are already lap tested to make sure that these are blue filtering. So these are the four foundations. And frankly, I thought that, well, I don't know whether people will follow or not. The target is 12 people should complete. So we recruited 17 people.

All of them are above the eyes of 55. So these are not young college kids that we're capturing. And the idea was only 60 days, we had to do this and then see what happens. And I'm really pleasantly surprised that all 17 people start. Wow. And, you know, this is serious discipline. It's like getting the kids not only to school, making sure that they're going to all these classes at the right time. I was surprised that these people also all followed it.

And then when we ask them, why are you following this, then they say, well, we feel more energetic. We are slipping much better. We already feel much stronger. So even within 60 days. So now we have completed, I think, 11 participants, six more to go within the next few weeks. And then hopefully, very hopeful that this is a positive result

and we'll go to the final. But the point is we took those four elements, and then we have this app called On Time Health. get on time health. And these are the four simple ideas that people can, if people can follow, then they will improve. And we are seeing a lot of improvement in many users. And these days, many of the apps do have AI agents

that will just talk to you or send you messages, but actually we make sure that one thing we have learned from all of this is this personal touch, a human talking to you or responding to your emails in a human way, not some AI-generated text. No AI-slop. That seems to be valued much more by users than these automated messages.

So we put that together into this On-Time Health app, and that's what we are testing. I love it. I use the app. I think it's fantastic, by the way. And anybody in our audience, you guys have given us a special code. It's the GetOnTimehealth.com.

We've linked in the show notes slash Drew Perot. And there's a seven-day challenge, a seven-day circadian challenge, where you can take these four pillars and try it out. Yeah, I think in the seven days, people actually begin to see some benefit. Why we say seven days is when you're going from a habit that has been ingrained in you,

it's almost in your epigenetically imprinted on your DNA. It takes some willpower in the first seven days to come up with that discipline. But once you build that discipline, then if you can practice it for the next three weeks, This is some collaboration we are doing with Colt Fit. There is a large chain of gym back in India. And we're trying to figure out how do people build a habit of going to gym?

And we're finding that, yes, three to four weeks if they can go, then they will stay. So this is something that we learned. So that's how I think we can slowly improve health. Yeah. Yeah. And, you know, it takes willpower in the beginning, just like when you're doing anything new. but the beauty of circadian biology, and I've been a fan of it largely because of your work for years, is that you're not having to wait till you're 70, 80 years old and saying,

okay, did I get dementia? Did I not get dementia? Or you're not waiting that long to find out if this is paying off. When you practice time-restricted eating, when you practice proper sleep hygiene, giving enough attention to it, when you practice not eating super late at night, when you practice appropriately fueling with like a Mediterranean diet, you notice these things right away.

Yeah. And it's not just in the things that you think directly. Like, oh, I'll see that I have, if somebody's struggling with weight gain, that I have improved weight, although that's something a lot of people see, you'll see it in your mood. Yeah. You'll see it in your energy levels.

You'll see it in your compassion. Yeah. these arguments that you're talking about that so many people find themselves in. So that's the beauty is that, yes, there is strong evidence to suggest you can minimize your risk of things that we've been talking about here, Alzheimer's, dementia, cognitive decline, cancer, which of course are multifactorial diseases. There's so many things that play into these genetics, toxins, et cetera, et cetera, but at least we can do some of the things that we know can minimize our risk to the best.

degree we have somewhat of control on them. And why not do it? Yeah. I mean, that's why I always go back to, you know, when you talk about circadian, you use the word multifactorial and that's why that kind of sparked a light going up in my brand. When you look at circadian rhythm as every cell has its own clock, that means it's telling every single gene to turn on and off at different time of the day. So this is the most complex and most challenging biological regulatory system in our body.

Then the frontier of human health will be to figure out how every single cell should function ideally in every hour of the day because we are very different between day and night. And that's why when the circadian rhythm disrupts, since it can affect any organ, depending on your background genetic makeup, or your other predisposition, for example, if I'm eating very unhealthy diet, on top of circadian rhythm disruption, on healthy diet will trigger, say, cardio, metabolic disease, heart disease,

or stroke, and all that stuff. But if I have a genetic predisposition, to say breast cancer, and we see that, even in animal models and also in humans, people who do shaped work, night shift workers, have a high risk. for breast cancer. So this is why circadian consolidation, circadian rhythm discipline is not a luxury. It's the foundation of health because, as you said, a healthy day is marked by healthy mood,

healthy compassion, feeling more energy, feeling more strength. And when you build that every single day with circadian discipline, then you are actually building that's the unit of longevity, healthy longevity, and that's why I'm super excited. And one thing that also comes to mind, learning about blood flow throughout the body, because we talked about exercise, how it pumps blood, and how it kind of irrigates all the system.

But one aspect of sleeping and staying awake during the day is when we sleep, our heart and brain are in the same plane. So the heart doesn't have to work too much. a brain actually gets enough blood flow. And actually this, again, came from some of these studies that Laura was studying and then sent me that I was surprised that our blood flow actually goes up during sleep, blood flow to the brain.

And then during daytime, as we stand up, then since our brain is 20 to 30 centimeter above our heart, our heart has to work hard to support. apply blood to the brain. And since we're standing, all the bloods, because of gravity, has to go to the leg, and we have blood pulling. And one benefit of exercise is exercise actually

pumps those muscles, so the muscles actually act as pumps to push this blood back to the heart, and then heart can send to the head. And that's why throughout the day, or actually, if we don't make any effort, if we're just sedentary, a blood flow to the brain goes down. So one of the reasons why we should exercise or be active is to increase blood flow to the brain. And another thing is when we do time-restricted eating or eat within a short time,

then when we eat, our blood goes to our intestine or gut to observe all this nutrient, and then that reduces net blood flow to the rest of the body and brain. So when you time-rested eat, then it also allows the heart to redistribute that blood to rest of the body, including brain. So we are seeing that many of the indirect benefits of exercise, sleep, even being active, maybe going through this circulation. So that's my new passion. So that's why I'm kind of trying this experimental device to see.

Yeah, you came in. I thought Scotty just beamed you down from the Starship Enterprise. Yeah. And I thought, hey, I need some of that technology. But really it's monitoring blood flow to the brain. It's not brain because my brain is inside still. Sure, sure, sure. Part of it is outside.

But, you know, for example, now when we have any wearable in our wrist, that's measuring, say, blood pressure or heart rate. It's actually not measuring from the heart, but from sorrogate. So similarly, is it measuring a sorrogate blood flow to the brain? So that's what I'm kind of super excited to see. We'll want to hear all about it when you come back next time. time. This is fantastic. You know, I had, as you can see in front of me, I had like six pages of notes. And I'm glad we truncated the list of things that we talked about because we only made it through page number one and two. But it was important because, again, when I survey

my audience, Alzheimer's disease, cancer, two big things that are on people's minds. Unfortunately, two diseases that are continuing to expand and more people are finding themselves in a diagnosis of these. And a lot of people are worried. You know, there's a lot of different information that's out there and not enough information when it comes to circadian biology. So for somebody like you to drive up from San Diego, take some time over here, talk about the research, talk about the practical things that we can do that consistently over a period of

time can measurably add up and hopefully help us reduce the risk of these diagnoses in our life, it means a lot. And I want to thank you on behalf of our audience of you really giving us your time and attention to break down these important topics. Dr. Such and Panda super appreciate you being back on the podcast. Thank you, Lou. Hi, everyone, Drew here. Two quick things. Number one, thank you so much for listening to this podcast. If you haven't already, subscribe, just hit the subscribe button on your favorite podcast app. And by the way, if you love this episode, it would mean the world to me. And it's the number one thing that you can do to support this podcast is share it with a friend, share with a friend who would

benefit from listening. Number two, before I go, I just had to tell you about something that I've been working on that I'm super excited about. It's my weekly newsletter. And it's called Try This. Every Friday, yes, every Friday, 52 weeks a year, I send out a an easy-to-digest protocol of simple steps that you or anyone you love can follow to optimize your own health. We cover everything from nutrition to mindset to metabolic health, sleep, community, longevity, and so much more. If you want to get on this email list, which is, by the way, free and get my weekly step-by-step protocols for whole-body health and optimization, click the link in the show notes that's called Try This or just go to Drew Perot.com. That's D-H-R-U-P-U-R-O-H-I-T.com and click on the tab that says

try this.