Dr. Patrick: For those of you that don't know who Dr. Satchin Panda is, I've done a couple of podcast episodes with him over the past few years. He's a pioneer in time-restricted eating and also an expert on circadian rhythms. If you don't know what either of those things are, don't worry, we're going to get into those shortly. We'll talk all about optimizing circadian rhythms, and sleep, and time-restricted eating and how time-restricted eating relates to circadian rhythms and just a lot of really cool stuff. So maybe we should go ahead and get started. And again, as Satchin mentioned, he is a professor at the Salk Institute and runs a phenomenal laboratory there where he is publishing just extremely high-impact studies and that really have a major impact on public health. So maybe we can start chatting a little bit about the world of chronobiology and circadian rhythm. I mean, many people listening to this conversation may have a general sense of what a circadian rhythm is, but a lot of people have never heard of it. So maybe you can sort of explain what it is, Satchin, and why they're important.

Dr. Panda: Yeah, so just imagine, if you have to do a lot of different things in a day, you just can't do them at random. So that's why you come up with a calendar and put what time you want to do certain things so that you are more productive. So similarly, our body does zillion different tasks in a given day. For example, there are dozens of hormones, there are many digestive juices, then there are brain chemicals, there are genes that have to turn on and off. So that's why our body also has a daily timetable that repeats itself every single day, so that's why the term circadian rhythm. Circadian literally means approximately a day and rhythm is rhythm. So this is a timetable that repeats every single day. So what it means is the first thing that comes to your mind is sleeping, because sleeping is a big chunk of time that our body devotes to at a specific time of the night. So similarly, almost every organ in our body, whether it's liver, kidney, heart, or even your skin or even your hair follicle has to do certain tasks. So that means every single organ, every single cell has its own daily timed circadian rhythms.

Dr. Patrick: And what's so interesting is that everything from, like you said, every organ in your body has a circadian rhythm. And I find it when you think about when you're...a lot of people are interested in when their optimal peak cognitive performance occurs. A lot of people take nootropics, or they'll drink caffeine, or do a variety of things to try to improve their cognitive performance. But even time of day actually is important for that, right?

Dr. Panda: Yes, so just like the brain has to sleep for certain hours at night, it also has a narrow window in the first half of the day when it has the best cognitive ability, problem-solving ability. And maybe that's why, Rhonda, you just scheduled a call at this time of the day...

Dr. Patrick: Yeah.

Dr. Panda: ...in the morning. What happens is when we don't sleep enough, then our brain is foggy and we just can't think clearly. And people think that by drinking a cup of coffee, we can start thinking clearly, which is actually not true. Caffeine just wakes up our brain, but it doesn't make us think clearly. And those experiments have been done extensively. So we have to still respect the number of hours we sleep the previous night to be fully awake and can be fully functional.

Dr. Patrick: And what about the time of day in terms of like when neurotransmitters are being produced? I mean, is there a circadian rhythm to that as well?

Dr. Panda: Yeah, almost every neurotransmitter has a circadian rhythm. When I said every neurotransmitter, it's normally the neurotransmitter, or maybe the receptor that receives the signal from neurotransmitter, or the system that recycles the neurotransmitter. Any one of them can have a circadian rhythm. So that means, at certain time of the day, we are more prone to feel happier, at certain time of the day, we may be more prone to feel a little sad. Those things are ingrained in our circadian rhythms.

Dr. Patrick: Some people are natural early risers and other people are night owls. For me, I'm a pretty normal riser. I mean, I guess ever since I had children, I started to wake up earlier than usual. But I usually am up around 7:00 a.m., and I find that my peak mental performance is sort of late morning-ish, around 10:00 I feel like I'm the most mentally alert. But what about people that are naturally early risers or people that are night owls and so they wake up much later in the day? Is it a good idea for them to force themselves to wake up early or...?

Dr. Panda: Well, one thing is irrespective of whether you are early riser or late riser, what's much more important is how many hours you sleep. And many sleep scientists would agree that an adult should sleep around seven hours. So that means if you're in bed for eight hours, then you'll get approximately seven hours of restful sleep. So now, let's go back to early risers or night owls. Night owls, they may be night owls for many different reasons. One, they may be genetically programmed to be night owl. And that number seems to be extremely low because many people who think they are genetically programmed to be late nighter, they turn out to have certain other things, for example, caffeine habit, or binge-watching movies, or even having some work at home that gets them awake until late night. And the challenge for night owler is although they're a night owl, the whole world is programmed to start, or your work is more likely to start at 8:00 a.m. So that means you have to get up and start your day around 6:30 or 7:00 a.m., depending on your commute time. So the late nighters therefore, have a big challenge that if they cannot go to sleep before, say, 1:00 a.m. in the morning, then they're not getting enough sleep. And that becomes very challenging for them to function at peak human performance on the following day. So that way, what might be a potential solution is to figure out what is the cause of your night owl habit. A lot of people may or may not pay attention to the idea that a lot of people will have a cup of coffee or tea in the evening, late afternoon, or when we socialize. We drink caffeinated drinks, or even chocolate or hot chocolate, that can keep us awake. Then the second thing is we also are exposed to a lot of bright light in the evening. And a lot of people I had seen if they take care of the lighting and caffeine, then they become "normal." So that means they can go to sleep, say, between 9:30 and 11:30 so that they can get seven hours of restful sleep. And that way they can function normally from the next day. So that's kind of my long-winding answer to a very simple question, how night owls can manage their human performance every single day.

Dr. Patrick: You brought up a lot of really important points for, one, talking about avoiding bright lights or blue light exposure in the evenings. And some people may not be familiar with why that is. So a key driver of the body's circadian rhythms is melatonin, which people probably have heard of. It's a sleepiness hormone. But it rises towards the evening because blue light inhibits it. So can you talk a little bit about maybe that and perhaps, even the opposite of avoiding bright light in the evening would be actually seeking it out in the morning.

Dr. Panda: Yeah, so this discovery of melanopsin, of the blue light receptor was considered to be one of the top 10 breakthroughs of the year in 2001 when three different labs including mine, we discovered it. To give you a context, if you're living in the nature and you don't have access to electrical lighting, then the day length changes between summer and winter. And accordingly, our sleep and wake up time also has to change, our circadian rhythm has to adjust to this changing daylight. So as a result, our nature has...we have evolved to have this light sensor, this specialized type of light sensors. These are called melanopsin or blue light sensing light sensors that are present in our retina. These are not necessarily for seeing the outside world, but this light sensor senses blue light. And why blue light? Because the sunlight is the best source of blue light. When we say blue, it's around 450 nanometer to 500 nanometer, that range. So these light sensors in our retina, they actually are slightly different because they need a good dose of blue light. When I say good dose, that means, for example, in a full moon night, your regular light sensors can help you find their way or you can take a walk, but that level of light is not enough to activate melanopsin. So that means if you stay awake and you are taking a night hike in a full moon night, it's not going to reset your circadian clock. And now, fast forward few years, what we understand now is this melanopsin blue light sensor actually senses light, bright light during the daytime or blue light from electrical lighting, and then tells our master circadian clock in the brain depending on what time it is and might say, "Hey, it may not be evening, it's actually extension of the day. It's a long summer day, so please stay awake," or at the same time it can also send a signal to this melatonin which is the sleep hormone because when melatonin goes up, we tend to feel sleepy. It tells melatonin that, "Hey, it's not time to go up because it's just a long summer day." So that's the way this blue light sensor in our retina connects to our brain to reset our clock or to tell when melatonin should rise or fall. So now, what are the functional consequences or how we can use this information in everyday life? One is since melatonin has to rise, a melatonin rise correlates very well with how we feel sleepy and how we fall asleep. It's a good idea to let it rise naturally so that we can fall asleep. And to let it rise naturally, we have to release the brake and the brake here is blue light. And that's why dimming down light in the evening is a good idea to release that brake so that melatonin can begin to rise. And since we know that this is blue light as the cause of suppressing melatonin, we can also do another thing, we can change the color of the light. And based on this science, almost all the cell phones or laptops now have a night shift or night light feature. And you can program it to turn it on around 8:00 or 9:00 in the evening when these screens will dim down and will turn it orange in color. They may or may not help you to increase your melatonin, but at least they will signal that it's time to wind down and go to bed. Then, conversely, during daytime, it's very important to get a good dose of bright daylight. So that means if you are sitting next to a window, a large window and having your breakfast although you don't have sunlight falling on your eyes, you still get around 1000 lux of daylight. And if you have that exposure for half an hour to an hour in the morning, then that's pretty good enough to again put a strong brake on melatonin, which might be slowly going down in the morning. And at the same time, that melanopsin receptor, it does slightly different things during daytime. It sends a signal to the brain to increase alertness and make us more functional, so it reduces depression and makes us more happy. So that way, we can use this information that we learn from a very fundamental discovery in neuroscience to our advantage by getting at least 30 to 60 minutes of daylight, even sitting next to a large window during the first half of the day, and dimming down light, and maybe switching to yellow or orange-shifted light or wearing even blue filtering eyeglasses in the evening to improve our sleep.

Dr. Patrick: So a couple of questions, one, you mentioned avoiding the blue...sorry, wearing the blue filtering glasses at night, perhaps to filter out some of the blue light. What about avoiding sunglasses early in the day to make sure you're activating the melanopsin receptor and getting that resetting of the circadian clock?

Dr. Panda: Yes, that's a good question because we also have to strike the balance between protecting our eyes and getting enough blue light. So let's talk about some actual numbers of how much light we experience. So if you are outside in a sunny day in California, or sunny day in any place, and if you're looking at the sky, not looking at the sun, you get somewhere between 100,000 to 200,000 lux of light, so very simple calculation. And if you're inside your car and there is no direct sunlight falling on your face or inside your car and you're just driving, looking horizontally, then you're getting somewhere between 5,000 to 10,000 lux of light, which is similar to standing outside your car in a cloudy day, that's also 5,000 to 10,000 lux of light. So now, in a cloudy day or sitting inside your car, there is not enough UV light to hit your eye and damage your cornea or damage your skin. So in that case, driving without sunglasses is fine because you are not getting too much UV light exposure. But if you are in the beach or you are outdoors skiing in a very sunny day and you have a lot of UV exposure, then it may not be a good idea to abandon your sunglasses.

Dr. Patrick: Interesting because the singlet oxygen produced by blue light can damage the rods and cones.

Dr. Panda: There is a ton of UV light outside too.

Dr. Patrick: And what about, on the flip side of that, people actually being exposed to the bright light in the evening oftentimes think, "Well, I can take a melatonin supplement. And that should sort of help me increase my melatonin." Is there a difference between the melatonin produced in the pineal gland versus melatonin being made in your gut, which is something that is even produced from eating food that contains the amino acid, tryptophan, which gets converted into serotonin in the gut and ultimately into melatonin? What are your thoughts on supplementing with melatonin maybe regularly, or even is there an age-dependent factor in there?

Dr. Panda: So that's a very tricky question because melatonin is not regulated in the U.S., but in other countries it is regulated. And the reason why it's not regulated in the U.S. is you can feed a lot of melatonin to a mouse and the mouse will never die. In that sense, when you give various drugs or chemicals to an animal, then there is LD 50 or lethal dose 50 at which some animals would die. So based on that, we think that melatonin is safe and, of course, there is not much adverse effect of melatonin shown in any major experiments. But having said that, we don't know what are the long-term adaptation of our body to melatonin, whether you start with a milligram of melatonin and your body will slowly become resistant to that milligram and we'll need more and more. But at the same time, people think that melatonin is a good alternative to sleeping pill, which can have more adverse side effect. And maybe that's one reason why we have seen almost 40% to 60% rise in melatonin use in the last couple of years alone. So, coming back to your question about melatonin, the natural melatonin versus supplementing melatonin with a pill, it's really hard to make those connections because, as you know, melatonin rises in the middle of our sleep and there's a kinetic to it. It's not easy to detect melatonin. It's not like a continuous glucose monitor that you can stick to your arm and it will collect melatonin data because melatonin is present in such a low concentration that it needs more fancy method to detect it. So that means we have to sample blood in every 30 minutes or an hour when we're sleeping, and then use that inexpensive method to measure melatonin. And that might be one reason why not much studies have been done to differentiate between exogenous application or taking a melatonin pill versus pineal melatonin. The second thing is when we take a melatonin pill, nearly 70% to 90% of it is broken down in the liver and kidney within an hour. So whatever we take, only a small fraction of it stays in our bloodstream during our sleep. So as a result, melatonin in experimental and clinical studies has been shown to improve sleep latency. So that means it can help people to fall asleep. But it might not be that good in sustaining sleep throughout the night. At least that's what the clinical studies have shown. But in some people, they feel that melatonin helps them to stay asleep throughout the night. And unlike this pill, our endogenous melatonin actually rises roughly a couple of hours before our habitual sleep time. It slowly rises and then it reaches almost its peak up to one hour into our sleep and maintains that peak throughout the night. And after we wake up, around that time, it begins to decline, and it goes down to its lowest level, maybe two hours after we wake up. Whereas if you take a pill, it will just spike for 15 minutes to half an hour just after you took the pill, and then it will come down and slowly continue to go down throughout the night. And by the morning, when you get up, there might be very little depending on how much melatonin you took. These days, a lot of people are...and actually there is a shift in the dosing of melatonin. For example, almost 20 years ago when I was a student, I could find 1-milligram melatonin pill. And it was very difficult to find a 3-milligram pill. And now, it's almost impossible to find a 1-milligram pill in any drugstore, and the common is around 3 to 5-milligram pill. So that means when people are taking this 5-mg, it's possible that they have a very huge spike. And then when it comes down, it actually stays at a pretty high level throughout the night. And maybe even two to three hours after they wake up, they still have significant amount of melatonin in their system. So unfortunately, these are some of the studies that need to be done and have not been systematically done.

Dr. Patrick: So what's interesting about what you just said about them possibly the melatonin levels being elevated even two to three hours after waking up, you have previously said in another podcast, you've talked about how melatonin actually can inhibit the secretion of insulin from the beta cells in the pancreas, the islet cells in the pancreas, and that would obviously affect your blood glucose levels. Do you think avoiding eating food, even waiting an hour or two after you wake up, before you start to eat would be something that would be helpful for regulating glucose levels?

Dr. Panda: Yes, this connection between melatonin and glucose is relatively new because in 2009, simultaneously four different papers came out from human genetic studies showing that people with diabetes or increased fasting blood glucose level have a polymorphism or mutation in the melatonin receptor gene. And that was really perplexing because until then melatonin was supposed to have its function only on sleep, and people never thought that it can affect blood glucose. And then from 2009 until, say, 2015, '16, there are a lot of studies that started to understand why melatonin affects blood glucose. And slowly, a much better picture is emerging that melatonin, just like it makes our brain to sleep, it also makes our pancreas to sleep, or islet cells to sleep. That means it makes these Insulin-producing cells less responsive to glucose so that they don't produce as much insulin as they should when we eat something that has carbohydrate or glucose. So that means that if our melatonin level is high in our system, and we eat something, and blood glucose level goes up, the beta cells can sense that blood glucose, but they cannot produce or release enough insulin. Since the function of insulin is to absorb some glucose into muscle cells, into many different types of cells, without that glucose being absorbed, it stays in our blood system so our blood sugar level rises. And to make it even more complicated, going back to the discovery of that melatonin receptor variant, nearly one-third of the population had that variant. So that means they're more likely to be influenced by this relatively, benignly moderately high level of melatonin being in their system and not being able to control their blood glucose. So it might be difficult to go get your sub-genotype and figure out whether we are more or less sensitive. But then the bottom line is there's a consensus that one should not eat too close to bedtime when our melatonin levels may be high, and that's when if we eat, then our blood glucose level may remain high. In fact, this has been experimentally shown almost half a century ago. In '70s and '80s, there was this talk about evening diabetics. So that means go in the morning to a clinic and get a bolus of glucose, and then after 90 minutes, you measure your blood sugar level, it may come down to normal level. But the same person, if he or she goes to the clinic in the evening or late night, gets the same bolus of glucose, and after 90 minutes the blood glucose may remain at a high level which would qualify him or her to be diabetic. And even now, people observe the same effect. So that means in late night, a body cannot respond to glucose and produce enough insulin. And now, we are coming to understand at least part of it is due to melatonin. So now, coming back to your question, yes, that's why we suspect that people who get up and immediately eat something that has sugar, carbohydrate, then they may not be able to completely bring down that blood glucose level in the next 60 to 90 minutes. So that's why it might be a good idea to wait for an hour or two after waking up for the nighttime melatonin levels to come back to daytime level before you eat. And conversely, at night also, it's a good idea to not eat or drink anything that has carbohydrate or glucose two hours before bedtime.

Dr. Patrick: What about maybe eating a higher fat meal in the morning as opposed to eating something with more carbohydrates or glucose?

Dr. Panda: Well, so this is where we have to think of numbers. So, for example, if you drain all of my blood, you will get 5 liters of blood. And if my safe blood sugar level is 100 milligram per deciliter, so that means from that 5 liters of blood, you will get 5 grams of sugar. And if you have 1 more gram of sugar, then my blood sugar level will become more than 20-milligram per deciliter. So that's almost the definition of diabetes. What it means is if in the morning, if I eat even anything that has 1 gram of sugar, that's 1/5 of a teaspoon, and my pancreas is not at all functioning and none of the blood sugar is absorbed by any cell, then I will have dangerously high level of blood sugar. So when you think of fat-rich food, except for pure fat, I think almost every other food will have some carbohydrate. And that carbohydrate will be equivalent to one gram of sugar or carb. So that's why we have to be a little bit careful in recommending what people should be eating because even with that carbohydrate...sorry, fat or protein-rich diet, even if you are having a couple of boiled eggs with a toast, that toast has enough carbohydrate that needs to be absorbed properly.

Dr. Patrick: Good point. Kind of shifting back to the melatonin and its role in circadian rhythm, there are a lot of people that have altered circadian rhythms because either they are shift workers, or perhaps they have traveled into another time zone. Can you maybe first kind of just define a little bit and explain why...? Some people actually may be shift workers without even realizing it.

Dr. Panda: Yeah. I said that almost all of us are shift workers because the definition of shift work is very immense if you strictly go by what is a shift work. And it's very hard to get a clear definition because some may be working very early in the morning, someone may be working late in the evening, some may be night shift workers. So that's why the international level organization in some of the European countries, they have come up with a working definition of shift work, which essentially translates to a very simple term, like if you stay awake for 2 to 3 hours between 10:00 p.m. and 5:00 a.m. for 50 days in a year, so that is on an average one day in a week, then you may be considered as a shift worker. And now, if you think about yourself, almost all of us kind of either we go to bed very late or we wake up very early to do something, to take care of someone or to finish an assignment very frequently. So that's why I say that all of us may be shift worker. And why this two to three hours? Because if we delay our sleep by two to three hours at night, or we wake up two to three hours before our usual wakeup time, then when we're awake in the morning, we're usually exposed to light or we try to stay awake by eating or drinking some coffee and all of these events actually try to reset our clock. And it takes almost two days to adjust to a two hours change in wake-up time or two hours change in sleep time. So that means by disrupting our sleep-wake cycle just for one day, we perturb our circadian rhythm for the next two to three days. So our daily habits are not in alignment with our internal clock for those two to three days. So that boils down to 40% to 50% of the week, we may be out of sync, including the day on which we disturb our clock. So that's why we have to keep in mind what is the definition of this shift work and how we all may be shift workers because even if you stay awake for a couple of hours extra to socialize and have a late-night dinner, you may be living the life of a shift worker.

Dr. Patrick: Is there anything we can do to sort of mitigate the negative effects? I mean...or is it just sort of don't...

Dr. Panda: Yeah, I mean, that's just... Well, so that's the thing. We built this anthropogenic world in the post-industrial era without knowing the relevance or the significance of circadian rhythm in our life. So that's why our personal choices, the way we live in the family, or the way we socialize, or the way we even pick to do a job, whether it's a night shift work or we just stay awake late into the night binge watching, or as a professor or teacher correcting grades, all of these are based on the lack of knowledge of circadian rhythm and how it is important. So in that way, I always say that we're experiencing what I call the lead and asbestos moment in human health because until 1970s, we thought that lead and asbestos are safe and we could use them in any building construction. So similarly, without knowing the relevance of circadian rhythm, we thought that it's just a momentary discomfort to stay awake for a couple of nights, or to do a shift work, or we conducted late night socializing and binge eating with some food hangover that will go away after a day or so. But now, we are realizing that these are serious issues. So that's why it will take maybe a decade, three or four decades to rebuild an anthropogenic world that actually not just our circadian rhythm. So a few things we can do is if you want to socialize in the weekend, instead of choosing to socialize late into the night, try to go for the happy hour. I mean, the food is cheap, you can finish your dinner early, and you can still go back to sleep at the regular time. And when it comes to shift work, then we have to keep in mind that we have to be extra careful than people who are doing daytime job. And we have to stay away from, say, caffeinated drinks and a lot of alcohol because shift work combined with alcohol or too much caffeinated drink is quite toxic to our body. It disrupts our sleep-wake cycle, and we're actually more sensitized to be damaged by alcohol if we're doing shift work. Then we have to judiciously choose what time we eat or sleep and try to be within that window almost every single day, even on the off days. It's relatively easy to do that if you're a morning or evening shift worker. But for night shift worker, it's very difficult. So that may be something that we can even bring up with your employer to see whether we can be on night shift continuously for several days so that your body adjust to night shift and then come back to a few days of off days. And this is a method that's used in many countries where people stay on night shift or 24-hour shift even for several days in a row, and then they come back and take off days for a week or two. So there are multiple methods. But anyways, it's still a new field of science, and we're still learning how to come up with personal habit, family rituals, and societal norms to adjust to or to reduce the incidence of circadian rhythm disruption and adopt habits that will make us resilient against circadian rhythm disruptions.

Dr. Patrick: I find for myself, as a parent now, my sleep is very beholden to what my child does. And when my child wakes up, I have to wake up for the most part, unless he stays quiet for an hour, which sometimes he does. So when I put my son down for bed, I have an option, I can watch a show that I'm really into and I've been waiting to see the next episode of. And, in fact, it's a very stimulating show. So I find myself if I watch it, I'll often want to, as you said, binge watch. I want to watch the next episode and just go to bed an hour later, maybe two hours later. And I find that because I have to wake up...people have all sorts of reasons they have to wake up, like you mentioned work, and children...and also in my case, I don't have any blinds on my windows in my bedroom. And so I wake up sort of gently when the sun comes out, which means that if I go to bed later, I will be losing sleep because I wake up at the same time pretty much because the light is coming in. So do you think that also just maybe avoiding some of these stimulating shows, like TV shows at night...it's kind of a trade-off because, on the one hand, you're kind of relaxing and you're forgetting all the worries of work and you kind of immersing yourself in this other world. But the flip side of that is you're also probably stimulating yourself more and maybe getting a little bit of blue light from the TV screen and then going to bed later.

Dr. Panda: Yeah, so you kind of touched on many, many important issues. You pointed out how after your son goes to bed, that's the only free time you have. And that's true. In fact, the social scientists, they agree that nighttime is the time of freedom, human expression, human creativity because this is when a lot of people who do a job that we don't like are people who care for other children, people who are not well at home, they get that free time late in the evening. And that becomes a challenging issue, where to draw the boundary between your personal freedom of expression, of enjoyment versus your personal duty to nurture your health. And if we think about circadian rhythm disruption, then it entirely boils down to how we manage those three to four hours of freedom time after we have finished doing what we are supposed to do for others and we have that personal freedom time. And that's for a bigger discussion because that involves many different pieces. So coming back to the other side of the story, you said how you don't have blinds in your windows so you wake up at the same time every single morning. That would be wonderful if you also have the freedom to go to bed at the same time every single day. So that's why circadian rhythm disruption, the fact that we are living like shift worker brings up another necessity that is we have to have complete control over our bedroom. We should be able to make that bedroom completely dark or inspiringly bright at any given time of the day or night. So this is where I always tell people that try to design your bedroom or at least have good blinds that will make the room completely dark, have earplugs handy, an eye mask handy so that you can at least get those one or two hours of extra sleep during daytime when it's difficult to fall asleep. So I guess and just how to go to bed and how to wake up itself can be a separate topic for discussion.

Dr. Patrick: Yes, absolutely. I'm fortunate to have darkness. There's not any street lights or anything. But I think I have blinds on the way because I realized that just that early morning, I am missing out somewhat on a little bit of extra sleep I could get early in the morning when that sun is coming up. But you kind of mentioned something else, napping. Are naps beneficial?

Dr. Panda: Of course. If you are sleep-deprived, then napping is a very good way to catch up with the lost sleep. And, in fact, we are designed to be napping because we humans are not strictly diurnal. We are crepuscular. So that means we are more alert in the morning and evening and little less alert right after lunch. Our internal sleep pressure actually goes up physiologically right after lunch. So we are designed to have maybe 30 minutes to an hour of nap.

Dr. Patrick: Interesting. Do you think part of the reason we are sleepy right after lunch, and you probably know the answer, but does it have anything to do with a postprandial glucose response or postprandial inflammation, or is it totally circadian regulated?

Dr. Panda: I think it's a combination of both because there is a sleep pressure, and if we have some food then the postprandial change in physiology in combination of the sleep pressure make us sleepy. So as a result, you can fight off many different ways. For example, you can have a smaller lunch so you don't have too much disturbance to your physiology and you can fight off that postprandial intake. Or since bright light actually makes us more alert, then maybe having that lunch outdoor, under a canopy, or maybe going for a short walk after lunch will keep you awake.

Dr. Patrick: What about offices? Are there any way we can optimize the light indoors?

Dr. Panda: Yeah. So there are many new technologies and architectural designs that those are now coming into picture for office design. The open office design and having large windows, those are all part of this new scheme. And the fortunate thing is now glass manufacturing has come to a point where glass can be both aesthetic, as well as load bearing. So some of the glasses are strong enough that they can even take some of the load of the building. So that enables designers to come up with large walls, which are just glass walls that will allow enough light to seep in. And then in large offices having cubicles with enough head space through which daylight can come through and kind of distribute throughout the large space is helping to bring daylight, at the same time reduce energy bill by reducing artificial lighting. All of these are helping. Then at nighttime, there's also innovations in office space design. You can have light layering so that you can have more personalized light because you can light up a cubicle or office with LED lights that can be dimmed or brightened up to the occupants own choice. So there are a lot of innovations that will actually help to optimize this anthropogenic world for circadian rhythms. And lighting itself is a $27 billion industry. And for the first time in human history, we have near complete control over the quality, quantity, and timing of light that we can have in our workplace or in our home. So there will be a lot more innovations in this area where, maybe in future, we can have our body sensors talking to the building sensors and building control system to automatically adjust lighting, adjust temperature that will nurture our health.

Dr. Patrick: What about in countries with very little winter daylight? I mean, is there something like some sort of lights indoors that you can buy to kind of help stimulate the daylight?

Dr. Panda: Yes. If you look at many of the big lighting companies, they're actually from those northern latitudes because I guess they have been experimenting with light for such a long time that they come up with all these innovations. And the rule of thumb is if you go to buy purchase a light bulb, then you will see there are three different flavors of light. One that looks orange color, and it's very much like candlelight or firelight. And that's good for evening time in your bedroom or wherever you don't like to have too much bright light. And then there is blue-shifted light, which looks very blue, very alerting, super bright white. And those are the lights that can help us in wintertime. And many of the cold countries of Northern latitude or extreme Southern latitude countries, they have adopted using light to uplift their mood. So many of those designs now incorporate both orange-shifted light and blue-shifted light at different time of the day or in different seasons so that in winter time you can have more of the blue-shifted indoor light to improve your mood and alertness and even brighter light to improve your mood and alertness. And conversely, in summertime, when the days are extremely long, they're also adopting good window blinds, window shades, and orange-shifted light to simulate evening time so that they can go to bed and they can get restful night of sleep.

Dr. Patrick: Cool. Kind of going full circle here, back to the circadian rhythms and how every organ in your body essentially is on a circadian rhythm and including your organs like your liver that are involved in metabolism, you mentioned when we were talking about shift workers, people eating within a certain time window, so time-restricted eating, most people here in the Clubhouse chat probably have heard of time-restricted eating. They're familiar with your work. But maybe we can kind of just briefly explain what it is and why eating within a more narrow window range, your research had shown and others, to be beneficial.

Dr. Panda: So time-restricted feeding, time-restricted eating is something that was discovered in our lab and the term was also coined in our publication. And it has been now used more loosely in popular culture as intermittent fasting. Intermittent fasting, in fact, in scientific literature refers to alternate day fasting, two days of fasting in a week, or even periodic fasting, but people will fast for four or five days in two to three months. But we didn't want to use the word fasting because fasting usually refers to reducing calories for one or more days, whereas the term time-restricted eating generally refers to eating within X number of hours, where the X can be somewhere between 8 to 12 hours in experimental models, preclinical models, and without explicitly reducing calorie. And that's a big caveat between caloric restriction, scientific term intermittent fasting and time-restricted eating. So now, coming back to the science, why we think it is important is if we think of why circadian rhythm is important, one big thing is circadian rhythms actually help our body to repair and rejuvenate itself. For example, we always equate a human body to a car or an engine. And we say how we describe how our body works by connecting it to an engine. But there's a huge difference between a car and our body, and that refers to you can start a car and take it for a spin at any time of the day or night and it will function the same way. It will go from 0 to 60 if you're riding a Tesla, maybe 3.5 seconds, or some other cars, maybe 5 to 6 seconds, it doesn't matter whether it's day or night. But our body doesn't work that way. If I wake you up in the middle of the night and ask you to do a complex piece of math, you might take an hour, whereas in the middle of the day, it might take you only 15 minutes. So the reason being the car doesn't have to self-repair itself. We have to send the car to a body shop or to a repair shop to repair it once every three to four months or tune it up, whereas a body tunes up and repairs itself every single night. And that's why when we misuse our body, we have to send it to the body shop or repair shop, aka a hospital or emergency room. And so that's why you don't want to use your body as a car. So now, coming back to the repair and rejuvenation, now, if you think of sleep as a perfect example, when we sleep for seven hours or eight hours, during that seven to eight hours, our brain is repairing and rejuvenating itself by taking out the toxic materials, by strengthening the synaptic connections or connections between our neurons and resynthesizing some of the neurotransmitters. All this repair and rejuvenation is happening for those seven to eight hours. So now, just like the brain, every single organ in our body also needs to repair and rejuvenate. And for that process to work, you don't want to...so just like the brain is unplugged from all the outside sensory stimulation for this to happen, similarly, all the cells, all the organs in our body has to be unplugged from outside input. And one of the outside input that influences almost all of our organs is food because when we eat, it changes quickly the levels of many hormones. It even changes the nutrient level and all cells in our body have to process or break down, interconvert all the molecules that we get from our food. So that's why we need to stop eating. But then the question is, if our brain needs only seven to eight hours of sleep, why do we need 12 to 16 hours of no food? And the answer is when we eat, it takes at least five hours for our stomach to digest that food. And after five hours, then our intestine might take several hours to absorb nutrients, some of the nutrients, and then send them to our liver and other parts of the body. So that means if you finished your dinner at 6:00 in the evening, then your stomach is still working until 11:00 pm or even later, so it's not actually getting to sleep, or repair, or rejuvenate itself. So that means how many hours you are not eating, you subtract at least five hours from that, that's the number of hours your organs are resting, preparing or sleeping. So that's why if we eat for 8 to 10 hours, then we give our organs some rest for 16 to 14 hours, and that translates to roughly 8 hours of really no digestion, no nutrition interconversion, and that's the time our organs are getting to repair and reset, rejuvenate. So as an experiment, we have done this experiment in mice and fruit flies because we can control eating there. When we give mice ad libitum access to food, they can eat anytime, then they will eat nearly 85% of the food during nighttime when they're awake, 15% to 30% of food during daytime when they typically sleep. And in this lifestyle, the mice will slowly gain weight. They will slowly become diabetic, they will have high plasma fatty acids that will make them prone to heart diseases, and many other bad things will happen. But if we feed the mice the same number of calories from the same diet source, whether it's healthy diet or unhealthy diet, they get to eat all of that food within 8 to 10 hours, then we can protect them from all these diseases. And if the mice are already having a disease and we put them in time-restricted feeding for 8 to 10 hours, we can reverse those diseases. We have done a lot of molecular studies now looking at different organs, looking at the whole genome sometimes, hundreds of metabolites, and we find the molecular mechanisms by which this time-restricted eating is triggering breakdown of toxic materials, detoxification during the fasting time, better uses of fat, protein, and carbohydrate during day and night, and improvement in metabolism and mitochondria function that reduces reactive oxygen species, all of these good things, and improved autophagy. All of these things are happening when mice eat within 8 to 10 hours. And some of these have been now translated to human studies. And some of the pilot studies have come in. The results have come in. They're very promising. And some of the randomized clinical trials are ongoing, and hopefully, we'll get those results from 2021 onwards.

Dr. Patrick: And you've also found that people follow, generally speaking, an eating pattern, like if they're not trying to eat within a certain time window, with your My Circadian Clock app, you found naturally people eat within a longer window than they thought they would eat. Is that correct?

Dr. Panda: Yes. So when we started these mouse studies, then we realized that we're kind of adding another leg to human nutrition research. That is we know that the number of calories and the type of food that we eat have a huge impact on our health. And we just started when we eat is also important, that it becomes an important issue to understand when people eat because we do have different methods, for example, 24 hours dietary recall to understand how much and what type of food people ate in the last 24 hours. Similarly, there are methods to measure what diversity of four people have eaten in the last three months or a year to a tool called food frequency questionnaire or FFQ. But there is no method to really understand when people eat. We can ask people, "When did you eat breakfast? When did you eat lunch, dinner?" but that doesn't give us the correct view because we often ignore the occasional eating or snacking that we might have done late at night or early in the morning. And we consider them to be benign and we don't report them. But as I mentioned, even one gram of sugar can change my blood sugar level, so we wanted to capture every single eating event that happens. And from circadian rhythm point of view, even if you ate or drank something that has calories maybe two to three hours after your dinner time just for one day in a week, that can have an impact on your circadian rhythm for two to three days. So even if people eat outside that usual dinner time or breakfast time for one or two days in a week, they might ignore it and may not respond to questions. But if we can capture that, then we objectively know their eating patterns. So that's why we started this app called My Circadian Clock. People anywhere in the world can go to the website, sign up for the study. It's an academic study. There is no commercial interest here. And they share their data with us. What we found is nearly 50% of adults have an eating window of 15 hours or longer. So that means in a given week, there is a 95% chance that they would eat within that 15 hours window. That means that if somebody wakes up around 6:00 and has a cup of coffee with cream and sugar, a little bit of sugar immediately after waking up, then this person is also going to bed, say, at 9:00 or 10:00 at night and is having a glass of milk or beer or something else that has some calories, then that is roughly 15 hours of eating window. And even if this person does this only a couple of times in a week, still the circadian system is anticipating that that's the eating window. So that way, we develop this app to measure when people eat, in addition to the tried and tested methods of what and how much we eat. And we figured out that nearly 50% of adults eat for 15 hours or longer, and only 10% of adults actually eat for 12 hours or less interval in a day.

Dr. Patrick: And what percentage of people think they eat for 12 hours or less if you ask them without...?

Dr. Panda: That's almost 100% because in this first study, when I did the study on 156 people, we had a questionnaire where we asked them, "What time do you eat your breakfast, lunch, and dinner? What is the interval of time when you eat?" and when we compare their own response, it was only less than 5% of people who said that they eat for more than 13 hours. So what we perceive how we eat and how we actually eat is very different. And all of you, listeners, if you just think back and ask yourself is there any day in the last seven days when you had a piece of cookie, or a glass of beer, or wine a couple of hours after your dinner time, after your dinner was finished, I guess that at least half of you would remember at least one day in the last one week you had done that. And this is almost like your body flying to a different time zone and coming back from the circadian point of view. So that's why when we think of when we eat, it also brings up other aspects of the timing. And since the research is very new, it will have more variations to the timing. People will start thinking, "Okay, what happens if you eat after an hour of waking up versus six hours after waking up? What happens if you eat only 2 meals in a day versus six meals within that 8 hours or 10 hours?" So all of these variations of human nutrition timing are yet to be fully studied. But I'm glad that our research has put focus onto this timing of food as a variable impact.

Dr. Patrick: Is it better to have an eating window that if, let's say, you're eating within an 8-hour time window, I guess, you're not eating for 16 hours? Is it better to have that eating window end at 7:00 p.m. versus, let's say, 11:00 p.m.?

Dr. Panda: So this is where biology, and our human behavior, and personal choices come into play. For most of us, what we see from the app data is there is a circadian pattern or the time of the day pattern to what people typically eat. For example, if you ask what time of the day people are more likely to drink alcohol and have more sugary treat, it's between 7:00 p.m. and 11:00 p.m., or midnight. So then, if you're eating alone, and if you have complete control over your diet, and you have this very strict diet regimen, what you want to eat, then it doesn't matter whether you are finishing dinner at 7:00 p.m. versus 11:00 p.m. But if you target that you are ending that 8 or 10 hours window at 11:00 p.m., and that includes socializing with other people and sharing food, or being even influenced by what other people ordered for dinner, then you're likely to consume a lot of unhealthy food during that extra...between that 7:00 p.m. and 11:00 p.m. So that's why setting aside the biology in real world, what time you end your dinner will indirectly influence what type of food you are more likely to eat. So that's why we suggest that you try to finish that window relatively early so that one thing is you have less chance for consuming too much alcohol and unhealthy food, and second is your last meal is likely to happen at least two to three hours before your habitual bedtime so that you can have a better night's sleep.

Dr. Patrick: What sort of time-restricted eating pattern do you follow, Satchin?

Dr. Panda: So I try to do around 10 hours' time restricted eating. So that means if I start my breakfast around 8:00, then I try to finish dinner by 6:00, 6:30. And what is interesting is if I occasionally eat at 8:00 or 9:00, even if it's a small snack or something, then that night my sleep is bound to become really fragmented. So I have a negative feedback loop that if I eat less then I don't sleep well, and then the next day will be really crappy, I need more caffeine and other stuff to stay awake. So that's my eating habit these days.

Dr. Patrick: Do you personally count caffeinated beverages that don't have any calories like black coffee resetting your clock in the morning?

Dr. Panda: Yes. There are actually studies showing that a cup of coffee is equivalent to an hour or two hours of bright light. That's the impact on circadian clock. So it does impact our sleep. And definitely, no coffee after 2:00 in the afternoon because if I drink coffee after 2:00, then my sleep will be totally impaired. The other day I had coffee, a big cup of coffee actually around noon and that completely disturbed my sleep that night. So we do consider that coffee might disrupt your circadian rhythm. But at the same time, we understand that a lot of people cannot function without coffee, particularly night owls who are getting less sleep. It's much better to be caffeinated than be sleepy when you're driving to work. Also, some people though, the work requires them to be completely alert. For example, people who work in the entertainment industry who have to go in front of the camera at 4:00 in the morning, if they don't have enough sleep, it's better to be caffeinated to do your job, otherwise, you'll lose your job. So we make those exceptions. And in our studies, we ask all of our participants to log everything so that we can go back and redo the calculation to see whether caffeine intake, even without cream and sugar or with cream and sugar, had any impact on time-restricted eating, which led to some changes and health consequences. But I must say that since all of our studies are relatively small in number, and also the number of people who drink black coffee outside the eating window in our study is maybe even smaller, we're yet to see strong statistical power to dissect this effect.

Dr. Patrick: Great. Have you seen any data, are you aware of any data suggesting any time-restricted eating differences between men and women? Perhaps, there's obviously a fasting component to time-restricted eating when you're not eating. Other than pregnancy and breastfeeding, do you know of any concerns for women, for example, regarding time-restricted eating?

Dr. Panda: No, time-restricted eating is a very loose and broad term. So that means even if somebody...as I said, only 10% of adults eat for 12 hours or less. So that means if somebody was eating for 16, 17 hours, and even if they're pregnant or breastfeeding, they can come down to, say, 14 hours or 12 hours of eating, 13 hours of eating. And if they continue with that routine, they may still see some benefit. But for medical risk reason, we don't suggest that people who are pregnant or breastfeeding sort of even try to think of time-restricted eating. But it's a common sense that if you adopt a good habit, even when you're expecting or when you're breastfeeding, even if it's 13 hours of eating and 11 hours of constant downtime, that will have an impact on the family because when your baby is growing up on that 3 to 5 years of age, they'll slowly pick up that habit of eating so within 14 hours or 11 hours and then slowly they can sync. So now, coming back to the adverse effects, so that's why I say that anyone from 5-year-old to 100-year-old year old can do 12 hours' time-restricted eating without much concern about adverse side effects unless the person has type 1 diabetes, which is equivalent to brushing your teeth once a day. And if you are trying to do 10 hours' time-restricted eating, then it may be better that if you're breastfeeding or if you're pregnant, then it may not be the ideal time-restricted eating window. Ten hours might be too restrictive. But for the rest of them, again, without type 1 diabetes, it might be brushing your teeth twice to take care of your health. And if you are doing eight hours' time-restricted eating, it's almost like brushing your teeth twice, flossing your teeth, taking too much care of your health. So if you can do it for lifelong, then it may be better. But at the same time, be careful about not reducing your calories too much because occasionally we do see some people try to do 8 hours' time-restricted eating, at the same time reducing calories to almost 1000 kilocal per day and increasing their activity level, running half a marathon once a week or a 5K 3 times a week. And that can adversely affect your body weight, can affect even your bile acid metabolism and might increase risk for kidney stones. So we don't try to combine too many things at the same time. And 12 hours' time-restricted eating, as I said, maybe safe for most of us, except a type 1 diabetic, unless they have a continuous glucose monitor and they have some calories handy if they become hypoglycemic.

Dr. Patrick: And you mentioned children five and over, do you think that, kind of much like your anecdote, if you eat a snack or something later in the evening, you have more fragmented sleep? Is that something that you think maybe hold true for younger children like preschool age as well, or is there any evidence of that?

Dr. Panda: No. I don't think there is any evidence because it's very difficult to do studies on children. We don't want to intervene too much. But if you think about...the general recommendation is children of that age should sleep for 9 to 10 hours every night. So if you're a good parent and you're putting your child to sleep for 8 to 10 hours, then hopefully, you are not waking up your kid in the middle of the night to feed something... so they're fasting for 10 hours when they're sleeping. And then after waking up, it's not that they wake up and immediately eat something, they have to brush their teeth, and then maybe get cleaned up. And let's add one hour there. So that's almost 11 hours. And similarly, just before going to bed, they might have half an hour to one hour before bedtime when they had their last calorie. So in that way, you can see how a 5 to 10-year-old can easily fall into eating within 12 hours or, say, 13 hours window, which is not that bad. It means if you put together the sleep hygiene, and the common sense bedtime ritual, and wake-up time ritual, then you can easily see how we can maintain a 12 to 13 hours eating window for a 5 to 10-year-old.

Dr. Patrick: So there's one more area I kind of just wanted to touch on, mostly out of my own personal interests, and that is exercise timing and the circadian clock. There's been a bunch of studies that have come out over the past few years suggesting there are better times for humans to exercise.

Dr. Panda: Yes. So there are a lot of studies that are coming out saying that by...so the late afternoon or evening may be the best time for exercise. And there are many physiological reasons for that. One is, for exercise, we need much better muscle tone, joint flexibility, and less risk for injury. And all of the stars align in the late afternoon because that's when our heart rate is relatively high, our core body temperature is warm. We don't need that warming up that we typically need early in the morning, that much warming up. And the muscle tone is better, joint flexibility is much better. So the risk for injury is less. So that's why all of the studies are finding that late afternoon exercise is much better. So this is for healthy people who are trying to get the gold medal instead of silver, reducing their risk for injury. Then if we think of people who are sick, or who are trying to manage their glucose, say, people with diabetes is late afternoon exercise better than early morning. And in fact, there is at least one study that came out of Stockholm showing that the same people, when they did exercise high-intensity interval training in the morning versus the same people doing the same high-intensity interval training in late afternoon, they found that people who did the morning, when they did the morning HIIT interval training, the blood glucose level actually went up, whereas doing the same exercise in the evening helped them to reduce their blood glucose level, 24 hours blood glucose to those who have diabetes. So that's a very strong result. And what we know is, as I said, our pancreas has a clock. That means the pancreas produces more insulin in the morning or the first half of the day. And the second half of the day, even in the absence of melatonin, it doesn't produce that much insulin as well as in the morning. So that means any help in managing glucose independent of insulin is much better in the evening. And when we exercise, our muscles actually take up a lot of glucose without the help of insulin. And this might be one reason why late afternoon, early evening exercise or even brisk walking may be much more beneficial for people with diabetes in managing their blood glucose. So the bottom line is, whether you're healthy or less healthy, it seems that late afternoon, early evening exercise is better. But at the same time, if you have time to exercise only in the morning, then you should not stop exercising. Go for that morning exercise.

Dr. Patrick: Completely agree. There was a very interesting, very recent study showing that fat oxidation was about almost 13% higher in the afternoon compared to the morning. But if the participants took in...it was actually quite a large amount of caffeine, 30 minutes before exercise in the morning, their fat oxidation was equivalent to if someone exercised in the afternoon without any caffeine. So, for me, I like to exercise first thing in the morning, I'm sort of mostly fasted. I do have a cup of coffee. But it's kind of nice to know that maybe that caffeine...and I don't exactly know the mechanism, but may actually boost the fat oxidation a little bit more than if it was just morning without the caffeine. And also just one more question, there was another study showing that performance, athletic performance actually varied depending on when a person wakes up, so whether they're an early riser versus intermediate or late riser. And what I thought was so interesting about that study is that their peak performance was very different. So if it was an early or intermediate riser, your peak athletic performance happened between five or six hours after they wake up. But if they were a late riser, their peak performance was almost 12 hours, it's 11 hours after they basically woke up. So I thought that was interesting. So last, to kind of wrap up this discussion, could you discuss some of your circadian resolutions for 2021, things that maybe anyone could use, anyone could follow as well?

Dr. Panda: Yeah, so we thought, "Okay, so how do we put all of this together?" because we talked about light, we talked about sleep, not having light exposure before sleep, having light exposure during the day. It can be all confusing. So with that, an ideal circadian day might be try to be in bed for eight hours consistently every night, when I say consistently, try to go to bed within an hour window, and be in bed for eight hours so that you can get seven hours, seven and a half hours of sleep if you're an adult. And then after waking up, try to avoid food for one to two hours because that's when your melatonin hormone is slowly going down and cortisol hormone is spiking. And then after waiting for an hour or two, have your first bite and then count 8, 10, 11, or maximum 12 hours, that's the window of time when you should be eating. And also make sure that the last bite or the last calorie is at least two hours before your bedtime. You don't want to have that last calorie too close to the bedtime so that you can avoid food and avoid bright light for two to three hours before bedtime. And then during the daytime, particularly in the first half of the day, if you can, try to go outside. Even if it's a cloudy day, there is enough light to uplift your mood because light is the best antidepressant. It's plentiful and free. You just have to step outside. And when you're stepping outside, you can also take a brisk walk for 30 minutes, and that way you can get both your exercise and light dose of the day. So that's the bottom line, 8 hours in bed, wait for 1 or 2 hours before fast calorie, eat everything within 8 to maximum 12 hours, no food and no bright light for two to three hours before bedtime, and 30 minutes outdoor, brisk walking during the day.

Dr. Patrick: Great pointers. So thank you so much, Satchin, for having this Clubhouse chat. People can follow you obviously on Clubhouse, but you're also on Twitter, @satchinpanda. Your website is mycircadianclock.org. Your book, which is fantastic and I've read a couple of years ago, "My Circadian Code" has a lot of the information we talked about today and so much more. Also, your ongoing crowdsourced data using your My Circadian Clock app that's available on the App Store or Google Play. Is there anything else where people can find you or you want to direct them to?

Dr. Panda: No. You had a very comprehensive list. We actually like when people...the My Circadian Clock app is an academic app. So it's not as fancy as some of the other apps. But I'm really grateful that thousands of people have shared their eating habits, sleep habits, and socio-economic demographic information. And that has been extremely useful for many ongoing and future studies. We have nearly now 10 different clinical studies going on in parallel on the My Circadian Clock app platform. And then the book has been very gratifying because the book has been now translated to 10 different languages. While writing the book, I also came to understand how to think of my experiments in the light of public health. And whether we do an experiment in Drosophila fly or mouse, we're always thinking is it going to have an impact? So that opened my eyes. And Rhonda, you were the first one who...I remember the first time I did a podcast, that was with you. That was the first time. I didn't know what is a podcast. When I got an email from Rhonda, I went back to the lab and I asked, "What is a podcast?" and a lot of people explained to me and here we are again. So, Rhonda, you're always ahead of all of us. And you are doing a fantastic job in communicating science to millions of people because we, scientists, we are not very good at that. And science has to be disseminated. And thank you for doing such a fantastic, fabulous job.

Dr. Patrick: Oh, I appreciate that, Satchin. Thank you. And for those of you here on Clubhouse listening, this conversation was recorded and you can find that podcast on your favorite podcast player. Just search for "Found My Fitness." You can also sign up for our newsletter on foundmyfitness.com and keep up to date with all the things we're doing including podcasts like this one. So thanks again, Satchin, and I look forward to talking to you soon and keeping up with all your wonderful research.

Dr. Panda: Yeah, thank you, and have a perfect circadian day.

Dr. Patrick: All right, sounds good. You do the same. Bye-bye.

Dr. Panda: Okay, bye-bye.