#065 Dr. Satchin Panda on Circadian Insights into Exercise Timing, Melatonin Biology, and Peak Cognition

Every organ has its own daily timetable - why timing of caffeine matters

Every organ has its own circadian clock governing daily tasks. Caffeine timing should align with these rhythms for optimal benefit.

"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 deborts 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 time table or circadian rhythms. What's so interesting is that everything from, like you said, every organ in your body has a circadian rhythm. And I find it like 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 nootropids 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? yeah 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 in the morning. And 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 to think clearly and those experiments have done extensively. So we have to still respect the number of hours we sleep the previous night to be fully awake and to be fully functional. And what about the time of day in terms of like when neurotransmitters are being produced? Like, is there a circadian rhythm to that as well? Yeah, almost every neurotransmitter has a circadian rhythm. When I say every neurotransmitter, it's not only the neurotransmitter, it may be 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 a certain time of the day, we are more prone to feel happier. At a certain time of the day, we may be more prone to feel a little sad. Those things are ingrained in our circadian rhythms. Some people are natural early risers and, you know, other people's people are night owls. Like for me, like I'm a pretty normal riser. I mean, like I, I guess ever since I had children, I started to wake up earlier than usual, but I usually I'm up around 7am. And I find that my peak mental performance is sort of late morning-ish, you know, like around 10, I start to, I feel like I'm the most mentally alert. But what about, you know, 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? Well, one thing is, irrespective of whether you our early riser or late riser, what matters, 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 all the risers or night owls. Night owls, there 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 a 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 keeps them awake till late night. And the challenge for night owlers is although they are night owls, the whole world is programmed to start or your work is more likely to start at 8 a.m. So that means you have to get up and start your day around 7, 6.30 or 7 a.m. depending on your commute time. So the late nighters therefore have a big challenge that if they cannot go to, say, 1 a.m. in the morning, then they're not getting enough sleep."

Dim lights in evening to release the melatonin brake; bright light in morning to set clock

Blue light suppresses melatonin. Dim evening lights to let melatonin rise naturally; use bright morning light to anchor the clock.

"One is, since melatonin has to rise, 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 break and the break here is blue light. And that's why dimming down light in the evening is a good idea to release that break so that melatonin can begin to rise. And since we know that this is blue light, that's 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, all laptops now have a night shift or night light feature. And you can program it to turn it on around eight or nine o'clock in the evening when these screens will dim down and will turn little 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, large window and having your breakfast, although you don't have sunlight falling on your eyes, you still get around 1,000 locks 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 break 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 learned 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-sifted light or wearing even blue-filtering eyeglasses in the evening to improve our sleep. So a couple of questions. One, you mentioned wearing the blue filtering glasses at night, perhaps to filter out some of the blue light. And 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? Great 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 actually not looking at the Sun you get somewhere between 100,000 to 200 200 000 lux of light it's a 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 you're getting somewhere between 5,000 to 10,000 locks of light, which is similar to standing outside your car in a cloudy day. That's also 5,000 to 10,000 locks 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 outdoor 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. Interesting, because the singlet oxygen produced by blue light can damage the rods. UV light, there is a ton of UV light outside too. And what about on the flip side of that, you know, people actually being exposed to the bright light in the evening oftentimes think, well, I can take a melatonin supplement and, you know, that should sort of help me increase my melatonin. But 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. You know, what are your thoughts on supplementing with melatonin maybe regularly, or even is there like an age-dependent factor in there? Yeah, so that's a very tricky question because, you know, 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 the sense, when you give various drugs or chemicals to an animal, then there is a LD50 or lethal dose 50 at which some animals will die."

Melatonin is not just a sleep hormone - it rises naturally when you dim evening lights

Melatonin rise correlates with sleepiness. Let it rise naturally by reducing blue light at night rather than supplementing.

"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 now fast forward a 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 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 tell to reset our clock or to tell when melatonin should rise or fall."

Caffeine after waking delays circadian clock; late caffeine compounds sleep debt

Delaying sleep by 2-3 hours with light, food, or coffee compounds circadian disruption. Each late night shifts the clock further.

"Because if we delay our sleep by two to three hours at night, or we wake up two to three hours before our usual wake-up time, then... If we delay our sleep by two to three hours at night, or we wake up two to three hours before our usual wake-up time, then when we're awake in these modern days, 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 we are not in our daily habits and not in alignment with our internal clock for those two to three days. So that means 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. Is there anything we can do to sort of mitigate the negative effects?"

In countries with little winter daylight, light therapy can simulate circadian signals

Major lighting companies now sell circadian-friendly indoor lights to simulate daylight for people in dark winter climates.

"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, you know, simulate the daylight?"

Finish dinner early: late eating leads to more alcohol, junk food, and worse sleep

Finishing dinner early means your last meal is 2-3 hours before bed, reducing chances of late-night alcohol and unhealthy food consumption.

"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 better night's sleep. What sort of time-restricted eating pattern do you follow, Sachin? Yeah, so I try to do around 10 hours time-ricting. So that means if I start my breakfast around 8 o'clock, then I try to finish dinner by 6, 6.30. And what is interesting is if I occasionally eat at 8 or 9 o'clock, 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 late, then I won'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."

Late eating window overlaps with alcohol and caffeine consumption

Eating late indirectly increases likelihood of consuming alcohol and caffeine closer to bedtime, compounding circadian disruption.

"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 better night's sleep. What sort of time-restricted eating pattern do you follow, Sachin? Yeah, so I try to do around 10 hours time-ricting. So that means if I start my breakfast around 8 o'clock, then I try to finish dinner by 6, 6.30. And what is interesting is if I occasionally eat at 8 or 9 o'clock, 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 late, then I won'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."

Afternoon exercise is metabolically optimal but morning exercise is still better than none

Late afternoon/early evening exercise shows 13% higher fat oxidation. But morning exercise is far better than no exercise at all.

"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. Completely agree. There was a very interesting, very recent study showing that fat oxidation was about almost like 13% higher in the afternoon compared to the morning. But if you took in, if the participants took in, it was actually quite a large amount of caffeine."

Exercise timing and melatonin: how physical activity interacts with circadian rhythms

Exercise timing interacts with circadian rhythms. Afternoon aligns with metabolic peaks, but consistency matters more.

"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 our 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 than the second so this is for healthy people who are trying to trying to get the gold medal instead of silver or reducing the 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 people who the same people when they did exercise high intensity interval training in the morning Thank you. 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 heat 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, those who had 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."