Why is Circadian Rhythm Important?
Improving Sleep and Metabolic Health

The body clock plays a crucial role in sleep and overall human health. Greg Potter, Ph.D., an expert in sleep, diet, and metabolic health, joins our own Greg Kelly, ND to lead us through a journey in cultivating a healthy circadian rhythm. We discuss the importance of timing around light exposure, eating, sleeping and physical activity. We then explore the science of the master clock and peripheral clocks. Join as we go in-depth on how to entrain a healthy circadian rhythm and address what to do when unavoidable stressors and disturbances, like shift work, jet lag, and social jet lag impact our ideal routine.

If we disrupt our circadian rhythms, there is rapid deterioration all aspects of human health and function. -Greg Potter, Ph.D.

Join us as we define circadian rhythm and explore why it’s important.

In This Episode We Discussed:

00:54 Practical tips on optimizing circadian rhythms
07:59 What to do if you wake up in the middle of the night
10:31 Importance of a consistent sleep schedule
12:20 Catching up on sleep debt
13:15 Coping with sleep loss with creatine
17:05 How do you get rid of jet lag fast?
21:49 Circadian rhythm as a foundation for human health
24:06 The types of body clocks
26:46 Health benefits of anticipation
29:46 Entrainment of our circadian clocks
32:15 We have multiple internal clocks
34:22 Hypothalamus: Regulates appetite, thirst, adaptation to temperature, sex drive
36:50 How light exposure and temperature influence the circadian rhythm
38:06 Biological day and biological night
40:20 Indoor light: Interrupting natural light-dark cycles
43:27 Peripheral clocks: The science of clocks in cells and organs
48:57 Meal timing benefits
52:07 Melatonin and meal timing
56:28 What is the importance of breakfast?
1:01:42 Entraining your hormones to control appetite
1:19:23 Effects of shift work, jet lag, social jet lag
1:25:46 Humans can’t adapt to disruptions in circadian rhythm
1:28:29 Most important things to maintain a healthy circadian rhythm
1:29:31 Work Greg is doing with humanOS.me

Mentions (People, Products, Technology)

Epidemiology of the Human Circadian Clock
Light as a Central Modulator of Circadian Rhythms, Sleep and Affect
HumanOS.me use code "neurohacker" to get your first month of Pro membership for $1

Dr. Carl Johnson
Joseph Takahashi, Ph.D.
Samer Hattar, Ph.D.
Ken Wright, Ph.D.  
Daniela Jakubowicz, MD
Chris Morris, Ph.D.
Frank Scheer, Ph.D.
Dr. Till Roenneberg
Francesca Damiola, Ph.D.
David Berson, Ph.D.
Dr. Markus Dworak

Free Access to Chapter 12: Lighting and Shape from Shape Shift

Full Episode Transcript:

Greg Potter:Most of us have some residuals sleep debt to pay off, and we can't fully pay it off. But when you get the chance to sleep in and catch up on sleep that you've lost, sleep in, please.

Speaker:Welcome to the Collective Insights podcast where we explore topics and technologies revolutionizing human wellbeing. Dr. Greg Potter, an expert on Circadian Rhythms, how they interact with nutrition, and how they interact with sleep, joins our own Dr. Greg Kelly for this episode. Dr. Potter is the content director at HumanOS.me where he works with Dr. Dan Party, who we've had on the Collective Insights podcast twice in the past, going deep on the science of sleep. So, if you're wanting to learn more on sleep after you listen here, then there's plenty more to dive into on our website. Today, we'll be discussing circadian rhythms and why are they important to our health.

Greg Kelly:So, one of the things now is that we're getting towards where I'd like to start focusing on some things that you might give insight to our audience on what we might be able to do to more fully optimize our circadian systems function. So, I know one of the things you've mentioned briefly, and towards the beginning was this idea of blue light, and how in the morning blue light's really important. It helps really what I would think of is our alerting circadian system. But at night blue light could be detrimental. So, could you talk a little bit about that and strategies that might help mitigate blue light at night?

Greg Potter:Yeah, so I suppose I should just preempt this by saying that the same things that you can do to improve the functioning of your body clock will also improve your sleep. And I think people often focus on the nighttime stuff, and they ignore the daytime stuff. So, during the day if you are physically active, especially outside, then you're going to help anchor your circadian rhythm. And we can speak about light boxes and that kind of thing, but I do think that if it's at all possible, just doing things like getting outside for half an hour during your lunch break is going to be such good thing for many reasons too. I think if I just continue down that route, then you want to try and make sure that if you're doing stressful tasks, you do them earlier in your day too, because if you do them too late, then that could interfere with your ability to fall asleep at night.

Greg Potter:I think likewise, if you're going to do strenuous exercise, then you probably don't want to do that too late, so I'd cut that by three hours before bedtime. And then I'd also generally avoid napping too late in the day, probably in the sort of seven hours or so before bedtime. And then going back to light, before bed I think what you typically see is that your body will start producing melatonin roughly two hours before your normal bedtime. So, that's the time for you to start dimming the lights and engaging in what you might call a digital sunset too. So, you might, for example, you use apps on your phone, and on your computer. So, if your computer you can use f.Lux. If you've got an iPhone, you can use Night Shift Mode. If you've got an android phone, you can use Twilight, and you can also dim the brightness settings on all of those things.

Greg Potter:In your bedroom, I recommend that you remove anything that emits blue light if possible. So, if you must have an alarm clock that does admit light, then you'd want one that emits red light, because that has a much smaller effect on your body's production of Melatonin. And I think it's also just important to keep your bedroom relatively clutter free and as stress free as possible. You want it to be cool because if anything, you want your body temperature drop as you start to fall asleep. And that will therefore be pulling your body in the right direction. But perhaps counterintuitively shortly before bed, you actually want to raise your skin temperature, because when you do so, you basically encourage the heat from deep within your body in its core to be drawn towards its extremities. And it's especially important to eats up your hands and your feet, because they've got a big surface area and a small volume, which means that you can gain or lose heat through them very quickly. So that's important too.

Greg Potter:And then I think generally our lives now are often full of stress. So, things that you can do to reduce that in the buildup to sleep are very important. So, do something relaxing the last half hour or so before bedtime. One thing that's been studied recently, which is very interesting, is making a to-do list for the next few days, shortly before bedtime. If you do that, then you basically unload things that might otherwise stay in the back of your mind as you're trying to fall asleep. And what they found is that when people did that, they fell asleep faster. And interestingly, people who listed more things and in greater detail tended to experience that effect to a greater extent too. So, I think that's probably a useful tip as well. And then ... Sorry, just while I'm on this little monologue, if you're going to use an alarm clock then if possible set it for the start of your pre bed routine. And in the morning maybe you have to use one, but you'd want it to go off as late as possible, and you don't want it to go up multiple times. Because actually each time your alarm clock goes off, it's a stress to your body, especially to your cardiovascular system.

Greg Potter:So, give yourself as much time in bed as you can, and if you have to wake up to an alarm, consider whether you can use changes in your light dark cycle to shift your body clock earlier. So if let's say that you have to wake up at 6:00 AM in the morning, and you're used to going to bed at midnight. So, you only have a six hour opportunity in which to sleep. Well, if you could shift your body clock earlier and fall asleep at 10:00 PM, then all of a sudden you've got an eight-hour sleep opportunity. So in that situation, my suggestion would be to get outside as early as possible after waking. Expose yourself to lots of blue light early in the day, and then be very, very particular about your exposure to blue light at night. And one strategy that you can use is using something like blue blocking glasses to reduce your exposure to those wavelengths of light later in the day.

Greg Kelly:Great. I actually was wearing my blue blockers last night while I was watching TV. And one of the things I've found for me, and this would be more of an analogy than something that's absolutely true. But I used to explain to patients that to think in terms of sleep is more of a bus that comes on certain schedules, and so sleeping tends to often come in waves. And if we miss that first wave, like essentially the bus pulls in the station, and for whatever reason we decided we don't want to get on, we want to finish the TV show we're on or finish a couple chapters in a book. Then when it pulls out, it could be another hour and a half to two hour before we get that next wave of sleep, where it's easy to fall into sleep.

Greg Kelly:And so what I've just found personally, I have the easiest time falling asleep is if I am aware of the feedback my body's giving me. Okay. Like sleeping, it seems to be coming in, now is the time to turn off the lights and whatever the TV show on hold. Put a bookmark in the book rather than forcing myself to finish the chapter, etc. So, would that idea hold any weight in terms of research or your experience?

Greg Potter:Yeah, I think so. I think it's especially relevant actually to people who wake up during the night, because sometimes you wake up at night and for whatever reason we can't fall asleep again within the first half hour. So, you could stay in bed and toss and turn, and think why can't I sleep? Why can't I sleep? And it's unlikely to get you anywhere. And actually you want to create an association between your bedroom and your bed and sleep. So, one thing that I didn't mention is that, if possible you basically want to leave your bedroom for sex and sleep only. And then if you wake up at night time, and you just can't get back to sleep, then use as little light as possible, but that leave your bedroom temporarily and just do something relaxing in very dim lighting.

Greg Potter:So you could, for example, read a book in as little light as possible. Or if you're meditator you could go and meditate. That's something that I find very. So, if I wake up and I just have a very busy mind for whatever reason, then typically the first thing that I do is a body scan meditation, because you can do those lying down. And quite often, I think, obviously I can't prove it, but I think that when I do that, just the meditation lying down. So, it's scanning through each region and my body sequentially, I basically quieten my mind and I let myself get back to sleep faster than I would otherwise have been able to. And then sometimes you wake up in the middle of the night and it's not because your mind's racing, you just have to go to the bathroom or whatever. I would just say that in that particular instance, just use as little light as possible and make sure that your pathway to the bathroom is clear.

Greg Kelly:Great. Now, you mentioned regularity in terms of food or consistency I think was the term that you used. And I know I've seen a few research papers where it might even have been that study you mentioned, where people that eat with the same consistency, regular meal timings, tend to metabolically do better, and to do better in these different ... I would think of response areas. And we also talked then about internal desynchronization and things that can disrupt the schedule. So, what I wanted to just touch on briefly is, similar to our eating regimes, which tend to optimize it. If we can be more consistent about those, would the same thing hold true for sleep and other things connected to the body clock? But you had mentioned social jet lag, so I'm guessing the answer is yes, but just wanted to give you an opportunity.

Greg Potter:Yeah, absolutely. Absolutely. So, you just want to try and keep sleep timing as consistent as possible between workdays and work free days. And I think one thing that is worth mentioning now, because it seems to divide people, and I often hear advice which to me is nonsensical, and it relates to wake timing. So, some people here that consistency is important and they think, "Well, I'm going to try and control one side of my sleep timing. So, either my sleep onset or my sleep offset." And somehow people have ended up thinking, "Well, if that's the case then I'll just make sure they wake up at the same time every day." But, of course, one evening they go out and they have some drinks with friends or whatever. And then they think that it's a good thing for them to still wake up to an alarm at 6:00 AM the next day. And what I would say is that most of us have some residual sleep debt to pay off, and we can't fully pay it off. But when you get the chance to sleep in and catch up on sleep that you've lost, sleep in, please.

Greg Potter:So, keep your sleep time as consistent as you can, but if for whatever reason you've got a hectic schedule, and you just have to compress your sleep periodically as we all do, let yourself catch up. But also, to avoid your sleep timing from drifting later on subsequent days, because let's say that you're used to waking up at 6:00 AM and then on the weekend you sleep in until 10:00 AM. What could happen is that for the next couple of nights you start going to bed later, and then wake up later. on the days that you sleep in, after you've woken up, get outside as early as possible. Do lots of physical activity. Don't mess around with caffeine or stimulants too much, and just try and get back on track.

Greg Potter:And actually just, while we're on this subject, something that's very interesting is how to cope with sleep loss, and many people they resort to using things like caffeine. But in my mind, one of the best strategies that people can use is actually taking creatine monohydrate. And this is related to how sleep is regulated. So, the longer that you've been awake, the greater the pressure there is to sleep, and that's because of the buildup of adenosine in the extracellular fluid in your brain. And if you take creatine, then you increase your Phospho creatine stores, and therefore the total pool of phosphates in your body. And by doing so, you can speed up the rate at which ATP, the energy currency of your cells is resynthesized. So, what that should then do is counter the increase in sleep pressure that you get after sleep loss.

Greg Potter:And there was a fascinating study that was published last year by Marcus Dworak, he basically found that if you take creatine and you add it to the chow of rats for four weeks, then the rats sleep less, and they don't sleep as deeply. But interestingly, in humans, when they're sleep deprived, the creatine seems to offset the deterioration that you see in things like cognitive performance. So, people's ability to plan and carry out, and monitor tasks that are directed towards achieving a specific goal. But it also counts as the negative effects of prolonged wakefulness and things like mood and balance and reaction time. So, even though creatine might be having this effect on reducing the pressure to sleep, and perhaps the total amount of time that animals do sleep. And you get lots of anecdotes about people having insomnia when they take creatine. What's fascinating about creatine is that actually in general it seems to be very good for our health.

Greg Potter:So, what happens when somebody takes creatine? They gain a bit of lean body mass, occasionally lose a bit of fat mass. It has positive effects on mood. It has positive effects on various things related to metabolic regulation. So, how will you process glucose for example. And so, even though if you restrict somebody's sleep artificially with an alarm or whatever, you see adverse consequences across the board, both in terms of their metabolic health but also their cognitive performance. If somebody takes creatine, then maybe they sleep slightly less. But actually if anything, you see beneficial effects on things like metabolic health, and cognitive performance. So, what I'm saying is please sleep in when you get the opportunity, but if you're somebody who goes through a period of time when for whatever reason, you can't get as much sleep as you need. If there's a supplement that you take, then I think that taking about maybe two and a half grams of creatine for every 50 kilos of body mass. So what's that? Five grams for ...

Greg Kelly:Yeah. The five grams is kind of the average for maybe 170 pound person. That's-

Greg Potter:Yeah. That's a good starting point for people in that situation.

Greg Kelly:Great. And the answer to this might be we don't know, but is there any best time? I know often it's thought that creatine only about a gram to a gram and a half can be absorbed well at a time. Do you think it would make any difference that we all [inaudible] the creatine earlier in the day, later in the day? Divided doses? Any opinion on that?

Greg Potter:Yeah, I'm not sure. So, people used to do something cool creatine loading. So, for a period of a couple of weeks, they might take 20 grams a day and they're divided into four or five-gram doses. And that will saturate your body's Phospho creatine stores faster than you would do otherwise. But actually, if you just took two and a half grams a day every day, then after a few weeks you would actually reach the same levels. It would just take you longer to get there. Anyway, in terms of things that you can do to increase creatine uptake, exercise is one of them. Another one is consuming creatine with carbohydrates, and sodium. And with respect to timing, if it has this effect on sleep, then that suggests maybe then consuming it earlier in the day is a good idea, because it could have this smaller alerting effect. But also because it does accumulate in your body over time.

Greg Potter:I'm not really sure if that's going to make a big difference in the longterm. So, I would just say take it every day if you're going through that period of sleep loss. To help you buffer the consequences of sleep loss, probably take it with breakfast, take it with something containing some carbohydrate, and something that contains some sodium. And it's not very soluble, so maybe mix in a warm beverage.

Greg Kelly:Great. Now, I saw you obviously in Toronto, so I flew from San Diego there. You flew from the United Kingdom to get there. What did you ... Did you have any personal things that you do to deal with basically jet lag, long distance travel, because I'm sure you travel a fair amount that might be applicable to our audience. Even if they're not like 100% studied. Just things that you personally do as a bio hacker.

Greg Potter:Yeah. So, I mentioned earlier the importance of mealtime me, in setting our peripheral clocks, and that can take place very quickly. So, one thing is to shift your eating patterns to the new timezone quickly. And some people they like going through a prolonged fast during that initial stage, and then when they wake up on their first full day in the new time zone, beginning their eating patterns on the new time zone, at that point in time. So, that's one thing that people can try. Another one relates to taking Melatonin exogenously. So, the master clock in the brain has its own Melatonin receptors, and if you take Melatonin as a supplement then you can actually overcome jet lag a little bit faster than you will be able to otherwise. And for the purpose of reentry following jet, you need a slightly higher dose than for effects on sleep.

Greg Potter:So, there was a metro analysis that was published 2002, and they basically found that doses of Melatonin in between about 0.5 and five milligrams is similarly effective. But people do fall asleep a little bit faster, and sleep a bit better after the higher dose. So, personally I take five milligrams of Melatonin about half an hour before when I plan to fall asleep at the new time zone, during jet lag. And there are different types of Melatonin you can take, but it seems that the regular form is more effective in this instance than the slow release formulation that you can sometimes get your hands on. And then, the final thing that I'll mention is just that physical activity and light exposure specifically are really important. So, of all the things that you can focus on, I think optimizing your light exposure and spending lots and lots of time outside during the daytime in the new environment will help you get over jet lag faster, than anything else.

Greg Potter:And do your physical activity at that time of day. You might feel bad for first few days, but it will help you overcome the jet lag faster. And then one thing that I'll mention finally that I've just found recently with myself, no evidence of this because theoretically you should be able to use caffeine to help you get over jet lag quicker if you're flying to the West. But I've just found that when I consume caffeine, I don't get over jet lag as quickly. I'm certain of that. And I think for me personally, I can't sleep on planes, so when I go to a new time zone, if I just end up staying up for a long period of time without caffeine. Then by the time I try and fall asleep, even if I'm trying to fall asleep at the wrong biological time. I'm so tired, that coupled with the Melatonin to give me the darkness signal at that time, I can only pretty well. So, my function on that first day might not be very good. I might not be very sharp, but I will be able to sleep that first evening. So, those are just a few ideas.

Speaker 2:Thanks for tuning in today. In the second half of our show we'll explore, more deeply, the science behind the rhythms of our bodies. Dr. Potter and Dr. Kelly explore numerous studies that have been done on how the circadian rhythm impacts various aspects of health. Stay with us to learn why your circadian rhythm is so important. Thanks again for listening to Collective Insights. Our podcast is brought to you by Neuro Hacker Collective, where we offer a line of cognitive enhancement supplements. Check the website to see how you can save 50% off your first order of quality of mind or quality of focus. We have good news for our listeners who are outside of the US, we're working on new fulfillment options so we'll have significantly shorter shipping times for non US countries. And also good news for our Australian listeners, we'll be on Amazon Australia very soon. If you liked this episode, then please share it with your friends and leave us a review on iTunes. And remember for full show notes, visit neurohacker.com/collectiveinsights. All right, let's jump back in.

Greg Kelly:And that's really what we're going to focus on today. So, we want to give a big picture of the importance of the circadian system, but we'll definitely be spending time on really the more implementation of what you can do to take better advantage of how our body clock can be optimized. Now, one thing before we jump into this, Greg, at one point in the early 2000s I was teaching clinical nutrition at the University of Bridgeport. It's in Connecticut, and they had a at the time of relatively new nature-pathic program. So, in my clinical nutrition class we had to cover really the big buckets, areas like immunity, GI health, blood sugar regulation, things like that. And when I would give the syllabus out to my students, the very first lesson, first day of class was about circadian rhythms.

Greg Kelly:The second lesson was on sleep. So, before we get into any of these, what would have been, I think, conventionally thought of as the more important systems to target. I started there, and with what you know, I'm sure you can understand why. But back then, and I think it's still the case today, is people under appreciate how profound the effects of optimizing circadian rhythms are on our biology. So with that, can you tell our audience a little bit about the big picture circadian system?

Greg Potter:Sure. Yeah, and I suppose something that allowed to just, what you said there is that, what's nice is that people's appreciation of it, I think, is growing over time. So last year, for example, the Nobel prize in physiology or medicine went to three circadian biologists for work that they did on the period gene. And I think the interest in sleep has increased remarkably in the last few years, and that's in large part due to the work of a few people who have done a really good job of educating people about the importance of sleep. But with that said, I suppose that it makes sense to begin with, why they're important from an evolutionary biology perspective. And people should understand that all life on the planets involved in the presence of relatively predictable environments or cycles, and things like lights and temperature, and food availability. And these occur across different timescales.

Greg Potter:So, we've got daily cycles from the rotation of the planets about it's axis. We've got tidal rhythms as well, which are about 12 and a half hours long, lunar rhythms from the movements of the moon about the earth. And then we've got seasonal changes too from the rotation of the Earth about the sun. And in response to these changes, organisms evolve their own biological time keeping mechanisms. So, they have predictable changes in biology, and hence behavior across different timescales. And I'm going to take a little bit of time with this just because I think that it tees up the rest of the conversation nicely. But broadly, we can think of our bodies as having three different types of rhythms. So, you've got ultradian rhythms, which are typically thought of as being rhythms of up to about 20 hours or so. And our heartbeats are an example of these rhythms.

Greg Potter:We have circadian rhythms, which are typically 20 to 30 hours. And an obvious example of this is the circadian rhythm in body temperature, or the sleep-wake cycle. And then we have infradian rhythms, which are rhythms of 30 hours or longer. So, these would include things like the menstrual cycle. And then also some organisms have circannual rhythm, so rhythms that take place across about one year. An example of this would be antlers shedding ... Sorry, a deer shedding their antlers each year, which is to attract mates. Anyway, the purpose of these rhythms is twofold really. One purpose is to anticipate these changes in the environment. So with humans, for example, around the time that we wake up each day, adrenal cortices producer a sharp spike in cortisol production. And this is to increase arousal and mobilize our stored energy reserves, and raise our blood pressure in anticipation of the day ahead.

Greg Potter:But then, the rhythms also help us adapt to changes in the environment. So, not all cells in our bodies are directly exposed to the external environment. So, we need our own internal time cues if you like. And Melatonin is a hormone that's synthesized in the pineal gland in the brain and this takes place during darkness. And that therefore signals the biological nighttime. And Melatonin is very important in these seasonal organisms to changes in their biology across the year. And that's signaled via a structure in the pituitary stalk called the posterior [inaudible 00:26:30], which has a very high density of these Melatonin receptors. Anyway, these biological rhythms have certain co-characteristics. One is that they're direct entrainable, and this is very important when it comes-

Greg Kelly:Greg, can I just pause here for a second before we jump into talking about entrainment?

Greg Potter:Yeah, sure.

Greg Kelly:I want to highlight a few points for our audience, just that I know when I was in practice in coaching people that I used to point out. And one gets into what you were mentioning is that we have these rhythms across different scales. So, one of the ways I would language that when I was teaching or working directly with patients is to think in terms of us being clocks, and calendars. That we have these timekeeping mechanisms that realistically affect most of our biology, and how we respond to things. Circadian rhythms being a big focus of what we'll be discussing today. But seasonal rhythms affect things like cholesterol and blood sugar, and body weight, all kinds of things. Menstrual rhythms, as you mentioned for women. So, very important I just think conceptually for people to remember this idea that we have, as you said, rhythms across multiple timescales.

Greg Kelly:And the other key thing, and this goes, I know it's one of neuro hacker's core things, is that the idea of complexity science. And so you said anticipation, that one of the things these rhythms allow us to do is to anticipate and prepare, and another is they allow us to adapt. So those are really profound concepts in complexity science, and the idea of self regulation. So, before we jump into entrainment, can you just maybe give a little bit of insight into why anticipation is important?

Greg Potter:Well, it's important really so that our bodies are primed for the needs of the present moment. And later I think we'll probably speak about peripheral clocks and how the clocks and each of our organs make sure that our organs are best prepared for the functions of the present moment. So, fundamentally as diurnal organisms, meaning daytime active organisms, we humans need to be up and active, and out to find food and water during the daytime. And then the nighttime is a time of resting and fasting. So, that's our temporal niche, and we exist in that niche because it's going to help us survive. And just as an example of this, it's difficult to demonstrate in humans, but there are experiments in animals that show that the more accurate their timekeeping mechanisms are, the more likely they are to actually pass on their genes.

Greg Potter:So, this was first shown, I think, in 1998. There's a guy called Carl Johnson from Vanderbilt University, and he showed this in a type experiment called the resonance experiment in Cyanobacteria. And those are the bacteria that are thought to have first oxygenated our planet's atmosphere. And more recently there's been work done on mice. So [Mckayla Howe 00:29:28] for example, showed that mice that have near 24-hour rhythms survived longer and reproduced more than mice with rhythms that were shorter, as a result of a mutation in their circadian systems. So, at their core, circadian rhythms are important because they actually help us survive and pass on our genes. And what I learned is that numerous studies, which we'll get to later, have shown that if we disrupt our circadian systems, then there's rapid deterioration in all aspects of human health and function.

Greg Kelly:Great. Well thank you. So, before I interrupted you, you had started to bring in this concept of entrainment. Can you give our audience a bit more, what entrainment means?

Greg Potter:Sure. So, we're going to focus the thing on the skating system. And what's important to recognize is that our circadian rhythms typically aren't precisely 24 hours. And the actual words circadian hints that circa, meaning about, dian meaning a day or 24 hours. So, about 24 hours. If we all went and lived in a cave for several days without knowledge of what time of day it was outside, or exposure to light dark cycles, or temperature cycles, or changes in food, then on average our clocks would keep ticking at about 24 hours and 15 minutes. So, what this means is that our clocks needs to be reset each day to 24 hours. And this resetting takes place by way if time cues, or site is the technical term to use for it. And the most important one is the light dark cycle in resetting the human circadian system.

Greg Potter:And then, biological rhythms have two other characteristics really. One is that the temperature compensated. So if you look at plants, for example, then if you increase the temperature, then the rates at which photosynthesis proceeds increases. But what's important with the circadian system is that if the temperature's higher, as during the summer for example, our circadian rhythms don't get faster. Our internal days don't get shorter across the year, and that's why that's important. And then the other one is that, for something to be a true circadian rhythm, it needs to persist in the absence of time cues. So, what I mentioned earlier, the idea of us go into caves. There are no time cues there anymore.

Greg Potter:What you'd probably find is that some of your hormonal rhythms in those circumstances might not persist if you didn't have food, for instance. Whereas others, such as the [inaudible] rhythm would persist with these nice high amplitude rhythms over time. And these rhythms, they have three parameters. One is the amplitude, so the difference between the peak of the rhythm and the trough. One is the phase, which the timing of the rhythm. And one is the period, or how long it lasts.

Greg Kelly:And then, one of the things that I know we had spoken about in our precall call was about the difference between ... because I often seen it portrayed as if we're just one clock, but the truth is we're multiple clocks, and so there's this idea that we have a master clock and peripheral clocks. Can you talk a little bit about that?

Greg Potter:Sure. Yeah. It's a very important concepts. So, I suppose if we begin with the master clock, then we should begin with how our bodies respond to light exposure. So, I mentioned earlier that light is the most important time cue ind resetting our clocks each day. And listeners would probably know that we have rods in our eyes which are important seeing during darkness, and cones which are important to color vision. But light also has the so-called non image forming functions. And one of these is circadian system entrainment, or the resetting of our clocks each day. And this was first shown in the early 2000s by David Burson and [Mahata 00:33:14]. But we have these specialized cells in the eyes, called IPR Gcs, and basically they contain this photo pigment. And in response to light, signals from our eyes, fire back directly to the master clock in the brain. And the master clock sits above where the optic nerves from the eyes cross, and it samples this information about light exposure to update a running record of our light exposure history.

Greg Potter:And an important concept to understand is that whereas the rods and cones in the eyes respond rapidly, these specialized cells respond much more slowly. So, they keep this record of light exposure over a longer period of time. And that's very important when it comes to entrainment. But anyway, this master clock then has a pathway back to the pineal gland where melatonin is synthesized, and then melatonin is synthesized only during darkness. It then relays this darkness signal throughout our bodies to other tissues, where acts as receptors to tell them that it's the nighttime and therefore to do their nighttime activities. And melatonin's important in things like sleep-wake timing.

Greg Kelly:Great. Now, I just wanted to touch on a few things with what you just covered before we move on. So, one of them, you mentioned that these retinal neurons essentially go to a special part of our brain. That's the SCN, correct, in the hypothalamus?

Greg Potter:Yeah. So, the master clock, it's called the suprachiasmatic nucleus, this pad wing-shaped structure in the front of the hypothalamus.

Greg Kelly:Great. Now, and the main reason I wanted to point that out is because there's a ... The hypothalamus is also where a lot of our, what I would think of as our core self regulatory drive exist. So appetite, thirst, adaptation to temperature, the sex drive. So, the body clock is so important, at least our master one, it's like literally located in that same small area of our brain that does tons of things with self regulation. And I think intuitively, my hypothesis would be that part of the reason is because these all are necessary for essentially survival and adaptation. So, where we think of things like, we can die really quickly if we don't have water in a few days. We can fast for a while, but eventually we would run out.

Greg Kelly:Obviously, exposure to cold, extremes of heat are things that we can adapt to within reasons. But I think it's important to me to conceptualize the circadian system as equally important in evolution, because it's placed right next to those things. I don't know if that makes sense to you, Greg, but that's generally the way I've thought of it.

Greg Potter:Yeah, that makes perfect sense. And it's definitely there for a reason. And there was some really nice early experiments that showed this, I think. So, in the '70s, various people basically lessened the master clock. And what they found is that if they did that, then circadian rhythms and things like locomotor activity, so physical activity in rats, but also some hormones and feeding behavior were basically completely nullified. And I suppose something that I didn't get to before that's very important for people to understand is that when we're exposed to light is important. And the time at which we're exposed to light will determine how our bodies' clocks respond to light. So for example, if you increase your exposure to bright blue light early in your biological day, so shortly after waking, then that will tend to advance your master clock and advance your sleep time accordingly. So, you want to go to bed earlier and wake up early the next day.

Greg Potter:Likewise, if you increase your exposure to bright blue light late in the biological day, then that will delay your master clock. So, you will start falling asleep later. And then waking up later too. And then finally, just to circle back to something earlier, this master clock doesn't only relay this time of day signal throughout our bodies via melatonin, but also it acts by a neural projection. So, you mentioned where it's placed in the brain as these diffuse projections to various different brain regions. But also it produces its own secretions, and is very tightly involved in the direct ... in the regulation of body temperature. So, Joe Takahashi from UT Southwestern has shown that the [inaudible] aren't very sensitive to temperature themselves, but what they do do is they drive our circadian rhythms in body temperature, and then temperature acts as an important time of day signal to clocks elsewhere in our bodies.

Greg Kelly:Great. One thing I do want to just point out to make sure ... I'm not sure how familiar our audience will be with all the different terminology, but when you say biological clock, can you just quickly in a sentence or two, tell our audience what that means? Or biological day I guess is what you specifically set.

Greg Potter:Sure. So, very simply the way that I would define that as biological nighttime is when circulating melatonin is high, and biological daytime is when Melatonin is low. Because of all of our different biological rhythms, melatonin has the strongest circadian rhythm. And it's least sensitive to changes and things like physical activity and feeding. So, cortisol for example also has this big high amplitudes circadian rhythm. But obviously, if you come under stress, then that's going to strongly affect your cortisol production. Or if you go out and you do an intense exercise session, then it's the same thing. Whereas melatonin, it's not so dependent on those different activities. And for that reason, melatonin high, biological nighttime, melatonin low, biological daytime.

Greg Kelly:Great. And then in a general sense, would it be correct to say when our biological day is in sync with the actual sun scheduled day, then we tend to perform better? So, when our Melatonin is ... the peak of the amplitude is in the darkest part of the night, we would tend to perform a lot better than if we do things, whether by schedule, other choices, or some disorder that's causing it to shift out of that area?

Greg Potter:Yeah, I think in general that's fair to say. And something that's worth noting is that our biological clocks can adjust quite quickly to changes in our light dark cycle. So, Ken Wright from Boulder showed a few years ago that if you have people and they just go camping, and they're not exposed to any artificial light during that time. Then at the beginning of the camping experiment there's quite wide variation between people in the timing of their biological clocks. But then after a few days of camping, that dispersion is much narrower, and people's sleep-wake cycles, and also their melatonin rhythms synchronize much more tightly with the daytime and the nighttime respectively. And as we'll get to later, if you start disrupting people's biological rhythms, and they start behaving in a way that's discordant with the way that our ancestors once would have behaved, then they're predisposed to a range of health problems.

Greg Kelly:Great. Now, we've mentioned light a few times, and I guess one of the ways I tend to think about it would be naturalistic lighting. Because darkness is as important as you just highlighted in that study of people camping. So, we want to pay attention to light, but overall lighting and that includes darkness. I know that's how I've thought of it when I was both in clinical practice, and certainly it's one of the bio hacking things I follow. Is to try to do a really ... optimize my lighting during the day, but also optimize my darkness during the night. And do you have any insights of why or any opinion on whether that would be an overall good strategy?

Greg Potter:Yeah, I think it definitely would have been a good strategy. And just to take a step back, you can think of it as humans having once lived by two clocks. So, one was the environmental clock, so change in things like lights exposure. And one was our biological clocks. And obviously these people, they would have been physically active during the daytime and then at night they would have rested and fasted. But now we have all this artificial lighting. So, Edison invented the incandescent light bulb in 1879, and now 80% of the world's population is exposed to artificial light at night. And this is becoming more and more problematic too. So, between 2012 and 2016, for example, the amount of the earth planet that was exposed to artificial light, but also the intensity of the artificial light that we're exposed to intensified by over 2% per year during that time.

Greg Potter:And we also know that there are associations between nocturnal light pollution, and certain health outcomes. So, one of them actually is obesity. So, greater nocturnal light pollution exposure is positively associated with obesity prevalence in more than 80 countries worldwide. And now, as you mentioned, we spend too much of our time inside during the daytime. So, we spend about 88% of our time indoors in industrialized societies. And the difference in light exposure between the indoor environment and outdoors is enormous. Quite often inside, the intensity of the light you're exposed to will be less than 500 lux. Lux is just the units of measurement. And outside, it will be more than 200 times that much during the midday period. So, if you're outside on a sunny day in the middle of June in San Diego, then perhaps the amount of light you'll be exposed to, the intensity would be more than 100,000 Lux. It's more than 200 times greater.

Greg Kelly:And to put that in context, I know light boxes are used clinically for seasonal affective disorder, as an example of one thing. The Lux for us that is something closer to 10,000 lux, assuming it's only about a foot from your eyes. Is that kind of in the ballpark?

Greg Potter:Yeah. I think they're definitely useful, especially for people with that particular condition.

Greg Kelly:Great. I'm sorry to interrupt. We're definitely going to get into much more when we talk about tactics, or things that our audience can do to essentially improve naturalistic light and lighting. But the key thing at this point in our discussion, I just wanted to say in terms of an overall strategy, that focusing our behaviors in ways that tend to optimize naturalistic lighting. The types of lighting that we would have evolved to have if we were camping outdoors, and outdoors during the day, is the kind of the big picture goal. We'll get later in the talk with Greg, some of his suggestions for things we can do to, despite living in a modern world, to take advantage of that.

Greg Kelly:And what I wanted to do now is move a little bit into what we think of as peripheral clock. So, as you mentioned, the master clock is in the brain, very important for melatonin rhythm especially, tends to be more than anything influenced by exposure to light and darkness. But now talk a little bit about peripheral clocks, because I think these don't get quite as much attention.

Greg Potter:Sure. Yeah. I think we're realizing their importance more and more. That's probably part of the reason for that. But let me speak about peripheral clocks, we're really referring to all of the clocks in our bodies that exist outside of the master clock. So, there are peripheral clocks in our brains too, even though that initially seemed counter intuitive. But anyway, the purpose of these is really to set the time, your daily program of processes in each of our tissues. And to go back to the idea that our bodies are optimized for specific activities at certain times of day. We can speak about this very nice enough, we're discussing peripheral clocks. So, during the daytime for example, our bodies are optimized for digestion. So, we have this characteristic pattern in muscular activity in our digestive systems called the migrating motor complex. And it pushes indigestible food from the stomach to the small intestine. And the speed of this is more than twice as high during the daytime.

Greg Potter:We have circadian rhythms in diets and use thermogenesis, which is just the increase in metabolic rate that's present for several hours after eating. And Frank [Scheer] and Chris Morris showed a few years ago that you burn more calories after eating a meal in the biological morning, than after the exact same meal in the biological evening. We have circadian rhythms in incident sensitivity. So, each cell in our body has it's own circadian clock, and clocks in our fat cells have a circadian rhythm and incidence sensitivity such that its highest at about midday. And this actually has quite pronounced effects on our bodies' metabolic responses to meals. so Frank Scheer and Chris Morris again did some other very cool work showing that our glucose tolerance, so how our bodies' respond to a fixed amounts of glucose, is about 17% lower in the bottle we evening than the biological morning.

Greg Potter:And then, just this one more example of this. We have circadian rhythms in immune function, so physical activity and eating and drinking, they will increase our exposure to pathogens. So, the circadian system needs to tweak various things in accordance with this. One of them is the microbiota, but also other determinants for immune function. And just to show you how important this is, if you take mice and you expose them to foodborne and airborne pathogens, at the beginning of when they naturally sleep, they're less likely to survive than if they're exposed to when they've been actually awake.

Greg Kelly:Wow. Wow. What a big difference. So, the big picture is, at least what I think I heard you say, was that our physiology because of these peripheral clocks, is optimized to eat during the day. And really to sleep at night. And we've also talked, I know, you mentioned briefly that our fat cells have clock function. And I know the way I tend to think of it is that all of these cells, but also all of our organs have clock function. And I think, well I'm going back to that idea of entrainment. You mentioned earlier you were talking about why it's important to entrain our circadian rhythms, our internal clocks to the external world. Can you also talk a little bit about why it's important to entrain our master clock to these peripheral clocks?

Greg Potter:Yeah. So, I don't think we actually know for sure how important synchronization between the master clock and the peripheral clocks in humans is just yet. It's a difficult experiment to do, but what I can do is I can speak about how the timing of our peripheral clocks is set. And then later, obviously if we speak about the importance of meal timing, then that starts to suggest that if the time of the peripheral clocks shifts, and it's very different from the time of the master clock, then that's probably a negative thing. But anyway, the timing of the master clock is mostly set by light exposure. But at the time of these peripheral clocks is mostly set by food intake. And this was first shown in 2000 by Francesca [DamYole 00:48:39]. And she basically found that you feed one group of mice from 6:00 AM to 6:00 PM and another group from 6:00 PM, 6:00 AM. Then within a few days, the timing of gene expression in clocks and organs such as the liver is completely out of phase between the groups. So, it shifts by 12 hours.

Greg Potter:But the timing of the master clock in the brain barely budges. And then last year, some research at the University of Surrey showed that change in meal timing also only seemed to shift the time you have peripheral clocks in humans. So, they took people and for six days they had them eat three meals a day. And then for the next six days, they delayed the meal timing by five hours. Same three males just five hours later. And they found that when they did that, the plasma rhythm and blood glucose shifted by nearly six hours during that time. And then the timing of clock gene expression in fat cells from the buttocks was also delayed.

Greg Potter:And just to add one final comment, the clocks that keep the master clock ticking fundamentally are much the same as those that keep the peripheral clocks ticking. So, in all of our cells we have these molecular clocks, and the purpose of these is basically to separate the timing of incompatible cellular activity. So, building new structures and breaking down damaged ones, for example. And we don't need to go into the specifics, but that's an important concept to know. And these are very pervasive, and their effects on gene expression particularly seem to be very, very widespread. So in mice, for example, it seems that more than 50% of protein coding genes have 24 hour changes in gene expression in at least one set of conditions.

Greg Kelly:Well, so one of the ... I'll probably oversimplify this to the point where borders or maybe not even being correct. But when we think in terms of these different clocks, the peripheral clocks, the master clock, but especially the peripheral sense as you mentioned, their performances so dictated by food. At least their orientation in time. And earlier you'd mentioned that anticipation, that one of the reasons that we believe we have these different rhythms is because it's an anticipatory function. The way I tend to think of it is digestion's hard. Like food is a stress. And if we have a schedule that's regular enough that are essentially the complex intelligence within us can anticipate, say when we're going to have breakfast tomorrow. It can get all the various jobs needed synchronized, basically scheduled so that we can optimize digestion.

Greg Kelly:And so, when I was just listening to you speak, one of the things that I tend to think about is, as you mentioned, it's very easy to shift the orientation of time of numerous, numerous genes. Yet we need these things to really be scheduled, or the schedule optimized to do some of the jobs well. Like, so I tend to think of repair versus breaking down. Digestion as I mentioned, is a time event.

Greg Kelly:So, I guess the key thing I'd like you to speak about next is doesn't matter when we eat in relation to Melatonin rhythms? Or like how different things might be oriented at time. So, you've mentioned in this study that by simply shifting not what they ate, but when they ate it, it changed a lot of genes. And I know this would be preliminary in terms of making hard conclusions, but is there any potential ramification of that on other rhythms like Melatonin or on things like sleep wake cycles? Or how different things might be scheduled to interact together?

Greg Potter:Yeah, definitely. And I'll focus on Melatonin specifically. But one of the functions of melatonin seems to be that it inhibits glucose stimulated insulin secretion. So, at nighttime we don't want our blood sugar to fall down too low, and melatonin acts on the pancreas to inhibit glucose stimulated insulin secretion and that should prevent that from happening. And interestingly, people vary in how they respond to melatonin. So, about 30% of people worldwide, they carry this variance in one of the melatonin receptor that's associated with increased risk of type two diabetes. And what that seems to do is it seems to amplify how much melatonin reduces insulin secretion.

Greg Potter:So, for these people it's probably more problematic for them to eat food during the biological nighttime. And these people also seem to have slightly different Melatonin rhythm's. So, they have prolonged Melatonin synthesis duration, which means that when they wake up in the morning, they're more likely to have melatonin circulating their bloodstream still. So, maybe the oral glucose responses to breakfast wont be as good. And people have done some work recently where basically they've taken people and they've stratified them according to their melatonin receptor genes. And then they've seen how much the effects of exogenous melatonin, so melatonin that you take as a supplement, worsens glucose tolerance in response to a standard meal. And people that carry this risk therein respond much more negatively.

Greg Potter:But anyway, in general, the implication of this is that we really want to be digesting food during our biological nighttime if possible. And there are various other reasons that it does make a lot of sense for us to consume food during our biological daytime. And then especially earlier in the day too. So, one of the things I mentioned earlier was the idea that diet induced thermogenesis is earlier in the daytime. Then insulin sensitivity is highest during the daytime too. And actually there've been a couple of really nice experiments that have basically looked at what happens when people shift where most of the calories are concentrated between meals. And maybe the best study in explaining this or showing this was done by Danielle [inaudible] in 2013. And basically what she did was she took overweight and obese women and divided them into two groups.

Greg Potter:So both groups, they consume the same number of calories each day and they consume the same number of meals each day, the same macronutrient meal compositions. But the difference was that one group had half the calories at breakfast, and then one group had half of their calories at dinner. And both groups did quite well. So, after the 12 weeks of this diet, the group that had half their calories at dinner, the late eaters, they lost 4% body weight, and they lost 3% of their waists. But the women who had 50% of their calories at breakfast, the early eaters, they lost 11% that body weights, and they lost 8% of their waists. And they also had greater improvements in their blood glucose and blood lipids. So, what that suggests is that if everything else is held constant, then if people redistribute their calorie intake earlier in their biological days, then that's probably going to be a good thing for metabolic health.

Greg Kelly:Wow great. So, I know one of the things to me is thinking in terms of what we do is important, but when we do it can also be sometimes more important. And in this case, the what was the same, but the response was vastly different when the research has changed the when essentially. And I just for our audience, I was an officer in the navy in my 20s, and because of I guess different circumstances during that five and a half year time period. At one point I was in basically more of a training situation, where we had to access food in the cafeteria, so to eat. I didn't have a lot of options. I think breakfast time ended by 7:00, dinner time was somewhere in the maybe 4:00 to 5:00. But for sure by 5:00 we were moving on to kind of plan B for the rest of our, I guess, our work and activities.

Greg Kelly:So, there wasn't another chance to eat between 5:00 and dinner. And so what ended up happening during that brief period of time, I think it was about four to six weeks, is I would eat these huge breakfasts. Because by the time I woke up after not having food from say 5:00 at night until 10:30 or 11:00 when I went to bed, I had ... essentially was feeling like slight hunger going to bed most nights, and waking you up very hungry. So, we did a big breakfast. Usually, I think we ate around 11:30, I'd eat a fairly big lunch. And by dinnertime at 4:00 I was often not particularly hungry, because I ... At that point, I guess, the way I would think of it, I'd eaten most of the calories my body needed. So, I would have, I'd say, a moderate sized dinner and then like I said, I tended to go to bed with just a bit of appetite coming back on. But food wasn't on the menu at that point in the night during this time period.

Greg Kelly:And so, the big picture is that was the leanest I ever was in my time in the navy. And I wasn't doing anything else differently. I wasn't really exercising differently. And so the big thing that I could pinpoint was that just shifting more of my calories earlier in the day and then crunching all of my calories into what ended up being about a nine-hour window seems to me to be something that my body thrived on at the time.

Greg Potter:Yeah. And I think that something that's relevant is that, that study that I mentioned there, it controlled everything. But also we don't live lives in controlled conditions like that. So, it's useful to compare what happens when you just tell people to consume breakfast, and you tell other people to skip breakfast. Because in recent years people have heard of time restricted feeding, or time restricted eating. Time restricted feeding is something that people use to study how animals respond to changes in food intake. So, time restricted feeding is typically restricting food intake or food access in other animals to a period of 12 hours or less each day. And in humans, we refer to that as time restricted eating. And a common way to implement time restricted eating is by skipping breakfast.

Greg Potter:And the studies of animals show that time restricted feeding has these protective effects against the obesogenic effects of bad diets basically. If you give mice very obesegenic diets, but you restrict their food access to certain times of day, then they won't get as fat as the other mice. So, if this translates to humans, then skipping breakfast might be a good idea. But what happens when you tell people to skip breakfast? Well, there was some work by scientists at the University of Bath. They did two very nice studies on this question. In the first study, they looked to what happens in lean young adults as I'm sure you used to be, Greg. And what they did was they had them either consumed zero calories before mid day, so that was the breakfast skipping group, or at least 700 calories by 11:00 AM in the morning. And the two groups lasted six weeks.

Greg Potter:And what they found is that those who skip breakfast, they did consume about 500 fewer calories, but they also burned about 400 fewer calories each day. And what they found is that there are no real differences in sleep over that time, or various measures of cardio metabolic health. But they did find that the people who skipped breakfast had more variable blood sugar in the afternoon, and that's not a good thing. And then they basically repeated the exact same experiment, but this time using obese young adults. And this time they found that those who skip breakfast, they burned fewer calories in the morning, but not over the whole day. And the only difference was the incident sensitivity was worse in the afternoon in the breakfast skippers. So, in these uncontrolled conditions where you just tell people skip breakfast or consume breakfast, it seems that at least blood glucose regulation is better among the breakfast consumers. So, I think in general, the old adage that breakfast is the most important meal of the day might not quite be accurate, but also there's an old carnal of truth in there somewhere too.

Greg Kelly:Yeah. And I know when I work with patients, one of the things that was a truism is that the same tactic may not work identically for everyone. So, I think it's always important to self experiment, but one of the things that I would say was also a truism, my practice at the time was in Greenwich, Connecticut, so I had a lot of people from that end of Connecticut, near New York City. And also a lot of patients from New York City. So, skipping breakfast was a fairly common thing, at least among patients that I had seen at that point in time. And another common thing is when they skip breakfast and had their first meal much later in the day, so say lunchtime, is their appetite rhythms tended to skew towards the evening.

Greg Kelly:So, what they would also then tend to do would be to get hungry, what I would think of as the, in the time period leading up to bedtime. They would want a big snack at 9:00 or 10:00 at night, or right before bed. And as you mentioned, it's our physiology at nighttime isn't optimized for digestion in the same way it might be during the day. And so one of the things I saw that would sometimes correct that tendency to eat at night was shifting some of the calories earlier in the day. So, not that it was necessarily going to work for everyone, but quite often if my patients had difficulty snacking at night, the solution wasn't to try to exert willpower then, it was to eat some more calories early in the day.

Greg Potter:Yeah, perfect. And I think some people will say, "Well, I don't feel hungry when I wake up in the morning," but actually quite quickly what would happen is if they started eating breakfast, then they would entrain certain hormones to peak at that time of day. So, ghrelin for example, is a hormone that tends to stimulate appetite, and we see spikes in ghrelin production at around the time that our body anticipates meals. And what you'd find is that after a few days of that new meal pattern, you would then have a spike in ghrelin production at the time of breakfast. People will get hungry at that time of day, and there'd be a smaller spike in the evenings, so they'd be less likely to want to overindulge at that time. And then I think that having that smaller evening meal is probably a good thing for other reasons too.

Greg Potter:So, there was work published recently, for example, showing that if people will consume fewer calories at dinner, then they had greater para synthetic nervous system activity overnight, which should be conducive to restorative sleep. And one of the things I mentioned earlier, diet induced thermogenesis is also relevant here because each time you have a meal, your body temperature goes up temporarily. And actually, around the time that you sleep in the evening, you want your body temperature to go down. You specifically want the temperature of your brain to drop by a couple of degrees overnight because that helps you enter the deepest stages of sleep. And if you can seem that big meal too late, then you're probably going to interfere with that process. It's going to take you longer to fall asleep, and perhaps just impair your ability to consolidate restorative sleep too.

Greg Kelly:And I think that's the key point because I think what ... the tendency is often to somewhat competent ... I'm sorry, but you can understand what I'm shooting for. But we tend to think, okay, like eating just has to do with eating and sleep has to do with sleep, but it's all connected. And part of the reason it's all connected is because these different cellular body clocks are constantly sinking up together. So, if we're having with sleep that could be because of the timing of food. Another thing with food that I think this would fall maybe more into the, needs more research, but I tend to think of digestion, digesting food requires getting a lot of stomach acid released at the right point to break down heavy proteins. It requires keeping the sphincter at the top of our stomach tightly closed. So, reflux doesn't come up into our esophagus. As you mentioned earlier, it requires the peristalsis to move things through our intestines.

Greg Kelly:And I remember at some point, I don't know if it was research or more notional, this idea that our stomach would also have a time over a 24-hour period where it's not trying to digest things. But that it does produce a lot of acid, and the notion was it does this to decontaminate itself. To break down the things that didn't get to that might have built up. And that, that process tends to happen at night, that the stomach would try to essentially clean itself. And so I think, this was probably over simplistic. But if I was working with patients and they had a lot of GI issues or reflux, that having more, I guess more space to do that cleaning up at night, instead of still trying to digest food, sometimes could make a big difference in their symptoms.

Greg Potter:Yeah, I think that makes a lot of sense. And I think in years to come as we start to look at the effects of this time restricted eating approach on different clinical populations, I suspect that we'll see that one of the groups of people that benefits most from it is people with Gi pathologies. And there is some preclinical research on other animals that shows, for example, that if you use this time restricted feeding approach, then you increase the amplitude of changes in the gut microbiota. So, if you feed mice high fat, high sugar diets, then what happens is they spread out their feeding because their circadian systems are disrupted, and their microbiomes don't change as much over the course of 24 hours.

Greg Potter:But then if you keep them on these same diets but restrict the food access to a period of say 12 hours a day, then they consume the same number of calories but their microbiomes look much more like mice that are fed regular healthier chow. And also their metabolic health is better too. So, I don't know of any research that's looked at things like stomach acid production or anything like that. But I just think that intuitively it makes perfect sense that we really want to give our systems a break, and that includes things like our digestive tracts for a period of time each day. And if we can aim for consistency when doing so, that makes a lot of sense too. And for reasons that also relates to metabolic health.

Greg Kelly:Great. Now, I'm going to just detour for a second because one of the ... I mean, you just mentioned time restricted feeding, and when you were at the bio hackers summit speaking, I fairly sure I remember you speaking about calorie restriction at one point leading into your, I guess, discussion more about time restricted feeding. And I know here in the Neuro Hacker Collective office, we've been doing a lot with intermittent fasting, time restricted feeding. No one's trying to live longterm on calorie restriction at this point. But those are, at this [crosstalk] I was just at the aging conference in Las Vegas last weekend. And I would say that the number one tool in the toolbox for anti aging that kept coming up over and over were these types of tactics. Things like time restricted feeding, intermittent fasting.

Greg Kelly:They talked a little bit of calorie restriction in the context of animal studies. And what I think I remember you saying in your presentation was when animals are calorie restricted, in general organisms tend to live longer. But a couple of things that they haven't, I guess get as much publicity is that when they're calorie restricted, they also tend to almost by default do what time restricted feeding type of protocol. Is that correct?

Greg Potter:Yeah, that's right. So, Joe Takashi's group published some work last year and an issue in calorie restriction researchers that we haven't necessarily had very precise high resolution measures of, when animals feed, when you restrict their calories. And let's say that you restrict their calorie intake by 40% or 25%, what you'll find under those conditions, when you have higher resolution measures, is that they self imposed time restriction. So, you give them small amounts of food and they consume it all very quickly. And what Joe Takashi's group showed is that calorie restriction actually affected food intake patterns more severely than time restriction did. So, if you have a group that have time restriction, but they're allowed to consume as much food as they like during that time, then let's say that they consume it all within 10 hours. I'm just making up that number.

Greg Potter:But then if you give them, let's say 25% calorie restriction, so they've only got access to a total amounts of food each day, then they will actually have a shorter feeding period than the mice in the time restricted feeding group. And they also found that the calorie restriction affected the timing of patterns of wheel running behavior. So, their physical activity more than time restriction did too. So, what this suggests is that many of the benefits that have been shown in calorie restriction studies could have been due to time restriction.

Greg Potter:And just to go back to one other idea, there's this division between intermittent fasting and time restriction, or time restricted feeding, which I think is not always very clearly spoken about. And in my mind intermittent fasting is periodic use of a longer fast. So, 24 hours for example. And this sounds like semantics, but actually I think it is important to note because fasting tends to flatten many of our biological rhythms. And this is actually obvious when you think about it. If you went for the next five days without eating any food, then your sleep at night wouldn't be as consolidated. You'd be more likely to wake up because your body wants you to go out and find food. And then during the daytime you'd be really tired, so you wouldn't be as physically active. So, your rest-activity cycles would have a lower amplitude. That's circadian rhythm in sleep and wake would be flatter.

Greg Potter:Whereas with time restricted feeding, if anything, such rhythms tend to have a higher amplitude. And actually there was some work that was published this year by researchers at King's College in London showing that fasting tends to flatten 24- hour changes in gene expression in some of our peripheral clocks too. So, I just think that it's important to make that distinction between intermittent fasting and time restricted feeding, and then also recognize that time restriction probably underlies many of the benefits that are seen in calorie restriction. And then finally that many of the calorie restriction studies we need to think carefully about because we're humans, and we're not mice, and the experiments' conditions that they use aren't necessarily very representative of our own lives in the big world.

Greg Potter:We're tall bipedal organisms that are very prone to accidents in old age, and we need to stay strong. We need good musculoskeletal system function, and if we just dramatically restrict our calories for a long period of time, then we're going to have weak immune systems. We're probably going to be weak. There's not going to be much life in our years. And I think those are really important things to think about when we start drawing comparisons between studies of other animals and ourselves.

Greg Kelly:Great. And I know one of the things, I've been a long time fan of the TV show Survivor, which I'm not sure whether you'd be familiar. And being in the UK, I don't know if you even get. But in that TV show, have they in essence can't get enough calories for the 39 days, assuming that they stayed till the end, because typically they don't have great survival skills. So, they're doing it at least a short term calorie restriction type of eating regime, just because of circumstances. And one of the most common things you see as very, very quickly, they are obsessed with food. But two other things that you see is sleep's disrupted, and that activity is ... Like they'll, they'll be able to get up for challenges, but they're fairly lethargic. They lay around a lot.

Greg Kelly:And I think one of the things I remember first reading about calorie restriction in animals back in the '90s at some point and thinking, "Huh, I wonder if anyone's actually spent time watching how much these animals move. Do they end up sleeping more? Are they as active?" And my impression, and you might know more about this, is they tend to have bursts of energy, because as you mentioned earlier, when we're hungry, it would be evolutionarily an advantage to go looking for food. But it's hard to sustain the kind of high level performance and activity that we would typically want if we want to live a robust health span. Would that be correct?

Greg Potter:Yeah, that's right. And I think if you think about it evolutionarily, then there's pressure on the animals to find the food they need to support their bodies, and they need that energy so that they can reproduce ultimately. And if they're not getting that during their biological daytime. So for us during the daytime outside, then maybe if they go looking for food and other times of day they'll be more successful in finding that food. So, one area of research in the chrono biology world has been something called temporal niche switching. So, the idea that if you look at rodents for example, that are nocturnal, and you restrict their food access to the daytime. Which is their biological nighttime, then quickly their patterns of waking and sleeping will reflect that change in food intake. So, be up and active when they'd naturally be sleeping so that they can get food. And then during the time when they're naturally, if they had enough food, be awake, they're more likely to sleep. So, because food is so important to us, that makes perfect sense to me.

Greg Kelly:Great. And I know one of ... With intermittent fasting, so you had mentioned it's really important to you that we be precise in our terms. That we use time restricted eating, time restrictive fasting, to refer to the context of a day when we're just limiting our eating window towards a certain number of hours, or a certain period of time. And that intermittent fasting, a better use of that would be short periods of fasting for at least 24 hours. And I agree, that's how I ... We're doing a series of blogs that Neuro Hacker Collective on different eating regimes that have to do with fasting and calorie restriction. And we're using it in exactly that same way. I think it's important to be precise. And one of the key things I think in terms of tactics to optimize body clock, as you mentioned, when we do these periodic fasts, those can be useful for certain things. But on a day to day basis, our circadian rhythms are more robust. They have better amplitudes, they orient and stays stable in time by more of a time restricted eating, time restricted feeding regime. Would that be correct?

Greg Potter:Yeah, absolutely. And I think also that consistency is important from one day to the next, especially when it comes to setting the time peripheral clocks, but also it's a metabolic health generally. So, there's a guy at the University of Nottingham called Ian McDonald who's done some really nice work on this in recent years. And just as an example of this, he compared the responses of women who consumed six meals every day for two weeks, to when they consumed a varying number of three to nine meals each day. So, in both conditions they consumed six meals on average, but after the consistent six meals each day condition, they had greater diet induced thermogenesis and better blood sugar regulation, and lower hunger. So, that consistency is very important, and then periodically throwing in a longer fast I think makes a lot of sense for many people. And all of this does come down to what suits your lifestyle.

Greg Potter:So, I don't want to sound like I'm saying that I don't think that intermittent fasting, periodic use of a longer fast is useful. I think it absolutely is. I think it works for many people, but also there are certain things I think that needs be in place before people consider doing that. And I think that many people who gravitate to that type of approach are the types of people who will put themselves under quite a lot of duress anyway. So, maybe they are very type A. They work hard, they exercise hard, and then they think, "Well, I heard that if I do this prolonged fast, then I'll reduce my risk of developing cancer because my body will clear out all of these cells which could be becoming senescence." So, they'll then do a three or a five day fast, when the bodies were actually already under quite a lot of stress.

Greg Potter:But for those people they'd be better off actually probably refeeding, trying to reduce their stress levels and then once their bodies are ready for it, they can then consider those longer fasts. But otherwise for most people, I think that time restricted eating is something that they can use on a daily basis to make sure that they've got those healthy, robust, high amplitudes circadian rhythms in place. And then just punctuate their lives periodically with those longer fasts.

Greg Kelly:Great. Now, one of the areas that you're considered like the subject matter expert at this point is really what I think of as the intersection of circadian rhythms with Metabolic Health, with sleep with eating. That clustering of four things. And we've talked a lot about, at this point I would say, more of the eating side of things and I wanted to shift gears a little bit and start to talk a bit about some things to do with sleep, and any tips that you can give our audience. And I guess before jumping into this, when I read circadian research, one of the terms that I see frequently is this idea of internal de-synchronization. And we've talked about the need for things being in sync. But my impression is to get our metabolism to work really well in internal de-synchronization is bad, and synchronization is good. Could you just touch quickly on what those terms mean? And then some common things in our, I guess our modern world that can contribute to the internal de-synchronization?

Greg Potter:Yeah, so as you mentioned, internal de-synchronization is just this idea that our own biological rhythms are misaligned with one another. And it's difficult to show that that's actually the case experimentally. As I mentioned before, if you change somebody's meal timing, then you can shift the timing of their peripheral clocks, but not the timing of their master clock. So, that is a form of internal desynchronization. But whether that actually affects health than the longterm hasn't really been shown. With that said, what we do know is that if we look at people who are exposed to the kinds of things that regularly disrupt their circadian rhythms, then they're predisposed to various different diseases.

Greg Potter:So, just as an example of this, you could take shift work. So, maybe a sixth of the people in the US work shifts, and then if you think about it, there are secondhand shift workers. So, the people that live with those people, who are probably also predisposed to many of the same things. And if you look at all of the different studies that have been done on shift work, then what we know is that regular or rotating night shift work is consistently associated with increased risk of things like diabetes, weight gain, coronary heart disease, stroke and certain cancers. And we can't say that this is just due to circadian system disruption because actually it's a complex exposure scenario, so these people are more likely to drive when they're tired. They're under psychosocial stress because they're trying to maintain their relationships with people who work during the day, for example. But that does suggest that these types of de-synchronization are problematic.

Greg Potter:As another example of this, you've got jet lag, which typically occurs we cross more than about three timezones and you then have poor sleep, and the new time zone. During the nighttime you've got delayed sleep onset, your sleep fragments, but then during the daytime you're tired. You don't perform as well as you do normally. You don't feel good. You're more likely to have headaches and more irritable. You can't concentrate as well, and you're also more likely to have gastrointestinal problems. As another example of this though, there's been this term in recent years coined called social jet lag, and it was coined by Till [Roennenberg] out of Munich in 2006 I think. And the idea is that for many of us, our sleep timing shifts between the days on which we work and the days on which we're free. And if it shifts by more than an hour, that would fall into the category of social jet lag.

Greg Potter:And Till Roennenberg did a study in 2012 of more than 65,000 people using questionnaires. And he found that about 69% of people who experienced at least one hour of social jet lag each week. So, their sleep timing shifts by at least an hour when they transition to their free days, typically gets later. And what they found is that beyond the effects of sleep duration alone, this change in sleep timing is associated with BMI among overweight and obese people. So, that's also suggestive that it's a problem. And part of the reason for this is probably related to mid sleep time. So, because we don't spend as much time outside as we used to, and because we're exposed to artificial light at night for many of us, the time at which we go to sleep is delaying. We're going to bed later over time, and that's because our clocks are longer than 24 hours, so they tend to shift later when they're not anchored to the daytime as they should be.

Greg Potter:And what we know is that this delay in sleep timing is associated with things like substance abuse, lower school performance in kids, worse driving, worse mental health metabolic problems too. But all of this is just epidemiological. So, you're just studying people in the real world, and you're trying to make associations between things. But you're not showing that one thing caused the other. So, to actually do that, you need experiments in which you actually disrupt somebody biological clock. And you can do this using various types of experiments, one is called a fourth dyssynchrony protocol. But basically the idea is that you impose days on people that their body's clocks can't synchronize with. So, whereas our bodies clocks are about 24 hours, if you give somebody a 28-hour day, and I'm using that in inverted commas, then what happens? Their body clocks, they can't synchronize with that 28-hour day, so they start running free.

Greg Potter:So, after three of these 28-hour days, their bodies' clocks are completely misaligned with the day that's being imposed upon them. And what you find is that after just those three days, some people are temporarily pre-diabetic if they were otherwise healthy. But also you see things like increased blood pressure, especially during sleep. You see increased inflammation and people's bodies. You see changes in cortisol rhythms. You see reduced heart rate variability, showing that they're more stressed than they used to be. And over time there's some evidence that this can actually lead to organ dysfunction. So, if you keep imposing this upon people, especially when combined with insufficient sleep, you actually see that their pancreas can't produce as much insulin as they need to.

Greg Potter:And interestingly, people don't adapt to this overtime. So, a longstanding question is, well, is it that people who do regular shift work adapt to this? Can their bodies get used to it? And it seems that that's absolutely not the case. So, there was some work published by Frank Scheer a couple of years ago, and basically showed that if you take healthy chronic shift workers, and you put been through these same types of experimental situations, then they still experienced all of the bad effects that you see in people that don't do shift work. So, that's really strong evidence that this type of de-synchronization is very problematic.

Greg Kelly:Well, I know I'm, again, going back I guess to when I was in the navy, when you're out at sea, there's a ... shift work is a constant, at least back when in the '80s. The watch I stood in, and in engineering there was only two of us on the ship that were qualified to stand it for the better part of a year. So, what that amounted to was that, we did six hours on, six hours off. And so for however it worked out, I drew the midnight to six in the morning, and the noon to six at night watch. And then you still had to do your actual job, and feeding, eating and exercise and things like that.

Greg Kelly:There was also four watch stations where there will be more people available to do it. You might have more of a rotating schedule between four people. But at the time the navy had this huge problem with weight standards. People over time in the navy would come out of bootcamp or out of college, if you were an officer, in reasonably good shape and then progressively get less metabolically healthy over time. And there was obviously multiple factors that play into that. But one that was ignored at that point was this role that chronic disruption of the body clock might be contributing. Well, we're getting towards the end of our time and I wanted to just to give you at this point, maybe a minute to wrap up a few of the big picture things. And then if there was only three things you could tell our audience that you thought were the most important to do to optimize circadian health, what would those be?

Greg Potter:Wow. That's a difficult question. So, I think one of them would be-

Greg Kelly:Before you do that, these aren't things that are set in stone. A month from now, if you had better ideas you'd be ... permission to change your mind. But given where ... And I would say these are big picture things, so regularity of eating and sleep times might be one of those. That's kind of what I'm looking for.

Greg Potter:Yeah, and I think that definitely is one of them. So, the most important time cues are food and light exposure. So, I would say trying to keep the timing of your lights exposure and your food intake consistent from one day to the next is probably the most important thing. What's most important for you is probably dependent on where you're coming from at the moment, but I think fundamentally very simple strategies are going to be useful. So, let's say that you're not used to doing so, but you now go and spend half an hour outside during your lunch break. That's going to be a really good idea for you. Before going to bed time, reducing your exposure to artificial lighting and reducing your exposure to anything that you find stressful is going to help you sleep. And then finally, I'll just say that if you get the opportunity to catch up on sleep, then please do so.

Greg Kelly:Wonderful. Wonderful. So, as we're wrapping up, I just wanted to give you a moment to talk a little bit more about humanOS.me where your hacker collective we're big fans of the work that you're doing. So, could you just, in I guess to wrap up, let our audience know a little bit about that, and the opportunity there?

Greg Potter:Yeah. HumanOs.me is the company that I work for, and it's a web application and the idea is that rather than having multiple different apps for your health, or meditation app, and an app on which to track your physical activity and sleep, we try and consolidate all of that in one place. So, you can go there and you can find out, what do I need to do to be healthy? What lifestyle behaviors do I need to engage in? And then also how do you enact those behaviors. So, as well as us teaching you about those important behaviors through things like courses and guides and blogs and podcasts, we try and give you tools to help you put that to practice. So, things like recipes for example, to show you how you can eat a Mediterranean diet.

Greg Potter:And then we also synchronize with different wearable devices. So for example, if you have a fitbit that you use to track your physical activity in your sleep, then that will synchronize with the platform so you can see those data on the platform. And then eventually we'll also try and show you whether the way that you're behaving is moving you towards or away from your health goals. So, we're going to be thinking very carefully about what the most important things related to your health are to track? And you'll soon be able to do so on the site too. And I suppose that what I mentioned is that if you go looking for information about health now, then there's lots of competition for your attention, and for that reason you need a filter and at humanOS, what we try and do is create educational content that's been peer reviewed by academics who are well qualified, and well versed in the subject areas.

Greg Potter:So, we try and make sure that everything is scientifically accurate, but also useful and translate it to a level that you can put to use. So, if you come along to humanOS.me, that would be great. And if you use the code Neuro Hacker, then you can get your first dollar of pro membership, which gives you access to everything on the site for just $1.

Greg Kelly:Wow. Well thank you. Well, thanks for joining us at Collective Insights, Greg. It's been a real treat to connect with you again after meeting up with you originally at the Bio hacker summit. So, thank you for all the great work you're doing and I look forward to hearing you speak again soon.

Greg Potter:Thanks very much.

Speaker 2:Thanks for joining us for this conversation with Dr. Greg Potter. If you liked this episode, then please share it with a friend or leave us a review on iTunes. If you're hungry for more information to take control of your overall health and wellbeing, check out our free ebook that offers a well rounded approach to brain health. The Foundational Guide to Neuro Hacking at neurohacker.com/guide. And if you're wanting to hear more from the humanOS team on sleep, check out our previous podcast episodes with the CEO and founder of HumanOS, Dr Dan Pardi. Make sure you subscribe to Collective Insights wherever you listen to podcasts so you don't miss an episode. See you next time.

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