How to Entrain Your Circadian Rhythm for Perfect Sleep and Metabolic Health [transcript]

Written by Christopher Kelly

July 4, 2018


Tommy:    Hello and welcome to the Nourish Balance Thrive podcast. My name is Tommy Wood, and today I am joined by Greg Potter. Hi, Greg.

Greg:    Hi, Tommy, great to be here.

Tommy:    Thanks for joining me. Greg works as content director for which is a health-tracking tool that uses peer-reviewed courses, blogs and podcasts to help people live healthier lifestyles. Greg recently handed in his PhD thesis at the University of Leeds in England, congratulations, and there his research focused on sleep, diet and metabolism. Greg also has Bachelor's and Master's degrees in Exercise Physiology and has experienced coaching multiple sports, including sprinting and rugby.

    Greg, I think you know that I previously read your work when you published a couple of review papers on circadian biology about a year or so ago and then more recently we were introduced by Dan Pardi who you obviously work with at humanOS. We promised Dan that this episode would be called High Tea with Thomas and Gregory, so maybe we should start there. Very importantly, how do you like your tea and what's your favorite biscuit for dunking? For our US-based listeners, we'll put some stuff in the show notes about what a real biscuit is because US biscuit isn't a British biscuit, so we'll give you some details there. Greg, maybe you can tell us a bit about your favorite teatime.

Greg:    I think that my answer is going to be quite controversial. The run of the mill response would be to have milky tea, wouldn't it?

Tommy:    Yeah.

Greg:    Maybe on the side, I live in Yorkshire, so it should probably be a strong Yorkshire tea, minimal milk, probably full fat milk because that's what men drink, and maybe three sugars to give you a bit of an extra buzz, but I'm actually not really a milky tea person.

Tommy:    Oh, well that is controversial.

Greg:    The New Age health enthusiast that I am, I probably gravitate more to green tea. However, green tea does not lend itself to dunking biscuits, so if I was having a nice tea session then I would probably go for something like a weak Yorkshire tea, no sugar, it's sweet enough as it is, and the choice of biscuit would probably be something like a dark chocolate digestive. How about you, Tommy?

Tommy:    Yeah, that's a good choice. I ate a lot of dark chocolate digestives in my youth, definitely. I like my tea, I take like a PG Tips and I'd let it brew for ages, like 20 minutes.

Greg:    You don't take the tea --

Tommy:    Don't take the teabag and then it's stewed and then you have stuff, tannins aggregate and they float on the top of the tea and then I put loads of milk in. From there, I quite like just a regular digestive for dunking. I'm also quite partial to the Hobnobs, but they're really dangerous to dunk because they can fall apart real easily. But the chocolate does help so if you went for chocolate Hobnob, that can give you some more structure and integrity.

Greg:    I think broadly speaking, the more gluten, the better.

Tommy:    Definitely.

Greg:    That is [0:02:43] [Indiscernible].

Tommy:    Yeah, I think a gluten-free biscuit is just going to dissolve the minute you put it in the tea, so gluten very important for that aspect. Before anybody or everybody switches off, maybe we could head toward safer ground and talk about circadian biology. I actually like to start by asking about your PhD because a PhD thesis is something that you spend years working on, months writing and in the end, four people read it. You probably can't talk all about it yet and some of it is yet to be published, but can you give us a bit of an overview of the work you did on your PhD and what you found?

Greg:    Sure. I'll keep this brief. There are a few different components to it and as is true of most PhDs, the PhD morphed from its inception to the end of it, quite a lot. I was involved in the validation of a new dietary record method called myfood24 which is a shorthand, acronym for measuring food on one plate, 24-hour day, something really contrite like that. What it is, is a nutrient database designed specifically for use in the UK. It has over 50,000 branded items within the database which is larger than any other dietary record method out there, so it has strong advantages.

    I did a bunch of lab work for that, mostly related to using urinary nitrogen to validate people's intakes of protein. Because the more nitrogen that you excrete in your urine, the higher your protein intake, assuming energy balance, so that was one component of it. What we did was we took that tool and I used it to look at things that I'm more directly interested in.

    I was just speaking to you before we hopped on this call, about looking at when people relative to when they sleep, so I took the original data set and looked at that. I can't really speak about it because that work hasn't been published yet, but I'll just say that there have been several studies recently suggesting that if people eat at a later time of day, particularly if they eat at a later circadian phase, then they're more likely to be overweight or obese or to have high body fat. Our findings were largely consistent with that.

    Other aspects in my PhD included a nutritional epidemiology study in which we used a UK database to look at associations between self-reported sleep duration and a variety of metabolic health outcomes, so things like BMI but then also metabolic syndrome risk and markers of inflammation, thyroid status, a few other things.


    Finally, this work hasn't been published at all yet, but we also did a relatively long-term study of whether chronic melatonin supplementation influences risk factors associated with type 2 diabetes development, and people who are at high risk for type 2 diabetes, so people who have first degree relatives with type 2 diabetes, brother, sister, father, whatever, are at higher risk of diabetes than people who don't.

    What we did is we took people and then randomized them into a slow-release form of melatonin group, it's called Circadin, they take 2 milligrams each night, about an hour before they go to bed, or a placebo group. Over a space of six months, we have them come in three times and looked at all sorts of health outcomes most related to metabolic risk. I also did some dietary analysis using the myfood24 software. After that, they came back after three months to see if any effects of the treatment persisted after a three-month wash-out period.

    So the different components of the PhD are loosely related and I'm trying somehow to weave it all together into some sort of coherent narrative that I've been up to for the last few months, but now I turned it in and got a short time before my viva so, petrified about that.

Tommy:    You just need to remember to read your thesis before you head into the viva, that's the most important thing. It's a rookie mistake that some people don't make, I think. Quickly, did you look at genetic aspects in your melatonin study? Did you look at MTNR mutations or polymorphisms?

Greg:    Yeah, and that would have been the really obvious thing to do. If I had to study myself then I would have loved to have done that and, no, we didn't. So just to expand on what Tommy is alluding to there, you have two types of melatonin receptors in the humans, MT1 and MT2, and those are encoded by the MTNR1A and MTNR1B genes, respectively.

    There's a common variant with the MTNR1B gene, about 51% of Northern Europeans carry this variant and about a third of all people carry it, which is associated with a high risk of type 2 diabetes. It seems to be a gain-of-function variant which just means that the effects of melatonin in people with that variant seem to be amplified.

    What melatonin does, one of its many actions, is to inhibit glucose-stimulated insulin excretion, so people with that particular variant tend to have more exaggerated postprandial glucose responses to some sort of glucose load and for that reason, you might expect that people with that variant respond less favorably to the melatonin supplementation than the people without it.

    That would be my speculation, but of course we didn't look at it. It would have been lovely to, and I suspect that might have drowned out some of the results too because perhaps some people responded favorably and others didn't, but didn't have a large enough sample size or the genetic testing to be able to stratify people in that kind of way.

Tommy:    Okay, well, that was one of my questions I was going to ask later about the effects of melatonin on those receptors and those polymorphism. Anyway, that was a nice segue to bring it in. I know that when people are thinking about how they might respond to melatonin supplementation, that might be something that they need to take into account.

    To jump back to some of the things you mentioned, one of the things that you were researching that you brought up was around a paper you published last year looking at sleep duration, food intake and then those weight and health metrics, and I was wondering if you can just expand on that a little bit. For instance, if you're using food frequency questionnaires, how reliable are you finding those? How reliable are you finding that compared to this other system that you put in place?

    Because we know that as BMI increases, people tend to under-report the amount of food that they're eating and obviously that is going to really sway any kind of outcomes you have in terms of then looking at food intake and sleep and weight gain and those kinds of things, so can you give us a bit of perspective on how that stuff fits together?

Greg:    Yeah, that's exactly right. What we principally found is that people who report at sleeping less, have higher BMIs and larger waists, but we didn't find any associations between their self-reported sleep duration and any dietary outcomes. One of the reasons for that, as Tommy is hinting at, is perhaps people just don't recall their diets accurately, perhaps the measurement tool that you're using isn't precise enough for you to be able to tease apart small differences in the diets of different people, and it's a longstanding issue in nutritional epidemiology.

    As you said, people who are obese tend to under-report their intake, so what could be the case is the sleep durations associated with obesity, so you'd expect that the duration is associated with energy intake too, so people who sleep less eat more, but if the obese people aren't reporting as many calories as they actually eat then you don't see that in the data and then you have to speculate about other mechanisms that might be at play.


    Actually if you look at precise lab experiments of what happens when you artificially restrict someone's sleep then summarizing the results of all relevant studies, on average people consume about 165 more calories per day if you restrict their sleep than if they're allowed as much sleep as they like. That doesn't sound like much. That's about how much energy there is in four apples but of course effects of that are cumulative and if you tied that up over the year, 365 days, then that's actually about the same amount of energy that's in 17 kilos of fat tissue. I'm of course not saying that someone who ate that many more calories would gain 17 kilos of fat tissue, but I think the point is still well made.

Tommy:    In terms of the other metrics you're looking at, do you think that the data you collected is accurate enough to make specific inferences, or did you find that there was still an under-reporting issue or do you have any idea where that was going on in your data set?

Greg:    Sure. I suspect that under-reporting is at play. It's funny because you always want to speak about your own results in some sort of positive light, but actually that had we had really good methods for diet analysis then we would have seen the differences because you've got these carefully controlled lab experiments that do show differences.

    We also understand the mechanisms that contribute to people eating more when they lose sleep. I have to think that actually it's just an issue with the measurement all itself, so food frequency questionnaires, as you mentioned, are problematic. In that particular study, they didn't use food frequency questionnaires. They did use food diaries, so people were given diaries and then they record all their food intakes and those are coded by trained nutritionists to estimate their energy intake.

    Of course it's still an issue, when you're writing down what you eat because the mere act of doing so is going to interfere with what you do eat. Maybe you have a cup of tea and you add three sugars because you like a nice sugary tea with you biscuits, and you forget to add the sugar. All of those small discrepancies do add up over time, so it's going to be really important in the coming years to develop tools that more accurately track people's diet.

    It's interesting now because in the digital age, you're seeing all these new developments coming along where people are using things like photos of the foods that they eat and various other devices to better track their food intake. That's going to be really useful too especially in the chrono-nutrition world where people are trying to understand how, when people eat influence their health, not only what people eat.

Tommy:    You published two pretty comprehensive review papers towards the start of your PhD about circadian biology and the effects of an altered circadian rhythm. Can you maybe tell us a bit about those and perhaps summarize the effects of poor sleep duration or short sleep duration, what you've been talking about previously and then also, disruption of circadian rhythm and then in the downstream, health effects of that?

Greg:    Sure, so I'll start with short sleep. Should we focus on metabolism, Tommy?

Tommy:    Yeah, that's a good place to start.

Greg:    Okay, so as you can imagine, if you sleep less then you have more time in the day in which you can consume food, so you might expect to eat more food. Not only that, there are many other changes in your body that contribute to changing your food intake, not only that you eat more, but also you tend to gravitate towards very calorie-dense, very palatable foods.

    So if you consider the brain to stop then what you see is changes in brain activity patterns in regions of the brain that are associated with the rewarding properties of foods after somebody loses sleep. If we then consider the peripheral tissues then what you find is that people become less insulin sensitive after sleep loss. Typically, about five nights of sleep of only five hours of sleep per evening will reduce someone's insulin sensitivity by about 20%.

    There are various things that contribute to that. One of them is that your fat cells themselves become less sensitive to the effects of insulin. In other words, if you shorten someone's sleep then it's a stress and your sympathetic nervous system changes its activity accordingly such that various stress hormones are raised and that tends to mobilize fuel stores, say stores of glycogen from your liver and from your muscles, for example, and that will raise your blood glucose which further contributes to this issue.

    Then if we think about other endocrine effects then short sleep tends to lower someone's leptin levels. Leptin is a satiety hormone. It principally moves in lockstep with how much fat mass someone is carrying. What you find is that after sleep loss, leptin levels fall so the brain effectively thinks that there's less energy available. You need to increase your food intake accordingly.


    Another satiety hormone is ghrelin which is secreted by the oxyntic cells in your stomach and has this pulsatile pattern where in anticipation of food availability, you see these spikes in ghrelin which stimulate food intake, so they make people want to go out and find food.    Typically, over time, ghrelin levels will increase after insufficient sleep, so you've got this double whammy of lower leptin levels and increased ghrelin levels too. All of those things effectively conspire to make people consume more calories, make worse food choices and then process the calories they do eat, less effectively.

    There are other aspects to this too, of course. If, for example, you restrict someone's sleep then, as a male, your levels of testosterone will drop. As you can imagine, that might influence or contribute to change in body composition. There has been work in which people have either been assigned to a condition where they're allowed as much sleep as they like or their sleep is restricted, and during both conditions they're given identical diets, weight loss diets, and when they don't get as much sleep as they would like, the differences in total amount of weight that they lose might not be that big but if they don't get enough sleep then they lose more of their weight from the body mass and from fat mass which is exactly not what you're looking for.

Tommy:    What about the long-term effects in terms of other disease risks, particularly we talked about short sleep but then also altered circadian rhythm, so night shift workers, people who are sleeping out of phase for other reasons, can you briefly cover what that might look like in terms of future disease risk?

Greg:     Sure, so if you consider night shift work first then it's important to bear in mind that night shift work is a complex exposure scenario. It's not only circadian misalignment that's going on, of course you've got sleep loss but then you've got stress from people who are trying to maintain relationships with non-shift workers, we've got people here engaged in activities at the wrong time, so as you can imagine, they're going to be at high risk of accidents because they're driving home after night shift at 6 in the morning after 12 hours of being awake when their bodies are crying for sleep. So you can't necessarily attribute all the negative effects of night shift work to circadian misalignment, but that definitely seems to be a contributing factor.

    Night shift work is associated with all sorts of diseases. There was recently a review published in BMJ which looked at associations between night shift work and various outcomes, and they only looked at meta analyses. That's just the type of study in which researchers aggregate their data from various studies and they weight the data such that they give more emphasis to the better studies. Many people consider that to be a gold standard in research.

    What they found is that night shift work is associated with things like diabetes and obesity, cardiovascular disease, heart attacks specifically, stroke also, and certain cancers, so there are strong relationships there. But whereas night shift work is severe and very pronounced, the rest of us probably undergo more subtle circadian misalignment on a regular basis.

    People like making catchy terms for things, so a few years ago, researchers referred to this phenomenon as social jet lag because most people now, in the presence of our artificially lit environment, go to bed relatively late and then they have to wake up to an alarm to get up for work in the morning. Then on the weekend, of course, they sleep in. They try to catch up on the sleep they've lost during the week. As a result of that, their sleep shifts a bit later. For that reason, more than two-thirds, about 69% of Northern Europeans have at least a one hour shift in their sleep time between their free days and their workdays each week.

    People have just started to look at the health outcomes that are associated with this phenomenon. One of them seems to be a predisposition to obesity among people who have higher BMIs. So if you look at all people who have a BMI over 25 or so, and you see this positive relationship between the extensive social jet lag that someone is experiencing, so, a greater discrepancy in their sleep timing and their body mass index. That's just one example of more widespread misalignment.

    It's not always driven by work schedules or anything like that of course because there are environmental influences that for some people are unavoidable. All 24 time zones, for example, converge at the North and South Pole and that means that people will have 24 hours of sunlight during the summer and 24 hours of darkness during the winter. Trying to keep your body clock on time in those circumstances is pretty hard.

    Just as one more example of misalignment and how widespread it might be, everybody in China sticks to Beijing time, but China spans five time zones, so some people's 8:00 is effectively other people's 1:00, if that makes sense. For that reason, if everyone is trying to stick to the same schedule then chances are, some people are probably going to be very short on sleep, some people, the lucky few, are going to be on the correct time zone, and it will be interesting to see in the coming years what health outcomes that's associated with.



Tommy:    That also reminds me of an article I was just reading about Spain, about why the Spanish eat dinner so late. Apparently it stems back to the fact that during the Second World War, the Spanish changed their time zone to be in line with the German time zone because of the Third Reich and the rule of Hitler, as they sympathized with that but then the population actually kept everything the same. They were doing things at the same time but the time became, automatically, an hour later even though they should be on the same time zone as the UK, to speak as to where they are in terms of longitude. I thought that was interesting. Everybody always talks about how the Spanish eat late, but it's just because of that one time they changed their time zone, and things haven't switched back.

Greg:    Yes, it's funny too because obviously they're renowned for their siestas. If they're going to bed late but still need to wake up at a reasonable time, then they're probably not getting enough sleep overnight. So they're going to bed late because of this enforced time zone rule and then they're waking up at the same time as people in Germany. Because they haven't gotten enough sleep, so come lunchtime, during this little dip in their wakefulness, they're going to want to have a nap.

Tommy:    While we're talking about that, what are your thoughts on naps in terms of their effect of, well, A, if you're short on sleep, can it be beneficial but do they then cause any issues with circadian regulation?

Greg:    Yeah, it's a very interesting question, and it's not a question I've spent as much time looking at as I would like. What I will say is that people who habitually nap, they don't seem to have problems with napping, so it won't interfere with their subsequent nocturnal sleep, but for people who aren't typical nappers, it can do. So this is related to how sleep is regulated.

    Each day when you wake up, from the moment you wake up, as we're having this conversation now, you have chemicals that are accumulating in your brain which are increasing the pressure for you to sleep. The pressure to sleep is paid off when you go to sleep. If you have a nap in the early afternoon, for instance, then after waking up, you then have less pressure to sleep later in the day, so it can cause people to take longer to fall asleep subsequently.

    With that said, I think the naps can be used therapeutically. There are definitely subsets of people who benefit from napping. For instance, athletes are renowned for napping because they probably have greater sleep needs than the rest of us, and you can use them in very targeted ways too.

    One thing that nap is routinely seen to do is enhance people's ability to form memories. So let's say if you're studying for an exam and you're a bit short on sleep, you can probably actually concentrate some of your work shortly before a nap and then use that nap as a strategy to help you retain that information you've just learned.

    Other things to consider with naps are how long the naps are. If you look at how we cycle through different stages of sleep then there are three stages of what's called non-REM sleep, and each stage is deeper. By deeper, I just mean that it's harder to wake someone from that stage, so as we transition into the deeper stage of sleep, people are really hard to arouse from that state.

    If you're artificially awakened from that deeper stage of sleep then you're going to wake up feeling quite groggy and pretty terrible. For that reason, naps that are around 45 minutes to 75 minutes or so are probably not what you want to do. Whereas shorter naps, let's say 20 minutes or so, will get you some of the benefits of napping. You'll feel more alert afterwards and will probably help you retain information too. They're probably better right there.

    Your alternative is to go through an entire sleep cycle. That sleep cycle involves both non-REM sleep and also some REM sleep at the end. REM sleep is so named because during REM sleep, rapid eye movement sleep, your eyes display this typical side-to-side movement. It's the stage in which you dream and it's a gateway to waking. So if someone wakes up naturally from that, they normally feel pretty good. So, in general, if you're going to nap then you probably want to keep it to either 25 minutes or less or around 90 minutes.

    So just to summarize things, I would say, if you're a regular napper then go for it. If you're not a regular napper but you're very short on sleep then there are definitely instances in which it can be useful. If you're not a regular napper and you're not that short on sleep then you might find that it disrupts your ability to fall asleep later that evening.

Tommy:    Okay, that's a great summary, and I think there are some great tips there. Going back to the social jet lag component that you mentioned earlier, I was thinking about some of your humanOS courses on circadian biology, which I think they're really great. The graphics are awesome. There's some really nice, interesting details about the history of circadian biology which people probably wouldn't know otherwise.

    One thing that really stuck out to me was you talked about how circadian rhythm is designed to help anticipate daily changes or exposures, so people always talk about entraining the rhythm with the inputs, but you're doing that so that you can anticipate things that will happen in the future. I think that's missed when people often talk about circadian rhythm, so I'd be really interested if you could expand on the importance of routine and the regularity of exposure to your zeitgebers and exposure of the body to what it's expecting.


    One thing that this made me think of was a recent study that I'm sure you've read that came out from the Harvard Group including Steve Lockley and others, looking at academic performance and regardless of sleep length, those that went to sleep at a similar time or had a very regular sleep time seemed to do better academically. So can you maybe talk about all of that importance in terms of routine exposures and what we can maybe do to improve that?

Greg:    Sure. I haven't actually read that paper, by the way.

Tommy:    Sorry.

Greg:    Just for the sake of transparency, but I'm keen to. Actually, someone that I've worked with, Debra, was Mr. Lockley's PhD supervisor, and they do fantastic work regularly. I've got a huge amount of admiration for pretty much everything that comes out of Harvard related to circadian biology, so I have to track down after this. But what you're getting at there, it comes up to the zeitgeber which is just a German word meaning time-giver or time cue or synchronizer.

    People should understand that, left to its own device, the body clock isn't exactly 24 hours. That's the reason that we use the term circadian, circa meaning about and dian being a derivative of dias which means day, so it's about a day but it's not exactly a day. On average, the human body clock is about 24 hours 15 minutes. There's variability. Some people might be up to 26 hours or so. Some people might be a little bit less than 24 hours. The point is that you need these zeitgebers or time cues each day to synchronize you with the 24-hour world.

    In Germany, that's not too hard. You don't need especially strong time cues for your clock to be 24 hours. With that said, the stronger the time cues that you're exposed to, the more likely you are to be better aligned with the light-dark cycle. When I refer to strong time cues, principally what I'm referring to is the light-dark cycle itself, so the main time cue for the human body clock is the light-dark cycle.

    We've got these specialized cells in our eyes and they keep a running record of how much light they're exposed to over the course of the day. These specialized cells then relay this information back to the so-called master clock in the brain and this master clock then sends these messages to a structure called the pineal gland, and the pineal gland is where melatonin is synthesized.

    Melatonin is the so-called hormone of darkness. What this means is that as light comes in through the eyes, this light exposure makes the master clock in the brain send a signal back to the pineal gland and shut off melatonin synthesis. What all this means is that if you want to synchronize your clock with the 24-hour day, with the light-dark cycle then it's really important to spend lots of time outside and be exposed to lots of bright light during the day and then to avoid light at night in particular, blue light because this blue light that more strongly shifts the body clock.

    The problem is that if you spend a lot of time indoors then you're not exposed to that stronger zeitgeber stimulus and because your body clock is typically more than 24 hours, what happens is that your body clock tends to shift a little bit later, so you're finding yourself wanting to go to bed later and then probably sleep in later in the morning too.

    This explains why when people go out and they live in nature for a period of time, the dispersion between different people in terms of timing of their bodies' clocks becomes much more narrow. People are much more closely aligned with each other because they're getting all these strong time cues. They're spending time outside during the day, and at night, let's say, that they're just exposed to firelight and moonlight. So in this instance here, you're speaking about people going to bed later.

    It's easy to conflate that with other health behaviors because if someone is spending more time inside then their clock is going to shift later and perhaps they're going to be living less healthy lives in general. Whereas the outdoorsy people are going to be doing more physical activities and so on. In short, they would have control for that variable.

    Anyway, what all this comes down to is just that in today's 24/7 culture, people really need to make an effort to spend time outside during the day and to be very vigilant about their light environment indoors too, particularly at night. Fortunately, it's now becoming easier than perhaps it was ten or 15 years ago because people's awareness of this is increasing. Now various devices have apps built into them that will help you filter out blue light and reduce the brightness on your screens and so on, and those are really encouraging developments.

    The problem is still, actually if you look at nocturnal light pollution worldwide, it continues to spread and intensify. There was work published, I think last year in Science Translational Medicine, perhaps the year before, and it showed that from 2012 to 2016, the pervasiveness and the intensity of nocturnal light pollution had increased by over 2% each year, so this problem is getting worse.


Tommy:    So this was going to bring you over to my questions on chronotype. That was the perfect jumping off point that you've given me, but just very briefly I was thinking of this other paper that was looking at artificial light at night, it was in the UK particularly, and obesity rates. They actually plotted back to the 1800s, and it was from the 1800s to the early 2000s, light at night had increased by 10,000 times or something. They used a logarithmic scale just to show it on the graphs. It's just vast amounts of lights that we're being exposed to at night which is obviously having an effect.

    So let's talk about chronotypes. Can you briefly describe what a chronotype is and how you might measure it?

Greg:    Yeah, so chronotype is fundamentally whether someone is more of a morning lark or a night owl. There are ways of accurately assessing this in the lab, and you'd want to take precise measures of the time you get someone's body clock. To do so, you typically look at melatonin or core body temperature and you look at the time [0:30:58] [Indiscernible] relative to the outside day.

    So, some people's body rhythms would be earlier and some would be later. Those who are early would be the morning types and those who are late would be the late types. Obviously that's difficult to do especially in the noisy real world and for that reason, people normally just use questionnaires to assess this, particularly in large scale, observational, cross-sectional studies. There are various ones out there. They're quite interesting.

    A lot of people will use midsleep timing to try and get their chronotype, and that's one way to look at it, but the actual original construct itself was trying to get more than that. It's when people feel best during the day. It's when they do their best work. It's when they feel strongest, the most productive. It's not just a question of sleep timing. So there are different ways of looking at it, but people have started to look at chronotype in relation to health outcomes, and they're starting to unveil some quite interesting results.

Tommy:    From there, I'm interested in your thoughts on chronotype and the environment. You kind of alluded to the question I was going to ask. We know that chronotype has a genetic component, but I feel like it's almost overplayed because it looks like, rather than the chronotype being just determined by your genetics and that tells you whether you're a morning lark or a night owl, it might be more that it determines your susceptibility to some of these other cues you're getting from the modern environment that might make you more likely to become, say, a night owl.


    So I was just wondering whether you thought people are born night owls, or are they made night owls by the modern environment, or is there a combination of the two?

Greg:    Genetics loads the gun, environment is the trigger, [0:32:32] [Indiscernible] and all that. There's something to that. In rare instances, there are strong homogenetic causes of people with unusual chronotypes. The people with these genetic barriers which make them very early types, for instance, are extremely rare. There's a highly cited study published in 2001 which just found a family of people, all of whom went to bed at about 7 pm and woke up at about 3 am. They found this mutation in one of the core clock genes which is really interesting, but of course these people are extraordinarily rare. For most of us, that finding isn't very relevant.

    People now look at heritability and they start to try and identify how much of this seems to have a genetic basis and how much is the result of other factors. Genome-wide association studies which basically study the full complement of somebody's genes to try and identify which genes are associated with a given trait, they're starting to identify a few genes, normally clock genes and related ones, but none of them seems to have a particularly strong effect.

    I think that actually, this speaks to a broader issue in that things like genetic testing data are very interesting and I think they'll be more and more useful in years to come, but actually I'm not sure how much someone's knowledge of their variance of these genes should influence their behaviors. I think fundamentally, the behaviors that improve the function of someone's body clock are probably going to be quite consistent from one person to the next.

    For most of us, if we expose ourselves to very strong time cues then we're probably just going to be better aligned with the day outside and most aspects of our lives are going to improve because not only are we going to better anticipate that that's the day, but also probably that you should sleep more because a lot of us need to be up relatively early, and we're a pretty sleep-deprived society.

Tommy:    Yeah, I think that's the perfect advice and the perfect answer. I always like it when somebody agrees with me. That always makes me feel much better, like I know what I'm talking about. So going from there, and if I can briefly ask you to take off your academic hat and be willing to give more of an opinion rather than something that's maybe truly grounded in fact, so a lot of people are talking about how people have different chronotypes and therefore we should be adjusting the work schedules to allow people to then work when they work best. Should we be changing work schedules so things are adapted to chronotype, not everybody has to work a standard 9 to 5, or should we be educating people to improve their circadian timing and then the issue goes away? Where would you see the balance of that?


Greg:    That's probably the most difficult question I've been asked on a podcast.

Tommy:    Yes!

Greg:    Congratulations. Yeah, I think addressing both things would probably be nice. For me, it's difficult to actually give an answer because I don't know how feasible adjusting work schedules is for many employees. Of course early starts are so baked into society that there's going to be a lot of inertia trying to overcome norms. The more progressive thinkers are starting to tailor people's work schedules to their chronotypes, and the results of those studies, so far, are quite interesting. People tend to sleep better, quality of life tends to improve a bit, people have looked at this specifically in relation to rotating shift work. There's work by Celine Vetter who is now in Harvard, but I think that she probably did the work while she was in Munich in Germany.

    Anyway, education is going to be really important, and I think that in general, what I favor is the powers that be making good decisions that basically nudge people into behaving in more healthy ways. To use a pretty example of this, if you're walking up to a cafeteria and the first thing that you see is fish and chips then you're going to be more likely to reach and eat fish and chips than if the first thing that you see is beetroot and smoked mackerel, for instance. So, is it possible to design a society in a way in which people are effortlessly pushed towards making better decisions? I think that that's going to be really important.

    How can you incentivize people to make better decisions but also, how can you actually just construct and build an environment to do so, so, over time, there will be greater things like light exposure in offices was thought about more carefully. Because in a span of room, in a relatively well-lit room, most people are probably exposed to about 500 lux, just that's the unit of light intensity, whereas outdoors on a sunny day, they might be exposed to 200 times more than that. So the difference is so vast.

    Now, though, of course things are changing so quickly, we have all these developments in technology, so can we leverage those to build better environments for our workers and then people are effortlessly, hopefully, going to transition into having circadian systems that function in a more healthy way? Anyway, slightly rambly again, but I think that where possible, if employees have the ability to give their workers some flexibility then that's going to be great. Otherwise, if it was possible to shift everyone a bit later, to start work later then I think that would broadly have beneficial effects.

    You see this with school start time, for instance. There have been lots of studies now. There have been mathematical modeling studies, for example, where people have tried to forecast the savings and the reductions in accidents and so on, that would result from relatively small changes in school start times, and the results were astonishing. I think that there was a paper published last year, maybe, by the RAND group which suggested the US economy would save $83 billion a year if people started school at 8:30, and that's really remarkable.

    So maybe something as simple as everyone starting work a little bit later, because they're getting that little bit more sleep, they're going to make better decisions during the day, there are going to be fewer sleepy accidents on the roads and so on. Anyway, where possible, it willl be great to give people some flexibility in their workplaces, otherwise, shifting everyone a bit later will be a good thing and then people who design our environments, if we can educate them about how to optimize the functions of people's body clocks then that will be really advantageous, I think.

Tommy:    Okay, so a combination of all of the above, that probably makes sense.

Greg:    What do you think, Tommy?

Tommy:    I'm somebody who is always going to be more rooted in more of the evolutionary, so looking everything is pretty evolutionary then, I guess that's the way that we phrase it. I think there's definitely, in terms of school starts, kids seem to, particularly teenagers, seem to have a slightly later chronotype and then I believe that gets slightly earlier as we get older. You could correct me if I'm wrong.

    But particularly with school start times, and the light in buildings is really important. I know Satchin Panda, who is one of the big names in the circadian biology field, he's now working with architects to try and produce buildings that expose people to as much natural light as possible during the day and then when you're exposed to lots of natural light during the day then you're protected from some of the effects of artificial light at night.

    So, certainly at some point, allowing people to work when they work best but then I'm always going to be on the side of there is a natural daylight cycle which is something that we evolved under, existed, to predict and time ourselves to that as much as possible. You can jump in and add something to that, if that makes sense.

Greg:    It makes a lot of sense. I think that incentive is a big issue. For a lot of companies, it's going to come down to bottom line. So if they understand the financial implications of work as you get more sleep and are more healthy, you make better decisions, you perform better at work then that's going to shift them into seriously considering some of these changes. Also, something that I was thinking about which I didn't mention earlier is how relevant this is to everything, and it's probably worth thinking about other examples of how you can use an understanding of circadian biology to optimize various things.


    One of the things that comes to mind is medicine. For example, and it's great to hear that you like the circadian course at humanOS, one of the things that we speak about is how time of drug delivery in particular can potentially reduce side effects and reduce the cost or reduce the doses that are required of the given medication in treating someone with a disease because many of the targets that these medications pinpoint are targets that are regulated by the circadian system, and this looks great on paper.

    The issue of course is that, let's say that we find out that a cancer drug is best taken at 4 pm and you've got a cancer ward with dozens of patients, how are you supposed to give dozens of patients the drug at 4 pm without there being absolute chaos? So those practicalities in getting these things on the ground are going to be tricky. I don't think they're insurmountable but actually we have a lot of work to do. If we can get that work done and just push things in the right direction, to move the needle in the right direction then that's really going to pay off over time. I don't see things changing dramatically in a very short time frame.

Tommy:    Yeah, I think that's always going to be the case with everything, but in medicine particularly, even though, like you said, that's a great point, if you've got a ward full of patients and giving a drug at a specific time, you only have so many nurses who can go around, particularly if it's intravenous or whatever, it's going to be difficult to administer that same thing at the same time. I think there are simpler things that can be changed.


    I know there are some research on people in intensive care units. When you're in intensive care unit, you're often not eating so then you have a nasogastric tube, goes from the nose down to the stomach, and you're fed a liquid diet. It's often just easier to feed people overnight. While they're asleep, this drip feeds in and then you're giving food-based zeitgeber in exact opposite of the light-based use even though, actually, in fact in intensive care units, they often don't turn the lights off because they're running 24 hours a day. There are things like that which I think could be more easily improved.

    When they've looked at that, people who were fed overnight have an increased risk of fatty liver and insulin resistance, all that kind of stuff because they're giving cues out of synch, and which transitions me over to questions on nutrient timing. I wanted to start by asking you a question about carb backloading which I'm sure you must have an opinion on. I know you like to lift. You have a PhD in circadian biology or you nearly have a PhD in circadian biology, so particularly your thoughts on the general tip in that arena which is that you should only eat your carbohydrates when it's dark outside. What do you think about that?

Greg:    I think that for most people, that's bad news. That by itself will sound like a very controversial statement so just let me expand on it. What you have to consider is that these people are training in a certain time of day too, so after exercise, of course, you see increase in GLUT-4 activity and skeletal muscles and so on. You have all of these changes that are happening to improve somebody's carbohydrate tolerance. Their response is to feed it.

    If somebody goes to the gym and does a heavy weight training session or does some high intensity interval training, whatever it might be, bout of activity that expends a fair amount of energy and which is going to encourage nutrients to be favorably partitioned then that might offset some of the effects of the circadian system on somebody's glucose tolerance, their lipid tolerance, whatever, but if you look in isolation at how your body clock programs your responses to feeding during the day then I have to think that all the evidence suggests that you're better off eating during the daytime.

    So I'm going to say the daytime, it's a bit vague obviously because people who live at high latitudes are going to have short days or long days. What I mean is, let's say, you maybe start eating two hours after you wake up and you stop eating two hours before you go to bed. That's when your body is going to be relatively well-programmed to eat whereas if you're eating when you'd otherwise be sleeping. You've got all this change which is going to impair your response to feeding.

    Anyway, going back to carb backloading, we need studies on this kind of thing in which people are followed over time, and exercise itself is a variable which hasn't really been thrown in the mix yet, so circadian biology is that people are trying to build on scientific findings by changing one thing at a time. If you throw an exercise training program in the mix too then that's one more variable to consider, and that makes the study more difficult to do.

    Lots of people, they seem to respond well to carb backloading and for that reason, I'm not going to just write it off, but fundamentally, what happens later in the day? Your resting metabolic rate is going to be lower. Your insulin secretion by pancreatic islet cells is going to be lower. Your lipid tolerance is going to be lower. You're going to be less likely to be physically active, in general, and that's important because actually aligning your physical activity with when you eat is key. You might have some melatonin floating around in your bloodstream, and melatonin is going to worsen your carbohydrate tolerance and so on.

    I don't know for sure but I think that if you exercise late in the day then consuming a fair share of calories and carbohydrates later in the day might not be a bad idea, but in particular on non-training days, I don't think it's the right way to go. I do also think that doing both of those things, training late and eating late is probably going to hamper your ability to get restorative sleep. Just looking at exercise, for instance, you go out and train hard and you see an increase in production of a bunch of weight-promoting hormones in your modulators in the brain. That's going to keep you up.


    You exercise hard, your body temperature goes up, your heart rate goes up, your sympathetic tone goes up, all those things are working against your ability to sleep well that evening. You come back afterwards and you eat a big meal. That's going to amplify the increase in body temperature that's all from the exercise. It isn't going to amplify it necessarily but it's going to prolong it or prevent it from coming down quickly as it would have done otherwise.

    So, again, a slightly rambly answer but I think that in general, my advice would be you're better consuming most of your calories earlier in the day for the reasons the I mentioned, as well as the fact that the actual number of calories that you burn after eating is higher, earlier in the day. If you exercise late and you have to then eating late probably won't be such a bad thing. The effects of it will be buffered by the exercise, but it's probably not going to help you sleep. So, there are practicalities. People work during the day and they often go to the gym after work. Actually, mid-afternoon, late afternoon is really not a bad time to go to the gym because your body temperature is high, you're going to be stronger that time, but doing those things too late, in my mind, is almost certainly a bad idea.

    We still, fundamentally, need to understand if adaptations to these particular patterns of behavior do take place over time, and not all of the literature necessarily points in the same direction with that. There's one example. The University of Surrey published a paper last year. Actually, when people ate later in the day, I think that some of the measures related to carbohydrate metabolism, they weren't significant because when you measure lots of things, you account for that in the statistical testing that you do but they tended towards actually being just slightly better one day later. So it's not like all of the evidence unanimously points in one direction. We still need those studies but for right now, I have to think that the weight of it indicates that it's not wise.

Tommy:    Yeah, I think you made a good point which is the exercise component of a carb backloading approach definitely buffers a lot of the potential issues, and maybe a better example would have been the carb night version which is maybe more for people who are training less but have more of a metabolic type of disease, they're trying to address some kind of pathology. In that case, the advice obviously is the same without necessarily having an exercise component, but the studies that do exist particularly in people who have type 2 diabetes or some kind of insulin resistance, they seem to do better if their carbohydrates are loaded towards the front of the day or earlier in the day than they are later in the day. So particularly in that kind of population, maybe you have some other evidence that disagrees with that.

Greg:    Is that, effectively, a big carbohydrate binge every few days and then otherwise relatively low carb?

Tommy:    Yes, exactly, but only when it's dark outside.

Greg:    Is that John Kiefer stuff?

Tommy:    Yes.

Greg:    Okay, yeah, that doesn't make any sense to me.

Tommy:    Okay, that's the answer that I was looking for, thanks. So maybe we can briefly touch on the exercise component. You obviously mentioned mid to late afternoon is perhaps the body temperature is highest, strength is going to be highest but then you obviously have to counterbalance the stimulating effects of exercise versus later sleep. Do you have some thoughts on -- and there is an adaptive response so people tend to also perform better at the time they most regularly train, so you can overcome it -- thoughts on maybe when the latest people should exercise to make sure that all balances out?

Greg:    Yeah, it's difficult to give hard and fast rules. I think what you want to do is you want to think about anchoring, so the latest relative to what? Because late relative to clock time is going to be pretty useless when you have this big variation in chronotypes between people, so I'll probably look at timing relative to when somebody intends to fall asleep or to go to bed to fall asleep.

    Let's say that tonight you want to go to bed at 10 pm, and it's also going to depend on the type of exercise that you do, so if you go out and do some low-intensity, steady-state exercise, you go and you cycle for a bit in dim lighting and at a relatively low heart rate reserve, for instance, you can do that probably late without having such a strong knock-on effect on sleep. On the other hand, if you go into a brightly lit gym and you do some deadlifts and ten sets of ten squats or something crazy like that, that's going to mess with your sleep.

    So with that disclaimer aside, in general, I am just plucking number out of thin air because I'm trying to think about whether there's some sort of basis that we can use to make an informed decision but nothing really comes to mind. What I'll say is that dim light melatonin onset which is a spike in melatonin usually they see before you sleep basically indicates the start of your biological night, typically occurs about two hours before sleep onset, so you certainly want to finish your exercise before then. If I was going to pick a number out, I'd probably want to keep the end of exercise at least three hours before sleep if you want a restorative night of sleep, but that's with all of those disclaimers [0:50:10] [Indiscernible].


Tommy:    I can think of one study, I think it was students at the University of Washington, where they looked at timing of exercise and sleep, and I think that they actually got that same number. It was three hours from the end of exercise where it wouldn't then affect sleep quality afterwards. So, from first principles, you managed to get the same answers as they did in that study which is pretty nice.

    So maybe we can start to wrap up with some tips from you on how people can improve some of these things. What's the lowest hanging fruit in terms of improving circadian rhythm, where should people start, and do you have any other tips and things that people can use to try and improve quality of sleep and then creating robust anchors in terms of the circadian rhythm?

Greg:    Sure. So if you start with the circadian system and we start with daytime then spending at least 30 minutes outside during daylight is a good place to start. Let's say you're a night owl or, if anything, you want to shift your sleep earlier because you have to wake up to an alarm in the morning then if you could do that before midday then that's probably quite a good place to start. But in principle, the more time that you spend outside during the day, the better. Obviously if you're living in Dubai or somewhere like that then you need to be smart. That's not relevant to most of us.

    Okay, other things, physical activity, so think physically active during the days is going to help both of your circadian system function but also with your sleep too. We haven't spoken about this but if you look at how sleep is regulated, as I mentioned before, you have this sleep pressure that builds over the course of the day, and the main correlate of that is the levels of adenosine in your brain. Fundamentally, the more energy that your brain burns during the day, the stronger the pressure will be to sleep at night.

    Actually doing exercise will help that process. Exercise also heats the body during the day, and that activates these warm-sensitive neurons in the hypothalamus which have sleep-promoting effects and particularly, they promote [0:52:04] [Indiscernible] which just deepens the deepest stage of sleep. So physical activity during the day is going to be really important. I do sound very fast. I won't go so fast, so I'll try and get some more clear points, going forward.

    Anyway, we didn't speak about diet as a zeitgeber, whereas the light-dark cycle is the main time cue for the master clock in your brain. Diet seems to be the main time cue for the clocks elsewhere in your body. I can't say that for sure in humans yet. It definitely appears to be the case in any other animals. The animals they've studied most are rodents, as you might expect.

    So keeping your mealtime consistent is going to be important and, again, if I was going to just give a rule of thumb then I would say, you probably want to wait until at least an hour until after you naturally wake up in the morning to eat your first meal, and you probably want to keep your last meal at least two hours before you go to sleep. Of course no one wants to go to sleep hungry because if that happens then you're basically sending a signal to your body which is going to wake it up. Because if you're short on food and your body is effectively starving then its priority is going out to find food so you can stay alive to pass on your genes, of course. So keeping a consistent eating schedule is going to be useful.

    I wouldn't make it too short. I wouldn't, for example, eat one big meal a day. Also, you don't want it to be too long. As a rule of thumb, maybe consuming all of your calories, and that includes calories from drinks, between a window of about six hours and 12 hours is a good place to start. For instance, that could be between midday and 6 pm, or it could be between 7 am and 7 pm. It depends on your goals.

    In general, I find that people have quite good success with consuming their calories over slightly longer period of time if they have high energy intake, so they're athletes or they're trying to gain weight. Whereas for many people, if they're short and their eating window is a bit then that helps them at least maintain their weight. When they're short then people tend to eat less. They often move around less too, but they do generally tend to eat less.

    So, consistent meal timing, that's going to be, the composition of your diet is important too, as you can imagine. Caffeine is a sleep killer. The half-life of caffeine is about six hours, and the more caffeine you consume, the longer the half-life is, of course. So if you want to go to bed at 10 pm tonight and you consume coffee at 4 pm then the amount of caffeine in your system is going to be half the peak amount that it reached after consuming the coffee, and that's going to mess with your sleep because caffeine blocks the interaction of adenosine receptors and therefore blocks the sleep-promoting effects of adenosine too.

    So with caffeine, maybe capping your intake at about 2 milligrams per kilo which is about a cup of brewed coffee for a 75-kilo person, capping it at that level roughly nine hours before you go to sleep is a good starting place. So if you go to bed at 10 pm tonight, you're 75 kilos then you want to consume no more than a cup of coffee by 1 pm.

    Alcohol is another consideration. Alcohol reduces the amount of time it takes for people to fall asleep but then it tends to disrupt their sleep later in the evening. What happens is alcohol increases the amount of time you spend in non-REM sleep but then later at night when your liver has cleared the from your system, your brain frantically tries to catch up on the lost dream sleep which it should have had earlier in the night. You end up with these crazy vivid dreams but also your sleep fragments. So sleep is not going to be as restorative after drinking alcohol.


    Generic guidelines are 2 units a day for adults which is a pint of beer or a medium glass of wine, and I'd probably want to keep that maybe no later than four hours before you try and fall asleep. That might be hard work for some people but if you can move your alcohol intake a little bit earlier then that's probably generally going to help you improve your sleep.

    Other things, if we now turn to sleep specifically, are temperature, so you want to sleep in a cold bedroom but perhaps counterintuitively, you actually want to raise your skin temperature shortly before you go to sleep because around when you sleep, the temperature of your brain drops and that helps you fall asleep. It drops by about 2 degrees. If you actually raise your skin temperature then what happens is you effectively radiate heat out from your core. You create this radiant where your core is not so warm but your skin temperature is increased and then it just flows out of your core as a result of that, so having a warm shower or a bath relatively soon before sleep will help you with that.

    Then something as simple as keeping socks on at night has recently been shown to reduce how long it takes people take to fall asleep then also to sleep longer as well. The reason is just that in your hands and your feet in particular, you've got all these little blood vessels, anastomosis, and they have big surface areas too, so your hands and your feet are very well built for you to gain or lose lots of heat through, so keep your socks on even if you don't look very cool.

    The other thing is, if we're now thinking about bedtime, of course removing sources of light from the bedroom is going to be useful, especially blue light. If you have blue light in your lamps or whatever then maybe putting tape over them if you can't get rid of them, but otherwise doing away with those. Using apps like f.lux on your laptop or Twilight on your phone or, what's the name of the iPhone?

Tommy:    Night Shift.

Greg:    Night Shift? Yeah, using Night Shift on an iPhone, all those things are going to help. You want to reduce the brightness settings as low as possible too. If you want to go that route, you can use blue-blocking glasses. I don't personally. You can just dim the lights also. Of course in the future it's going to be cool because you'll have these smart lighting environments, hopefully. They're getting more widespread and maybe even the norm one day. So those are probably the low-hanging fruit for most people.

Tommy:    That was great, and you mopped up all the other areas that I'd been thinking about asking. Obviously we don't want to take too much of your time, so that was perfect. Where can people find out more about your work? Maybe tell us a little bit about upcoming stuff on humanOS that you're excited about. Obviously as content director, I'll either putting that kind of stuff together. I myself certainly am very interested to see that, and I'm sure the other people listening will be too.

Greg:    I'm delighted to hear that. Yeah, so people should come over to to find more of our work, and what am I excited about? I'm excited about doing a deep dive on sleep, so recently I've been compiling lots of information related to sleep and we're thinking about how to best help people improve their sleep and keeping all that information in one spot.

    So we have upcoming courses on sleep which will be out relatively soon, but then also there will be more sleep content too, and the purpose is just to have a one-stop shop where people can come and find out everything they need to know to help improve their sleep, so how can I fall asleep faster, how can I improve my total sleep time, how can I improve my sleep quality, how can I refuse how sleepy I feel during the daytime, how can I feel reinvigorated the next day and so on. I'm pretty excited about that.

    Otherwise, I'm speaking shortly in Sweden on behalf of humanOS, which I'm pumped about, and it's going to be a lot of fun I think. It's the first event of that kind that I've done. I'm really looking forward to it. Other humanOS developments, we're just going to keep rolling out more useful content, I hope, all the time. I actually love working with humanOS because I really believe in the vision of the CEO, Dan, and what a lovely bunch of people that are really dedicated to the cause.

    I think that it's a void that needs to be filled because people are so often quick to hop on bandwagons today in this particular culture and everyone will join the latest craze but actually fundamentally, we know what we need to do and that is behave in certain ways. We need to eat more vegetables, be physically active, attend to our sleep, prioritize these things, and we need tools that will increase our awareness of our behaviors. That really is where humanOS comes in. It's a one-stop shop where people can come to find out, what do I need to do, am I doing it, is it working and, yeah, I'm pretty pumped about tracking on with all of that work.

Tommy:    Fantastic. I've spent some time looking at the humanOS system recently and speaking with Dan. I think it's awesome. Hopefully we'll be doing some work together soon on it. Certainly I'm excited about that too. So, thanks again, Greg, I encourage everybody to go and find your courses, find your other information, maybe read your papers. We'll certainly link to them in the show notes if people are super interested in reading your work. This has been fabulous, thanks so much for your time.

Greg:    Thanks very much, Tommy. A pleasure.

[1:00:22]    End of Audio

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