#579: Is Your Chronotype Hard-Wired or Modifiable? And What Does It Mean for Health?

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Hello and welcome to another episode of Sigma Nutrition Radio. My name is Danny Lennon, and of course joined by Dr. Alan Flanagan. Alan, how are you doing? Very well, thank you. I have two groups down from our current study. Two to go. That'll be an interesting data set when we're finished, looking at the kind of influence of fasting duration before breakfast, essentially, before the first meal of the day on synchrony in circadian rhythms in metabolism. So it's an interesting study. Cross over, both groups have done one of their respective conditions, and we will be welcoming back another group this coming weekend Saturday, and then we will welcome the other group back for their crossover early October, and then we'll be done. So so far so good, touch wood. Given from some of the details that you've shared so far and how the study is running, I'm sure there's lots of interesting stuff that we will discuss at our future time point, and in a doubt you'll get some interesting publications from that. And of course, some of that relates to what we're planning to discuss today, the whole concept. Some of the things related to chronobiology as we'll get into, of course, on this podcast, many of our regular listeners will know we've addressed aspects around chrononutrition in various episodes and quite in depth. And one part that's being brought up from time to time relates to chronotypes, and we've had some requests from some of our premium subscribers to maybe go into some of that component in a bit more detail. And so the idea today is maybe leaving aside the specific sub-topic of chrononutrition, coming back out to think more about chronobiology, but focusing in on what chronotypes are, what they mean, and then some of the implications of that. So maybe the best place to start, is obviously when we say chronotype, what exactly is that? What is the best way for people listening to think about what a chronotype actually is? Yeah, so the term itself does provide a degree of giveaway in chrono, obviously, time, time type, so to speak. And is chronotype essentially denoting an individual's behavioral expression of their sleep-wake timing preferences? We would often colloquially refer to this concept as a morning lark for a kind of a morning chronotype, or an early chronotype, as we'll be referred to, or night owls, which would be a late or an evening chronotype. And I use the word behavioral expression quite particularly, because this is related to the period of their internal biological time, so to speak. So the sleep-wake cycle provides essentially a proxy, particularly if it's an individual without any time constraints. So left to one's own devices, what would their self-selective sleep-wake timing be? So that sleep-wake timing is a behavioral expression, but it's an expression of internal, largely genetically driven preference for time of day-related behaviors. And this is important to distinguish between some of the previous ways that various questionnaires that could be used in research would assess time of day or diurnal preference, but a preference could be expressed independent. Now they do tend to correlate, but a preference may still be expressed independent of chronotype. So chronotype is a biological construct, and that's quite important. Whereas other aspects of diurnal preference are almost psychological constructs or traits, and this is what distinguishes chronotype as a biological construct that reflects endogenous or internal circadian timing rather than a psychological construct or trait. And so chronotype we can kind of conceptualize it as that external behavioral phenotype expression of your internal circadian timing. So I think that's a really important distinction because we could have, like you say, that psychological aspect where someone says, "Oh, I really like getting up early. I already have a preference for doing that. I set my alarm at six in the morning because I like to be productive and get things going." That is a preference for what that person might like to do, but that doesn't necessarily correlate with their chronotype. It might, but in the sense of this biological phenomenon, you're saying, if we took away those external stimuli like an alarm or like external lighting or whatever the case may be and left someone to sleep and wake at the natural rhythm that they would wake up, there's differences among people and where that falls would be indicative of that internally driven chronotype that that person has. And so they do tend to correlate quite well with, chronotype will tend to correlate quite well with something like diurnal preference simply because an early morning chronotype will tend to exhibit a preference for earlier sleep phase, preference for waking earlier, and generally, for example, there'll be certain psychological correlates like they'll be or feel subjectively more alert and active during the early part of the day, whereas a late or evening chronotype will typically display a delayed sleep phase preference for a later rising and feel most or more alert kind of into the later afternoon evening or even the night for very late chronotypes. But like you said, importantly, there are social clock factors. We're talking about the internal biological clock and a big feature of why this is important for population health is that internal clock then interacts with our external social clocks. So someone like you said might decide, I've listened to Andrew Huberman, and I'm going to get up at 4 30 in the morning and do all these behavior adaptations, but they may not necessarily be congruent with someone's internal clock. So within that before getting into some of that interaction between this internal biology and some of our external behaviors, when we go about measuring someone's chronotype or assessing that, first of all, through if you're running a study or someone is in the realms of research, what are some of the ways that chronotype typically is assessed, and do we have like gold standards for how we might assess one's chronotype? Yes, and there are two and their distinction primarily is in the burden of the measurement versus the ease of the measurement. So the gold standards, so to speak, would be to conduct a laboratory measurement of what's known as dimlyte melatonin onset. And this can be used to determine the clock time at which measured melatonin levels cross a pre-specified threshold. Those thresholds can often be arbitrary. So for example, over 10 pg per milliliter per plasma or 3 pg per milliliter if it's saliva measurements of melatonin, but a more refined measurement because there is quite significant inter individual variation in the amplitude of a melatonin rhythm in an individual i.e. what's the concentration in their plasma, for example, at the peak time point? That very much varies between individuals. So chronotype, if you have the capacity to measure dimlyte melatonin onset in a lab, which is burdensome because it requires, it's burdensome and expensive because it requires repeated blood or saliva samples over probably anywhere from 12 to 16 hours to actually capture that. Typically, it would be calculating dillmo as above 25% of the difference between the peak and the kind of three average of the three lowest values. So it's possible to do that in a kind of field study context if people are willing to provide their own saliva samples and wake themselves up to do that over the cross, but you can obviously see that that would be a bit messy and burdensome on participants. So dillmo is typically something that is confined to laboratory studies. We're measuring dillmo as our primary outcome essentially and in the study that we're conducting right now in our previous November study, but obviously that's not accessible for all research groups. So the other less invasive, obviously less expensive, but very well validated method of assessing chronotype is by the Munich chronotype questionnaire. dated by a professor Till Rohnenberg's group in Munich, and the NCTQ is a questionnaire that essentially asks the same questions, but distinguishes the questions by whether the answer is related to an individual's workday, typical workday, or their free day, which for most people is their weekends. And the reason that distinction is important is because of what we just mentioned, that on an individual's workday, that person may have to wake up at 5.30 in order to get ready and do a commute to their place of work. But on three days, assuming there are no social clock interactions, what would an individual's preferred sleep wake timing be. So this is important because a free day is more likely to represent an individual's internal phase, because they will self-select according to their internally driven behavioral preference. And you conduct those assessments for both workdays and free days, and what the NCTQ provides is a calculation of what's known as the midpoint of sleep. It is based off self-reported sleep wake times, but there have been studies that have correlated NCTQ to Dilmo, and you get an R strength of correlation of.68. So a moderate strength of correlation between the NCTQ and objective measures of dim light melatonin onset. And the calculation for the NCTQ involves correcting for sleep debt. So to describe that concept, let's assume you have an individual and their preference for an eight-hour sleep window is from midnight to 8 am. And that would be their free day sleep wake timing, their absolute behavioral preference that they would like to sleep if left to their own devices. And let's say because of their workday, they wake up at 6 am. So they still get a bed of midnight, they get six-hour sleep, and they wake themself up by way of an alarm at 6 am. This is important because all of the evidence we have suggests that chronotype individuals tend not to modify their bedtime. What tends to be modified is wake time. So people typically do not compensate for if they have to get up earlier by necessarily advancing bedtimes. So what happens is their total sleep duration is curtailed. So if their preference is for eight-hour sleep between midnight and 8 am, but Monday to Friday they sleep six hours between midnight to 6 am, they've accumulated 10 hours so to speak of a sleep debt that is then incorporated into the calculation to determine their true midpoint of sleep or a more reflective midpoint of sleep of their internal circadian phase. And generally speaking, late chronotypes accumulate more sleep debt during the working week because, like I just said, they don't tend to compensate by advancing bedtimes. But early chronotypes also can experience sleep debt by the tendency that people have on weekends, for example, to have later nocturnal social schedules. And so there can still be sleep debt that accumulates in early chronotypes if they would also be someone who's, for example, eight-hour preference would be 10 pm to 6 am, but they're at a social event on a Friday and a Saturday night where they're getting to bed at midnight. So the interaction of their internal circadian preference, largely genetically driven with external social clocks is what creates that sleep debt. That can be accounted for in a calculation of midpoint of sleep using the Munich chronotype questionnaire. And that provides a valid assessment of chronotype that shows a good correlation with objective measures of dim light melatonin onset. One more thing on the measurement because I'm sure given the amount of wearables and technology of people rely on for things like sleep or activity tracking nowadays, I'm sure that we can find some that offer some type of chronotype information. Are any of these validated, or do we know anything where some type of wearable or aquaphase tracking or anything like this has some validity or approaches anywhere close to what the benefit of using a Munich questionnaire would be? I mean, not that I've seen, unless you were using for a field study an actigraph watch, and you're then using that to take the data like an algorithmically driven, a quantification of sleep wake timing, and you're using that to determine an individual's kind of sleep wake timing preference. But those are typically devices that are used in a research context, and I know that some of the technologies is incorporated into some commercially available wearables, and there has been some research using data derived from some of these wearables, but I wouldn't say that the validation necessarily at this point is particularly strong for a specific determination of chronotype, rather than unless it was just a crude determination based on sleep wake timing from that, but it wouldn't be something that potentially would allow for the adjustment for sleep debt, for example. Right. I guess it doesn't either directly speak to that component you mentioned earlier, that it's this inbuilt biological phenomenon. It's more giving us information of if this person is moving or sleeping at these certain times, but that's not telling us whether that's just a preference or not. Or do you mention that there is a genetic component to this? So to what extent is one's chronotype genetic, that is to say is this a solely genetic thing that is set, or how much beyond, can you maybe explain to us a bit about the genetic basis of a chronotype? It is the most important basis, but it's not the sole basis. So the three primary factors that are thought to influence inter-individual variation in chronotype at this point are genetics, which includes sex, different strength of exposure to environmental time cues, second, and then third age. So in the general population, chronotypes follow a normal distribution. They're also considered genetically what's known as a complex trait. So genome-wide association studies indicate that your the phenotype, phenotypic expression of chronotype is influenced by the additive effect of a large number of genes with modest effect sizes that collectively add up to influence, rather than a single monogenic gene that like totally explains a morning chronotype versus a late chronotype. So that is the most important, and there's a few genes that we can mention and come back to that may be important to discuss with some of the associations that have been observed genetically for that. The second is the strength of time cues. So I think our listeners that are interested in this will know at this point or recall that the circadian system synchronizes to the 24-hour day, to the period of that 24-hour day, and it does so by the signaling from environmental cues. So light and dark, the cycle of light and dark is the most potent signal to the central melatonin driven clock in the brain, and then we also have the influence of physical activity, of meal timing, of social cues, and all of these other kind of behavioral factors can influence peripheral clock timing as well. So all of these external inputs allow the system to synchronize to the 24-hour day, but the strength of those exposures is a factor that can influence an individual's chronotype. And so for example, we typically, as human mammals, have a free running period, if there was no environmental signals, circadian rhythms would run for a little over 24 hours. It was about 24.2 hours. And so if you have strong environmental signals, like you are outdoors in natural light exposure all day, for example, you will typically see that with that strong strength of that time cue, which is known in the literature by the German word zeitgabre, literally time giver, that will typically result in circadian rhythms synchronizing an earlier phase to the 24-hour day, whereas if we have weak strength of zeitgabers, which we typically do in Western industrialized countries, we have urban environments, indoor lighting, artificial light exposure, this typically results in the phase of the internal clock drifting later rather than earlier, whereas as I said, when the environment admits strong time cues such as natural light conditions, the internal clock advances by an average of about 30 minutes per 1 hour of outdoor light exposure. Now this is still chronotype dependent. If you're a late chronotype, that shifting forward is not you shifting as forward as an early chronotype, if that makes sense. It's still chronotype dependent. So if you fly from London to Sydney and you are massively for her up to a week, your chronotype doesn't change when you have synchronized and adapted to your new time zone. You remain an even in chronotype, you remain it. But the strength of those time cues can influence the phase, shall we say, of the internal clock timing. And then the final factor, as I mentioned, is age. So adults aged between 21 to around 30 years of age, typically exhibit the latest midpoint of sleep on work days. Adults over 31 and adolescents under 21 years, typically have an earlier midpoint of sleep. On three days or weekends, there's substantial differences between age groups. And this is particularly acute in adolescence. So they typically will delay sleep by about three hours. And we know now that there is a phase delay in adolescence, which is one of the reasons why a lot of researchers in this field are very adamant that things like, daylight savings time are abolished, or there is calls for delaying the start of school timing in order to allow children to cognitively better function. And so it's not just that teenagers are lazy and sleep in for three hours on weekends, it's that they genuinely are sleeping, reflecting their internal preference in that life stage. And then it changes. And then in older adults, there's a kind of shift again over age, over 50 years of age. So there are the three factors in order, genetics, different strength of time, cues, and age. And all of those can go into individual expressions of difference in chronotype. So with that genetic component, we have this, that we have this kind of set genetic component of what we're going to be in terms of that chronotype. But as you mentioned, there's these other factors that can modify or at least see slight changes to some degree, based on the strength of those cues as an example. If we look at that on an individual basis, do we see a variation in how people might respond to that? Or in other words, if we take light as that kind of main exposure, do people differ in how light has an ability to shift that clock? And to what extent do we see variation in that? So the magnitude of the shift with exposure to, for example, strong time cues such as outdoor light exposure, daytime light exposure specifically. The magnitude of this shift does appear to be relatively similar within individuals. It's just that it remains chronotype dependent. So let's say, for example, we have two people, and we have assessed one using a dim light melatonin onset, very robust measurement, and we have a late chronotype whose dillmo occurs at 1 a.m. clock time. And we have an early chronotype whose dillmo occurs at 9 p.m. So quite a big difference between the two of them in their measured dillmo. We would see that reflected in their choice of bedtime and wake time, for example. Now, let's say we take both of those individuals and we bring them camping, somewhere very remote in Montana, and they have no exposure to their phone. They don't have handheld devices or any artificial light, and they are just under natural light dark cycles. What we would see is that shift in that internal clock would advance, like I said, by about 30 minutes per 1 hour of outdoor light exposure. But it would remain chronotype dependent. So let's say, for example, the early chronotype person shifts forward because of the strength of the outdoor light exposure, and their dillmo is now 8 p.m. And the late chronotype shifts forward, and their dillmo is now 12 p.m. So the actual difference, the inter-individual variation between them has remained, but there has been an internal phase shift forward because they're exposed to quite strong environmental time cues. And then beyond that, do we know much about, say, if we have two people, the exact same type of chronotype, the exact same dillmo, and we exposed them to that same condition. You've just outlined where they have this exposure to outdoor lighting. Do we have any evidence to suggest there might be differences in how much that shifts one individual compared to the other, even if all other factors are more or less the same? Or could we expect that the degree of that shift is the same? We would largely expect magnitude of that shift would be similar if we were talking about two similar chronotypes with all other factors held constant. It would potentially differ if other time cues were manipulated or introduced. But if we're assuming that those factors are held constant, then we would expect to see relatively similar interactions with that environmental exposure. And we can see, for example, that in some of the genetic studies in terms of heritability of meal timing or in relation to risk factors and genetic risk scores for evening chronotypes, fairly consistently associated with certain directions of effect or genetic risk scores for less evening or more morning types associated with similar consistent directions of effect. So within a certain chronotype, it appears that the interactions with the environment produce relatively similar outcomes. And the variation that we see relates to inter-coronotype differences, not necessarily intra. Although I'm sure that exists, because at least I would hypothesize that exists, given that this is something that was still making headway in the research with particularly related to the genetic aspects. And there's a lot that you can't necessarily do in humans, because so much of the research that allows us to understand the detailed mechanisms of clock gene architecture and circadian clock architecture comes from rodent studies where you can knock out a gene in their brain and look at what happens. And we obviously can't do that in humans. You mentioned jet lag, which I suppose is one of our most extreme examples of when misalignment happens and this then can set the stage for several problems. And you've also mentioned we can see different phase shifts, whether that's a delay or advanced. Do we have anything to suggest that when there's misalignment due to a phase delay or a phase advance, those, for a lack of better way of phrasing it, would end in differential effects, depending on if it's a delay or an advance that leads to some degree of misalignment? Well, typically what we know, because human free running circadian rhythms tend to drift later than the 24-hour day. What that typically means from a kind of transmaridian air travel perspective is generally going-- and I'm sure most of our listeners probably in their own subjective experience can maybe relate to this-- going west tends to be easier. Again, if we fly from London to New York or Chicago, that involves essentially a delay. It's essentially like staying up later in the day. That tends to be slightly easier on the system. And there is less pronounced jet lag, or it's easier for the system to overcome that kind of delay. Advancing the system tends to-- again, if you are flying east from London to Hong Kong or London to Singapore or London to Sydney, that is more challenging on the system because the realignment that must occur, it's more difficult to advance in that kind of context. And what's really occurring with jet lag is we've got the central circadian clock, which is light driven primarily, and our peripheral clocks, which are very much influenced by behavior such as meal timing, they're misaligned to these environmental time cues in the new time zone. Now, because we're in that new time zone with the timing of these zeitgabers, these cues in our new time zone, we will gradually realign to that. And that does depend on the direction of travel, like I said, so whether it's east or west, and of course, the number of time zones crossed. So the magnitude of adaptation typically is rate limited by melatonin, which, on average, adjusts by about one hour a day to the timing of a new light dark cycle. There is inter-individual variation in that. There is some older jet lag research where they flew people from the east coast of America to the UK, and they had an average adaptation of about 1.3 hours per day. So there will be inter-individual variation in that adaptation. But it's not chronotype necessarily specific entirely, although it could be related to the direction of travel and the number of time zones crossed. So a later chronotype might fare better flying directly from London to LA, which is westbound at a number of time zones, because that kind of delay is possibly something that they would be more suited to, for example. So maybe let's start talking about some of the main health outcomes that we see associated with different types of chronotypes, or where there may be differences in various outcomes based on one's individual chronotype. What are the some of the areas that have been most explored where we see quite a difference between, let's say, that early chronotype versus late chronotypes in some of these primary health outcomes? Yeah, I think an interesting question. posting port of coal or a port of departure for this is the relationship with Dilmo, and I know we've discussed this kind of previously in some resources, but given that Dilmo is the most robust marker of circadian phase in humans, given that we have sometimes inconsistent associations and epidemiology related to later meal timing and adverse cardiometabolic outcomes and consequences, and potentially that inconsistency may be because those kinds of epidemiological analyses are simply relying on the clock time reported by the participant at which they consumed a meal. So let's say for example, you've got an average dinner time and a cohort of 7 pm, but you have a subgroup within that who eat dinner at 9.30 pm, and you've some associations with high risk of diabetes or otherwise, but maybe that's not replicated in another cohort where the late group are eating at 9 pm or 8.30. So is it only the clock time at which meals occur that we should be thinking about, or given everything we've just talked about about inter-individual variation, is it actually more a relationship between an individual's meal timing and their internal endogenous circadian timing. There's a number of studies that have been very interesting and at least mounting some support for this hypothesis, although it's far from conclusive. Two were observational studies by the Harvard group Andrew McKill was lead author on both, and what they looked at cross-sectionally in university students was the relationship between their meal timing, and they used a metric known as the midpoint of energy intake, which is essentially the clock time at which they had reached 50% of their total reported daily energy intake for that day. It was really interesting about their analyses. Their analyses didn't show any strong associations between body fat percentage, which was their outcome, and food intake or midpoint of energy intake, when clock time was the metric that they looked at for meal timing. But when they looked at it in relation to measured dillmo, and they had measured dillmo in a lab in the same participants, there was a significant relationship between the proximity of later timing of energy intake of a later midpoint of energy intake with higher body fat percentage. They have observed this in the two of their cross-sectional studies that they have looked at. So no association between temporal distribution of energy and body fat went analyzed only in relation to clock time, and these associations were only evident when analyzed in relation to circadian phase, again relation to dim light melatonin onset. And of course, we've discussed previously some of Marta Garele's research, which, to kind of summarize some of their large intervention trials, has shown associations with insulin resistance and impaired glucose tolerance from both exogenous melatonin supplementation and from measured endogenous dim light melatonin onset. So there appears to be some relationship between elevated melatonin levels endogenously, and potentially elevated melatonin levels from taking an exogenous supplement and impaired glucose tolerance. And there are mechanistic reasons why that might be in terms of melatonin receptors in the pancreas and insulin secretion, etc. So I think that's a very interesting aspect of this literature and something that may be able to explain some of the inconsistencies we've seen in epidemiological analyses that have only considered the clock time of a meal or energy distribution. And there's some additional support emerging from that in recent years in relation to certain genes. For example, the epic spain chrono diet study, they looked at 12 genetic variants associated with six different circadian genes, calculated a genetic risk score for more evening like chronotypes, or less evening like chronotypes, and found higher risks of obesity in the evening risk chronotypes. That is something that has been observed observationally as well, just in perspective analyses that have used immunicronotype questionnaire and related it to meal timing. And so there's some signal in the noise here for the interaction between circadian timing and metabolic risk that may be genetically mediated as well. And of course, the kind of real impact of these genes is likely it's not that being a late chronotype per se is associated with these higher kind of risk profiles. I think that's important to state. It's the interaction between having a late chronotype and environmental, social time interactions that precipitates some of these potentially adverse impacts of the interaction between being a late chronotype in a social world that is essentially designed between work start time, school start times and everything towards an earlier phase of the day. And that's a crucial thing that is worth maybe us digging into a bit. If people do want to get into the real details of some of that aspect around melatonin and glucose tolerance that you've raised, we have a few episodes specifically on this and looking at martygarolates timing model in quite some detail. So I'll link to those in the description for people listening. They're definitely worth going through. But some of those key things that you've outlined. One was that looking at someone's that say dim light melatonin onset versus clock time is more instructive in this sense. For example, we could take two people that have the same meal at, let's say, 8pm, but knowing the potential impact on their glucose response that could be different depending on if that person has an earlier or late chronotype because of when their melatonin is likely to elevate. And so we could foreseeably have yet the same meal time by the clock. But the response that an individual may have is likely going to be more mediated through their rise in melatonin that's going to correspond with their chronotype as opposed to it just being because it's at 8pm per se. Yes, exactly. And again, it's this kind of interaction between chronotype, the underlying kind of genetic drivers of behavior and/or that expression and the kind of social world, so to speak. That does appear to be a factor that explains some of these associations that you would typically see. For example, late chronotypes associated with greater risk of obesity associated with less or lower diet quality associated with some of these kind of adverse behavioral, like lower physical activity levels. But again, the cause effect direction here is really important. And at this point, it is likely the hypothesis kind of points more to the fact that those adverse consequences are themselves a consequence of the circadian disruption and dysregulation that a late chronotype experiences by having to force themselves to get up at 6am for work or whatever. And so all of these kinds of consequences flow from the interaction between being someone who might want to left their own devices, sleep from 1am to 9am, right, and their interaction with the social world forces them out of that preference into a series of kind of sleep wake timings or whatever, that accumulation, heard sleep quality, downstream effects on appetite, poor diet quality, energy intake, et cetera, et cetera. And that's the crucial thing that it's not an inherent characteristic of, let's say, a late chronotype that it is something inherently unhealthy or driving any of these risks in that if you gave someone that perfect situation where they could wake and sleep at those times, they could do activity at the time that they naturally would, that the world was geared around that, those risks would probably not be evident, but it's rather placing someone with a late chronotype in how society is currently structured is going to create some of that mismatch because they have to get up a time that is not natural or they have to change all the other things that come off the back of that. And so I think we could then potentially see depending on someone's chronotype that there might be both advantages or disadvantages for certain behaviors. So the, I think the example of someone with a late chronotype, the disadvantage of having to get up, say, very early for work and all those are quite intuitive, could we then see on the flip side, let's say this common discussion around late night eating and having a meal later towards night, potentially, if we're just looking at that, would that be something that is even more detrimental than someone with an incredibly early chronotype in that they're likely to have their deal mode earlier? And so they would get more of a negative response than someone with a real late chronotype if they both ate a dinner at 9 or 10 pm as an example. Yes, and this is where I think the direction of the research and the experimental studies considering melatonin, either endogenous or exogenous supplementation, like we've discussed before, I think where this appears to be pointing in a direction of. is that it's likely the interaction. So previously, we've been focused on clock time, actually just saying broadly, for example, do not eat at nine p.m., right? That may actually not, because it's too blankish, it's focusing on clock time, rather than an internal biological time in a given individual. So for someone who's dillmo, it doesn't occur until, let's say midnight, then that nine p.m. meal conceptually could be the same as an early chronotype, whose dillmo occurs at nine p.m., having their dinner at six p.m. I.e., it is the interaction between endogenous biological timing and the timing of the meal externally, according to clock time, that is the most important determinant of whether that individual has an adverse metabolic response to that meal or not. And that's really, but that's the kind of working hypothesis, I think, that the McKill Group's research and Marta Garrale's intervention trials have pointed us in the direction of. One of the things you mentioned earlier was around, based on age, we see differences in the likelihood or the distribution of those chronotypes or we see in the example of adolescence, for example, sleeping later, isn't just a function of being lazy, it's more related to this actual biological phenomenon. And that has led to some different conversations and calls for people about the potential problem with school times as an example or how early adolescence might have to get up to be able to get to school and then in a situation where ideally, they'd want to be sleeping longer. And then that, if it causes a lack of sleep, might have not got effects and say cognitive performance, presumably in those hours throughout the school day. Do we see other things related to cognitive performance more generally and diurnal rhythms or that might relate back to chronotype that again, extends more broadly to some of these time of day effects? - It does seem to be something that carries that kind of adolescent life stage associations with cognitive performance have been a big focus because there is a kind of a drive for people to consider at a public health level the possible implications of forcing people with a natural midpoint of sleep at four or five a.m. to actually get up at that time in order to go to school. So this is a whole conversation in that literature and very much emphasizing cognitive performance in that life stage and the benefit to actually doing school when your cognitive performance is more likely to be aligned with that. But it does appear that the cognitive aspects do continue in terms of they are to a degree then chronotype dependent. So let's say the late chronotype advantage is that a lot of reports that you hear from late chronotypes would be that they have a natural preference for working later into the evening. And you would not get that with an early chronotype. So the relationship of that kind of sense of subjective alertness and cognitive function does also appear to be a factor that is chronotype dependent and is not necessarily confined to say like adolescent life stage with that kind of adolescent phase delay and that it would be something that is a characteristic of an individual's chronotype in adulthood, for example, such that an early chronotype with a preference for an earlier rising would typically report. And this is what you see. These types of questions are incorporated into a lot of the diurnal preference questionnaires such as the horn osper questionnaire which will ask people, you know, if you were free to self-select five hours of the day where you feel you would be most cognitively productive and have to do like good work, when would that be? And typically you will see a correlation between an individual with an early chronotype and a self-selection for that five hours being earlier in the day compared to a late chronotype who would opt for later in the day. So it does appear that that cognitive performance rhythms within the course of a given waking period of the day is something that is also chronotype dependent. One of the other areas people have kind of picked up on is some of these associations between some of the psychological outcomes. For example, risk of depression or maybe various mood disorders. In this area, do we again see that difference at a level of associating with different chronotypes? And in a similar fashion to these other outcomes is that simply a result or a consequence of a mismatch with our typical societal setup or is there something else within that? Possibly both. There's always that kind of social clock interaction. And you know, we know that for example, being chronically sleep deprived or sleep curtailed is associated with lower mood and depressive like symptoms, although not necessarily uppercase D depression as a diagnosis. There is a correlation with that as well. I think what's really interesting within this is the fact that there are potentially underlying correlations with kind of personality traits and diurnal preferences and chronotype. So recall that we defined chronotype as a biological construct that results in a behavioral phenotype. And there's been some fascinating research, for example, in looking at associations between either chronotype as measured by the MCTQ or time of day preferences, diurnal preferences look using morning this evening this questionnaire such as the Horn Osberg or the morning this evening this questionnaire, which is literally just called that. And looking at, for example, the big five personality traits or the big five inventory. So you've got the key constructs within that of extroversion and introversion, neuroticism versus stability as the two dominant personality dimensions where, for example, extroversion is defined by sociability, friendliness, slightly more carefree attitudes and impulsivity and introversion is characterized by more introspection, seriousness, reservedness. And then with neuroticism and stability, you've got neuroticism characterized by apprehension, irritability, worrying, negative effect, and emotional stability is kind of the opposite to that. And there's some pretty consistent associations between extroversion, more consistently associated with early chronotypes and neuroticism, more consistently associated with evening chronotypes. There are within that inconsistencies, but that's the kind of broad contours of the relationships that have looked at these big five factors. With the full big five factors, you've also got additional dimensions like agreeableness and conscientiousness. Agreeableness being good nature and cooperative and conscientiousness being orderly and dependable. And these are broad representations of personality and each dimension represents slightly more specific aspects of kind of personality characteristics. And so again, you tend to see correlations between preference for mourningness and conscientiousness and agreeableness and then eveningness with neuroticism as well. And so like I said, some of these have used time of day or diurnal preference questionnaires. There's also been associations noted using the midpoint of sleep derived from the immunochronotype questionnaire. And they show those directions of effect as well. Yet to what extent does that translate into certain other behaviors possibly? And this is quite interesting. There have been, for example, like analyses that have considered both chronotype, mourning preference, behavioral, big five inventory, behavioral personality traits, and meal timing, for example. And I've shown relationships between conscientiousness and habitual breakfast consumption. So people that score higher on trait conscientiousness, more likely to consume breakfast, possibly because it's in the popular consciousness, the most important meal of the day, quote-unquote. And it's associated with wider health habits. And that's correlated to their time of day preference and chronotype. And so I think that there is some really interesting stuff here that probably can warrant some further research. But there does at least appear to be a degree of relationship between chronotype as a biological construct and an expression of a behavioral phenotype resulting from that and other personality traits and constructs. And this is something that then may relate to adopted behaviors in other domains, such as meal timing or dietary habits themselves or physical activity habits or otherwise. One of the other things that relates to chronotype and this may be beyond the scope of what we're getting to, but relates to things like exercise or athletic performance. Have you seen much of the literature in this area suggesting that on the basis of one's individual chronotype, there would be, let's say, better or worse times for someone to do training or to try and get exercise adaptations? Do we have much in this area? I can say I've looked much into sports performance literature related to chronotype. I do, I am broadly aware that there have been some loose associations between, and again, I'm not sure how strong they are, between some aspects of circadian rhythms that may not necessarily be entirely chronotype specific. specific, but for example, circadian rhythms and resting metabolic rate tending to peak at certain times of day, that may correlate with exercise performance or output. But I'm not necessarily too familiar with the exercise literature. It would be interesting. I think given everything that we've discussed, if you were to ask me without having a familiarity with that literature, what would your working hypothesis be? I think we would kind of end up running with. I don't think you'd wake a late chronotype at 7 a.m. and ask them to max ed on deadlifts like I'm not sure. I'm not sure how appropriate they'd be. It would be a very plausible hypothesis, I think, to state that there may be time of day variation that is chronotype-dependent in terms of at least a preference for performance. But that could likely be overcome by like vigorous warm-ups and caffeine and other external exogenous aids potentially. I don't know. It would be really interesting to see something in that area. Yeah, I even think of like where some teams might have to fly distances to play games and they end up finishing quite late. Would there be a difference in the recovery over those next couple of days of someone who has a late early chronotype? But again, in a lot of those circumstances, I'm sure there's lots that you could do to offset some of that. One final thing just related back to sleep, because obviously we've talked about that. Obviously it's direct connection with sleep and if there's something within someone's life that dictates a different wake time, that kind of an impact. But even beyond that, if we were to give people the preference of when they could sleep, is there anything to suggest that based on their chronotype, they would be more predisposed to better or worse sleep or would we likely expect a similar sleep quality and duration if we just give people the exposure and the time of death that they want to sleep? If we provide them with that, would we expect similar sleep outcomes? Yeah. I think we would end up expecting particularly based on some really interesting research came out during and just after the COVID pandemic and obviously lockdowns were quite a unique social experiment, so to speak, particularly from a circadian biology standpoint, because you suddenly had individuals who were no longer required to commute or were much more suddenly, probably for the first time in their adult working life, essentially in charge of their own schedule. And there were some nice studies that came out showing quite significant reductions in sleep death. That was more pronounced in late chronotypes, because for the first time, probably in quite some time, they were actually able to sleep in accordance with their particular sleep wake preferences. So left to no interaction, so to speak, or no external barrier to that self-selected behavioral timing of the sleep wake cycle in a given individual, particularly a late chronotype, we would I think expect to see that the sleep itself is the sleep, the quality of the sleep itself is not necessarily impaired if that sleep architecture in the context of their overall 24-hour day is kind of allowed to occur when they would like it to occur. So maybe to finish, maybe we can give some kind of practical application here for people of let's say that they've taken that first step and they've went and determined what their chronotype is. They can go and take the Munich chronotype questionnaire and they have a result or they've got some measure where they are fairly confident in what their chronotype is. And now they have to use that within the context of their real life and that may have some degree of conflict with that chronotype. So maybe if we think of two examples, we have the classic where someone is maybe a slightly later chronotype, but because of their work schedule or life commitments, they have to get up very early in the morning, they've just set an alarm and get on their with their day and then maybe try and get enough sleep that night. In that particular case, what are some of the things that you think are relatively good idea to do in order to work with the chronotype they have given their circumstances? It's tricky, right? So I think if you are able to exercise control over your day as someone who maybe works remotely or works from home, then there is more capacity to sleep in accordance with your preference for sleep wake timing. For a lot of people, even if someone worked from home, for example, but they have young kids, that's there are environmental factors, I think we'll consider young kids an environmental factor that could that go into whether they're able to do that or not. I think in the context of not being able to fully align their preferred sleep wake timing to what they're actually able to do, I think being careful to or mindful of like the potential for napping to be really beneficial if that's a possibility, considering I think meal timing as well, and then also considering that the consequences of potentially accumulating a degree of fatigue and kind of sleep can translate into other kind of downstream negative impacts on dietary intake and physical activity, if there's a kind of mindfulness of the disruption that can occur that can be mitigated against. I do think that from a meal timing perspective, most people do have a good handle on kind of when they're hungry in the morning. It doesn't really make much sense to me that a late chronotype, if they had to get up early, would suddenly decide to be an early eat or two, factoring in that they're endogenous melatonins also likely elevated, it's probably not metabolically a good time to eat for a late chronotype if they would like to preferentially wake up at nine and they're waking up at seven, having breakfast at eight is probably not a great idea metabolically for them either. So it would still be, but I think for late chronotypes that are prone to a degree of disruption from the external environment, so to speak, or the external social timing, I think there is a degree of merit in trying to aim for a level of consistency, and although most late chronotypes behaviorally tend not to self-select for an earlier bedtime, even trying to get an extra hour in advance of when one might actually like to go to sleep, could be something that helps mitigate some of the consequences of early waking in the context of late chronotypes. And then if we were to take maybe the converse of that someone who has a really early chronotype, that maybe works in hospitality or the nightlife industry and is therefore going to be working later in the day and getting home and sleeping later, is there anything else that you would put on the radar of things they could consider doing? I think it would be probably similar overall in terms of trying to maintain with the factors that one could control such as their meal timing, etc., like being relatively consistent with that, and perhaps for early chronotypes also considering, I think for both this can be helpful as well, but like a degree of good natural outdoor light exposure, like perhaps up to an hour's worth in the day can be helpful to maintain their overall sense of regulation of the system, but that can be difficult in different parts of the world when it starts getting dark and particularly if they're working late in a kind of artificial light environment and then sleeping late, but it is always a good idea even if it appears to be overcast, for example, natural light tends to be a kind of more potent time queue for the system than not than artificial light. So if they had to sleep late, getting up, perhaps going early after their kind of late sleep for a walk outside for some time to try and get that kind of exposure to try and get the system alert again, but yeah, we're always going to be dealing with really imperfect solutions in the context of people trying to manage whatever their self-selected preference would be relative to the kind of environmental disruption that they have to navigate. Yeah, so maybe it's an idea for study, let's get a late versus early chronotype on the performance of late night night club DJs, who does a better job and see if the late chronotypes are outperforming them in terms of song selection. That is it, Alan, thanks for covering all of this and everyone for listening to this episode. Again, we have multiple episodes that relate to things related to chronobiology, chrononutrition, going through a lot of this circadian biology that we've discussed throughout this episode and more. So I will link to a list of those if people do want to check those out and go back through our playlist on this topic, if it's something of interest to you. For those of you who are premium subscribers, of course, you can get study notes to this episode to go back and cover over everything that has been discussed. And Alan and I will be back in another episode very soon, so hopefully you rejoin us for that. And in the meantime, have a great week. Stay safe and take care. [BLANK_AUDIO]