Shedding Light on Our Circadian Biology with Greg Potter Nathan Rose: [00:00:32.34] Welcome to Metagenics Clinical Podcast. I'm Nathan rose and with me tonight is Greg Potter from the UK. Welcome, Greg. Greg Potter: [00:00:40.53] Good to be here. Nathan Rose: [00:00:42.24] Thanks for joining us. I think maybe just to give a bit of context it's a bit 18:10 over in Brisbane it's the heart of summer, and you're in England, and we're talking about circadian rhythms. Does that tell me where are you? What's the time and what's the temperature over there? Greg Potter: [00:00:58.75] I'm in central London. The time is 12 minutes past 8:00 in the morning ten years probably 10 degrees C It's freaky February so far the last three days it's been about 18 degrees C really wow I know unheard of. I've got friends who've been putting sun cream on in February which is often the coldest month of the year over here. So right now it's great, but I'm not sure how the summer will be it might be an absolute scorcher. Nathan Rose: [00:01:28.77] Maybe by your standards but possibly not ours, anything I could do about it but I want to just discuss how it takes a few attempts to connect because we're trying to get our timing right. We are here to look at circadian rhythm. Nathan Rose: [00:01:42.13] Now you've just completed your PhD in looking at circadian biology so perhaps just give us a bit of a background of your research and we right now. Greg Potter: [00:01:51.8] So my background is actually an exercise science. I did my undergraduate master's in those, and then towards the end of that time, I just realised that I wanted to help people primarily through lifestyle and I didn't know nearly as much about sleep and circadian rhythms as I did about exercise and diet. And so I want to add that strings to my bow so this opportunity came up with the University of Leeds in the north of England, and I finished halfway through 2018, and my PhD was broadly about sleep diets and metabolic health. So I had a few different components to it. One was validation of the dietary recall method. One was a cross-sectional study looking at associations between sleep duration and cardio metabolic health in adults. I did some work looking at melatonin and its possible utility as a prophylactic agent against the development of type 2 diabetes, and then I did a couple of other bits and pieces on the side some related to meal timing relative to sleep-wake cycles and whether that associates with health outcomes. Nathan Rose: [00:02:58.05] Fascinating got into all those. All right, So let's start off about circadian biology. What is the circadian rhythm or circadian biology Greg Potter: [00:03:08.5] So it's decayed in rhythm is just a repeatable predictable roughly 24-hour change in the biological output which is driven by an internal timing system and these evolved in response to predictable environments and cycles. So each day we have 24-hour changes in the light-dark cycle for example temperature and food availability to all as a result of the rotation of the planets about its axis. The issue is that these rhythms when left to their own devices on precisely 24 hours. So what that means is that they need to be reset to 24 hours each day. And if we can understand the most important cues that resetting process that we can better align oscillating rhythms with a 24 hour day. And it's thought that that probably has important health consequences. Nathan Rose: [00:04:04.81] Interesting. All right. So now there's a couple of clocks in the body the central clock, and essentially the rest of which will call the peripheral clocks disrupted the central clock to us in what sense synchronize is that. Greg Potter: [00:04:21.63] Yes. So the central clock is structured in the suprachiasmatic nucleus or suprachiasmatic nucleui. Actually it's two structures, and it sits in the front of the hypothalamus in the brain. And the most important Q and resetting this clock is the light-dark cycle. So we have specialised cells in our eyes which are named intrinsically photosensitive retinal ganglion cells, and these contain photo pigment named melanopsin. And this absorbs blue light. And then in response to this signals that information about blue lights back through the optic nerves to the master clock which sits above where the optic nerve is cross and samples information about light exposure to basically keep track of our light exposure history over time. This then relays a signal back to the pineal gland and that synthesizers melatonin during darkness. So melatonin in this way acts as an internal signal of the night time. So a Melatonin is high. It's a biological marker for nighttime, and then this circulates throughout our bodies ourselves. Elsewhere in our bodies, it's biological nighttime because of course not every cell in our bodies is directly exposed to the light-dark cycle. So we need internal time gives us as well, and melatonin is not the only one there are some others like cortisol. For example, is one of them they're also changed in body temperature each day which is probably important to resetting those peripheral clocks that you mentioned and then there are also signals that are relayed via the nervous system too. Nathan Rose: [00:05:59.08] Interesting. So with that melatonin, as you mentioned before our circadian rhythm is roughly over 24 hours, but it's not precise. Do we need that light-dark cycle to try and anchors back to being sync with our environment? Greg Potter: [00:06:15.79] We do we need it to anchor the master clock specifically. So if you take people, and you have to go down into a cave for example for a period of several days where they have no idea what time it is outside, and they do not really explain the changes in lights and change in temperature change the food availability then what you find is that on average somebody's internal clock is about 24 hours and 15 minutes. So what that means is that over time the person's clock would gradually become more and more misaligned with the 24-hour light talk cycle outside. And if you change the timing of food availability, then you can change the timing of these peripheral clocks which you mentioned which are basically all of those clocks that set outside of the master clock in the brain, but you don't seem to be able to shift the timing of the master the clock a great deal. That's been published in recent years showing that so there is some research by scientists at the University of Surrey two years ago and basically they took people through two conditions in which they shifted meal timing by five hours. So both conditions participants had three meals each day in one condition they then shifted at each of those meals five hours later. And what they found is that that altered the timing of some of the peripheral clocks and also the blood glucose rhythm which suggests that those clocks that are involved in regulation of that rhythm also shifted by the time you have the timing of the melatonin rhythm which is a proxy the timing of the master block didn't shift at all. So fundamentally the light talk cycle is the most important key in anchoring our rhythms each day, and then diet timing also seems important for peripheral clocks specifically show. Nathan Rose: [00:08:00.29] And I've heard you discuss a little bit about melatonin. It's probably somewhat stereotyped as this sedative sleeping agent, but it seems to be far more diverse than that and probably not a sedative itself. Greg Potter: [00:08:13.93] Yeah. So it, of course, depends on the species that you're looking at because actually you look at nocturnal animals for example then their melatonin level was all highest during darkness to just that daytime. So it's best to think of it as an internal signal of darkness for that reason I think. But in humans what's interesting is that if you look for example at people who have undergone a pinealectomy where the pineal gland is removed then they scarcely have any circulating melatonin and they probably have a tiny bit because melatonin is not only synthesized in the pineal gland, but they barely have any. However, their sleep seems to to be relatively normal. So I think the best way to think about physiological levels of melatonin is that they gave the time of the sleep-wake cycle. So it's as if they get all the other structures that are involved in the generation of sleep. In line for the sleeping race then they pull the trigger melatonin pulls the trigger, but it doesn't participate in the race of sleep itself. This said if you take exogenous melatonin so let's say you supplement with one milligram of melatonin or 5 milligrams of melatonin or even a lower dose such as 300 micrograms then the concentrations of melatonin in your blood will be dramatically higher than they would be physiologically and at those very high levels. Greg Potter: [00:09:38.65] Melatonin does have some somatogenic effects. But there's that discordance between physiological levels of melatonin and pharmacological levels. I think so melatonin. I would say that it is a weak sleep right. It has effects, so it interacts with orexin and dopamine in the brain. It also seems to facilitate heat loss. So if you take melatonin and it causes peripheral vasodilation and then when you lose heat the temperature of your brain tends to drop. And that's important to entering deep stage of sleep but I think that in general it's much better thought as a marker of the biological nighttime and what we're now seeing is that rather than just being involved in sleep-wake regulation melatonin has numerous other roles to say possibly it's important to immune regulation for example. It's probably also important to metabolic regulation to so, for example, melatonin seems to inhibit glucose stimulates insulin secretion by the pancreas. The reason for this is plausible to prevent blood sugar levels from dropping too low during the biological nighttime. The implication is that if you consume lots of carbohydrate-rich foods for example during the biological nighttime, then your body won't be able to dispose of those as effectively at that time. Nathan Rose: [00:10:59.89] Interesting. We'll touch upon the timing of food shortly. I just want to explore some sleep science. You've looked at now, first of all, let's have a broad look at I suppose the ultimate destruction circadian rhythm comes from shift work. What is epidemiological data showing about shift workers? Greg Potter: [00:11:24.68] I suppose it's probably important to preempt this by saying that shift works a complex exposure scenario it's not just about circadian misalignment. So shift workers, for example, are more likely right to drive when they're tired they're more likely to undergo psychosocial stress as a result of trying to maintain relationships with people who are working daytime shifts as opposed to nighttime shifts. But many people of course shifts it's probably about 15 20 per cent of people in countries such as Australia and the US and England. And. Shift work night shift work specifically has been associated with all sorts of adverse health consequences. Say for example if you look at all of the studies that have been done looking at people who do night shift work, and then they track their health outcomes over time then what you find is that it's associated with increased risk of diabetes increased risk of weight gain, coronary heart disease, stroke possibly some cancers too. So that cross-sectional evidence suggests that this type of exposure situation is problematic and then to actually try to understand the mechanisms, of course, people have tried to experimentally disrupt people's body clocks and then look at the health outcomes that result from that type of disruption. Nathan Rose: [00:12:45.79] And one of those experiments found. Greg Potter: [00:12:51.57] They found rapid changes in a variety of outcomes place metabolic health and cognitive performance. Much of this work's been done by a guy at Harvard named Frank Scheer, and he published a paper ten years ago which basically showed that within three days or so, many of the participants who were previously healthy temporarily became pre-diabetic. And there are different ways of studying this. So, for example, you could say people, and then the first night you could completely invert the light-dark cycle so there now active and eating during the biological nights are immediate. But what Frank Scheer typically does is uses a type of experimental protocol called named forced desynchrony. And what this basically entails is enforcing a light-dark cycle that body's concentrate to. So because our bodies clocks are about 24 hours if the lights dark cycle is about 24 hours plus or minus a couple of hours perhaps, then we can normally re-synchronise with that new light-dark cycle. But if for example all of a sudden you're imposing a twenty-eight-hour light-dark cycle then our clocks run free. And over time you can then understand the relative importance of the timing of behaviour and the timing of the biological clock on outcomes such as blood glucose regulation and so on. And that work is shown in all of these negative consequences that happen very quickly. Various others to such an increase in inflammation disruption to the endocrine system which is very widespread destruction such as gene expression as well. And then when people have brought people into what frankly quite brutal and experiments in which this type of paradigm is imposed over a longer period of time sometimes combined with sleep loss over time, it seems to lead so organ dysfunction. So for example initially you might see an increase in insulin production in order to try and better regulate blood sugar during this time of reduced insulin sensitivity. But then over time, you might actually see a reduction in insulin secretion by the pancreatic beta cells, probably because those cells are starting to fail. So this is starting to give us some strong evidence that circadian disruption per say is a direct cause of some of these health outcomes which have been associated with my night shift work. Nathan Rose: [00:15:22.15] Well, that is now getting a little bit alarming. Now you mentioned to say 20 per cent of the population might work shift, but there's a lot of people who probably have a less than ideal dark and light cycle, and this moves into chronotypes. Can you explain chronotypes and what that entails? Greg Potter: [00:15:45.01] Yeah. So in principle probably the best definition of chronotypes is differences between people in the phenotype expression of behaviours that are regulated by the circadian system. So, for example, we might look at the timing of the sleep-wake cycle and what's important to know is that when you're discussing prototype you're talking about the way you sit on a population distribution relative to others and we know that various factors do influence the timing of somebody's biology. So for example if you look at very young people they wake up early, they go to bed early then timing that the body clock delays during adolescence and people are typically at their latest at the end of adolescence. So actually some people would replace that. You can use chronotype as a marker of the end of adolescence and then after that point people start becoming earlier again and by reaching an advanced age people are often even earlier than they were in their childhood. And there's also a small difference between sexes such that on average women of a given age tend to be a little bit earlier, than men of a given age, and the reason for this is probably just the men or boys have a longer period of maturation. So they keep delaying for a little bit longer. So women for example or young women probably at least about 19, 19 and a half years old whereas men might be at least about 21 or so. And then by the time of the menopause that difference is largely nullified. Greg Potter: [00:17:28.59] What you see especially in the modern environment where we don't have such strong time cues So it's not like we're out living on the savanna and we're spending lots of time in daylight each day. Is that were inside 88 per cent of our lives on average, what you see is that the differences between people become exaggerated because we don't have these strong time cues that are anchoring us to that natural light-dark cycle and because of that the chronotype tends to disperse, and the distribution becomes wider. And this can cause various issues, and some of them, of course, relate to sleep loss because on average our bodies clocks along within 24 hours. If you're under these week time cues then for many people their sleep-wake cycle start shifting later, but if those people then have to wake up for work in the morning at a set time then they'll use alarm clocks that restrict their sleep, and then they suffer all the attendant consequences of that sleep loss. Nathan Rose: [00:18:27.21] So that they experience sleep restriction as you call it. Greg Potter: [00:18:34.23] Yeah much of the time. Nathan Rose: [00:18:35.97] Is there much data on increased risk of chronic disease with those with shortened sleep or those who possess or I suppose live an 'owl'chronotype lifestyle. Greg Potter: [00:18:48.95] Yeah, I think you probably need to make the distinction between an owl lifestyle and sleep loss because of course, it is possible to be an owl and get complete sleep. Greg Potter: [00:19:01.37] It's just that much of the time that's not the case so I suppose that I would probably deal with those two questions separately I don't know which one you want me to speak about first whether it's night owls or the effects of sleep loss per say. Nathan Rose: [00:19:14.91] All right let's start with the night owls vs. the larks Greg Potter: [00:19:17.94] Okay so nights owls have been shown to have a greater risk of various diseases, and if you look for example at all-cause mortality then that was work published last year by Kristen Knutson, and she looked at this huge database that we have over here in the UK called the bio bank. There are more than five hundred thousand people and it I think now an entire study. I think she looked at more than 400000 adults. But anyway she found that being a definite evening type and this is using quite a rudimentary questionnaire is basically asking people are you definitely a night person and definitely a morning person. Are you a bit of a morning person you are between night person anyway people who definitely evening people were at greater risk of psychological disorders, diabetes neurological disorders, the eye disorders, respiratory disorders and overall there was a very small increase in risk of all-cause mortality in the night owls compared to the morning larks, but that's just. One is that in process is cross-sectional data something that people become interested in recent years also such as a related construct to something called social jetlag. Which I'm sure you're familiar with, but in principle the idea is that for many people it's as if they fly one or more time zones on the eve of start of the working week because they have to try and go to bed earlier and wake up earlier to go to work and then the weekend rolls around and they follow their natural pattern and that entails probably going to bed a little bit late sometimes but certainly waking up much later, which is possibly a cause of circadian system disruption. Social jetlag has been associated with various health outcomes of course to so the first very large scale study of this was done by some researchers in Germany led by a guy called Till Roenneberg. And he found that in this population of more than 65000 thousand people more than two-thirds people experience at least an hour of social jetlag and beyond its effects on sleep duration alone social jetlag was associated with BMI. Among those adults who were overweight and obese and then since then we've had other studies which are associated with numerous other cardio metabolic abnormalities, so resting heart rate dysglycemia, dyslipidemia, inflammation excessive levels of cortisol, insulin resistance and all sorts of things. We see similar associates associations in many of those studies of chronic type 2 and the other thing to consider is that it's probably true that both the people who experience high levels of social jetlag and of night owls that they're more likely to engage in negative health behaviours such as smoking alcohol consumption and so on. So it's difficult to disentangle how much of this is due for example to sleep loss but since some of these behavioural consequences vs. the circadian system disruption that might company being a night owl and social jetlag. But in general, those associations seem to be that in rare instances it's been documented that for example being a late chronotype might be associated with better cognitive performance in some populations. But looking at the body of literature as a whole I would suggest that being a late chronotype and experiencing more social jetlag doesn't seem to be bad things. Nathan Rose: [00:24:53.42] So with social jetlag I did see some research exploring whether there was a bit of old age about try and keep a routine and keep continue to wake up at the same time every morning. Is it better for. Could you say for people that say go out on a Saturday on a Friday night to still wake up at their workday times at 6 a.m. or 7 a.m.. Or is it better actually try banks and sleep and sleep in a bit on the weekends. Greg Potter: [00:25:26.2] This seems to polarise people, and I can understand why but at the same time I can't think of a good rationale for one of the perspectives. So my perspective would be sleeping in. You've probably already short on sleep. Honestly get us to get as much sleep as you can when you get the opportunity to try and catch up somewhat. But with that said the issue is that is that if you sleep in, your then exposed to the less light the following day or early in your biological day and also you're likely to pay off some sleep pressure which means your less likely to be sleepy at the usual bedtime that you would have the following evening. Te risk basically is that your sleep-wake cycle might start to shift late. In response to sleep again. So I'd say sleep in, but then as soon as you up get outside spend some time outside in bright daylight because the intensity of the light the very exposed to outdoors is so much higher than what we're exposed to indoors. Just to give you an idea of this is measured in units named the Lux and 1 Lux is the amount of the intensity of light emitted by a single candle that is about one meter for a person and indoors around city while its office might be 500 Lux but outdoors at midday, in the middle of the summer it might be 150 thousand lux. So the difference is enormous in our visual systems aren't very good at picking up on this difference which is why we don't really notice it. However, our bodies clocks certainly do notice it, and the most important thing in synchronising our bodies clocks is the contrast between daytime and nighttime lights exposure. It's not just about the intensity of light the spectrum of lights is important too, and the composition of light we are exposed to indoors versus outdoors probably is a little bit different. So outdoors for example around twilight around dawn and dusk. That tends to be more blue light whereas indoors that's not necessarily the case and then the risk also indoors that were exposed to lots of blue lights at night which in the natural setting we would not be exposed to unless we were living at the North Pole. In the middle of the summer or whatever. So with that in mind the important things to take way really is to spend a bit more time outdoors during daylight especially early in the day. Especially if your sleep-wake cycle tends to be late than you would like it to be and then do what you can to reduce your exposure to nocturnal artificial light pollution and specifically blue light because we know that blue light has the most potent effects on both disrupting circadian systems at the wrong time and also our alertness. So it has an alerting effect probably independent of the effects on our bodies clocks. Nathan Rose: [00:28:20.86] Yeah okay so, let's explore that blue light and the light at night time because there is emerging evidence some suggestion this could be as problematic perhaps as the sleep restriction itself. What's the latest data on blue light. Probably first of all just explain blue light vs. other sources Greg Potter: [00:28:41.5] Yeah so blue lights. It has a particular wavelength. It's relatively short wavelength, and that type of short wavelength light is most absorbed by those specialised sounds in the eyes that I mentioned earlier. And the issue generally now in our modern society and the world, in general, is that artificial light pollution is more pervasive and we're spending so much time indoors, so it seems for example that about 80 per cent of the world's population is exposed to quite strong artificial lights at night. And this area is actually growing, and the intensity of light pollution is increasing too. So it certainly seems to be the case in recent years. Now how is this associated with risk of diseases? Stick with the study because if you gather data using satellites for example that give you ideas about nocturnal on a light pollution, then it doesn't tell you what's happening at the level of the individual. Just because there's artificial light pollution at night doesn't mean that people who live in those areas aren't indoors and sheltered from night pollution. But with that said if you look at these countries and nocturnal light pollution then it seems to be associated with health outcomes such as obesity and there's been a lot of attention in recent years that on the subject of artificial light exposure and breast cancer risk. And I'd say that the epidemiological studies are somewhat inconclusive but mechanistically it makes sense. So if you're exposed to artificial lights at that time, then it's going to suppress pineal glad synthesis of melatonin which I mentioned earlier. Melatonin has important functions obviously in our bodies clocks but also in the immune system. Because of those effects on sleep that I mentioned if our clocks shift later we're going to experience sleep loss and then sleep loss that's going to, for example, dis-regulate the immune system. You end up in this vicious cycle if you're not careful. So there's some evidence for roles of artificial lights at night in obesity and breast cancer. Depression is another subject which is studied a bit recently. So there was a study published last year and looked at elderly people in Japan, and they measured artificial light exposure in people's bedrooms. They found that people who were exposed to more than five locks in their bedrooms are more likely to have depression and there has also been some preclinical research on why this might be the case, and it seems to be that those specialised cells in the eyes are at play and it's possible that the effects of artificial light exposure at night on depression risk are actually independent of the circadian system. So I'd say that the effects of artificial light at night are far less conclusive than those of sleep loss. Sleep loss in my mind is a much more important thing to consider. But these two things are of course interrelated, and there's just been much more research on sleep loss. But I think that it's probably worth speaking a little bit about sleep loss just because as a body of evidence I think it's very persuasive that sleep loss and sleep disruption contributes to negative health outcomes but it's probably the case that no aspects of our biology escape the perilous effects of sleep loss. Nathan Rose: [00:32:33.19] If you want to give us an update on what the data says on sleep loss. Greg Potter: [00:32:40.17] It's vertigo and all sorts of different directions with this. So try to try and keep it somewhat brief but if you look for example at meta-analysis so studies that compile the results of all the studies that have done on the topic and then weight the results according to the quality of the study, then we know the shorts sleep is associated with outcomes such as risk of coronary heart disease. So it seems that each one-hour reduction in self-reported sleep duration below seven hours per night is associated with a 7 per cent increased risk of developing covering heart disease of course the cardiovascular disease is probably the biggest cause of death worldwide. It's thought to contribute to 31 per cent of all deaths. Actually. If we consider some other outcomes, then obesity, of course, is a risk factor for cardiovascular disease and probably contributes to about 7 per cent diseases and. In a meta-analysis published a few years ago of adults, they found that short sleep was associated with a 45 per cent higher odds of developing obesity in years to come. Obesity also risks factor for type 2 diabetes. Type 2 diabetes, of course, leads to blindness stroke and kidney issues all sorts of bad things and each one-hour reduction in sleep duration below seven hours per night is associated with a 9 per cent higher risk of developing type 2 diabetes. In a meta-analysis of nearly thirty-five hundred thousand people, and then the brain, of course, doesn't escape the effects of sleep loss, and people who report sleep disturbances are fifty-five per cent higher odds of developing Alzheimer's in years to come. Alzheimer's is the leading cause of dementia and the leading cause neurodegenerative cause of death worldwide too. So we look at all of these studies and look at all of the course mortality, and I often stop there actually because it gives you some idea of the overall burden of some sort of input on health outcomes. Greg Potter: [00:34:55.16] Then each one-hour reduction in self-reported sleep duration below seven hours per night is associated with a six per cent increase in the risk of dying from any cause. So that's cross-sectional evidence, and I don't mind focusing on one of those in particular if you like I know that before we were speaking today, you mentioned sleep and adipose tissue specifically so I can go a little deeper and that's if you like. Nathan Rose: [00:35:22.55] Absolutely. Sort of sounds almost counter-intuitive there that the most I suppose the passive thing you can do is sleep yet it's currently linked to being overweight. Greg Potter: [00:35:33.55] Yeah I guess it's ironic isn't it. So that was some cross-sectional evidence that we now consider experimental studies then there have been a couple of very good randomised controlled trials in which people aren't allowed as much sleep as they need. So one of these was done by Arlet V. Nedeltcheva in 2010 she was at the University of Chicago. She looked at overweight middle-aged adults, and they basically had two weeks in the lab of calorie restriction, and they were allowed either five and a half hours sleep or eight and a half hours to sleep. And what she found is that those allowed five and a half hours in bed each night lost last of the mass is less, so it reduced sleep loss reduced the proportion of weight loss as back to 5 per cent, and unsurprisingly it shifted the relative substrate utilization towards less oxidation of fat and the people in the sleep loss condition also had higher hunger. So the implication here is that these people are given controlled diets and in the free world it's possible that they would have just eaten more as well as losing less of their fat as fat mass. And these findings were broadly read capitulates recently. So last year Sean Young sats group published a study which tried to better mimic how people lose sleep in the real world. And in this instance that was a calorie restriction group or calorie restriction plus restriction group for the sleep restrictions on your five nights each week because of course, many people lose sleep from Monday to Friday or from Sunday to Thursday do they, and then they try and catch up on the weekend and after eight weeks. Again the proportion of mass lost this fat was greater than calorie restriction groups are lower and the sleep restriction group and they found similar effects on substrate utilisation and leptin was also lower in the sleep restriction group. Now, something else to consider here is the effects of sleep loss on how much energy people consume. And some research is just down the road from our live published a meta-analysis two years ago on studies of sleep restriction and energy intake. And they found that looking at the eleven relevant studies if you consume about 385 calories more each day off to sleep restriction. Which doesn't necessarily sound like much but if you tally that's over the course of a year then that would be how much energy is in 18 kilograms of taxation of course. I'm not suggesting that people here are strictly going to gain 18 kilograms of fat tissue every year because we have various mechanisms in our body which should try and defend against that happening. The other thing we are supposed to consider here is that people respond differently to sleep loss and there are quite big differences between people. So there's been some work, for example, looking at the effects of a single night's sleep restriction on energy intake and change in body mass to and at one end of the spectrum after single lines of sleep restriction you've got somebody you can lose over 2 kilograms of mass and at the other end you've got somebody can gain nearly seven kilograms, and if you look at energy intake then you also see quite big disparities. And what's interesting is that these differences between people seem to be stable over time so if you bring people in once and then have them come in 6 months later then whether they are one of those people who eats a lot more of the sleep restriction seems to be consistent between base lab visits. So why is this the case? There are probably a few different things that play here. One is simply that if you lose sleep, there's more time to eat. There was some just published by David Dinges last year which supported this idea. There are changes in the endocrine system, of course, say it's possible the data are actually aren't particularly compelling, but there's increasing ghrelin which stimulates appetite there's reduction leptin which would reduce appetite there's an increase in endocannabinoids and those are also stimulatory to appetite. But it's not just about how much food people are consuming because people also tend to make wise decisions and this is pretty important actually. And it could compound the effects of sleep loss on metabolic health. So it's unclear what sleep loss affects things like macronutrient composition of the foods that people select. But people do seem to gravitate towards very palatable energy-dense foods, and there's one example of this that I love which is that after sleep deprivation so big it out nicely what some other people purchased more calorie dense foods in a mock supermarket the next day so they would get given a fixed amount of money. When they tally the total number of calories in the foods that they selected it was much higher after sleep deprivation. The reason for some of these changes is probably changing brain activity. So you tend to see increases in activity in brain regions that are involved in reward in response to for stimuli and then also the frontal cortex which this recently evolved part of the brain is particularly prominent in humans seems to communicate less effectively with other brain regions that are involved in appetite regulation. There are lots of things at play. But the net result is an increase in energy intake. And the other thing I should mention is energy expenditure. And it seems that sleep loss scarcely affects energy expenditure. So in that same meta-analysis done by research that King's I mentioned earlier, they found negligible effects of sleep restriction on energy expenditure acutely. But of course over time, if sleep losses leading people to lose fat-free mass and potentially gain fat mass then resting metabolic rate would decline which would probably negatively affect energy expenditure because the main determinant of energy expenditure is surely fat-free mass. It's not a physical activity level. Nathan Rose: [00:41:52.44] Compelling reasons to promote a good night's sleep. I might use that as a bit of a Segway to ask you mentioned earlier that building up sleep pressure to fall asleep. I heard you mention mentioned somnogens what are some key strategies you would consider to prepare and go to sleep to ensure you get adequate sleep Greg Potter: [00:42:18.09] Yeah. So what I would say is it starts during the daytime. And I think this is something that people miss sometimes. So, for example, people often speak about the effects of artificial lights at night. But as I mentioned previously the contrast between daytime nights exposure nights on night exposure, it's very important there. What I would say is that it's, of course, important to build physical activity into your day, when possible do so outdoors. I know you live in a very hot part of the world and it's important in areas such as that to be wary of the fact that especially as somebody of Northern European descent you're at risk of damaging your skins. I'm not saying be reckless and then just go out midday and just work on the tan. But what I'm saying is that if you can spend at least 30 minutes outdoors during daylight then that's a good thing, and for many people who have to wake up to an alarm in the morning it's probably preferable to make that exposure relatively early in your waking day as soon as possible once the sun is up. So being physically active is probably important to building that sleep pressure and there's been some work showing that regular moderate to vigorous intensity physical activity tends to shorter how long it takes people to fall asleep. Improves the quality and then possibly slightly prolonged sleep duration too but you don't want to do very strenuous exercise too close to bedtime. Greg Potter: [00:43:44.88] If that's your only opportunity to do exercise because if you do very strange that size then you increase your core body temperature you'll increase activity in the synthetic branch of the autonomic nervous system and both of those things are going to interfere with your ability to fall asleep and of course if you go to the gym, for example, you're also being exposed to bright light and loud noise at that time which isn't good for sleep. So finish strenuous exercise at least three hours before bed finish moderate exercise possibly two hours before bed and then when it comes to sleep pressure even short naps pay off quite a lot of the pressure to sleep. So I'd say avoid napping if it's not part of your routine and certainly avoid it then six hours or so at bedtime. The other thing to consider doing the daytime is your diets of course. And what I generally suggest is not consuming caffeine within nine hours or so of bedtime. Keep your caffeine intake at about 2 milligrams of caffeine per kilogram of body mass per day. There's a website named caffeine informer which will give you some idea of how much caffeine and commonly consume products. And if you consume high doses of caffeine and that, then you certainly to happen early because the high dose of caffeine you consume the longer it lingers in your body and the more likely it is to interfere with sleep. Of course with respect to alcohol I think a lot of people feel "while I'll consume alcohol it's a sedative it's going to help you sleep" well what you tend to find alcohol as the people do actually pause a little bit Boston and they spend a greater proportion of the early sleep periods in the deeper stage of sleep but then later in the evening once your liver starts clear the alcohol sleep tends to break up and sleep becomes less restorative. And people are more impaired the next day. So current guidance around alcohol is limit yourself to two units of alcohol per day which is about the amount that's in a pint of beer or a medium glass of wine. And I would say stop consuming that within four hours or so at that time. It sounds very odd to a lot of people. I think that's smart and then fluid intake is an important consideration because you don't want to wake up to pee in the evening if possible during the sleep period. So as a rule of thumb stop consuming fluids at dinner time and finish your dinner and stop consuming any calories by about two hours before your planned bedtime. You want to go to bed neither hungry nor full. And I suppose the other thing is to consider when it comes to your diet we haven't really had time to touch on this too much but I would say front load your calorie intake where possible because your body clock regulates various aspects of your metabolism in a way such that it tends the better process the nutrients in the foods that you consume early in your waking day than later in your waking day. Greg Potter: [00:46:38.34] So for example because tolerance is higher in the biological morning than the ball. Good evening. The number of calories you burn in response to sorry the number of calories burned in response to X number of calories consumed tends to be higher in the biological morning than it isn't a biological evening to insulin sensitivity is higher during the daytime. And if you look at studies that have basically taken people through identical dodgy conditions and one in one instance just extends the calories, it can seem at breakfast in the other 50 per cent of calories consumed at dinner, and otherwise, the dots are exactly the same. Same macaroni chain composition and so on after the condition in which people consume a greater portion of their calories in the day they lose more than twice as much weight more than twice as many inches off their waistlines. And that's a blood sugar regulation, and they have better blood lipid regulation too. So it definitely to me makes a lot of sense to assign more of your calories in your waking day and of course that is contrary to how many people eat in the West in particular because a lot of people have very big and this relatively small breakfast probably because that sleep they're not hungry at that time and then moderate sized lunch and so front load your calorie intake. Greg Potter: [00:47:57.21] But also if you're physically active in your afternoon Don't be afraid to assign many of your calories around that bout of activity because this activity has lots of effects on nutrient partitioning which basically mean the calories you consume more likely to end up where you want them to end up and then the other thing is to keep your meal patterns consistent. That seems to be very important to metabolic regulation. Now if we then move to the evening, you want your sleep environment to be uncluttered. That would be good for your psychological health. I think more than anything else you want to remove any unnecessary sources of artificial light from the bedroom blue light as I mentioned is the worst offender. So if you have an alarm clock for them it's blue light for instance then you pick one that emits red light because red light is much less disruptive to your circadian system much less alerting to you. If you have some light pollution through your window for instance. Then consider using blackout blinds. You can use a sleep mask as an alternative or an addition to those blackout lines. And then when it comes to your sleep routine, I think it's really important to give yourself enough time in the bed of course. This is what I would focus on. You can't control how long you sleep for, but you can give yourself a sleep opportunity and be diligent about that. So track your sleep. Consider trying to shift your sleep-wake cycle earlier by exposing yourself to more bright blue lights early in your day. If you have to wake up to an alarm, I would say it's going to use an alarm then actually alarm for your pre-bed routine to try and ingrain good sleep habits. So if you create that routine, for example, starts two hours before your time bedtime. Set alarms then and then once this routine is ingrained, you don't have to worry about that anymore. And then when it comes to pre bad routine I would say dim your lights, so you use dimmers as well you can turn off some of the lights, or you can wear blue blocking glasses if you want to look 'really cool' about two hours before bedtime. Have a digital sunset so devices such as laptops and phones have apps such as Twilight Android phones, night shift my iPhones respectively which will filter blue light from those devices during the scoto period so when it's dark outside, which is definitely a good thing and you can also dim the brightness settings on them too which is going to be beneficial. I would say possibly the main thing that interferes with people's ability to fall asleep is cognitive processes such as rumination. Some of us just can't switch off our brains easily and much of the time that's replaced the work. So for example difficulty for sleep is actually most predominate it starts in the working week and something I find very helpful which is making a list for or the next few days shortly before bedtime. There's a guy at Baylor University named Michael Scullin, and he published some cool work last year on this, and he basically had people make a to-do list in which they listed as many items as possible for the coming days at bedtime and found that when people do that they fall asleep faster. Then interestingly those you listed more items fell asleep fast than those you listed fewer items or they tended to it wasn't statistically significant, but there was a suggestion that that might be the case. So I think that's a pretty useful strategy for those people and then when you're making that to-do-list try to assign tasks that you find stressful early in your waking day whenever possible. So if you have a difficult conversation with your boss for instance if you can do that in the morning, then that's definitely going to be a good thing if later in the day then your mind's probably still gonna be racing about time. It's gonna be hard for sleep. So consider the to-do list and then hot shower about an hour before bedtime so maybe 40 degrees C for 10 minutes tends to help people to fall asleep faster the way it does this is it raises the skin temperature of the extremities by a couple of degrees, and then this helps radiate heat out from the core. Again as I mentioned earlier the brain temperature then tends to drop a little bit faster, and people will fall asleep faster, and you want to keep your extremities warm so, as much as your bed partner is bound to love this if you keep your socks on in bed. Then that probably a good thing for sleep. And then in 30 minutes or so before bedtime do something relaxing. So that could be listening to an excellent podcast such as your Nathan. It could be reading a book in dim lighting, and it could just be hanging out with your partner. You certainly want to avoid anything that you find stressful. The news is especially stressful so don't find myself reading the news at that time. Also, this time around this time keep your bedroom cool so you might want to open a window. You might want to use a fan which I find very helpful because where I live relatively noisy outside. But the fan drowns out that noise alternately you could use earplugs around the time before sleep. To achieve the same purpose but the issue with earplugs is that you often end up just hearing your heartbeat ready loudly. You become very attuned to what's going on inside yourself. So I personally find it quite distracting a little uncomfortable but a fan for me it does the job very nicely. And then if you wake up in the evening using as little light as possible when you go to the bathroom. If you go back to bed, and then you struggle to get back to sleep initially, there's been no research on this, but I find that doing a body scan meditation basically just chills me out. Greg Potter: [00:53:32.63] That type of meditation has been shown to affect the autonomic nervous system in a way that should facilitate sleep. So basically there might be greater activation of the parasympathetic branch of the autonomic nervous system. And to me, mechanistic makes a lot of sense that that type of intervention should help men. If you still can't get back to sleep get out of bed because you want to associate your bedroom with sleep, so do something relaxing in the room next door or whatever so that might be listening to a podcast for instance. Again use as little light as possible and then when you're tired then go back to bed. And then in the morning, you wake up to an alarm. You have to wake up to the alarm 80 per cent of people do wake up to alarms then you want to set your alarm as late as possible because each time the alarm wakes you up, it's a stressor to your body. And for that reason, you should avoid pressing the snooze button and when you get the opportunity to not wake to the alarm as we spoke about earlier please please sleep in and try and catch up on lost sleep. You might be able to fully catch up but do so and then once you up to get outside. Expose yourself to lots of daylights and crack on. So I think that is probably the most important things. Nathan Rose: [00:54:45.5] That's amazing. I think you could rewind that. Hopefully, listeners can rewind that and listen to that again and make a list of all those things you said there; there are some great practical tips. Now we are almost out off time, I just want to quickly touch on, and I know you are a scientist giving very detailed answers. I just want to touch on, you mentioned the timing the front-loading calories the peripheral clock is said to be the most sensitive to the presence of nutrients and the time restricted feeding is becoming popular we have Professor Satchin Panda coming out to our conference Congress this year. What's your, if you can do an elevator pitch on some of the do's and don'ts or your takeaways of the time restricted feeding protocols? Greg Potter: [00:55:40.3] I think I touched on the most important takeaways earlier, but if I'm speaking about the takeaways of the studies that have been done so far then I suppose that what I'd probably say is that the preclinical research that's been done on non-human animals shows all sorts of beneficial effects. So time-restricted feeding is what we referred to in this instance and that typically entails giving animals access to food for up to 12 hours each day. Satchin has done the lion share of work on this subject, and he's found for example that if you give fruit flies access to food for just twelve hours each day and compare that to when they're allowed access to food around the clock. Then as they age they experience lower weight gain, they have better function of the heart and the muscles as well as the muscles outside of the heart, and they tend to sleep better as they age. And this is all despite consuming an equivalent number of calories in the two conditions. He's done some work on mice as well. So if you give mice a so-called high fat diet which is really high fat, high sugar diet, it's just it's a diet that's somewhat reminiscent of the typical western diet. Then it makes the circadian system of the animal function worse, and they tend to spread out their food and intakes. They consume more food when the lights are on which is the sleep period typically. And if you use time restricted feeding during exposure to a high-fat diet then basically the gut microbiota is more reminiscent of mice fed normal chow they gain less weight over time on the high-fat diet the time restricted protects against fatty liver disease and obesity. At least the lower inflammation, better insulin sensitivity, better coordination, better wheel running endurance and interestingly it seems to be the case that you don't have to use time restricted feeding every day of the week to get beneficial effects. Five days of time restricted feeding is similarly beneficial to seven days. The question is, do humans respond the same way? And to be quite honest I'd argued they don't. Based on what's been published so far. Something that we need to consider of course is that these mice are being exposed to unhealthy diets and in humans, that's not necessarily the case. So if you give people the same dietary composition in the two conditions, then you might not find such pronounced effects. And actually there is some evidence in mice that's the case too. So you gave mice normal chow vs. high-fat diets chow then time-restricted feeding doesn't seem to have some beneficial effects when the two groups are both consuming normal chow anyway. In humans, the common way to implement time restrictive eating, so I refer to it as time-restricted eating in humans is breakfast skipping. There have been some very large scale studies of this. So one of them was published three years ago in the American Journal of Clinical Nutrition. They looked at more 300 overweight and obese adults. They just randomly divide them into the breakfast skipping group or a breakfast group for 16 weeks, and there were no differences in weight loss between the two conditions. In my mind maybe the best studies that have been done on this specific subject so far were done by research university off Bath in England. So James Betts was the lead author on the first of these, and they looked at lean young adults, and they consumed zero calories before midday. So that was the breakfast skipping group or at least 700 calories by 11:00 a.m. And after six weeks they found that the breakfast skippers was consumed about 500 fewer calories. But they also burned about 400 fewer calories. As a result, there were no differences in cardio metabolic health no differences in sleep between two conditions. The only thing they found was that. Afternoon glycemic variability so blood sugar regulation was actually that was in the breakfast skippers. And then two years later they published the same type of study design but looked specifically at obese people, and they found again no real differences in energy balance between two conditions. The only difference they found was that the afternoon insulin sensitivity was worse in the people who skipped breakfast. So that's interesting I suppose that one thing to consider is that breakfast skipping means consuming a small proportion of energy early in the day which as I mentioned earlier is probably a good thing. So the alternative would be to skip dinner for example, and last year Courtney Peterson who is at Paddington published some great work on this. They had overweight and obese men with pre-diabetes go through two conditions, so in one they had three meals spread out over twelve hours each day five weeks and the other condition they spread out the same three meals of six hours each day five weeks and they finished the final meal by 3:00 p.m. Greg Potter: [01:00:40.75] So it's very very early in the day and they found that that early time-restricted eating condition leads to better insulin sensitivity, lower measures of oxidative stress, reduced appetite and a very pronounced drop in blood pressures, so morning blood pressure after the early time-restricted eating addition was about 10 millimetres of mercury lower. Which is an effect that's comparable to ACE inhibitors which are drugs that that are used the blood pressure. So I think there's more work to be done. The breakfast skipping certainly is a form of time restricted eating in my mind doesn't seem to be beneficial. Based on the studies that if implemented in a way which is representative of how people practice in the real world but, if people can undergo a form of time restricted eating in which they skip dinner, and that's practical for them. Then there might be benefits to that but, I don't know how many people that is practical food because many people live with their families or whatever and they want to sit around the dinner table with their kids and skip dinner because they think that it might have an effect on their blood pressure or is it more important for them to be with their families. You can always consider these things in isolation, but actually health is about so much more than diet timing of course and social relations are enormously important. Greg Potter: [01:01:58.45] I think that you always need to try and consider these things in the broader context of a person's life and when you do so I'm just not persuaded that time restricted eating is necessarily universally a good thing to do. The instance in which I do think it's like likely to be helpful is for example during the holidays because let's say it's Christmas time and everyone's round and there's lots of really tasty food around. And if you left your own devices and impose no constraints on itself whatsoever all of a sudden you find yourself eating chocolate at 10 p.m. and then the next morning know got a glass of box space at 7 a.m. and you're eating around the clock and your eating all this very tasty food and in these circumstances your diet probably actually somewhat representative of those high fat diets that have been used in those preclinical studies and I think that time restricted eating is a really smart thing to do at those times. When you restrict your caloric period in that way you're also likely to do away with some of those poor of choice and so let's say that you stop consuming calories off at 7:00 p.m. you're probably less likely to drink alcohol in the evening in that case. So it's it's probably gonna have a good effect on diet quality. So that was a very long answer. To what we asked. you asked specifically for an elevator answer on this one apologise. Nathan Rose: [01:03:20.74] It was a tall building. I don't think it's dissimilar to what Professor Satchin Panda will say what I have heard him say before of and what he will probably say Congress but yeah I'm looking forward to hearing his take on all his research. You've got an encyclopedic knowledge there. Probably why your content director for www.humanos.me do you want to give us a quick plug, pretty much of the website you work for and what you do. Greg Potter: [01:04:00.63] Yes so, I've been working with the human OS for a couple of years now. Dan Pardi the CEO is the person who brought me on board. I really enjoy my work. I'm very proud to represent Human OS idea behind what we do is that you could have a situation which people have all these different sources for the health information and for tracking their health behaviours and the health outcomes. But we want to try and consolidate everything in one place. Human OS is somewhere; we can go to find out what you need to do to be healthy. For example, we have blogs on various subjects which I greatly contribute to. We have podcasts as well; the podcast is the official podcast the sleep research society and the Canadian sleep society. But we have various topics on it, and then also we have courses that explore these subjects in more detail and guides that do away with details and just focus on what to do. So try and give people that type of information. That's primarily what my job centres around. But then an issue is that sometimes people know what to do. They don't know how to act on it. So take the example of diets maybe you know the consuming paleo diet is likely to be a good thing for you, but you don't know how to cook. We have a course on cooking for example which should help with that process. And then the platform which is a web application integrates with various different wearable devices such as fit bits so people can track their sleep on the platform the physical activity too. You can also do so manually if you like. And then this year we'll probably start to help people track their health outcomes on the platform too. The question really is which health outcomes are most important to track? And I'm not sure the there is very good evidence about exactly what is most important to track at the moment because there are just so many tests out there. We are in the process of trying to narrow those down because we really want to focus on the most important things for people to focus on because people micromanage their health and actually be better off probably worry less about minutiae and just focusing on those big rocks and otherwise leading enriched lives. So that is a little bit about the human OS. I know that you were speaking before the call - we have a discount code to the listeners who you wish to give Human OS a go so you can sign up for free and that will give you access to the tracking tools and also to our introductory course and the blog and the podcast are free regardless of whether you're a member. If you wish to have access to everything then you can sign up for a single dollar US dollar for your first month, and that will give you access to everything on the site, and you will use the discount code: 'metagenics' to do so. Ok so, come check it out say hi. Otherwise, you can follow us on Facebook and Twitter. I have my personal Twitter account, but it's probably only really of interest to people who are scientifically inclined because I normally just share studies that I found interesting that handle for that is just @GDMPotter. But I'm always happy to try and answer any questions and make myself handy if I can. So don't be afraid to get in touch. Nathan Rose: [01:07:15.03] Brilliant! Yeah your HumanOS.me the content there is incredible. The tutorials and all the education areas are amazing. Well, it's been a few attempts we had tried, but it certainly was worth the wait for me. Greg, I really appreciate all the insight and information and diving into the complexity of the science and having those clear simple but really profound strategies particularly for promoting restful sleep. So thanks for your time I'm about to sign off for the day, but you're about to start. Yeah, I really appreciate you coming on and spending some time with us today. Greg Potter: [01:07:49.65] Yeah absolute pleasure Nathan. Any time. Thank you. Nathan Rose: [01:07:55.05] Thank you for listening to the message and clinical podcast. Find us on iTunes and leave us a review join our Practitioner only Facebook group to be informed of new podcast releases. Keep up to date with key industry updates and more. Visit metagenics.com.au to find useful links and resources relating to this podcast and sign up for our email newsletter.