About Our Guest- Dr. Steven Lockley – Fix Your Sleep

Steven W. Lockley, Ph.D is a Neuroscientist in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital and an Associate Professor of Medicine in the Division of Sleep Medicine, Harvard Medical School. He is also an Adjunct Professor in the School of Psychological Sciences at Monash University in Melbourne, Australia, and an Affiliated Faculty member of the Center for Health and the Global Environment, Harvard School of Public Health. He received his B.Sc. (Hons) in Biology from the University of Manchester, UK in 1992 and a PhD in Biological Sciences from the University of Surrey, UK in 1997. He joined the faculty at Surrey in 1999 and the faculty at Harvard Medical School in 2003. “ The problems caused by jet lag cannot be tackled using generic advice, which is oversimplistic and can often be counterproductive, making jet lag worse. Each traveler and trip is different and requires a personalized approach taking your sleep pattern, chronotype, flight plan, and a range of personal preferences into account. — Steven W. Lockley, Ph.D. With nearly 25 years of research experience in circadian rhythm and sleep, Dr. Lockley is a specialist in ways to reset the circadian clock, particularly the role of light and melatonin. He has studied the effects of light on the circadian pacemaker extensively including the role of light wavelength, timing, duration and pattern. This work has led to development of ‘smart’ lighting applications designed to improve alertness, safety and productivity. He was also the first to show that daily melatonin administration could reset the biological clocks of totally blind people and treat non-24-hour sleep-wake disorder (N24HSWD), a serious circadian rhythm disorder. These studies inspired the clinical trials that led to the approval of tasimelteon, a melatonin agonist, as the first FDA- and EMA-approved drug to treat N24HSWD in the blind. Dr Lockley has also studied the impact of circadian disruption, long work hours, sleepiness and sleep disorders on performance and health in occupational groups, including doctors, police and firefighters, and has led several workplace interventions that have reduced workplace errors and injury. He also advises NASA on how to alleviate jetlag for astronauts traveling the globe and how to reduce the problems associated with shiftwork at NASA Mission Control. Dr. Lockley has published more than 150 original reports, reviews, chapters and editorials on circadian rhythms and sleep and his research is funded by NASA and the National Institutes of Health (NIH) among others. He has won a number of awards including a Wellcome Trust International Prize Research Travelling Fellowship, the Sleep Research Society Young Investigator Award, the Healthy Sleep Community Award (as part of the Harvard Work Hours Health and Safety Group) from the National Sleep Foundation, the Harvard Club of Australia Foundation Harvard-Australia Fellowship, the Taylor Technical Talent Award from the Illuminating Engineering Society of North America, and two awards from NASA: the Group Achievement Award (as part of the Chilean Miners NASA Rescue Support Team) and the Johnston Space Center Director’s Innovation Team Award (as part of the ISS Flexible Lighting Team). He co-edited the first textbook on sleep and health ‘Sleep, health and society: From Aetiology to Public Health’ and recently co-authored ‘Sleep: A Very Short Introduction’ from Oxford University Press.

Full Podcast Transcription

Dr. Steven Lockley 00:00
So it’s really important that we minimize electronic device use for as long as possible before bed and ideally for two to three hours before bed because then you allow the natural melatonin rhythm to rise and provide that signal of darkness to the brain. And so for as long as possible before sleep, we should be minimizing any light exposure and certainly use of electronic devices.

Diva Nagula 00:24
Hello and welcome to a another episode of From Doctor to Patient. Today, I am pleased to have Steven Lockley as my guest Steven Lockley, PhD is a neuroscientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and an Associate Professor of Medicine in the division of sleep medicine at Harvard Medical School. He’s also an adjunct professor in the School of psychological Sciences at Monash University in Melbourne, Australia, and an affiliated faculty member of the center for health and the global environment, Harvard School of Public Health. He received his BSC in biology from the University of Manchester UK in 1992, and a PhD in biological sciences from the University of Surrey UK in 1997. He joined the faculty of Surrey in 1999, and the faculty at Harvard Medical School in 2003. The problems caused by jetlag cannot be tackled using generic advice, which is oversimplified and can be often counterproductive. Making jetlag worse, each traveler and trip is different and requires a personalized approach, taking your sleep pattern chronotype flight plan and a range of personal preferences into account. Dr. Lockley with 25 years of research experience in circadian rhythm and sleep is a specialist in ways to reset the circadian clock particularly the role of light and melatonin. He has studied the effects of light on their circadian pacemaker extensively, including the role of light, wavelength, time, duration and pattern. His work has led to development of smart lighting applications designed to improve alertness, safety and productivity. He was also the first to show that daily melatonin administration could reset the biological clocks of totally blind people and treat non 24 hours sleep wake disorders, which is a very serious circadian rhythm disorder. These studies inspired the clinical trials to lead to the approval of tasimeltion a melatonin agonist as the first FDA and EPA approved drug to treat non 24 hours sleep awake disorder in the blind. Dr. Lockley has also studied the impact of circadian disruption, long work hours, sleepiness, and sleep disorders on performance and health in occupational groups, including doctors, police and firefighters and has led several workplace interventions that have reduced workplace errors and injury. He also advises NASA on how to alleviate jetlag for astronauts traveling the globe, and how to reduce the problems associated with shift work at NASA mission control. Dr. Likely is published more than 150 original reports reviews chapters and editorials on circadian rhythms in sleep, and his research is funded by NASA and the NIH among others. He has won a number of awards, including a Wellcome Trust International Prize Research Traveling Fellowship, to Sleep Research Society Young Investigator Award, The Healthy Sleep Community Award from the National Sleep Foundation, the Harvard Club of Australia Foundation, Harvard, Australia Fellowship, The Taylor Technical Talent Award from the Illuminating Engineering Society of North America and two awards from NASA to Group Achievement Award and The Johnson Space Center Directors Innovation Team Award. He co-edited the first textbook on sleep and health called Sleep Health and Society from Etiology to Public Health and recently co authored Sleep; a Very Short Introduction from Oxford University Press. Steven, how are you today? Thank you so much for joining me on this episode.

Dr. Steven Lockley 04:15
I’m very good, Diva, it’s nice to meet you.

Diva Nagula 04:17
Likewise. You’re such an expert on some of things that I have a great passion for. You have such knowledge with circadian physiology, jet lag and sleep so I really can’t wait to take a deep dive and have a nice conversation. But I’d like to first define, what really is circadian physiology and circadian biology and if you could just take a few moments to explain that to the listeners.

Dr. Steven Lockley 04:47
Of course. So the term circadian was termed over half a century ago and means rhythms that last about a day and so circadian rhythm is a rhythm which takes 24 hours to complete a single cycle. And so some examples of rhythms we know to be circadian are things like your daily sleep wake pattern, many hormones such as melatonin or cortisol, your temperature pattern is circadian, many aspects of your metabolism have a circadian rhythm, your mood, your ability to perform well, all of these are controlled by our circadian clock. And what’s quite unique about circadian rhythms is that they are self generated. And by that I mean, we have a clock in the brain that spontaneously generates rhythms, without any help from the outside world. And so we know that there’s a part of the brain, the suprachiasmatic nucleus, which is a group of about 50,000 cells in the hypothalamus in the brain. And each of these cells is a clock. And these cells can generate their own near 24 hour rhythms, and then send signals all over the rest of the brain and body to control the 24 hour rhythms in physiology that we then measure. And so we have this self sustained clock, this oscillator in the brain. And the point of it is to really do two things, we first of all need to make sure that all of our internal rhythms are synchronized. And by that, I mean you need to be awake at the right time to eat at the right time to sleep at the right time. So all of your internal processes work together. And then the other thing the clock in the brain does is make sure that we interact with the outside world in the right way. And so humans are diurnal, we are day active, so we stay awake in the day and sleep at night. And so our clock makes sure that we do that, so that we’re properly synchronized with the outside world. And that’s important because you need to be awake at the right time to find food, or sleep at the right time to recover. And so our clock helps maintain our internal synchrony. But also make sure that we interact properly with the outside world. So we do everything at the right time. And really, it’s so important to our biology that nearly all organisms on earth have a clock have a circadian clock. And if you experimentally remove that clock or damage the clock by, for example, changing the genes that control the clock, organisms do not do very well. They are hunted down more quickly, or they don’t live as long, or they’re not as efficient doing what they need to do. And so our circadian 24 hour clock is really fundamental to all aspects of our biology.

Diva Nagula 07:47
With our busy life in our schedules, I would imagine we are prone to have a disruption in our
circadian rhythm. What are the common causes that you see that can disrupt this rhythm?

Dr. Steven Lockley 08:05
So we evolved this rhythm in a natural world,in a natural environment. And the most powerful environmental signal is the daily light dark cycle. And so our brain through this clock tracks whether it’s night or day tracks, whether it’s winter or summer. And so we evolved to be very carefully in sync with the the light dark cycle. Of course, since the advent of manmade lights, our ability to produce light from a source other than the sun, we’ve now become much more disconnected from that daily solar light dark cycle. And so our use of electric light sources is one of the major causes of circadian disruption because we override the natural cycle by using electric lights to stay up later, for example, when we would normally have gone to sleep. Or in an even more extreme case, stay up and work all night if we’re a shift worker, when the biological clock is telling us to go to sleep. And so light is the most powerful time cue to to reset or synchronize our clocks. And we can use that in a good way. If we time light exposure at the right time. But when we see light exposure at the wrong time, and that can cause disruption and examples of that are shift work and jetlag where we force ourselves to see light at a time that the brain thinks we should be asleep. And so while light is the most important time queue, other things do affect us. So for example, if we’re awake and working at night, we’re also eating at night. And that’s something that we have not evolved to do, we would normally be eating in the day as a diurnal animal, and so that in itself as other consequences. And so we know that if we get away from that natural 24 hour rhythm that 24 hour light dark cycle, then the systems that the clock controls start to become less efficient. And we know that there are consequences for that in terms of the higher risk of chronic diseases, if you’re a shift worker, for example. And so light is key, in all of this, that’s really the most important thing. And really, the clock is expecting us to live on a very regular schedule, as close to the natural, light dark cycle as possible. But as we deviate from that, we cause problems.

Diva Nagula 10:29
It’s very interesting that we live in a society where there’s so much of technological advances moreso than the last 100 years, and then anytime of mankind. And yet, we see so much disruption due to technology and our circadian biology. And you’d mentioned previously, how light exposure can benefit and can take away from our natural processes. What type of light are you referring to that has a an effect on disruption? And then is there a specific light that can actually reset our circadian rhythm?

Dr. Steven Lockley 11:07
Yes, so first of all, light is something that we see. And so all of these light signals, even for the clock, go through the eyes. And in fact, there’s a different photoreceptor that we use to detect that light. That’s different from the rods and cones we used to see, we can talk a little later about some of the mechanisms of how we detect that light. But we detect the light through the eyes and send a signal to the brain to tell the brain is it day or night, or is it winter, or summer, and all night will have that effect. But it can vary based on some of the properties of light. And so we know for example, because this new photoreceptor that’s been discovered, is most sensitive to short wavelength or blue light, the blue light is the most powerful wavelength of light within white light within the visible spectrum. blue light will be most effective at resetting our clocks or alerting the brain, keeping us awake. Now, in the daytime, that’s a good thing. Because you want to be alert in the day you want to be maximally alert and perform as well as you can. And so blue enriched white light, bright blue enriched white light in the day, just like sunlight, is very good for us in terms of keeping our clocks synchronized and our brain alert. But when we get into the evening, and once you start to go to sleep, we don’t want that blue enriched bright light, we want to take away that blue part of the spectrum and have a more radium rich, red-orange looking light. Because that will start to help calm the brain down and prepare us for sleep. Now in the real world, that would happen at dusk, in that when the sun goes down, that would be a very strong signal that it’s night to the brain. But of course, we override dusk, most of us don’t go to bed at dusk, we carry on using light. And so if we choose to carry on using blue enriched light, the brain still thinks is daytime and keeps going with our data and physiology. And that means stay awake, stay alert, be active, have a high heart rate have high temperature, the brain still keeps going with its daytime physiology. And that’s why we then can’t fall asleep. But if we start to remove those blue wavelengths and have a red- orange light, like a fire light or a candle like that, that type of light and dim it down, then the brain starts to realize, well, it’s getting close to nighttime and starts to induce the systems that help us fall asleep. And so it’s not necessarily that the light always has the same effects all the time. It’s about creating that day night contrast. And so we want high intensity blue enriched light in the day, bright days. And then for as much as possible after dusk, dim and blue depleted or red enriched light. And then of course sleeping in darkness because we want to really be in the dark while we’re asleep. And so we can use that information to try and optimize our light dark cycles. Even if we don’t have natural light. We can use electric light in a good way to enhance the blue and the intensity in the daytime and then bring it down in the evening before bed.

Diva Nagula 14:15
And I would imagine that this has some correlation with our internal melatonin production?

Dr. Steven Lockley 14:21
It does and so melatonin is the hormone of darkness. Sometimes people refer to it as a sleep hormone. But it isn’t really sleep hormone because rats produce melatonin at night. And rats are active at night. They’re nocturnal. And so what melatonin does is tell the brain that it’s nighttime. And for us, for humans that means go to sleep. But if you expose your eyes to light when melatonin production starts and it usually starts two to three hours before you go to bed, then the light suppresses melatonin. And that’s part of this signal to the brain that it’s still daytime because you suppress the hormone melatonin, you take away that signal of night, and the brain still thinks it’s day. So anytime that you see light, the brain interprets that as being daytime, even if it’s the middle of the night. And so we really have to be careful about creating that night day cycle, that dark light cycle. So we don’t confuse the brain with with light in the middle of the night. And then it’s starting to induce all this daytime physiology because the only way you would have ever seen light in a natural light dark cycle is if it was daytime, because you have very low levels of light at night with moon or starlight. And so by suppressing melatonin, you’re telling the brain it’s still daytime. And that’s again, one of the reasons why we remain alert and find it hard to go to sleep.

Diva Nagula 15:48
Will supplementation of oral melatonin, counteract this issue of having artificial light depleting
our own internal melatonin production?

Dr. Steven Lockley 16:01
No, it won’t. And so there isn’t really very good evidence that the amount of melatonin is important for melatonin’s internal properties is really the duration of melatonin. And so for example, when we change our physiology between a winter and summer, it’s the duration of night length measured by the duration of melatonin, which tells the brain what season it is. And that becomes very important in seasonally breeding animals. And they begin their reproductive cycles based on season which is based on melatonin duration, the amount doesn’t really matter. Because if you take 100 individuals, there are very wide ranging levels of natural melatonin. And so amount doesn’t really seem to help. It’s really about keeping a consistent schedule, a consistent light dark schedule, which then means a consistent melatonin rhythm, which tells the brain then each and every day, when to go to sleep. Some people have studied melatonin as a soporific or something to help you fall asleep. But it isn’t really very good at that, unless you’re trying to sleep at the wrong time. And what I mean by that if you’re working a normal day shift and you’re trying to sleep at night, melatonin isn’t a very good drug to help you fall asleep. But if you’re a shift worker trying to sleep in the day, or if you’ve traveled across many time zones, and I tried to sleep in a new time zone and let’s say in Europe or in Asia, then melatonin will help you sleep in the new time zone while your body gradually readjust to that new time zone. And it does that by sort of killing the brain into thinking that it’s nighttime, when it when it isn’t. But if you’re producing your own melatonin at night, adding melatonin to that as a pill won’t really help with sleep.

Diva Nagula 17:51
Now, I may be mistaken. But is there a correlation with external melatonin supplementation with suppression of your internal melatonin production?

Dr. Steven Lockley 18:05
Again, not really, there’s not good evidence that you can alter your own melatonin production very much. What that may do is alter the the number of melatonin receptors. And so we know that the clock has melatonin receptors. And that’s thought to help internal feedback to help maintain that local time to maintain that internal tone properly. And it may be that if you take lots of external melatonin, you may down regulate your melatonin receptors and then make you a little less sensitive to your own melatonin. But again, there’s not hugely convincing evidence that you can have any real impact of doing that. It really is about that duration of melatonin rather than the amount. And you wouldn’t affect that as much with that type of effect.

Diva Nagula 18:58
You were involved with some studies where melatonin administration helped reset the
biological clocks of totally blind people. Can you talk about that a little bit?

Dr. Steven Lockley 19:10
Yeah. So as I mentioned earlier, all of the effects of light to the clock go through the eyes. And so if you are unfortunate enough to not have eyes or totally blind and your eyes can’t detect the light, then the internal clock in the brain has no way to synchronize with the outside world. That doesn’t mean that there’s no rhythm. What it means is that the internal rhythm runs on its own time on its own daylight. And all of us have our own slightly different internal clock. And it ranges from around 23 and a half hours to around 25 hours with an average of around 24.2 hours or 24 hours and 12 minutes. And so all of us have a slightly different clock and in fact that clock determines whether we’re a morning or an evening type. People with quicker clock tended to be more morning type and people with slower clocks tend to be more evening time. And so your internal clock determines where you line up in the world if you like relative to the light dark cycle. And then each and every day light resets that clock, if you have eyes that can detect light. But if you don’t have eyes you’re unable to reset in the clock then runs on its own time. So if you’re someone with an internal clock, that is, say 24 and a half hours 24.5, your brain would try to send you to sleep half an hour later every day. Because that’s the timing of the internal clock. So it would say, make you want to go to sleep at 10 o’clock tonight, 10:30, tomorrow 11 o’clock the night after. And that’s fine for a few days. But of course, after 24 days, your body clock will be telling you to go to sleep at 10am in the morning, then 10:30am and then 11am. so on. And so blind people who can’t entrain their clocks. And these are usually people with total blindness, often develop a disorder called non 24 hour sleep wake disorder, meaning that their internal clocks can’t synchronize the 24 hour day. And they run on a non 24 hour day. And that can be really very debilitating. Because while it is fine for a few days to manage with that type of change, it continues for life, and you go round and round the clock. And that can be really problematic. Now, if you’re someone with a long clock or a long period of clock, you may be able to manage it better than someone with a shorter period. And let me give you an example of that. If your clock is running 24.5 hours, that it takes 48 days to go all the way around the 24 hour clock. And so if that was the case, 48 days-49 days is about seven weeks. And so you might have three or four weeks of bad sleep and three or four weeks of good sleep and bad sleep and good sleep and bad sleep as you go round and round the clock. And that would be bad for those three or four weeks of bad sleep, but it would go away again, and then it would come back. But if you’re someone who has a clock, that’s 24.1, it takes eight months to go all the way around the clock. And that may be more difficult to deal with because it would mean you would have maybe three or four months of really bad sleep when you’re out of phase with with the outside world. And then three or four months of good sleep. But for those three or four months of bad sleep that would be really quite difficult to deal with. And so your internal clock determines how long that cycle takes, and can determine the severity of the problem. Now, because lights can’t reset the clock, well what else can we use. And I mentioned before that there are melatonin receptors on the clock. And so back in 1988 the professor who I trained with a woman called Professor Josefina Arendt was the first person to give melatonin to a blind person to try and mimic the 24 hour clock that was missing by light, in order to try and replace the time cue. And she gave melatonin to a blind man every day at the same time for a number of weeks and was able to synchronize his sleep-wake cycle, and really treat his disorder. Now at that point, we didn’t know that it reset the clock. In fact, later studies in that individuals show that it didn’t. But in the year 2000, we were the first group to show that you could indeed reset the clock itself, not just the sleep by giving daily melatonin at the same time every day. And that’s the important part. It’s about providing a 24 hour time cue and giving it at the same clock time every day to replace the light that is lacking. And then more recently, I was the principal investigator of a clinical trial for a melatonin agonist called tasimelteon, the trade name is Hetlioz, and that is a melatonin like drug that we tested in a clinical trial that was then approved by the FDA to treat non 24 hour sleep wake disorder in the blind. And so it works very similarly to melatonin it has the same sort of binding to melatonin receptors. But of course went through all the safety trials and all the requirements of a of an FDA trial before approval. And so we know that melatonin or tasimelteon in this case can reset the clock and bring everything back into line as long as you keep taking the melatonin or tasimelteon and as soon as you stop taking it, you go back to having that non 24 hour or free running cycle. And so it essentially replaces light in providing a substitute time cue.

Diva Nagula 24:54
Does this medicine have any effect on people who are not totally blind? And if so does it have any utility on people who are shift workers or have sleep disorders, any of those occupational groups that may be suffering from regular sleep wake cycles?

Dr. Steven Lockley 25:15
So melatonin has been shown for many years to be able to reset the clock in sighted people, you have to be careful about the light-dark exposure because you could undo the benefits of the melatonin if you give light at the wrong time. But certainly in controlled large experiments, you can shift the clock with melatonin and help people sleep at the wrong time, as I said
earlier, so if you’re a shift worker trying to sleep in the day, melatonin can be useful to helping you sleep if you’re trying to reset yourself when you timezone. Melatonin is helpful at resetting the clock in that way. So if you have a circadian rhythm disorder, then melatonin can be used to help reset your rhythms back to normal. And so other examples of that would be something like delayed sleep phase disorder or it’s called delayed sleep wake rhythm disorder now, but if your rhythms are set too late, and you can’t fall asleep, until very late in the night, melatonin can help shift you earlier. And if you’re someone who has to advance a sleep pattern, melatonin could be used to shift you later. So it can be used to reset the clock in circadian disorders. If though you don’t have a circadian problem, if you have a sleep disorder, which is not related to the clock, then melatonin is not really useful. And so if you have insomnia, but not a circadian problem, then melatonin hasn’t really been shown to pick that effective.

Diva Nagula 26:52
What about those who are suffering from jet lag? I mean, there’s a lot of biohackers that are out there that claim to have the secret sauce, if you will, on curing or alleviating jetlag. And some of these include devices, diet changes, hydration, the use of melatonin and other medicines. What’s your opinion on that? And do you find it effective? Or do you have your own methodology to alleviate jetlag?

Dr. Steven Lockley 28:20
So the short answer to the last part is yes, I do have my own methodology and in fact have an app which allows people to help reset their clocks using light and melatonin. So the basis of any jetlag solution has to be first of all, light and dark. As I said before, it is really only light dark that resets our clocks in in the real world. And in fact, the disruption of light and dark that causes jet lag or shift work is that we force ourselves into a light dark cycle that our body clocks can’t keep up with. That’s why we get jet lag or shift work problems. And so you have to first of all time light and dark properly. And there are ways to do that. And it’s governed by a function called a phase response curve. And a phase response curve is the description of the effect of light in terms of what direction it will shift you. And in terms of how much it will shift you. And just as a general rule of thumb, if you see light late into the evening and into the night, if you see light late and sleep later, then your clock will shift later. If you see light early and shift your sleep early in the morning, you’ll shift your clock earlier. So that’s a simplified summary of what a phase response curve is, but they’re the general principles you start to use. And so by timing light properly, to shift you in the right direction, and avoiding light, when it would shift you in the wrong direction. Then you can start to speed up the resetting of the clock. The second component of that would then be melatonin. As I explained earlier, you can reset the clock with melatonin if you’re sleeping at the wrong time. And so taking melatonin at the right time to help shift you is also helpful. So really, you have to deal with melatonin, to deal with shift work, and jetlag, you really need to reset the clock. And the only things that we know reset the clock are light and melatonin. The other some of the other solutions you mentioned, don’t really have an effect on the clock itself. And so while there were some animal experiments, looking at diet or or looking at fasting, for resetting clocks in mice, there are no real data in humans to show that that would be effective. And then it’s quite complicated to examine, because we need to start looking at effects of fasting on the clock in the brain versus clocks throughout the body. And when we have clocks, in all of our organs, as well as our brain. And so the effects of restricted feeding or mealtimes or fasting is really not very clear yet, in humans. It’s only really been done in, in animal studies. Hydration, yes, of course, that would be a good thing just for general health, but there’s no evidence that hydration affects the clock, in terms of its resetting capability. And then there are other things people have looked at like timed exercise, which is which is I’m afraid quite a weak time, cue, or acupressure, and again, there’s no evidence that that would shift the clock. So really, in order to correct circadian disorders of any type. Light dark cycles are the first protocol and then melatonin and its agonists next.

Diva Nagula 31:52
With melatonin mean, what kind of a dose are you advocating for this resetting? There’s so much literature about the varying doses, there’s people that advocate high doses and medium doses all for different functionality. High doses have been shown to reduce cancer cells, moderate doses have some efficacy in reduction in inflammation and light doses are sufficient to reset the clock. So what’s the dosage that you would advocate for resetting the clock?

Dr. Steven Lockley 32:23
Right, So remember when we’re taking something like melatonin, we’re taking it at much, much higher levels than a naturally occurring amount that we produce. And so really, any melatonin you take is at a pharmacological level. And so the cells, the receptors probably don’t see much difference between those doses, because you’re likely to saturate the receptors with any of the doses we would take artificially, and so higher doesn’t necessarily mean better, because you may have already saturated the receptors with a lower dose. So in terms of phase shifting studies, where people have looked at shifting the clock, they’ve tended to be done between either somewhere between half a milligram and five milligrams. Sso you are probably going to get most of the effects on the low side with a one milligram dose or a three milligram dose, which is a compromise between sort of getting the best bang for your buck in terms of the dose, and keeping the dose as low as possible. And so a one or a three milligram dose, for example, would be fine. What’s important, though, to realize, certainly in the US, is that melatonin is not really regulated, it is classified as a food supplement. And so when you go to a health store or pharmacy and buy melatonin off the shelf, you really no idea what’s in it. It’s not regulated very carefully, and is often sold with other things like Valerian or St. John’s Wart or Vitamin B12, or other supplements. And we’ve no idea of the interactions between melatonin and these other substances. And so I’m not a physician, I’m a PhD, so I can’t recommend clinical therapies. But if people are taking it themselves without going through a doctor, then you would want to choose a preparation that only has melatonin and nothing else. Because we don’t know what the interactions are. People do get side effects with melatonin headaches are side effects, which is often dose related. Some people get nausea, some people get a sort of a hangover feeling. And of course, as with anything, people can have allergic reactions, and so you should never take melatonin for the first time on a plane. For example, you would want to test melatonin at home before you travel. Just in case you have you happen to have an allergic reaction to it. And there are groups of people who really shouldn’t take melatonin so there have been reports that migraine sufferers who can have a poor response to melatonin, people with a primary psychiatric disorder, we don’t recommend pregnant or lactating women wouldn’t necessarily take melatonin. And so you know, there are some groups that you might want to consider not using it. There’s also an increasing use of melatonin in children. And again, I would be very cautious about that, because in animal models, melatonin does interact with reproductive development. And so we don’t really know what happens if pre-pubertal children take melatonin extensively in terms of what happens to their pubertal development. And so it’s not really something I would recommend regularly for children either. So it is a hormone we naturally produce. And it’s a real product that has effects on us. But it isn’t something that you should really take lightly. And really, you should be taking it under the direction of a physician.

Diva Nagula 35:56
That’s really good information. And there’s also various formulations of melatonin, there’s an extended release formulation, there’s sublingual, and there’s just a regular oral dosing. Does it matter which of these formulations for efficacy, or are they all kind of the same?

Dr. Steven Lockley 36:13
Not really, there have not been very many direct studies testing the clinical application of those, the extended release versions are proposed to be more helpful to sleep to help you sustain sleep longer, by providing that signal for longer. But again, what happens at the receptor level, we don’t really know, the faster release preparations are probably more of a discrete signal to the clock. So if you’re trying to reset the clock, quickly, for example, with jetlag, then a fast release preparation might be a more discrete time cue, in terms of trying to help reset the clock. The way of taking it, whether it’s sublingual, or oral or you can even get melatonin patches, and so on and so forth. None of them really probably make much difference. The bioavailability of melatonin is really not that high. But again, all of these levels are pharmacological way beyond what we would produce naturally so the body and brain sees what would see many of these doses as, as very high.

Diva Nagula 37:18
You were mentioning earlier about an app that you have was I mistaken?

Dr. Steven Lockley 37:23
No, no, I did say that. I just didn’t give you the name of the app. Because I have to be careful of conflict of interest declarations. So I do have a commercial interest in the app. And so I won’t say its name. But people can find information around a range of different products that try and help shift the clock.

Diva Nagula 37:42
Got it. And in general, I mean, for people who truly struggling to sleep, and stay asleep, aside from your shift workers or people who have a disruption in their circadian rhythms, what do you suggest from a research perspective and from your own clinical experience?

Dr. Steven Lockley 38:02
So I think the first thing for any sleep problem and I think the first thing the sleep physician would would address with the patient is sleep hygiene is your your general day to day habits. And so many sleep problems are caused by things that we do to ourselves, first of all, rather than a real physiological disorder. And so something that people can can tries to think about things that affect their sleep and try and change those. So we talked about light earlier. And so light is a stimulant. And if you see that light before you go to bed, it’s going to take longer for you to fall asleep. And in fact, you’re going to have less quality deep sleep. And so when we think about light exposure in the evening, what are we thinking of? Well, nowadays, it’s electronic devices. And those electronic devices pump out a lot of blue light, and the light is very close to the eyes. So it’s a very high intensity light that hits your eyes, even compared to a TV that might be you know, eight or 10 feet across the room. And so it’s really important that we minimize electronic device use for as long as possible before bed, and ideally for two to three hours before bed, because then you allow the natural melatonin rhythm to rise and provide that signal of darkness to the brain. And so for as long as possible before sleep, we should be minimizing any light exposure and certainly use of electronic devices and so that means dim light, buy a light bulb that that is designed to help with sleeping so it’ll have a red orange color. There are lots of companies that produce that sleep promoting light. And so use that just have one lamp on in the in the lounge, sit as far away from the TV as you can. And then don’t take your phone or laptop or tablet or TV to bed and give yourself that time in that dim light to calm the brain and prepare yourself asleep. So light it is first and foremost key. Regularity is key. The circadian system has evolved to really reset itself to the daily light dark cycle. And that doesn’t change very much day to day, it’s only going to change by a few minutes a day. And so keeping a stable sleep-wake cycle, which then for therefore means a stable light-dark cycle, because we’re asleep in the dark, essentially. So stable sleep-wake, doing the same thing every day. And even thinking about keeping more regular mealtimes, keeping more regular exercise schedule, all of these things will help to reinforce your circadian synchronization of sleep, and help the clock reset itself to your more natural rhythm. But it isn’t just about the circadian system, there’s another control of sleep, called the homeostatic regulation of sleep or sometimes called Process S to go with Process C for Circadian. And Process S tells the brain really how long you’ve been awake and how long you’ve been asleep. And so the more time you spend a wake, the tiny you become and then the more time you spend asleep, the more alert you become. But we can interfere with that. So light interferes with that, because light is a stimulant. But if you’re using caffeine, for example, caffeine will also be a stimulant and keep you awake longer, pushing off sleep later, making it harder to fall asleep and stay asleep. And so caffeine is a very powerful drug. We overuse it in society, it really props up much of what we do. But it’s the cause often of many sleep disorders. And so really stopping caffeine after lunch is advisable. And then really minimizing caffeine, even in the morning, it would again be advisable and if you’re trying to use it to help stay awake at work or as a shift worker, don’t use caffeine on your days off. So that then has a bigger impact on you when you need it, for example, to stay awake at work. And so regular schedules, regular light, dark exposure, light control, caffeine control, and then other good practices. So doing something relaxing before you go to sleep. And that can be read in a book in a dim light a real book, not an E book, doing some relaxation exercises, yoga and meditation have both been shown to be effective and helping people sleep, even a warm shower can can help you because then you’re able to lose heat, which is a key component of falling asleep. And so having a relaxing ritual, before bed is often thought to be to be good as well. So that’s advice for people who don’t have a formal disorder, but want to improve their sleep. And some of those same principles apply if you have a sleep disorder, and so if you were to see a sleep physician, and complained of insomnia, those would be some of the things a doctor would look at. And there are in fact, some quite good online tools now to help you manage your your behavior. It’s called cognitive behavioral therapy for insomnia CBT-I. And some of those tools are quite effective at helping you manage behavior and getting things regular and getting your sleep back on track.

Diva Nagula 43:27
And lastly, I’m just curious, because there’s so much talk about optimizing your sleep through devices and through manipulation of the ambient temperature. What’s your thoughts on on those types of things like technology specifically, like utilization of like blue light blocking glasses and there’s also technologies that it can modulate your temperature. Do those have any impact positively or are they all just gimmicks?

Dr. Steven Lockley 43:58
They’re not gimmicks, most of them are based in some degree of science. And so if we think first of all, say, blue blocking glasses, it’s true, as I’ve told you earlier, that blue light is most effective at suppressing melatonin and alerting the brain. And so if you block the blue light in the evening, you’re helping to block those negative effects of light. Where they fall short slightly is that it isn’t just blue light that affects the brain, all wavelengths of light effectors, it’s just that blue is the most effective of all those wavelengths. So if you only block blue light, you’re still getting effects from other wavelengths. And so yes, the blue blocking glasses will help to some extent, but it’s not going to be the same as darkness, it’s not going to be the same as very dim light. There’s also software you can put on your computer that will help dim and redden the screen in the evening. But that’s still not the same as darkness. And so those touching devices will do something but it’s not going to completely deal with the issue. When it comes to temperature, temperature is a very important part of sleep regulation. You can’t fall asleep without losing heat. And so when you measure someone’s temperature as they fall asleep, they have a very steep decline in their core temperature. And you need to be able to do that to fall asleep. And so if you’re too hot or too cold, then you will find it really difficult to fall asleep, because you can’t lose heat. And so that’s why grandmas bed socks and a nightcap are a good idea in the winter, because you need to be warm enough in your core to be able to lose heat in your periphery in order to fall asleep. Similarly, in the summer, if you’re too hot, and there’s no gradient to lose heat in the room, then you find it hard to sleep in the summer. And so having a room temperature, which is cooler, will help you to lose heat and help you fall asleep. So these products are often based in in reasonable science. But they sometimes don’t go quite as far as as you would want or don’t really treat the whole problem on their own.

Diva Nagula 46:14
Exactly. Yeah. And that’s that’s the bottom line is we have to take things from a holistic perspective, and not just prescribe these band aids that are often used to try to alleviate sleep disorders. So you have to take everything into consideration when not only diagnosing but treating a sleep disorder. So thank you very much. I appreciate this very, very awesome conversation about circadian rhythms and sleep. For our listeners, if they want to find out more about you. What’s the best way for them to locate you on the net?

Dr. Steven Lockley 46:49
Yep. So first of all, there’s a very good sleep health education site that that we’ve developed at Harvard Medical School, which is www.understandingsleep.org. And that’s free website. It has lots of great information for many of the faculty here at Harvard, on general sleep and sleep disorders. And so that would be a great source for bill to go and find out more. If I’m allowed to advertise a little bit. I wrote a book a few years ago called Sleep; A Very Short Introduction – which is the bargain price of $11.95. And I get 40 cents a book, there’s my conflict of interest, and that’s available on Amazon. And that’s a short, short introduction, as it says, which covers a lot of different topics that people might find interesting, you can sort of dip in and out of those. And then if you search for me, the Harvard site, you’ll be able to find a page with my links. And so there’s a lot of good resources out there for sleep. And I would say as you were saying earlier taking a holistic approach is exactly right. But changing sleep is like changing any behavior, you’re not just going to get all the benefits in one night. If you tonight, go to bed early, put your bed socks on, wear your blue blocking glasses, it’s not going to magically change everything in a single night. Just like a new nutrition regime for dieting, just like a new exercise regime, it takes time to redevelop a new sleep regime. And so if you change your behavior, change your sleep environment, do these things that we’ve talked about today, it will take you some weeks before you start to notice that difference. But as the clock starts to adjust itself and puts your sleeping in the right part of the day for your clock, and then you start to feel more alert in the day and start to have more energy and start to feel the benefits. Then like any of these behavior changes that will reinforce what you’re doing and help and so don’t expect anything to work overnight in terms of sleep. But if you work at it, and put the right behaviors in place, you’ll feel the benefits and then continue to get the benefits.

Diva Nagula 49:09
Fantastic last thoughts, I appreciate it Dr. Lockley, and thanks again. It was great to have you
on the show and appreciate you taking the time to be with us today.

Dr. Steven Lockley 49:17 Thanks very much.