Huberman Lab - Dr. Matthew Walker: The Science & Practice of Perfecting Your Sleep

Episode Date: August 2, 2021

In this episode, my guest is Dr. Matt Walker, Professor of Neuroscience and Psychology and the Founder & Director of the Center for Human Sleep Science at the University of California, Berkeley. He is... also the author of the international best-selling book Why We Sleep and the host of "The Matt Walker Podcast." We discuss the biology of sleep, including its various stages and what specifically happens to those stages when we don't get enough sleep. We also discuss the effects of sunlight, caffeine, alcohol, naps, hormones, exercise, marijuana, sexual activity, and various supplements on sleep. The episode consists of both basic science information and many science-supported actionable tools.  For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Introducing Dr. Matt Walker (00:02:16) Sponsors: AG1, LMNT (00:06:00) What Is Sleep? (00:10:20) REM (Rapid Eye Movement) aka 'Paradoxical Sleep' (00:16:15) Slow Wave Sleep aka 'Deep Sleep' (00:24:00) Compensating For Lost Sleep (00:32:20) Waking in the Middle Of The Night  (00:39:48) Uberman (Not Huberman!) Sleep Schedule (00:42:48) Viewing Morning SUNLight (00:49:20) Caffeine (01:07:54) Alcohol (01:14:30) Growth Hormone & Testosterone (01:16:14) Emotions, Mental Health & Longevity (01:20:40) Books vs. Podcasts (01:21:20) Lunchtime Alcohol (01:25:00) Marijuana/CBD  (01:36:00) Melatonin (01:54:14) Magnesium (01:58:10) Valerian, Kiwi, Tart Cherry, Apigenin (02:15:00) Tryptophan & Serotonin (02:19:24) Naps & Non-Sleep-Deep-Rest (NSDR) (02:28:23) Is It Possible To Get Too Much Sleep? (02:34:35) Sex, Orgasm, Masturbation, Oxytocin, Relationships (02:47:30) Unconventional Yet Powerful Sleep Tips  (02:59:10) Connecting to & Learning More from Dr. Walker (03:04:42) The New Dr. Matt Walker Podcast, Reviews & Support Title Card Photo Credit: Mike Blabac Disclaimer

Transcript
Discussion (0)
Starting point is 00:00:00 Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today I have the pleasure of introducing Dr. Matthew Walker as our guest on the Huberman Lab Podcast. Dr. Walker is a professor of neuroscience and psychology at the University of California Berkeley. There, his laboratory studies sleep. They study why we sleep. What occurs during sleep, such as dreams and why we dream, learning during sleep, as
Starting point is 00:00:37 well as the consequences of getting insufficient or poor quality sleep on waking states. Dr. Walker is also the author of the International Best Selling Book Why We Sleep. Our discussion today is an absolutely fascinating one for anyone that's interested in sleep, learning, or human performance of any kind. Dr. Walker teaches us how to get better at sleeping. He also discusses naps whether or not we should or should not
Starting point is 00:01:03 nap, whether or not we can compensate for lost sleep, and if so, how to best do that. We discuss behavioral protocols and interactions with light, temperature, supplementation, food, exercise, sex, all the variables that can impact this incredible state of mind and body that we call sleep. During my scientific career, I've read many papers about sleep and attended many seminars about sleep. Yet, my discussion with Dr. Walker today revealed to me more about sleep, sleep science,
Starting point is 00:01:34 and how to get better at sleeping than all of those papers and seminars combined. I'm also delighted to share that Dr. Walker has started a podcast. That podcast, entitled The Matt Walker Podcast, releases its first episode this month, and is going to teach all about sleep and how to get better at sleeping.
Starting point is 00:01:53 So be sure to check out the Matt Walker Podcast on Apple, Spotify, or wherever you listen to podcasts. Before we begin, I'd like to mention that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens.
Starting point is 00:02:19 Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking athletic greens and the reason I still take athletic greens once or twice a day is that it helps me cover all of my basic nutritional needs. It makes up for any deficiencies that I might have. In addition, it has probiotics, which are vital for microbiome health. I've done a couple of episodes now on the so-called gut microbiome and the ways in which the microbiome interacts with your immune system, with your brain to regulate mood,
Starting point is 00:02:52 and essentially with every biological system relevant to health throughout your brain and body. With athletic greens, I get the vitamins I need, the minerals I need, and the probiotics to support my microbiome. If you'd like to try athletic greens, you can go to atlettagreens.com slash Huberman and claim a special offer. They'll give you five free travel packs,
Starting point is 00:03:10 plus a year supply of vitamin D3K2. There are a ton of data now showing that vitamin D3 is essential for various aspects of our brain and body health, even if we're getting a lot of sunshine. Many of us are still deficient in vitamin D3. And K2 is also important because it regulates things like cardiovascular function, calcium in the body, and so on. Again, go to athleticgreens.com slash uberman to claim the special offer of the 5 free travel
Starting point is 00:03:34 packs and the year supply of vitamin D3 K2. Today's episode is also brought to us by Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are an element and those are sodium, magnesium and potassium, but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body.
Starting point is 00:04:04 If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells function properly and all our bodily systems can be optimized. If the electrolytes are not present and if hydration is low, we simply can't think as well as we would otherwise. Our mood is off, hormone systems go off, our ability to get into physical action, to engage in endurance and strength, and all sorts of other things is diminished. So with element, you can make sure that you're staying on top of your hydration and that
Starting point is 00:04:32 you're getting the proper ratios of electrolytes. If you'd like to try element, you can go to drink element that's elementy.com slash huberman, and you'll get a free element sample pack with your purchase. They're all delicious. Again, if you want to try element, you can go to elementlment.com slash Hubertman. And now my discussion with Dr. Matt Walker. Great to finally meet you in person. Wonderful to connect. I mean, it's been too long, but I suspect it would have been a show to time before we'd met less the pandemic. Yeah. Thank you. Thank you. Yeah, I'm delighted that we're finally sitting down face to face.
Starting point is 00:05:06 I've been tracking your work both in the internet sphere, and I read your book and loved it, and also from the perspective of science. You actually came to Stanford a couple of years ago and gave a lecture for Brain Mind. Oh yeah, yeah, yeah. And there, of course, you talked about sleep and its utility and its challenges and how to conquer it, so to speak. Let's start off very basic.
Starting point is 00:05:34 What is sleep? Sleep is probably the single most effective thing you can do to reset your brain and body health. So that's a functional answer in terms of what is sleep in terms of its benefits. Sleep as a process, though, is an incredibly complex physiological ballet. And if you were to recognize or see what happens to your brain and your body at night during sleep, you would be blown away. And the paradox is that most of us, and I would think this too, if I wasn't a sleep scientist, we go to bed, we lose consciousness for seven to nine hours,
Starting point is 00:06:15 and then we sort of wake up in the morning and we generally feel better. And in some ways, that denies the physiological and biological beauty of sleep. So upstairs in your brain, when you're going through these different stages of sleep, the changes in brain wave activity are far more dramatic than those that we see when we're awake. And we can speak about deep sleep and what happens there.
Starting point is 00:06:39 REM sleep is a fascinating time, which is another stage of sleep, often called dream sleep, which is rapid stage of sleep, often called dream sleep, which is rapid eye movement sleep. That stage of sleep, some parts of your brain are up to 30% more active than when you're awake. So again, it's kind of violating this idea that our mind is dormant and our body is just simply quiescent and resting. So I would happy to sort of double click on either one of those and also what changes in the body as well, but it is an intense evolutionary adaptive benefit and system. That said though, I would almost push back against an evolved system. When we think about the question of sleep and what sleep is, our assumption has always been that we evolved to sleep. And I've actually questioned that, and I have no
Starting point is 00:07:32 way to get in a time capsule and go back and prove this, but what if we started off sleeping? And it was from sleep that wakefulness emerged. Why do we assume that it's the other way around? And I think there's probably some really good evidence that sleep may have been the proto-state, that it was the basic fundamental living state. And when we became awake, as it were, we always had to return to sleep. In some ways, at that point, sleep was the price that we paid for wakefulness.
Starting point is 00:08:09 That's another way of describing what sleep is. But again, I think it sort of denies the active state of sleep. It's not a passive state of sleep either. And then finally, you can say what is sleep across different species. And in us human beings and in all mammalian species and avian species as well, sleep is broadly separated into these two main types. And we've got non-rapid eye movement sleep on the one hand, and then we've got
Starting point is 00:08:36 rapid eye movement sleep on the other. And we can speak about how they unfold across a night and their architecture because it's not just intellectually interesting from the perspective of what sleep is. It's also practically impactful for our daily lives and I'd love to sort of go down that route too, but you navigate, you tell me. I can let's definitely go down that route. So you mentioned how active the brain is during certain phases of sleep. When I was coming up in science, REM sleep rapid eye movement sleep was referred to as paradoxical sleep. Is that still a good way
Starting point is 00:09:10 to think about it? Paradoxical because the brain is so active and yet we are essentially paralyzed, correct? Yeah, it really is a paradox. And where that came from was simply the brainwave recordings. That if all I'm measuring about you is your brainwave activity, it's very difficult for me sitting outside of the sleep laboratory room to figure out, are you awake or are you in REM sleep? Because those two patterns of brain activity are so close to one another, you can't discriminate between them. Yet the paradox is that when you are awake, I go in there and you're sort of sitting up, you're clearly conscious and awake.
Starting point is 00:09:50 But yet when you go into REM sleep, you are completely paralyzed. And that's one of the, I think that's part of the paradox, but the paradox really just comes down to two dramatically different conscious states. Yet brain activity is dramatically more similar than different, and the way I can figure out which of the two you are in is by measuring two other signals, the activity from your eyes and the activity from your muscles. So when we're awake, we will occasionally have these blinks and we'll have sort of secades, but during REM sleep you have these really bizarre horizontal shittling eye movements that occur, and that's where the name comes from rapid eye movements.
Starting point is 00:10:36 They always horizontal. Mostly they are horizontal, and that's one of the ways that we can differentiate them from other waking eye And that's one of the ways that we can differentiate them from other waking eye movement activity, because it's not always let it can be sometimes horizontal, but can also have diagonal and also vertically in that plane. But then the muscle activity is the real dead giveaway. Just before you enter REM sleep, your brainstem, which is where the dynamics of non-REM and REM are essentially played out, and then expressed upstairs in the cortex and downstairs in the body. When we go into REM sleep and just a few seconds before that happens, the brainstem sends a signal all the way down the spinal cord,
Starting point is 00:11:19 and it communicates with what are called the alpha-mote neurons in the spinal cord, which control voluntary skeletal muscles. And it's a signal of paralysis. And when you go into dream sleep, you are locked into a physical incarceration of your own body. Amazing. You know, why would Mother Nature do such a thing? And it's in some ways very simple. The brain paralyzes the body so that
Starting point is 00:11:47 the mind can dream safely. Because think about how quickly we would have all been popped out of the gene pool. If I think I'm one of the best skydivers who can just simply fly, and I've had sometimes those dreams too, and I get up on my apartment window and I leap out, those dreams too. And I get up on my apartment window and I leap out. You're done. You're done. So that's part of the paradox of REM sleep, both its brain activity, similarity, despite the behavioral state being so different. And this bizarre lockdown of the brain, of the body itself. Now, of course course the involuntary muscles thankfully aren't paralyzed so you keep breathing, your heart keeps beating. Is this why men have erections during REM sleep and women have vaginal lubrication during sleep? That's one of the reasons, part of the
Starting point is 00:12:37 other reason though there is because of the autonomic activity. So there is a nervous, a part of our nervous system called the autonomic nervous system and it controls many of the automatic behaviors. And some of those are aspects of our reproductive facilities. During REM sleep, what we later discovered is that you go through these bizarre, what we call, autonomic storms, which sounds dramatic, but it actually is when you measure them. That you'll go through periods where your heart rate decelerates and drops, and your blood pressure goes down, and then utterly randomly, your heart rate accelerates dramatically, and what we call the fight-or-flight branch of the autonomic nervous system, or the sympathetic nervous system, a badly named, because it's anything but sympathetic, it's very aggravating. That all of a sudden fires up
Starting point is 00:13:28 and then it shuts down again and it's not in any regular way and it's when you get those autonomic storms, you get very activated from a physiological perspective that you can have these erections and you have vaginal discharge except for totally paralyzed. But you are still paralyzed. There are only two voluntary muscle groups that are spurred from the paralysis, Bizarre. One, your extra ocular muscles, because if they were paralyzed,
Starting point is 00:14:00 you wouldn't be able to have rapid eye movements. And the other that we later discovered was the inner ear muscle. And we've got no good understanding as to why those two muscles groups are spurred from the paralysis. It may have something to do with cranial nerve, but I don't think it's that I think it's perhaps something more sensory related.
Starting point is 00:14:22 Some people have argued that the reason the eyeballs are spurred from the paralysis is because if your eyeballs are left for long periods of time inactive, you may get things such as oxygen sort of issues in the aqueous or vitreous humor. And so the eyeballs have to keep the drain in some way. The drain in systems of the anterior eye are made to require movement. Exactly. People with glaucoma have deficits in drainage through the anterior chamber. But there I'm speculating,
Starting point is 00:14:50 I'm also speculating when I ask this, I would imagine that there are states in waking that also resembles slow wave sleep, or rather that there are states that slow wave sleep also resembles waking states. You've beautifully illustrated how REM sleep can mimic some of the more active brain states that we achieve in waking. What sort of waking state that I might have experienced or experience on a daily basis
Starting point is 00:15:15 might look similar to slow wave sleep, non-REM sleep, if any? It's a genius way of thinking about it, turns the tables, I love it. We almost never see anything like the true ultra slow waves of deep non-REM sleep. So we spoke about these two stages, non-REM and REM. Non-REM is further subdivided into four separate stages, stages one through four, increasing in their depth of sleep. So stages three and four, that's what we typically call deep non-rem sleep stages one and two. So maybe take me through the arc of a night just so that, yeah, so I put my head down, well for you, what time do you normally go to sleep? So I'm usually sort of around about a 10, 30 p.m.
Starting point is 00:16:00 guy and usually I'll naturally wake up sort of a little bit before seven sometimes before 6.45 or 7. I have an alarm set for 704 am you heard it here folks Matt Walker does use an alarm clock. I really really I'm usually Recommended what he does use it. Yeah, usually human after all. Oh, I am so human and and I've had my sleep issues and I'd love to speak about that too, but it's only just you know in the event that You know because I like to keep regularity too. You've got to keep those two things in balance and 704 just because you know Why not be idiosyncratic? I don't know why we always set things on these hard numbers so Yep, so when you're to sleep around 10.30,
Starting point is 00:16:46 so using you as an example, because I imagine a number of people go to sleep at different times with 10.30s about when I go to sleep with 11 is for me, but so you go to sleep at 10.30, so for that first, let's say three hours of sleep, what is the architecture of that sleep look like as compared to the last three hours of your sleep before morning?
Starting point is 00:17:05 Yeah, so I should note that that sort of, you know, 10, 30 to 7, that's just based on my chronotype and my preferential. It's different for different people. I'm not suggesting that that's the perfect sweet spot for humanity's sleep. It's just my, but I imagine most people probably go to sleep somewhere between 10 and PM and midnight. And most probably like 9 and midnight. And it's 5am and 7am or 5.30 and 7.30. Yeah, yeah. At least in, if you look at sort of first world nations, that's a typical sleep profile. So when I first fall asleep, I'll go into the light stages of non-rem sleep stages one and two of non-rem.
Starting point is 00:17:47 And then I'll start to descend down into the deeper stages of non-rem sleep. So after about maybe 20 minutes, I'm starting to head down into stage three, non-rem, and then into stage four, non-rem sleep. And as I'm starting to fall asleep, as I've cast off from the usually with me, murky waters of wakefulness, and I'm in the shadows of sleep stages one and two, my heart rate starts to drop a little bit, and then my brainwave pantonectivity starts to slow down. Normally when I'm awake, it's going up and down maybe 20, 30, 40, 50 times a second. As I'm going into light non-rem sleep, it will slow down to maybe 15, 20,
Starting point is 00:18:30 and then really starts to slow down down to about 10 or 8 cycles per second, 8 cycles or waves per second. Then as I'm starting to move into stages three and four, non-rem sleep, several remarkable things happen. All of a sudden, my heart rate really does start to drop. Oh, and I'll come back to temperature. I'm going to write temperature down
Starting point is 00:18:54 because I always forget these things. Now I'm sadly in the foothills of middle age. So as I'm starting to go into those deeper stages of non-rem sleep, all of a sudden, hundreds of thousands of cells in my cortex As I'm starting to go into those deeper stages of non-rhym sleep, all of a sudden hundreds of thousands of cells in my cortex all decide to fire together and then they all go silent together. And it's this remarkable physiological coordination of the likes that we just don't see at
Starting point is 00:19:20 joining any other brain state. That's really interesting. Having recorded from the brains of animals and a little bit from humans, I don't think I've ever seen the entire cortex or even entire regions of cortex light up like that. Yeah, it's stunning. It's almost like this beautiful sort of mantra chant
Starting point is 00:19:38 or this sort of, you know, to slow inhale and then a meditative exhale, inhale, exhale. And these waves are just enormous in their size. And the body is capable of movement at this time. There is no paralysis. There is no paralysis, but for the most part, muscle tone has also dropped significantly. Interesting at that point. And then you will, or I will then stay there for about another 20 or 30 minutes. So now I'm maybe 60 or 70 minutes into my first sleep cycle. And then I'll start to rise back up, back up into stage two non-rem sleep.
Starting point is 00:20:13 And then after about 80 or so minutes, I'll pop up and I'll have a short REM sleep period. And then back down I go again, down into non-rem, up into REM. And you do that reliably, repeatedly, and I will be doing that, and I do do that every 90 minutes. At least that's the average for most adults. It's different in different species.
Starting point is 00:20:36 What changes to your question is the ratio of non-rem to REM within that 90-minute cycle as you move across the night. And what I mean by this is in the first half of the night, the majority of those 90 minute cycles are comprised of lots of deep non-rem sleep. That's when I get my stage three and four of deep non-rem sleep. Once I push through to the second half of the night,
Starting point is 00:21:00 now that sea sore balance changes, and instead the majority of those 90-minute cycles are comprised either of this lighter form of non-ramp sleep, stage 2 non-ramp sleep, and much more and increasingly more rapid eye movement sleep. And the implication that I was sort of speaking about pragmatically is let's say that I have to and I usually never do early morning flights or red eyes, just because I'm a mess if that happens. I'm not suggesting that other people shouldn't.
Starting point is 00:21:31 I'm suggesting people not do that. Every time I've taken a red eye or I've done that two or three days later, I get some sort of general feeling of malaise. My brain doesn't work as well. I think red eyes should be abolished. For the pilots too, I mean, and for the emergency room, I mean long shifts have been shown to lead to physician-induced errors that lead to a lot of fatalities.
Starting point is 00:21:54 I mean, there are a lot of reasons why staying up too long or being up at the wrong times, if you're not adapted to it, is just terrible. If the date in all of those cases, I'm particularly physicians too, there was some recent data looking at suicidality, and the rates of suicide in training physicians are, you know, far, far above the norm, and I don't suspect that, you know, the schedules are helping them. I suspect that sleep is a missing part of that explanatory equation, but-
Starting point is 00:22:23 I teach medical students, and they are phenomenal, but yeah, they're under extremely challenged conditions. It's a... We shouldn't put them under this. No, it's not optimizing performance. You know. I have one. Sorry, I was sorry.
Starting point is 00:22:35 No, no, no, this is important. It's an important digression. I have one question, which is you're saying that as across the night, a greater percentage of these 90 minute cycles are going to be occupied by REM sleep as you progress through the night. I'm aware that they're based on work that you've done and from your public education efforts and others, that we have so-called circadian forces and we have other forces that are driving when we sleep and when we
Starting point is 00:23:06 want to sleep, et cetera, without going into the details of those. Have a simple question. The experiment is the following. Let's say, God forbid, you are prevented from going to sleep at your normal time, and you stay up for the four hours or five hours that normally you would be in predominantly slow-wave sleep. If, let's say you finally get to lie down at 3 a.m., a time when normally your sleep would be occupied mostly by rapid eye movement sleep. Will you experience a greater percentage of rapid eye movement sleep because of these so-called circadian forces, meaning that's what's appropriate for that time, or will your system need to start at the beginning
Starting point is 00:23:47 of the race that we're, that as I'm referring to it, that we're calling sleep. And if that's not cleared anybody, basically what I'm asking is if you are forced to skip the slow wave sleep part of the night, will your system leap into rapid eye movement sleep or does it have to start at the beginning
Starting point is 00:24:04 and get slow wave sleep first? In other words, does one sleep state drive the entry to the next sleep state? Great question. So there is some degree of reciprocity between the sleep states, I should note, that when we drive one of those up, we often, but not always see a change in the other. There are some pharmacologies that have shown an independence to that and we've also played around with things like temperature and sometimes you can nudge one and not seem to upset or perturb the other. But to your, I think lovely point, the answer is it's a mix but
Starting point is 00:24:42 it's mostly the latter meaning you will mostly go into your REM sleep phases and be significantly deficient in your deep sleep. So just because I start my sleep cycle at 3am, rather than at 10.30pm, it doesn't mean that my brain just says, well, I've got a program and I'm just going to run the program and the way the program runs is that we always start with a first couple of hours of deep sleep. So we're just gonna begin act number one scene one. It doesn't do that. Now I will get some deep sleep to begin with.
Starting point is 00:25:18 And part of that is just because of how sleep works based on how long I've been awake. Longer I'm awake, there is a significantly greater pressure for deep sleep. of that is just because of how sleep works, based on how long I've been awake. Longer I'm awake, there is a significantly greater pressure for deep sleep. But we actually use exactly what you just described as an experimental technique to selectively deprive people of one of those stages of sleep or the other. So we will do first half of the night deprivation
Starting point is 00:25:43 and then let you sleep the second half. So that means that you will be mostly deep sleep deprived and you will still get mostly all of your REM sleep. And then we switch it. So you only get your first four hours, which means you will mostly get deep non-REM sleep, but you will get almost no REM sleep. So in both of those groups, they've both had four hours of sleep.
Starting point is 00:26:05 So the difference between them in terms of an experimental outcome is not the sleep time because they've both slept for the same amount. It's the contribution of those different stages. Now, we actually have more elegant methods for sort of selectively going in there and scooping out different stages of sleep, but that's the way we used to do it at old school, was just using this timing difference. And who suffers more? Those that lack the early phase, and were those that lack the later phase of the night sleep. In other words, if I have to sleep only four hours for whatever reason am I better off
Starting point is 00:26:38 getting the early part of the night sleep or the second half of the night sleep? Depends on what the outcome measure is. So, that gets right to the differences between slow wave sleep and REM. I was probably misinformed by my understanding, a very crude understanding. I should say before. I very much doubt it. No contra with someone like you. Which is that, very nice of you.
Starting point is 00:27:00 But the first part of the night, the slow wavewave sleep is restorative to the musculature, to motor learning, and that the dream content tends to be less emotional. The second half of the night being more emotional dreams and sort of the unparering of the emotional load of our previous day and other experiences. So in other words, if I were to deprive myself, deprive myself, excuse me of REM, I would be hyper-emotional, not maybe not as settled with the kind of experiences of my life. Whereas if I had to I would be hyper-emotional, not maybe not as settled with the kind of experiences of my life, whereas if I had myself of slow-wave sleep, I would feel a more physical malaise. Is that correct or is that far too simple? And if it is too simple, please tell me where I'm wrong.
Starting point is 00:27:37 No, I think much of that is correct, and it's sort of that plus. So, for example, during deep non-REM sleep, that's where we get this. It's almost a form of that plus. So, for example, during deep non-rhym sleep, that's where we get this. It's almost a form of natural blood pressure medication. And so, when I take that away from you the next day, we're usually going to see autonomic dysfunction, we're usually going to see abnormalities and heart rate blood pressure.
Starting point is 00:27:59 We also know that during deep non-rhym sleep, that there is a certain control of specific hormones. For example, we know that the insulin regulation of sort of metabolism, meaning how will you look from a regulated blood sugar perspective versus dysregulated pre-diabetic look of profile. That's where deep sleep seems to matter. If we selectively deprive you of that,
Starting point is 00:28:24 we can see them. Growth hormone is different actually. So that's a beautiful demonstration where growth hormone seems to be more REM sleep dependent. And that's why we can come on to the effects of alcohol. And there's some really impressive frightening data on alcohol in its disruption of sleep. But then we also know testosterone. Peak levels of testosterone happen during REM sleep. It's the second half of the night. It's the second half of the night. So it really just means that the your profile of mental and physical dysfunction will be different under both of those conditions. Which one would
Starting point is 00:29:04 you prefer? I would prefer neither of them and it really depends on what you're trying to optimize for. So it's just so complex. Sleep is just so pluripotent. It's so physiologically systemic that it's almost impossible not to undergo one of those two things, just deep sleep deprivation or just REM sleep deprivation, and not show a profile that you would really prefer to avoid. And that's the reason from an evolutionary standpoint that we have preserved those stages of sleep. I mean sleep is just so idiotic, you know, from an evolutionary perspective. Or maybe waking so idiotic from an evolutionary perspective. Or maybe waking is a diatic.
Starting point is 00:29:46 Or waking is, you know, I, well, yeah. I think it's on your previous idea. Who'd be been talking to it? I think I comment it's very specific to me. Yeah, I am normally always an idiot when waking. But I think this, this idea that sleep, is so profoundly detrimental to us, if you were to take it at face value,
Starting point is 00:30:08 you're not finding a mate, you're not reproducing, you're not foraging for food, you're not caring for your young, and worst of all, you're vulnerable to predation. On any one of those grounds, sleep probably should have been selected against. But it wasn't. Sleep hers fought its way through heroically, every step along the evolutionary path. And therefore, every sleep stage has also survived as best we
Starting point is 00:30:34 can tell. What that means is that those are non-negotiable. If Mother Nature had found a way to even just sort of, you know, thin slice some of that sleep from us. The would have been fast, I'm sure, evolutionary benefits, but it looks as though she hasn't. And I'm usually in favor of her wisdom after 3.6 million years. So it's incredible. I want to introduce a another Gadonkin experiment, another thought experiment. So in this arc of the night, slow wave sleep predominates early in the night and then REM sleep. There's a scenario that many people, including myself, experience on a regular basis, which is they go to sleep, sleeping just fine, three, four hours into it, they wake up.
Starting point is 00:31:20 They wake up for whatever reason. Maybe there was a noise, maybe the temperature isn't right, we will certainly talk about sleep hygiene, et cetera. They get up, they go to the restroom, they might flip on the lights, they might not, they'll get back in bed. Hopefully they're not picking up their phone and starting to browse and wake up the brain through various mechanisms, light and cognitive stimulation, et cetera. They go back to sleep. Let's say after about 10, 15 minutes, they're able to fall back asleep, and then they sleep till they're more typical wake time.
Starting point is 00:31:50 Yeah. How detrimental is that wake up episode or event in terms of longevity, learning, et cetera? I would love to sleep the entire night through every night, but most nights I don't, and yet I feel pretty good throughout the day, some days better than others. So if you were to kind of evaluate that waking episode
Starting point is 00:32:16 and compare it to sleeping the whole night through, what are your thoughts on that? So I think if you're waking up sort of frequently as you're describing, I would probably get your estate in order because my guess is within the next year you're going to be you're going to be done for. No, I'm kidding you. Absolutely kidding you. It is perfectly natural and normal, particularly as we progress with age. You know, Children tend to have typically more continuous sleep. Now, it's not that they aren't waking up for brief periods of time they are. And in fact, we all do. When we come out the other end of our sleep cycle, at the end of our REM sleep period
Starting point is 00:32:57 of the 90-minute cycle, almost everybody wakes up and we make a postural movement. We turn over because we've been paralyzed for so long and the body will also like to shift. Do we ever look around? We ever open our eyes. Sometimes people will open their eyes, but usually it's only for a brief period of time and they usually never commit those awakenings to memory. Your situation and it's my situation as well. I usually now at the stage of life, I don't sleep through the night. I'll usually have a bathroom break and then I'll come back. That's perfectly normal. We tend to forget that in sleep science, we think of sleep
Starting point is 00:33:39 efficiency. So of the total amount of time that you're in bed, how much of that percent time is spent asleep? And we usually look to numbers that are above 85% or more as a healthy sleep efficiency. So if you were to think about me going to bed and I spend, you know, let's say, eight and a quarter, eight and a half hours of time in bed, with a normal healthy sleep efficiency, I still may be only sleeping a total of seven and a half hours or seven and three quarter hours,
Starting point is 00:34:16 meaning that I'm going to be awake in total, not in one long bout, but I'm going to be awake for upwards of 30 minutes, net some time. Sometimes that can be after a 10 minute, you know, dalliance have to having gone to the bathroom and I'm just gradually drifting back off again. Other times it will just be for a couple of minutes and most of those you don't commit. So I think we need to stop, we don't need to get too worried about periods of time awake just because we're not sleeping throughout the night. I would love to do that too. And I remember when I, that used to happen and it still happens. Everyone
Starting point is 00:34:55 keeps going. It feels great when it does happen. It's a lovely thing. It's a surprise, right? It is not going to surprise. It's not going to surprise. It's not going to surprise. It's not going to surprise. Yeah, it is a surprise. But for the most part, I think we can be more relaxed about that. Where we have to be a bit more attentive, though, is if you are spending long periods of time not being able to get back to sleep. And usually we define that by saying, if it's been 20, 25 minutes, normally that's a time when we would really say, okay, let's explore this. What's going on? Let's see what's happening. The other thing is if it's happening very frequently. So even if you're
Starting point is 00:35:32 you know, not awake for 25 minute stretches, but you're finding yourself waking up and being consciously aware that you've woken up for maybe six, seven or eight times throughout the night and your sleep is very what we call fragmented. The great science of sleep in the past five or ten years has been, yes, quantity is important, but quality is just as important and you can't have one without the other in terms of a good beneficial next day outcome. You can't just get four hours of sleep, but brilliant quality of sleep and be unimpered. Nor can you get eight hours of sleep, but have very poor quality of sleep and be unimpered the next day.
Starting point is 00:36:19 So that's why I just sort of want to asterisk this idea of, let's not get too worried about waking up and having some time awake. That's perfectly normal and natural. But if it's happening very frequently throughout the night or those periods of time or long stretches of time, upwards of 25 minutes, then let's look into it. Well, I can assure you just helps a lot of people feel better about this waking up episode that I and many other people experience I hope so because I think it's really important that we you know I think I've been desperately guilty of perhaps you know early on being too pure
Starting point is 00:36:57 Attannacle about you know sleep and and I've I've retrospected and I've tried to explore why this was the case. It was almost sleep or else dot dot dot. At the time when I was starting to write the book, which was back in 2016, sleep was still a neglected step sister in the health conversation of today. That is a whole range. It's, and not because of my efforts, but because of all my colleagues. I would say, well, it's a great that you give attribution to your right. Other people involved in it, of course, it's a big field.
Starting point is 00:37:35 But I think you've done a great service by queuing people to the importance of this state, not just for avoiding troublesome outcomes, but also for optimizing their waking state. It's real, you know, I view sleep as this period that feels good, but we're not aware of how it feels when we're in it necessarily. Yeah. It has tremendous benefits when you're doing it well, so to speak, and it has tremendous deficits when you were not.
Starting point is 00:38:01 And I think it was an important thing for you to do to queue people to this issue. And I would say mission accomplished that people are aware of the need for sleep. I think that knowing that waking up in the middle of the night is normal, provided it's not too frequent is great and will also help people who may have been overly concerned about that. I do want to use this as an opportunity to raise something about the so-called uberman schedule not to be confused with the huberman schedule. Unfortunately, no one has confused those yet. Some years ago, there was a discussion about the so-called uberman schedule, meaning the superman schedule. So that's huberman without an H, which I have nothing to do with.
Starting point is 00:38:48 If you read your Nietzsche, this will have a subtext. But regardless, the uberman schedule as I understand is one in which the person elects to sleep in 90 minute bouts spread throughout the day and night in an attempt to get more productivity and or reduce their overall sleep need.
Starting point is 00:39:08 There was a paper published recently that explored whether or not this is good or bad for us. Maybe you just give us the take home message on that. Yeah, so these Uberman-like schedules and there's lots of different forms of that. They tried to essentially pie chart the 24-hour period into short bouts of sleep with some shorter, well slightly longer periods of wakefulness, then short bouts of sleep, then wakefulness. You know, you're, I sort of made it, I think a quip, it's almost like you're sleeping like a baby, you know, because that's the way that baby's
Starting point is 00:39:43 not in 90-minute maps. That they will have, you know, these brief naps, then they're awake, then they're asleep, then they're awake, and to the chagrin of parents, across the night, it's basically the same. They're awake, they're asleep, they're awake, they're asleep. And that's more the schedule that these types of protocols have suggested. And there was a really great comprehensive review that found not only that they weren't necessarily helpful, but they were actually really quite detrimental. And on almost every
Starting point is 00:40:12 performance metric, whether it be task performance, whether it be physiological, outcome measures, whether it even be the quality of the sleep that they were having when they were trying to get it, all of those were in a downward direction. And it's not surprising. If you look at the way that your physiology is programmed, if you look at the way your circadian rhythm is programmed, none of that screams to us that we should be sleeping in that way. Well, I'm struggling because we always hear sleep like a baby. This is our baby's sleep. And I would say, don't sleep like a baby,
Starting point is 00:40:46 sleep like an adult, be an adult. Yeah, I mean, get your solid eight hours. It's Billy Crystal's line. He was a, you know, a long-standing, suffering in Somniac. He says, I sleep like a baby. I'm awake every 20 minutes, you know? And I think this is another one of those demonstrations
Starting point is 00:41:01 that when you fight biology, you normally lose. And the way you know you've lost is disease, sickness and impairment. And I think if you sleep in accordance with the natural biological edict that we've all been given, life tends to be both of a high quality and a longer duration. Yeah, I agree. Along those lines, as a vision scientist, I've been very excited by the work on these non-image forming cells in the eye, the so-called melanops and cells that inform the brain
Starting point is 00:41:32 about circadian time of day. And I'm a big proponent of people getting some sunlight, ideally sunlight, but other forms of bright light into their eyes early in the day and when they want to be awake. Essentially during the phase of their 24 hour circadian cycle when temperature is rising and then starting to get less light in their eyes as our temperature is going down in terms later in the day and in the evening.
Starting point is 00:41:57 Are there any adjustments to that general theme that you'd like to add or is in any way? No, I think that's exactly what we recommend right now, which is try to get at least 30 to 40 minutes of exposure to some kind of natural daylight. Now, there may be parts of the world where, you're from a rather cloudy part of the world. I am from Liverpool, England, and the Northwest of England is not known for its beach results and
Starting point is 00:42:27 fine weather. I remember I sort of, I went back home for a trip when I'd first been out in California. I thought, why is the sky so low? You know, it's just, you know, constantly out. We joke that in, in the UK, we usually have nine months of bad weather and then three months of winter. And then that's your, that's your entire year of, in terms of a climate. But to come to your point, you're exactly right. Try to get that daylight. Now, it can be, you know, working next to a window and you're getting that natural sunlight. But that natural sunlight is even on a cloudy day in England, is usually far more potent than anything that you'll get from indoor lighting.
Starting point is 00:43:11 Despite you thinking, sort of from a perception-wise, maybe the much closer than I would think. Yeah, I've been, um, starting to interrupt. I've been a big one of, there's an app called Light Meter, which, well, it's a free app. I have nothing to do with it. I've been a big proponent of there's an app called Light Meter, which, well, it's a free app. I have nothing to do with it. They will allow you to get a pretty decent measurement of the amount of light energy coming toward you. And if you hold it up to a cloudy morning,
Starting point is 00:43:34 where you don't think it's very bright out kind of a dismal day, you'll notice that there'll be a thousand, two thousand, even the, oh, five thousand looks, looks just being a measure of brightness, of course. And then you can point the same Light Meter toward an indoor light that seems very bright and very intense and it'll say 500 looks and you realize that the intensity as we gauge it Perceptually is not really what the system is receiving so outdoor light is key. How do you what how do you get this natural stimulation or I should just say light stimulation early in the day? What is your typical, what does Matt Walker do
Starting point is 00:44:07 to get this light stimulation? I am no poster child, but usually I will, if I'm working out, usually workout most days. And I shopped around and I found a gym that has huge amounts of window exposure facing to the east. This is gonna sound so ridiculous. You know, Matt Walker chooses a gym on the basis of the solar input so he can, you know,
Starting point is 00:44:31 there are a lot of criteria for saline. This one is actually grounded in physiology and biology and so. And selfishness about my own sleep. Yeah, that's great. So you get your exercise and your light stimulation simultaneously. Yep, yep, yep.
Starting point is 00:44:44 And so you're stacking cues for wakefulness early in the day. Exactly. So both exercise and daylight are wonderful cues for circadian rhythm alignment and also circadian rhythm reset each day. And so I will use both exercise. I mean, I am neither a strong morning type or a strong evening type. My preference to exercise is probably some time in the middle of the day.
Starting point is 00:45:09 Probably somewhere around 1 p.m. Sorry, not 1 a.m. But I'm usually working out probably around the sort of 7, sort of 45, 8 a.m. time that's usually when I'll start my workout. And there I'll start with cardio, spin bike, facing a window, and luckily for the most part here in California, there's usually sunlight coming through.
Starting point is 00:45:33 But it doesn't matter to me because just as you said, even when it's a cloudy day, that looks coming through of light, the intensity is splendid. So I would prefer to favor my exercise just because for efficiency too, I want to get also working on the day. I'll try to match my exercise more with my circadian light exposure than I would probably if I'm going to do I really want a crescent workout or do I want to just, you know, make sure it's a good workout. I would going to, do I really want to crush a workout or do I want to just,
Starting point is 00:46:05 you know, make sure it's a good workout, I would prefer to work out, you know, at a different time. But I like that because of the daylight. And we can speak about exercise timing at some point, because there's a lot of discussion around that when it's the right time to exercise during sleep. And we can sort of bust some myths there too. So I think your spot on with the suggestion get some morning daylight, try to get that exposure usually at least 30 to 40 minutes. There was some great work recently coming out in the occupational health domain
Starting point is 00:46:36 where they moved workers from offices that were just facing walls and didn't have any exposure to natural daylight. And then they did a time period during that study where they actually were in front of a window and working. And they measured their sleep. And their sleep time and their sleep efficiency increased quite dramatically. I'm forgetting the numbers now, but I think the increase in total sleep time was well over 30 minutes,
Starting point is 00:47:02 and the improvement in sleep efficiency was 5 to 10%. If you're batting an 80% sleep efficiency average, we're a bit concerned about that, but at 10% to that, now you're in a great echelon of healthy sleepers, and all you did was just spend some time working in front of windows. That's great. And probably folks might want to consider spending a little less time with sunglasses provided they can do that safely, you know, driving, et cetera. You're not alone with your exercise behavior and facing ease.
Starting point is 00:47:32 So the one and only Tim Ferris told me recently that his morning routine nowadays consists of jumping rope while facing ease to get the sunlight stimulation of the eyes. And as Matt and I both know, it has to be of the eyes, right? I mean, these portals are the only way to convey to the rest of the brain and body about the time of day and wakefulness. Along the lines of wakefulness, have a number of questions about caffeine.
Starting point is 00:48:02 The dreaded and beloved caffeine. I love caffeine, but I like it in relatively restricted periods of time. So I'm a big fan of waking up and even though I wake up very groggy, allowing my natural wakefulness signals to take hold. Meaning I wake up very slowly, but I don't drink caffeine right away. I've sort of delay caffeine by a little while, usually 90 minutes to two hours. Okay.
Starting point is 00:48:31 And that idea came to me on the basis of my understanding of how caffeine and the adenosine receptor interact. I have a feeling you're gonna pronounce adenosine differently than I do. No, no, no, I will go with the adenosine. I'll try to go with your skeletal and skeletal synapses. I'll be scheduled. Schedule on schedule.
Starting point is 00:48:50 There you go. But to make it really simple for folks, how does caffeine work to make us feel more alert and does the timing in which we ingest, play an important role in whether or not it works for us or against us? So maybe we just start with, how does caffeine work? Why is it that when I drink mate or coffee, which are my preferred sources of caffeine, do I feel a mental and physical lift? Yeah.
Starting point is 00:49:19 So, I'm going to suggest counter to what most people would think, drink coffee. Or mate. Or mate. Is mate okay? Yeah, yeah. I would suggest counter to what most people would think, drink coffee. Or Mateo, or Gail. Whatever form you would be like. Well, we'll come on to sort of why I suggest that, but when it comes to coffee, I would say the dose and the timing makes the poison. So let's start with how caffeine works. Caffeine is in a class of drugs that we call a psychoactive stimulants.
Starting point is 00:49:49 So, it works through a variety of mechanisms. One is dopamine mechanism. Dopamine we often think of as a reward chemical. But dopamine is also very much an alerting, you're achemical as well. And caffeine has some role it seems to play in increasing dopamine. But it's principle mode of action we believe in terms of making me more alert and keeping me awake throughout the day is on the effects of a denocene.
Starting point is 00:50:19 And to explain what a denocene is from the moment that you and I woke up this morning, this chemical adenosine has been building up in our brain. And the longer that we're awake, the more of that adenosine accumulates. Is it, um, may I ask, is it accumulating in neurons, in glia, or in the blood vessels? Where, and, and is it also accumulating in my body? Where is this adenosine coming from? And where is it accumulating? Yeah, so the adenosine here that we're talking about that is creating the sleep pressure
Starting point is 00:50:50 is a central brain phenomenon. And it comes from the neurons themselves combusting energy. And as they're combusting energy, one of the offshoots of that is this chemical adenosine. And so as we're awake throughout the day and our brain is metabolically very active, it's accumulating and building up this adenosine. Now the more adenosine that we have, the sleepier that we will feel. So it really is like a sleep pressure is what we call
Starting point is 00:51:22 it. Now it's not a mechanical pressure. Don't worry, your head's not going to explode. It's a chemical pressure. And it's this weight of sleepiness that we feel gradually growing as we get into the evening. Man, I just, in general, again to just ask, do we know what the circuit mechanism is for that? I mean, not to go too far down the rabbit hole, but for the aficionados and for myself, we have brain mechanisms like locustsaruleus that are release things, that are brain areas, locustsaruleus just being a brain area, of course, that release things that proactively create wakefulness. So are those neurons shutting down as a consequence of having too much adenosine, or are there areas of the brain that promote sleepiness that
Starting point is 00:52:07 are being coming activated? Because you can imagine both things working in parallel, one or the other would accomplish the same endpoint. Yeah, and it's both. And so there are two main receptors for adenosine, the A1 receptor and the A2 receptor, and they have different modes of activating brain cells or inactivating or decreasing the likelihood of firing. And adenosine works in this beautiful, elegant way, where it will inhibit and shut down the wake promoting areas of the brain, whilst also increasing and dialing up the volume on sleep activating sleep
Starting point is 00:52:46 promoting. Oh, it's always a push. Yeah, I mean, we could have a larger discussion at some point about that everything seeing dark edges, seeing light edges, our ability to smell or to sense pressure on this. Everything's a push. Oh, it's great. Yeah. So this is another example where as I push. Oh, it's great. Yeah, yeah. So this is another example where as I'm awake longer, adenosine is released in the brain and my wakefulness areas are being actively shut down by that adenosine and my sleepiness brain areas, so to speak, are being promoted to be more active. Is that correct? That's right. And it's a very progressive process. It's not like a step function. And sometimes that happens occasionally, but it's usually because you've been sort of driving through and as we'll come on to have caffeine in the system.
Starting point is 00:53:32 And then all of a sudden you just hit a wall and it just engulfs you and you go from a zero to the one of sleepingness within a short period of time. What explains the fatigue after a hard conversation? The desire to go to sleep or the desire to go the fatigue after a hard conversation? The desire to go to sleep, or the desire to go to sleep during a hard conversation. That's an interesting one. I think it's usually just based on personality type interactions and for the most part,
Starting point is 00:53:54 most of the time I've ever experienced that before. No, people with you don't, but with me, they're the most thing. Oh no, no, no, no, no, no, no, no. I've experienced the desire to, some conversations, I'm halfway through them and I feel like I want to take a nap. Yeah. Right? And I would, to some conversations, I'm halfway through them and I feel like I want to take a nap. Yeah.
Starting point is 00:54:07 Right? And I would love to look at, you know, people's sleep history. We've sort of seen that time and time again. But, and then it could be, you know, with folks like me, people just lose the will to live within about five minutes of speaking with me. Not true.
Starting point is 00:54:20 That's the, that's the, that's the, the year the sleep was important. That's, that's, that's, that's, that's, that's, that's great. But, so the way that then caffeine comes into this equation, But they're as sweet as it is. It's important. That's why it's not even. That's flattery. That's great. But so the way that then caffeine comes into this equation, as I was saying, it's usually a kind of a linear process. Or maybe it's probably closer to an exponential in terms of your subjective feeling of sleepiness.
Starting point is 00:54:37 And we haven't really been able to measure that in humans because normally it's hard to actually stick something into the brain and be, you know, sucking, siphoning off stuff every couple of minutes as you could do in animal studies, and keep asking people every couple of minutes how sleepy do you feel, how sleepy? And track to see if there's a linear rise in, you know, a denocene, which then creates an exponential rise in subjective sleepiness, or what the dynamics are, but I'm kind of noting out. eventual rise in subjective sleepiness or what the dynamics are, but I'm kind of nerding out. Caffeine comes into play here because caffeine comes into your system and it latches onto those
Starting point is 00:55:20 welcome sites of adenosine, the adenosine receptors. But what it doesn't do is latch onto them and activate them because if it was doing that then it would, you know, in lots of ways, it would dial up more sort of sleepiness. It does the opposite. The way that caffeine works is that it comes in competes with quite sharp elbows with a dynasine, competitively forces them out of the way, hijacks that receptor by latching onto it, but then just essentially blocks it. It doesn't inactivate the receptor, it doesn't activate the receptor. It functionally inactivates it in the sense that it takes it out of the game for a denocene. So it's like someone, you know, coming into a room and you're just about to sit down on the chair and caffeine comes in and just pulls out the chair and you're like, well, now I've got nowhere to sit and caffeine just keeps pulling out the chairs from adenosine and adenosine even though it's at the same concentration in your brain. that you've been awake for 10 hours, 16 hours at that point when you've downed a cup of coffee because all of that adenosine, that's still there, can't communicate to the brain that you've
Starting point is 00:56:35 been awake for 16 hours because- But the adenosine is still in brain- Correscent. So the real question is what happens when caffeine is dislodged from the adenosine or something? Unfortunately, things happen. And that's what we call the caffeine crash, which is caffeine has a half-life and it's metabolized. And we recall what the half-life is. Yeah, the half-life is somewhere between five to six hours and the quarter-life there for is somewhere between 10 to 12 hours.
Starting point is 00:57:02 It's variable. Different people have different durations of its action, but for the average adult five to six hours, that variation we understand it's down to a liver enzyme or a set of liver enzymes of the class that we call the Cytocrom P450 enzymes. And there are two, I think last I delved into the data, which is pretty recently, there are two gene variants that will dictate the enzymatic speed with which the liver breaks down caffeine, and that's why you can have some people who are very sensitive to caffeine, and other people who say, you know, I just doesn't affect me really that much at all.
Starting point is 00:57:40 These are the people that have a double espresso after a 9pm dinner and you sleep just fine. Well, I'm willing to- Come on, Tobi. They think they're sleeping. Yeah, and we should speak about that that that's a someative danger to. So then the caffeine is in the system and after some time period it will be inactive in the system. So let's say that, you know, I've been awake for 12 hours now and it's, you know, 8 p.m. and I'm feeling a bit tired, but I want to push through and I want to keep working for another couple of hours. So I have a cup of coffee, all of a sudden I was feeling tired, but I don't
Starting point is 00:58:16 feel like I've been awake for 12 hours anymore, because with the caffeine in the system, maybe only half of that adenosine is being communicated through the receptor to my brain. 100% of the adenosine is still there, only half of it is allowed to communicate to my brain. So now I think, well, I haven't been awake for 12 hours, I've just been awake for 6 hours, feel great. Then after a few hours and the caffeine is starting to come out of my system. Not only am I hit with the same levels of a denocene
Starting point is 00:58:46 that I had before I'd had the cup of coffee several hours ago, it's that plus all of the adenosine that's been building up during the time that the caffeine has been in my system. So sort of an avalanche of... It is a tsunami wave, yeah. And that's the caffeine crash. And it's interesting because the caffeine crash had two o'clock in the afternoon when you have work to do is a terrible thing.
Starting point is 00:59:10 But what about the person, maybe this person is me in my 20s, who says, I'm going to drink caffeine all day long. And then I want the crash because at 9 or 10 p.m., if I stop drinking caffeine at, say, 6 p.m. and I crash, then I crash into a slumber, a deep night of sleep. Is that sleep really as deep as I think it is? Because given the half-life of caffeine that you mentioned a few moments ago, I have to imagine that having some of that caffeine circulating in my system might disrupt the depth of sleep or somehow the architecture of sleep in a way that even if I get aater who knows even 10 hours of sleep, it might not be as restorative as I would like it to be.
Starting point is 00:59:54 Yeah. And that is the danger, just sort of that, you know, those people that you described who say, and I, a lot of them will speak with me too, say, look, I can have two aspressors with dinner and I full asleep fine and I can have two aspressors with dinner and I fall asleep fine and I stay asleep because usually those are the two fiener types that we typically see with too much caffeine. I just can't fall asleep as easily as I want to
Starting point is 01:00:14 or I fall asleep but I just can't stay asleep and caffeine can do both of those things quite potently. How late in the day do you think is assuming somebody, translate this folks if you go to bed earlier or later, you have to shift the hours accordingly. But given somebody who typically gets into bed around 10, 10, 30 and falls asleep around 11, 11, 30, when would you recommend they halt caffeine intake? And these are not strict prescriptives, but I think people do benefit from having some fairly clear guidelines of what might work for them.
Starting point is 01:00:48 Would you say cut off caffeine by what time of the day? I would usually say take your typical bedtime and count back sort of somewhere between 10 to eight hours is probably getting a little bit close, but take back sort of 10 hours or eight hours of time. That's the time when you should really stop, you know, using caffeine is the suggestion. And the reason is because for those people who even just keep drinking up until, you know, into the evening,
Starting point is 01:01:17 you're right that they can fall asleep fine. Maybe they stay asleep, but the depth of their deep sleep is not as deep anymore. And so there are two consequences. The first is that for me, and it can be up to by 30%, and for me to drop your deep sleep by 30%, I'd have to age you by between 10 to 12 years, or you can just do it every night to yourself with a couple of espresso's. The second is that you then wake up the next morning and you think, well, I didn't have
Starting point is 01:01:47 problems falling asleep and I didn't have problems staying asleep, but I don't feel particularly restored by my sleep. So now I'm reaching four, three or four cups of coffee the next morning rather than just two or three cups of coffee. And so goes this dependency cycle that you then need your uppers to wake you up in the morning and then sometimes people will use alcohol in the evening to bring them down because they're overly caffeinated and alcohol and we can speak about that too also has very dilatirious impacts on your sleep as well.
Starting point is 01:02:17 So you're right that it's not just the quantity of your sleep or even difficulties falling or staying asleep, it can also be deep sleep. But here again, I think, you know, I don't want to be frightening people. And I mentioned this before, I think one of the real problems that I owe mistakes that I made, because I didn't, you know, I'd never had much public exposure before the book. And I was so saddened by, you know, the disease and the suffering that I was seeing as a consequence of a lack of sleep in our society.
Starting point is 01:02:50 And the fact that it wasn't really being discussed very much, I sort of came out, you know, a little bit headstrong, more than a little bit headstrong. And I think I was, you know, perhaps too much gas pedal and too little, you know, break, as it were. And I don't think that's the right way to approach health message within the public sphere. And I've become much softer in how I think about these things. I have ideas about what the ideal world looks like for sleep, but I also realized that none of us live in this thing called the ideal world.
Starting point is 01:03:29 We certainly don't. So, you know, I want to be really mindful of that, and I think I've done a really bad job of being sort of two-fourth right, particularly for people who struggle with sleep. You know, early on when I would offer these sort of messages about sleep, I want to be, you know, I want to be theoretical when it comes to the science. I want to be faithful to the science. But I also don't want to go out and scare the living daylights out of people, particularly people who are struggling with their sleep, because it's probably
Starting point is 01:03:57 only going to make matters worse. So I've been beautifully schooled by learning how to be a slightly better public communicator. I'm no in ear of the standing that you are, you're very elegant and it's very intuitive to you. I'm still with training wheels, but I'm getting a little bit better. But I just want to say that when I'm speaking about caffeine because it sounds as though I'm very sort of overt about it, but I will come back to why I say drink coffee, but I just
Starting point is 01:04:24 want to make that point. Well, I appreciate you making that point, and I'm sure our listeners will too. I still will stand behind my statement, which is that what you've done for the notion that sleep is vital for all aspects of health and for performance, mental, and physical and wakefulness. The messaging that I'm the packaging it was contained in has been clearly, clearly net positive. People needed to be queued to this.
Starting point is 01:04:52 I'll sleep when I'm dead. Mentality is one that I had. It's one that other people have. People in a huge number of vital communities, not just your students, but also people, the messaging that you provided and continue to provide has positively impacted the first responder community, the medical community, there's still steps that need to be taken, the military community, and of course, the civilian community.
Starting point is 01:05:18 And so I think these adjustments about, yeah, caffeine's okay, just restricted to the early part of the day if you can most days. I think the law of averages, it's like, just restrict it to the early part of the day if you can most days. I mean, I think the law of averages, it's like the light viewing behavior. I think it is critical to view sunlight or natural, some other form of bright light early in the day, but if you miss a day, it's not that your whole system is going to dissolve into a puddle of tears. That'll happen on the second or the third day.
Starting point is 01:05:40 No, I'm kidding. You've got a couple days. Biology works in averages except with respect to accident or injury. A car accident is a car accident, right? You don't get to have three of those before the brain damage occurs if the accident is severe enough. But with sleep behavior, these homeostatic type behaviors are with food. One chocolate Sunday, is it going to kill you?
Starting point is 01:06:01 No. Every night, yeah, it's going to make you demented and kill you early. We know this. And so I think the the middle ground is often a hard place to achieve. So I think you've done a phenomenal job, but I appreciate you raising these points. And I think it's clear that we all need to that we all can and should do certain things better, including being gentle with ourselves from time to time when we deviate from these ideal circumstances. Along these lines, I do want to talk about alcohol, because I think caffeine and alcohol
Starting point is 01:06:34 represent the kind of two opposite ends of the spectrum. Clearly, there are other stimulants. They're your aderoles and your high energy drinks that people use. But alcohol and caffeine are the most commonly consumed. A stimulant and sedatives, depressants, as there's sometimes cold. What happens when somebody has a glass, we always hear a glass or two of wine in the evening or a cocktail after dinner, or before dinner, how does that impact their sleep?
Starting point is 01:07:07 And then we'll be sure to circle back in terms of what is reasonable ranges of behavior when it comes to avoiding alcohol or if it's age-appropriate, et cetera, enjoying alcohol. Yeah. So alcohol, if we're thinking about classes of drugs, they're in a class of drugs that we call the sedatives. And I think one of the first problems that people often mistake, alcohol is often
Starting point is 01:07:32 used as a sleep aid for people who are struggling with sleep when things like over the counter, remedies, etc., or herbal remedies have just not worked out for them. And alcohol, unfortunately unfortunately is anything but a sleep aid. The first reason that most people use it is to try and help them fall asleep. And this process of this event that we call falling asleep, I have to imagine, is a process like everything in biology. And that that process involves, in some way, as we talked about pushpull before, turning off, thinking,
Starting point is 01:08:05 planning, et cetera, and turning on some sort of relaxation mechanism. I have to imagine that these two things are knobs turning in opposite directions. That brings us this outcome we call falling asleep. Outcall, it seems, is helpful for some people to turn off their faults or their planning. Is that right? Yes, it is. And so I think, you know, if we look at the pattern of brain activity, if I were to place you inside an MRI scanner, where we're looking at the activity of your brain
Starting point is 01:08:32 and what you're drifting off, some parts of your brain will become less active. Other parts will become more active and this is the push-pull model. It's inhibition excitation. But alcohol is quite different in that regard. Alcohol is because it's a sedative. What it's really doing is trying to essentially knock out your cortex. It's sedating your cortex. And sedation is not sleep.
Starting point is 01:08:59 But when we have a couple of drinks in the evening, when we have a couple of nightcaps, we mistake sedation for sleep, saying, well, I always, when I have a couple of drinks in the evening, when we have a couple of nightcaps, we mistake sedation for sleep, saying, well, I always, when I have a couple of whiskies or a couple of cocktails, it always helps me fall asleep faster. In truth, what's happening is that you're losing consciousness quicker, but you're not necessarily falling
Starting point is 01:09:19 naturalistically asleep any quicker. So that's one of the first sort of things just to keep in mind. The second thing with alcohol is that it fragments your sleep and we spoke about the quality of your sleep being just as important as the quantity. An alcohol through a variety of mechanisms, some of which are activation of that autonomic nervous system, that fight or flight branch of the nervous system. Alcohol will actually
Starting point is 01:09:45 have you waking up many more times throughout the night, so your sleep is far less continuous. Now some of those awakenings will be of conscious recollection the next day. You'll just remember waking up. Many of them won't be. But yet your sleep will be littered with these punctured awakenings throughout the night. And again, when you wake up the next morning, you don't feel restored by your sleep. You know, fragmented sleep or non-continuous sleep in this alcohol-induced way is usually not good quality sleep, but you feel great on the next day. The third part of alcohol in terms of an equation is that it's quite potent to blocking your REM sleep, your rapid eye movement sleep. And REM sleep is
Starting point is 01:10:32 critical for a variety of cognitive functions, some aspects of learning and memory, it seems to be critical for aspects of emotional and mental health. You've described it before as a sort of self-generated therapy that occurs while we sleep. Yeah, it's overnight therapy. It's emotional first aid. It certainly doesn't get enough sleep. Our very easy to derail emotionally. Not that one would want to do that to people, but we all sort of fall apart emotionally.
Starting point is 01:11:00 I always think of it as almost like our skin sensitivity can be heightened. Yes. When we are sleep deprived, our emotional sensitivity is such that when we're sleep deprived, such that it takes a much finer grain of sand paper to create that kind of friction. Yeah. These bothers. Threshold to trick. Even online comments bother us when we're sleeping and never when we're I would love to say that I never look at them except I look at
Starting point is 01:11:30 Maybe everyone editorialized because the notion of not looking at comments is Is unreasonable for to ask of any academic because academics? We are all trained to look at our teaching evaluations Yeah, and just like with online comments to look at our teaching evaluations. And just like with online comments to ignore 20% of them, no I'm kidding, we look at them all. In any event, so in terms of translating this to behavior,
Starting point is 01:11:55 I'm not, I don't particularly enjoy alcohol. I guess I might be fortunate in that sense, but I also have never really experienced the pleasure of drinking alcohol. I sometimes like the taste of a drink, but I never like the sensation, so I don't have a lot of familiarity with this, but many people do, and I understand that. So let's say somebody enjoys a glass of wine or two with dinner, and they dinner at 7 p.m. Is that likely to disrupt their sleep at all? Let's just sort of, let's make this a series of gradations. Yeah, and the answer is yes.
Starting point is 01:12:30 I think once he just looked at a single glass of wine in the evening with dinner, and I would be untruthful if I didn't just simply say, it has an effect and we can measure that in terms of the right sleep. Less REM sleep. And one of the fascinating studies, I can't remember what dose, I think they got them close to a standard illegal blood alcohol level.
Starting point is 01:12:55 So maybe they were a little bit tipsy. And yes, you see all of the changes that we just described. They sort of lose consciousness more quickly. They have fragmented sleep, and they have a significant reduction in REM sleep. But what was also interesting because REM sleep as we spoke about before is a time when some hormonal systems are essentially recharged and refreshed, growth hormone being one of them, there was well over a 50% 5-0 drop in their growth hormone release during alcohol-laced sleep at night. Wow.
Starting point is 01:13:28 And your hormone is so vital for metabolism and repair of tissues and not just the case. It's essentially essential. Essentially. Yeah. Essentially. Along those lines, I just want to highlight the fact that this information that you're sharing that growth hormone is released is strongly tethered to the presence of healthy amounts of REM sleep is interesting to me because
Starting point is 01:13:52 I always thought the growth hormone was released in the early part of the night. Well, it is released across both of those, but across the different stages, but what we also know is that when you disrupt REM sleep, there are those growth hormone consequences. So it's not an exclusive system. Just like with testosterone, we can see changes throughout non-REM sleep. But if you ask, when are the peak release rates of testosterone, it's right before we go into REM sleep and then during REM sleep. And of course, testosterone being important both for males and females, right? For libido and tissue repair and well-being. Nobody regardless of chromosomal hormonal or any other background wants to have their
Starting point is 01:14:35 normal levels of testosterone reduced acutely. That's just a bad, it equates to a terrible set of psychological and physical symptoms. Yeah, and the mortality risk that's associated with low testosterone is non-trivial. Proceeding to the right. Exactly. So, coming back to just the point on REM sleep that you mentioned regarding emotional instability, and we see that, that's one of the things, one of the most reliable signatures of just insufficient sleep, doesn't have to be sleep deprivation. What we've discovered over the past 20 years here at the Sleep Center is that there is no major
Starting point is 01:15:11 psychiatric disorder that we can find in which sleep is normal. And so I think that firstly told us there is a very intimate association between your emotional mental health and your sleep health. But when it also comes to REM sleep, I think what's fascinating is that it's not just about your emotional health, it's not just about your hormonal health. We've also been seeing other aspects of cognition, but then there was a report I think it could have been about two years ago out of Harvard, I
Starting point is 01:15:45 think it was Beck Clemens group. They found that, and they replicated it in two different large populations, if you look at the contribution of different sleep stages to your lifespan, REM sleep was the strongest predictor of your longevity. And it was a linear relationship, but wasn't it sort of one of these U-shaped or J-shaped curves that we often see with total sleep and mortality risk.
Starting point is 01:16:14 It really was linear that the less and less REM sleep that you were getting, the higher and higher your probability of death. And then they did, was that death due to natural causes? It was accident. Because I can imagine if you're not getting enough REM sleep, you're more likely to drive off the freeway, step off a cliff. Yeah, I think it was all caused to have bad decisions about anything in relationships. Yeah, which can also be life-threatening. Yeah, I've tried to lean into that and claim that I, with those bad relationships, situations
Starting point is 01:16:40 that, oh, I just didn't have enough REM sleep. I sleep my darling. I don't have a sleep distance. Yeah. But she's far more eyes are than I thought. But so they did this great machine learning analysis and I may get these numbers backwards. But I think for every 5% reduction in REM sleep, there was a 13% associated increase risk of mortality. And I could have, I'll have to go back and check. But to me, and in the machine learning algorithm, what they ultimately spat out was that of all of the sleep stages, REM sleep is the most predictive of your longevity, of your
Starting point is 01:17:21 lifespan. So we often, I hear people saying, how can I get more deep sleep? Or they sometimes say, how can I get more dream sleep? And my answer is a question, why do you want to get more of that? And I'll say, well, isn't that the good stuff? And I'll say, well, actually all stages of it. It's all the good stuff. Yeah. Well, it's like the exercise question and it took decades for people to understand that moving around at, for about 150, probably 180 minutes a week at doing endurance type work, zone two cardio, type work.
Starting point is 01:17:55 It is correlated with living longer, feeling better, less diabetes, et cetera. There's really no way around it. You can ingest Metformin until the cows come home. You can take NMN, all of which I think have their place in certain contexts. I'm a big fan of the work surrounding all those protocols. But without getting proper amounts of movement,
Starting point is 01:18:19 meaning sufficient numbers of, it doesn't matter how many 12-minute exercise regimes you follow per week, you need that threshold level and it sounds like the same is true of REM sleep and total amount of sleep. There's just you pay the pipe or somehow. Yeah, the return on investment, I mean, to flip the coin, the return on investment is astronomical. I think of sleep. It is the tide that moves, is astronomical, I think of sleep. It is the tide that raises all of those health boats. And the most fundamental layer of mental and physical health.
Starting point is 01:18:51 Whenever people ask me, even though I'm not a physician, they'll ask me, what should I take or what should I do? The first question is, how's your sleep? Greening, how well do you sleep every night? And how long do you sleep? I always recommend your book. I always recommend your book. I always recommend your podcast. I, you know, the podcast you've been a guest on, et cetera.
Starting point is 01:19:11 Who knows, maybe you'll even release your own podcast at some point soon and keep, because I do think people need to hear from you more often. One thing I don't want to return to the notion of public health discourse too much, but I do want to say one issue with books in general is that they can be revised, but it's more or less a one and done kind of thing
Starting point is 01:19:31 until the next book comes out. One thing I like about the podcast format is that updates can be provided regularly, corrections and updates as new data come out. And so that's a wonderful aspect to this format and hopefully the format that you'll be embracing. I think the world needs to hear more from you, more often, about sleep and its various contours, not less. And so I do have a question about drinking alcohol,
Starting point is 01:20:00 not that we want to promote day drinking, but let's say that the one or two glasses of wine or cocktail is consumed with lunch, something that isn't traditionally done nowadays, or in a late afternoon happy hour cocktail, and then one is going to sleep seven or eight hours later. Do you think that that will improve or somehow mitigate the effects of alcohol? Or if you have a drink, are you basically screwed for the next 24 hours? No, I think there's going to be a time window dependency. Now, I don't know of anyone who's essentially done what you and I would like, which is the time separation dose dependent curve where, okay, you drink at 10am,m. then or 11 12 1 2 3 4 5 all the way up to you know 10 p.m and
Starting point is 01:20:50 Estimate what is the blast radius and is it linear or is it non-linear? Is it such that only when you drink in the last four hours? Do you just hit this exponential and it's bad bad bad, bad, or is the some other curve that we could imagine that would be many possibilities. But certainly what we know is that the less alcohol and the less and more specifically the metabolic byproducts, aldehydes and ketones, they're the sort of the nefarious players. And not the ketones that people are all excited about. No, the other ketones.
Starting point is 01:21:22 They come back. They come back. They come back. They come back. They comeones. They come back. They come back. The chemists know what we're referring to. This is not about ketogenesis. This is not about ketogenesis. These are ketone bodies that are released after ingesting alcohol that are not of the positive sort.
Starting point is 01:21:35 Correct. That ketogenic diet might promote. Right. So I think in terms of that alcohol profile, we certainly know that as you're heading into the evening hours, once again, timing and dose make the poison. But I think it's also important, once again, from that public message standpoint. And thank you. I think I am leaning into the sort of the podcast consideration arena at some point. But I don't want to be pure a tonical here. You know, I'm just a scientist and I'm not here to tell
Starting point is 01:22:09 anyone how to live. All I'm trying to do is empower people with some of the scientific literature regarding sleep. And then you can make whatever informed choices that you want. You know, unlike you, it turns out I'm not a big drinker. It's just because I've never liked the taste. I'm surprised that they haven't taken away my British passport because I don't like Lager or beer. I also want to say that life is to be lived to a certain degree. It's all about checks and balances. If I go out and I have an an ice cream Sunday, I'm not big on those either, but, you know, sure I know that my, you know, blood glucose is not going to be ideal for another 12 hours,
Starting point is 01:22:52 maybe. That's just the price you pay for having some kind of relaxed fun life. I don't want to look back on life and think, gosh, you know, I lived until I was 111, and it was utterly miserable. You know? Right, so, but it's all about some kind of a balance, and mine, my job is not to tell people a prescription for life, it's just to offer some scientific information.
Starting point is 01:23:19 Oh, I think you're doing a terrific job of that. People are, I always say, we have all these neural circuits, and if it's working properly, we all have a circuit that allows us to skip over information or as we wish, if the circuits between your brain and your thumbs are working, you can slide right along, you can drop to the next content.
Starting point is 01:23:38 However you like, I would like to ask about marijuana and CBD. This is a discussion that I think five years ago would have ventured into the realm of illegal. But now, in many places, not all, medical marijuana is approved or is legal. And certainly it's in widespread use. Certainly not recommending people do it.
Starting point is 01:23:59 I have my own thoughts about marijuana CBD. I've been fortunate. I suppose that I don't particularly like marijuana or CBD. I don't even know if I've about marijuana CBD. I've been fortunate, I suppose, that I don't particularly like marijuana or CBD. I don't even know if I've ever tried CBD. First of all, does marijuana disrupt the depth of sleep, the architecture of sleep? And if so,
Starting point is 01:24:20 as with alcohol and caffeine, does when you ingest it, or when it's in your bloodstream, does relative to when you go to sleep, does that play an important role? So does marijuana disrupt sleep? Yeah, it does, and there's a pretty good amount of data on. So we can break sort of cannabis down into two of its key ingredients. We've got THC tetrahydro-canabinol, and we've got CBD.
Starting point is 01:24:48 And CBD is sort of the less psychoanxiety, what we think of as the non-psychoactive component. In other words, when you take CBD, you don't get high. If you take THC, you can get high. That's the psychoactive part of the equation. Are both considered sedatives in the technical side? No, they're not. Neither of them have that class right now. THC can seem to speed up the time with which you fall asleep. But again, if you look
Starting point is 01:25:23 at the electrical brain wave signature of your falling asleep with and without that THC, it's not going to be an ideal fit. So you could argue it's non-natural. But many people use THC for that fact because they find it difficult to fall asleep. And it can speed the onset of at least non-consciousness, I guess, the best way of describing it.
Starting point is 01:25:45 But there are problems with THC, and there are twofold. The first is that it too, but through different mechanisms, seems to block REM sleep. And that's why a lot of people, when they're using, will tell me, look, I definitely, I was dreaming, I don't remember many of my dreams, and then when they stop using THC, I was having just crazy, crazy dreams, and the reason is because there is a rebound mechanism. REM sleep is very clever, and alcohol is the same way in this sense. It's the same homeostatic mechanism. Some people will tell me, look, if I have a bit of a wild Friday night with some alcohol,
Starting point is 01:26:24 maybe I'll sleep late into the next morning, and I'll just have these really intense dreams. So and I thought I wasn't having any REM sleep. Well the way it works is that it's during in the middle of the night really, when alcohol blocks your REM sleep. And your brain is smart. It understands how much REM sleep you should have had, how much REM sleep you have not, because the alcohol's been in the system,
Starting point is 01:26:48 and finally, in those early morning hours, when you're getting through to six, seven, eight, and... And like, all of a sudden, your brain not only goes back to having the same amount of REM, it would have had, it does that, plus it tries to get back all of the REM sleep that it's lost. Does it get back all of the REM sleep? No, it doesn't. It never gets back all of the REM sleep, but it tries to get back all of the REM sleep that it's lost. Does it get back all of the REM sleep?
Starting point is 01:27:05 No, it doesn't. It never gets back all of the REM sleep, but it tries. And so you have these really intense periods of REM sleep, hence you have really intense bizarre dreams. And that's what happens also with THC. You build up this pressure for REM sleep, this debt for REM sleep. Will you ever pay it back? Doesn't seem as though you get back everything that you lost.
Starting point is 01:27:28 But will you get back some of it? Yes, the brain will start to devour more because it's been starved of REM sleep for so long. But one of the bigger problems with THC that we worry about is withdrawal dependency. So as you start to use THC for sleep, there can be a dependency tolerance. So you start to need more to get the same sleep benefit.
Starting point is 01:27:54 And when you stop using, you usually get a very severe rebound insomnia. And in fact, it's so potent that it's typically part of the clinical withdrawal profile from THC, from cannabis. And there's anxiety withdrawal. I don't ask anybody to change their behavior. As you said, we try and inform people about what the science says and let them make choices
Starting point is 01:28:20 for themselves. People who are regular pot smokers, if you, that many of will insist they're not addicted. And, and maybe indeed they don't actually follow the profile of classical addiction. I don't know. I'm guessing some do some don't. But, um, if you ask them, well, what if I took away all marijuana consumption for, I don't know, two weeks? That thought scares many of them. And many of them will experience intense anxiety without marijuana, which speaks to perhaps not addiction, but a certain kind of dependency.
Starting point is 01:28:53 And again, I know many pot smokers, some of whom have jobs that are quite high performing and they manage. Here in Buckley, I don't know any of those. Yeah, no, no, that was right. The, what about CBD? I mean, we hear so much about CBD. I've been a little concerned about the fact that the analysis of a lot of CBD supplements out there is confirmed that much like with melatonin, the levels that are reported on the
Starting point is 01:29:17 labels in no way, shape, or form match the levels that are actually contained in the various supplements. Sometimes the levels are much higher than they're reported on the labels. Other times it's much lower. What is ingesting CBD due to the architecture and quality of sleep? Right now, I don't think we have enough data to make some kind of, you know, meaningful sense out of it. I think the picture that is emerging, however, is probably the following. Firstly, CBD does not seem to be detrimental in the same ways that THC is. So we can start by saying, does it create potential problems?
Starting point is 01:30:00 Not of the nature necessarily that we see with THC. But the devil is a little bit in the details from the data that we do have. And it comes onto your valid point of purity. At low dose, CBD can seem to be wake promoting. So in low doses that say, sort of five or 10 milligrams and trying to remember some of the studies off the top of my head,
Starting point is 01:30:24 there it actually may enhance wakefulness and cause problems with sleep. It's only once you get into the higher dose range that there seem to have been some, you know, increases in sleepiness or sort of sedation like increases. And that's usually, I think above about 25 milligrams as best I can recall from the data. And then when we look in animal models, you typically see the same type of profile too. So then the question becomes, and now again, you just don't know about purity, it's very difficult.
Starting point is 01:31:03 Although I think, and again, I'm not a user, not necessarily because I have anything against it. It's just that's not necessarily a micop of tea. There are some firms that are now doing third party independent laboratory tests. I don't know how game that is, so I've got no sense of it. I think some supplement companies are quite honest and accurate about the amounts of very substances that are in other products and some are not. I think there's just a huge range. I think the FDA is starting to explore CBD.
Starting point is 01:31:36 Certainly, I saw some grant announcements to explore function of CBD. Most of the work on CBD is being done by the general public, ingesting it and how they feel. I gave it to my dog who has had some dementia related sleep disturbances and it actually created a heightened wakefulness. It completely screwed up his sleep. It sounds as though he just...
Starting point is 01:31:54 He's a bulldog, so he's gonna get access to sleep. He's gonna take it. Really messed him up, took it away, he did better. But that's a canine, so. Right, and it could have been, you know, sort of dose did better, but that's a canine. It could have been dose-related too, but... Or binders or other things that are in there. Correct. Right now, if we were to, and I'm not making this statement, I don't think anyone can
Starting point is 01:32:16 make this statement now, but if it ends up being that CBD is potentially beneficial for sleep, how can we reconcile that mechanistically? And I think there are, to me at least there are, at least three candidate mechanisms that I've been exploring and thinking about. The first is that it's thermoregulatory. And what we found in some animal models is that CBD will create a profile of hypothermia.
Starting point is 01:32:45 In other words, it cools the body, the core body temperature down, and that's something that we know is good for sleep. The second is that it's an anxiolytic that it can reduce anxiety. And that data is actually quite strong, even with some functional imaging work that's been coming out recently,
Starting point is 01:33:00 showing that one epicenter of emotion called the amygdala, deep within the brain, is quiet and down with CBD. So I think that's at least a second non-mutile. That's great, that's conducive, you know, possibility. I think the third is some recent data that's come out that was suggesting that CBD can alter the signaling of a denocene. So it doesn't necessarily mean that you produce more adenosine, but what it can do is perhaps modulate the sensitivity, perhaps, of the brain, so that the weight
Starting point is 01:33:32 of that same adenosine is weightier in its brain signal and therefore it creates this stronger pressure for sleep. So I think these are all tentative mechanisms. I think any one of them is viable. I think all three are viable together. But right now I think does that sort of help think through the tapestry of THC and CBD? Yeah, very much so. And actually it's a perfect segue
Starting point is 01:33:59 from we've talked about caffeine, alcohol, THC, and CBD as sort of, we framed them anyway as things that done in moderation at the appropriate times are probably okay for most people. Certainly, not for everybody, there will be differences in sensitivity, but that done at the incorrect times, and certainly in the incorrect amount, will greatly disrupt this vital stage of life we call sleep. CBD, it seems, represents a kind of bridge to the topic I'd like to talk about next, which is things that promote more healthy sleep, or somehow contribute to enhancing the
Starting point is 01:34:37 architecture and quality of sleep. So I'd love to chat for a moment about the kind of grant, the original, I should say, that not the granddaddy, but the OG of sleep supplementation, which is melatonin. The so-called hormone of darkness that's inhibited by light, et cetera, frame for us melatonin in the context of its naturally occurring form. And then I'd like to talk about melatonin, the supplement, because in my experience, anytime I say the word melatonin, people think about the supplement melatonin, which in itself is an interesting phenomenon that people are so cute to its role as something you take, we often forget that this is something that we make endogenously. I'd love for you to comment in particular on
Starting point is 01:35:22 even though we, without necessarily getting into its precise nanograms, per desoleter values, what are the typical amounts of melatonin that we release each night? And then I'd like to compare that to what is contained in, say, a three milligram or six milligram tablet that one might buy at the pharmacy. Right. So, I go to sleep at night, has melatonin already kicked in before I shut my eyes and lay down my head? Usually, yes. If your system is working in the correct way, as dusk is starting to happen,
Starting point is 01:35:52 so let's say that you look at hunter gatherer tribes who aren't touched by electricity, and so that's sort of the puretentical state power excellence when it comes to electric light influence. And usually it's as dusk is approaching, that's when melatonin will start to rise. And so when you lose the brake pedal of light coming through the eyes, that normally acts like a hard brake pedal that stamps down and prevents the release and production of melatonin. As that light break pedal starts to fade with dusk, then we ease off the break pedal and melatonin, the spigot of melatonin is opened up and melatonin starts getting released. And usually we'll see this rising peak of melatonin. Some time, usually an hour, two hours later, or around, and it varies from different people
Starting point is 01:36:49 around the time of sleep itself, but it's already been on the march. For some hours before you actually hit sleep itself. Interesting. And I was always taught, and I'm assuming it's still true that the only source of melatonin in the brain In body is the pineal gland is that still true? Yeah, it seems to be from best that we can tell the pineal gland sort of meaning P like sort of shape. It's actually I think usually people say it's P like I think if you look at the Latin Derivative it's more I think it's derived from pine cone,
Starting point is 01:37:25 not peak, because in fact, if you look at the pineal, it is more pine cone shaped and so it's aptly named. Any human brain I've ever dissected, or I confess I've dissected a lot because I teach neuroanatomy and have for years, I love looking at the pineal. It's the one structure in the brain that's not on both sides. It's usually pretty easy to find. And it's pretty good size. It looks like a pea.
Starting point is 01:37:47 And it's sitting right there. And it's remarkable that it releases this hormone, essentially probably our entire lifespan, and is inhibited by light. The, so our pineal starts to release this into the general circulation. I have to imagine we have melatonin receptors in the brain and body.
Starting point is 01:38:04 It's correct. So yeah, essentially your brain has a central into the general circulation. I have to imagine we have melatonin receptors in the brain and body. It's correct. Yep. Essentially, your brain has a central master 24-hour clock called the superchiasmatic nucleus that keeps internal time. Now, it's not a precise clock if left to its own devices. Nothing that a Swiss clockmaker would be proud of. It runs a little bit longer laggy.
Starting point is 01:38:24 It's like an American clock. So there are a couple good American watches, by the way, Hamilton's over in time. It's very much like a bug. We're not famous for our timekeeping or our punctuality for them, but the Swiss are. It's very, it's not quite Swiss like it's more Berkeley, like, which is very relaxed. Oh, you know, whatever. So in most adults, at the average adults, I should say, your biological clock normally runs a little bit long. It's about 24 hours and 13 minutes, I think was the last calculation.
Starting point is 01:38:54 But the reason that we don't keep drifting forward in time and kind of running consistently, you know, more later and later, 30 minutes by 30 minutes by 30 minutes each day, is because your central brain clock is regulated by external things such as daylight and temperature as well as food and activity. All of these are essentially different fingers that come along and on the wristwatch of the 24 hour clock, we'll pull the dial out and reset it each day to precisely 24 hours. And I make that point because it knows 24 hour time, but it needs to tell the rest of the brain and the body the 24 hour time as well. And one of the ways that it does this is by communicating a chemical signal of 24 hour nurse of light and day using this
Starting point is 01:39:48 hormone melatonin. And when it is at low levels or it's non-existent, it's communicating the message, it's daytime. And for us, dienol species, it says it's time to be awake. Yet at night time when dusk approaches and the break comes off melatonin and we start to release it, then it signals to the rest of the brain and the body, look, it's dusk and it's nighttime and for us, dienol species, it's time to think about sleep. So melatonin essentially tells the brain and the body when it's day and when it's night and with that, when it's time to sleep, when it's time to wake.
Starting point is 01:40:25 And therefore, that's why melatonin helps with the timing of the onset of sleep, but it doesn't really help with the generation of sleep itself. And this is why we'll come on to what those studies of supplementation have taught us. So, it tells the rest of my brain and body, it's time to go to sleep. It perhaps even aids with the transition to sleep, but it's not going to, for instance, ensure the overall structure of sleep, or it's not the conductor that's guiding the sleep orchestra so to speak throughout the entire night. Yeah, it's more like the people that essentially take you to your seat and sit you down and
Starting point is 01:41:01 give you your program. Right, exactly. Yeah, the fall, less sophisticated analogy I have is, you know, melatonin is like the starting official at the 100 meter race in the Olympics. Not to better analogy. It calls all of the sleep races to the line and it begins the great sleep race. Yeah, better analogy by the way. Coming from the sleep researcher of all people.
Starting point is 01:41:24 No, but it doesn't participate in the race itself. That's a whole different set of brain chemicals and brain regions, which then brings us on to perhaps the question of supplementation, which is, is it helpful for my sleep? Will I sleep longer? Will I sleep better? And if I am, what doses should I be taking? Sadly, the evidence in healthy adults who are not older age suggests that melatonin is
Starting point is 01:41:56 not really particularly helpful as a sleep aid. I think there was a recent meta-analysis that demonstrated when it looked at all of the different sleep parameters, melatonin, and a meta-analysis for those, not knowing what that is, it's a scientific sort of method that we use where we gather all the individual studies and we put them in a big bucket and we kind of do this kind of statistical, fancy, slight of hand and we try to come up with a big picture of what all of those individuals to these tell us.
Starting point is 01:42:25 And what that metronalysis told us is that melatonin will only increase total amount of sleep by 3.9 minutes on average. Minutes. Not even a percent. No, and it will only increase your sleep efficiency by 2.2%. So it really is as they say in certain certain parts of California that's weak sauce. That's a weak sauce effect. The source is not strong. The force is not strong in this one. When it comes to a tool that in healthy people who are not of older age, it doesn't seem to be especially
Starting point is 01:43:03 beneficial. Now, you know, results can vary. Everyone is different, of course. So we're talking about the average, the so-called average human adult here. Well, melatonin in defense of what you're saying. And also I should mention, I have a colleague at Stanford, Jimmy Zitzer, who you know, wonderful.
Starting point is 01:43:18 Chuck Zicer's lab at Harvard Medwood. They also trained a terrific sleep researcher and I asked him about melatonin. And he essentially said the same thing that you just said, which is very little if any evidence that it can improve sleep. And yet it's probably the most commonly consumed so-called sleep.
Starting point is 01:43:33 A hundred million dollars industry. Yeah, so either massive placebo effect or it's operating through some other mechanism related to quelling anxiety, perhaps. Yeah, that is interesting. There are some studies where you do see some effects. Now, again, when you do the grand average of all studies, it just doesn't seem to have an effect.
Starting point is 01:43:52 But let's assume that for some people, it does have an effect. Let's not again be completely dismissive of that. How could it have that effect? One of the reasons that I've become a little bit more bullish on melatonin from a sleep perspective and then melatonin more generally for a, maybe we can speak about this too, as a counter measure when you're undergoing insufficient sleep.
Starting point is 01:44:18 There are two different routes there. The first reason that I think it could have a sleep benefit for some people is not because it helps in the generation of sleep. We know that it doesn't. It's because it too seems to drop core body temperature. There it is temperature again. I'm fascinated these days more and more by temperature as maybe not just a reflection of brain state and wakefulness in and sleep, but actually a lever that is quite powerful. And with all the interest in ice baths and wakefulness and sleep, but actually a lever that is quite powerful. And it's both.
Starting point is 01:44:47 And with all the interest in ice baths and hot showers and so on as and stuff, something that we'll definitely touch on, temperature variation is so key. So if melatonin is dropping body temperature by a degree or so, something that you've said before can help induce a sleepy state,
Starting point is 01:45:03 maybe that's what's allowing people to get in. That's one possibility. I don't think melatonin by itself for can help induce a sleepy state. Maybe that's what's allowing people to get in. That's one possibility. I don't think melatonin by itself will drop it by a degree, something in a degree Celsius. And for an order in us to full asleep and then stay asleep across the night, we do need to drop our core body temperature
Starting point is 01:45:18 by about one degree Celsius or about two to three degrees Fahrenheit. And that's why it's always easier to fall asleep in a room that's too cold than too hot. I think that that's one potential avenue that we are considering thinking more deeply about when it comes to melatonin. And then the other is melatonin as an antioxidant. But let's I let me table that for now because I'll just get a side-track. That's what we know so far about melatonin in terms of its supplementation, benefit or lack thereof. Two final points that I shouldn't forget.
Starting point is 01:45:55 One is, the only population where we typically see some benefit and it often is prescribed is in older adults. Older meaning, 60 and older? as we're meaning 60 and older. Yeah, 60, 65 and older. Because as we get older, you can typically have what's called calcification of the pineal gland, which means that back gland that's releasing melatonin doesn't work as well anymore.
Starting point is 01:46:17 As a consequence, they tend to have a flatter, overall curve of melatonin released throughout the night. It's not this beautiful, lovely peak and this bullhorn message of its darkness, please get to sleep. That's why older adults can have problems falling asleep or staying asleep. It's not the only reason by any stretch of the imagination, but it's one of the reasons and it's why melatonin supplementation in those cohorts, older adults, especially older adults within insomnia, people have thought about that as maybe an appropriate use case.
Starting point is 01:46:50 Well, on those lines, if we were to compare dosages, or do we know how much melatonin is typically released into the bloodstream per night, and can we use that as a kind of a rule of thumb by which to compare the typical amount that someone would supplement? I mean, typically the supplements for melatonin that I see in the pharmacy and elsewhere and online
Starting point is 01:47:12 range anywhere from one milligram to 12 or even 20 milligrams. My guess is that a normal night's release of melatonin typical for somebody in their 20s, 30s, 40s would be far lower than that. Is my correct or wrong? Yeah, it's a many magnitudes lower. This is one of the problems.
Starting point is 01:47:33 Is that I see that too. I see typical doses are 5 milligrams or 10 milligrams. Of course, if you're a supplement company, putting 10 milligrams versus 5 milligrams, if that's what you're actually doing, which we'll speak about purity as well. It's kind of like the super gulp size. Nobody wants to lower price. They just want you to, we'll just give you more for the same price and that's how we'll compete.
Starting point is 01:48:00 It's been this escalating arms race of melatonin concentration. And it really does not look meaningful for sleep in any way. What we've actually found is that the optimal doses for where you do get sleep benefits in the populations that we've looked at are somewhere between 0.1 and 0.3 milligrams of melatonin. In other words, the typical doses are usually 10 times, 20 times, maybe more than what your body would naturally expect. And this is what we call a super physiological dose. In other words, it's far above what
Starting point is 01:48:40 is physiologically normal. And to put that in context, imagine I said to you, I want you to eat 20 times as much food today. I thought you're gonna use testosterone as example. You know, you're gonna take 300 times the normal amount of testosterone. We know that would have tons of deleterious effects. Right, terrible.
Starting point is 01:48:58 Yeah. And yet you can do this. One thing that I'm concerned about about these super physiological levels of melatonin is that many years ago, actually here at Berkeley when I was a graduate student we would inject animals which were seasonally breeding animals with melatonin and the consequence of that was that their gonads either their testes are ovaries would shrink many hundredfold or more
Starting point is 01:49:24 in other words that they would go from having nice, healthy sized hamster testicles, what a hamster would consider healthy size for a hamster, and they would shrink to the size of a grain of rice. So from like an almonds to a grain size of a grain of rice, I had to see that only once for me to be very concerned about super physiological levels of melatonin. And I realized that melatonin does different things
Starting point is 01:49:44 in different species. We are not hamsters, we are not seasonal breeders. Seasonally restricted breeders, there might be more breeding during certain seasons. I don't know those data. But nonetheless, hormones are powerful. And sure there is an optimal. And sometimes we see that going slightly above
Starting point is 01:50:04 endogenous levels for certain hormones not always can have beneficial effects and sometimes it can have detrimental effects. I'm just concerned about taking high levels of a hormone that has effects on the reproductive axis and that's one of the reasons why I get very concerned when I see people really getting aggressive about melatonin supplementation taking a hundred ten five hundred sometimes even ten thousand times the amount that we would normally release. That's that's my concern although it's not nested in any one specific human study. I just I just don't like to see I certainly don't want to see other people and I don't want to personally take a hormone that's known to be Androgen-suppressive at high levels. Why would I take that? That's the question I ask myself.
Starting point is 01:50:51 I think it's a very good point. If you look at some of the evidence around melatonin's lethality, if you want to go to that extreme, for the most spot, it's pretty safe. You can take a lot of it before you die. Right. Exactly. Yeah. But I don't know that's the great thing. That's a great thing. You are a stick for it. Because you know, you really need to think about your, you know, your health, not just
Starting point is 01:51:15 whether the shooting is going to kill you or not as the decision matrix through which you pop a pill. Right. And it comes on to this concern around melatonin because there was a study, I think it's one that you mentioned too, where they looked it over, I think it was at least over 20 different brands of melatonin supplements. And what they found is that based on what it said on the bottle versus what was in the capsules themselves, It ranged from, I think it was 83% less than what it said on the bottle to 478% more than what it said on the bottle.
Starting point is 01:51:51 Now, if that's a 10 milligram, you know, pill, and it's 478% more than 10 milligrams, and we're already at 10 milligrams at many tens of times more than is a physiological rather than a super physiological dose We do need to be a bit thoughtful. Yeah, remember those hamsters Well, and I do appreciate the deep dive on melatonin because I think people Need to understand that it's it's nuanced. It's a matter of dosages and timing, etc. And then it may have its place, as you mentioned, in older
Starting point is 01:52:29 individuals. And I should mention that I'm an avid consumer of supplements that I believe in for me, and I have been for a very long time. So I'm by no means anti-supplement. Some supplements I refuse to take or avoid taking. Others I'm quite avidly take. Along those lines, I personally, and I don't know what your thoughts on this are, but there are a few things that I've personally found beneficial. I'd love your thoughts on them. I would love it if you would tell me that everything I'm about to refer to as placebo. That would be fine. So that's what we do.
Starting point is 01:53:06 We're scientists. We argue, and then we re-remain friends as it goes. So magnesium. There are many forms of magnesium. Magnesium citrate, as we know, is a terrific laxative. Magnesium malate seems, at least from a few studies, seems to relieve some of delayed onset muscle soreness, doesn't seem to create a kind of sedation.
Starting point is 01:53:27 Two forms of magnesium, the normal way of magnesium, bi-glycinate and magnesium three and eight. We believe, based on the data, can more actively cross the blood-brain barrier, so you put in your gut, but some of that needs to get into your brain, or to have the set of effect. What are your thoughts on magnesium supplementation? Do you supplement with magnesium? What studies would you like to see done if they haven't been done already? I don't supplement with magnesium, but I do think 3 and 8 is interesting because of that
Starting point is 01:54:00 higher capacity to cross the blood brain barrier and actually have a central nervous system effect. And the reason that that interests me is because the sleep is by the brain of the brain and also for the brain as well as for the body. We just don't have a particularly good set of studies that have targeted exclusively three and eight. We do have lots of studies that have just looked at magnesium in general for sleep. And overall the data is uncompelling.
Starting point is 01:54:29 Interesting. And for a while, I was confused as to why, where did this come from, this kind of myth of magnesium. So I started looking back into literature, and I've best traced it at least as far as I can tell to early studies showing that those who were deficient in magnesium also had sleep problems, they had other problems too of course, but sleep problems were one of that set of sequal eye that came from having lower magnesium and when they Supplemented with magnesium and tried to restore those levels some of those sleep problems dissipated and then that seems to have gotten lost in
Starting point is 01:55:12 Some of some game of sort of like whispers around the room and it's become translated into people who don't have sleep problems Who are healthy sleepers and who are healthy in general and who have healthy normal levels of magnesium. If they take more magnesium, they will sleep better. And the data really there is not good. Once again, the only study that I've seen where magnesium did have some efficacy was in a study with older adults. I think they were 60 to 80 years old. It may have been exclusively women, now I think about it.
Starting point is 01:55:44 And they also had insomnia. And in that population, you did see some benefits. And my guess is that because it's an older community as well, they were probably, probably deficient in magnesium. So they fit the former category of simply when you're deficient and you restore, you can help sleep sort of return to normal. But if you are not deficient and you restore, you can help sleep, sort of return to normal. But if you are not deficient and you're healthy and you're not old and you don't have insomnia, and you're supplementing thinking that it provides sleep,
Starting point is 01:56:12 right now the data isn't supportive of that. But I just don't think we have enough 3 and 8 data to actually speak about that, because it could just be a blood brain barrier issue so far with the other forms. So maybe some additional studies looking specifically at three and eight or by glycinate would be, would be useful. And magnesium is involved in so many cellular processes. You can imagine that
Starting point is 01:56:32 this effect, if it truly exists, is as we say in science, in the noise, meaning it's in the, it's in the, the jitter of the data, but to isolate the real effect, one needs to do some more refined studies. What are some things that are of interest to you, if not things that you happen to take? These are not things that I personally take, mostly because I just haven't experimented with them. Valerian root is one, tart cherry and kiwi fruit. To tell me about Valerian root, tart cherry and kiwi fruit. To tell me about, tell me about Valerian root, tart cherry and kiwi fruit.
Starting point is 01:57:08 This is new to me. I'm have certainly heard of them and tart cherry and kiwi sounds delicious. But what's happening with Valerian root, tart cherry and kiwi? And are we talking about eating tart cherries and kiwis and Valerian root? Or are we talking about taking them in pill form? Usually it's supplements, but it's also both for tart cherries and for Kiwis. It's the actual fruit themselves. Valerian often touted as a beneficial sleep aid, and lots of people swore by it too, but
Starting point is 01:57:42 the evidence is actually quite against that. Oh, really? Not that it makes you sleep worse, but of at least the seven good studies that I've been able to find, and typically these are of the nature of what we call a randomized placebo crossover design, and I won't bore people with what that means.
Starting point is 01:58:01 It's sort of one of the- Good studies, solid studies. It's one of the sort of gold standard methods that we have when we're looking at interventions that is such as drugs that means. It's sort of one of the gold standard methods that we have when we're looking at interventions such as drugs, these five of the seven found no benefit of Valerian route on sleep. Then two out of the seven, the data was just insufficient. I think it was a power issue where they just couldn't make any strong conclusions. And then I think there was the most recent study, I think looked at two different doses of fallerian. I could have this wrong.
Starting point is 01:58:36 And they just failed to find any effects once again, but the stunning part of that paper, as I recall, they had this big table with all of the different sleep metrics that they looked at. And there were well over 25 different things that they tried to see if fallarian impacted, and none of them were significant. Which stunts me because from statistical probabilities we know, if you just randomly perform 25 statistical tests, chances are probabilistically, you'll just get one significant result by random chance. And even with random chance on their side, they still couldn't find a benefit
Starting point is 01:59:12 of Valerian. So Valerian root might be worse than nothing at all if there is, so to speak. I mean, again, plus your effect, we can think about that too. And I would say that if you feel as though it's having a benefit for you and with all of the caveats that we have with supplements, things like melatonin, purity, concentration, et cetera, maybe it's no harm, no foul, but I'm not a medical doctor. And I don't tell anyone about, we have all of these disclaimers about not recommending some things. Sure.
Starting point is 01:59:42 And we'll include these things. I mean, I always say, we're not physicians. We don't prescribe anything. We're scientists and and we'll include these things. I mean, I always say, you know, we're not physicians. We don't prescribe anything. We're scientists and professors. So we profess things. It's up to people to be responsible for their own health, not just to protect us, but to protect themselves. I do want to hear about tart cherry and kiwi fruit.
Starting point is 02:00:01 What's the story there? Strange, isn't it? I was, you know, I'm kind of a hard-knows scientist. And when people, you know, some years ago started saying, oh, Tart cherries, it's the thing, or kiwi fruits, I was thinking, oh my goodness, this sounds a bit californial too long. Yeah, I know, yeah, the sun has softened me some. But I thought, look, one of the things that we have to do
Starting point is 02:00:23 as scientists is be as open-minded as possible and I should not be so quick to dismiss. So I went to the literature, just started reading as much as I could about it. And there were three really good randomised placebo crossover trials with tart cherries. And what they found was that in one study, it reduced the amount of time that you spent awake at night by over an hour. And then the other two studies, one of them found that it increased the amount of sleep that you got by 34 minutes.
Starting point is 02:00:57 The other, it increased the amount of sleep that you got by 84 minutes. Which, you know, these are, and what's striking is that they were independent studies. I think meaning that they were from independent groups. And these were, you know, some of these guys, you know, I, I, I, and Gels, I know pretty well. And they're in, you know, and trust their work. Right.
Starting point is 02:01:19 I really trust their work too. Were they ingesting actual tart cherries? Are they drinking the juice or in capsule? It was juice. So they, in all three studies, it was juice. Although you can, I think, as a supplement. You can buy it in a capsule and we've got no idea whether that changes the benefit or not.
Starting point is 02:01:33 What was also interesting in, I think it was that last study where they got an increase in sleep by 84 minutes, it also decreased daytime napping significantly. That's one that I could certainly make use of. So I love my day-time. You know, what I'd love to skip them too. Right, and we can speak about naps and the upside and downside of that, which then made me think, well, if that's the case,
Starting point is 02:01:56 maybe the net net benefit on sleep overall is no different. It's just that it decreases the amount of time that some people were taking to sleep during the day and giving it back to the night. But that wasn't the case because if you added the total amount of sleep that they were getting without tart cherries, both naps and likely sleep combined, still when you took tart cherries, you still got to net some benefit of total amount of sleep. So, you know, so far, when it comes to supplements and those types of studies, they're good studies and the data looks interesting. But as a drug itself, you know, if this was clinical drug, you know, three studies that are somewhat small in nature
Starting point is 02:02:38 and have some positive benefit, that's what we would call preliminary data of maybe a chin-sc chin scratching kind. So yeah, and depending on the margins for safety, one might think, well, given that it's a tart cherry as opposed to some pharmaceutical union prescription for, then, you know, some people they're threshold to experiment with supplements is quite low. Some people they're threshold is quite high. I feel like, you know, there are two categories or at least two categories of folks out there. People who hear, oh, Tart Sherry can improve sleep and will run out and try it. And people who
Starting point is 02:03:10 hear, well, that sounds crazy. Why would I do that? But of course, we have to remind people that Tart Sherry isn't really what we're talking about, presumably, if this is a real effect and sounds like it might be, that there's a compound in tart cherry, that if we were to call it whatever, whatever, five alpha six, some molecule, if we refer to it by its technical name, then people would say, oh, that sounds like a very interesting technical way to approach sleep,
Starting point is 02:03:37 but doesn't sound very natural. So both groups are a little bit misguided, in the sense that people who think that everything that comes from naturally occurring foods, plants, et cetera, things that grow out of the ground, that that's all safe, that's not true. And people that think that pharmaceuticals are the own, if it's not evidence with the purified molecule, then something's not of utility. Well, that's certainly not true.
Starting point is 02:03:59 Somewhere in the middle, I think lies the answer, which is, it sounds to me like tart cherries at least an intriguing potential sleep aid, intriguing potential sleep aid and I'm underscoring potential. I'm certainly intrigued by it to the point where I might experiment a bit, but I'm an experimenter for myself. Before I ask you about Kiwi, I've had quite good results from taking something called Apigenin, which is a derivative of chamomile, but in supplement form, I think I take 50 milligrams, about 30 minutes before sleep,
Starting point is 02:04:31 and I subjectively experience a better night's sleep. So as we go, I don't measure, I confess I don't measure my sleep. I'm not a sleep tracker guy. Yeah, I do. But, you know, there are a few papers out there. They're not what we would call blue, published in blue ribbon journals, but they have control groups and it looks somewhat interesting. And there when I say apigenin, people get somewhat intrigued over this molecule.
Starting point is 02:04:58 Chemomile has long been thought to be a sedative, a mild sedative, but a sedative. Do you drink chemical mild tea? Do you take appajanan? And what are your thoughts on appajanan? Yeah, I don't. And I have looked into some of the data regarding sleep as well. Right now, from best I can tell, it's mostly subjective data, rather than objective, hard sleep
Starting point is 02:05:19 measures. And that's why right now, I'd sort of unclear, not no comment, but just unclear, not no comment, but just unclear, not dismissing it, because I think you and I both scribe to the idea of absence of evidence, is not evidence of absence. So keep your mind open at least, I tell it to myself.
Starting point is 02:05:39 I think if you're finding a benefit and you can do what I would think of if I was personally experimenting, which is finding a benefit and you can do what I would think of if I was personally experimenting, which is both the positive and negative parts of the experiment, what I mean by that is, let's say that I now want to think about some kind of a sleep supplement. I will take some kind of baseline set of recordings for a month and I will just gauge where I'm at, sort of supplement free. Then I'll go on for a month to whatever I'm thinking of taking and I don't, you know, supplement, but let's say that
Starting point is 02:06:12 I want to and I experiment with that. And I feel as though based on my metrics, be them objective from my ororing or be them subjective from whatever I'm, you know, writing down in the morning and both are important valid subjective and objective. We like both in the sleep world. And I think, okay, look, it's clearly that it seems to have some kind of an effect. The key thing, however, is then do the negative experiment, which is now come off it for another month and see do things get worse. And if I can see that by directionality,
Starting point is 02:06:46 then I am starting to think, maybe I'm believing this a little bit more. So that's the way I would sort of typically approach, you know, a supplementation regiment if I were to do it. And that's just me, that's just the way my mind works. But no, that's great. I think it's very, very scientific and organized in a way that allows
Starting point is 02:07:11 You and and would allow other people to make very informed decisions for themselves. I like that I I like to think in terms of manipulating any aspect of our biology that behavioral tools always are the first line of entry. Yeah, then Nutrition everyone has to eat sooner or later, even if you're fasting, then perhaps supplementation, then prescription drugs, and then perhaps brain machine interface, devices that you use to induce something. And those could be done in combination, but what concerns me is when I hear people say, well, what should I take without thinking about their behavior, their light viewing behavior,
Starting point is 02:07:43 et cetera, but of course these things work in combination. I think you're right that there's many, when it comes to sleep, there are many low hanging fruits that don't necessarily require you to put sort of exogenous molecules, and other words, things like supplements into your body or use different types of drugs to help you get there. Now, when it comes to prescription sleep aids, I think I've been again a little bit too
Starting point is 02:08:11 forthright. We know in clinical practice that there may be a time and a place for things like sleeping pills. They are a short term solution to certain forms of insomnia, but they are not recommended for the long term. And we also know that there are lots of other ways that you can get a sleep help or you can get a sleep curative profile from things like cognitive behavioral therapy for insomnia, which is a non-drug approach. And quite effective from what I understand. Very effective as sleeping pills, great data, more effective in the long term. There effective as sleeping pills, great data. More effective in the long term, there's a recent study published that after working with
Starting point is 02:08:48 that therapist, some of the benefits lasted almost a decade. Now, if you stop sleeping pills, usually you have rebound in some way, your sleep goes back to being just as bad if not worse. And I think the same is true when we think about supplementation. There are so many things that are easy to implement when it comes to sleep that don't require venturing out into those waters. And again, we're not here to tell anyone about whether they should venture or not. That's completely your choice.
Starting point is 02:09:17 All I'm saying is that if you want to think about optimizing your sleep, there are a number of ways that you can do it that don't necessarily require you to swallow anything or inject anything or smoke anything. For which the margins of safety are quite wide. That's the other one. Yes, so speaking of low hanging fruit, I don't know how low hangs in reality, but what about Kiwi? They're delicious to me anyway. Yeah, the humble Kiwi fruit, named not not, shouldn't be mistaken for the, the, the,
Starting point is 02:09:48 the, um, flightless bird of New Zealand, which is the native bird, that we're talking about the Kiwi, the fruit here, which, um, those trees and shrubs are, um, mostly, um, southeast Asia. Kiwi fruits have been previously touted, as potentially having a sleep benefit, which again got me curious, and I first threw it out. To my knowledge, there's already only one published human study that's of any value,
Starting point is 02:10:16 but what they did find was that it decreased the speed of time with which it took you to fall asleep. These are really ingesting the whole kiwi. So it's ingesting the whole kiwi. With the skin, skin, people cringe when they see me kiwi. With the skin, I need to skin people. The skin, when they see me do it, but I don't need this. No, no, no, I think the idea is some of the good stuff
Starting point is 02:10:31 and I'll come onto this, may actually be in the skin, it's health. Thank you. I just want you just help me win a bet. I'll give you your... Okay, okay, yeah, you can familiarize, by the way, the skin is used, no, no, no, he just told me to say that,
Starting point is 02:10:42 so he went to the, no, he did not. So the skin seems to be part of this potential sleep equation. And that's the, yeah, the, um, you fell asleep faster and you stayed asleep for longer and you spent less time awake throughout the night. And I just thought, well, you know, that's one study. What can you really do with that? There is another study, however, in an animal model, which is, you know, that's one study, what can you really do with that? There is another study, however, in an animal model, which is, you know, a little bit more interesting. And once again, they found a very similar phenotype that the rats, oh, sorry, they were mice,
Starting point is 02:11:16 the mice fell asleep faster, and they also spent longer time in sleep, the sleep duration also increased. What was also interesting mechanistically, and this is not the mechanism that I think ties together, tart cherries, kiwi fruit, and things like melatonin, because I think there could be one common binding mechanism. What they found in the animal study is that they could block those kiwi fruit sleep benefits using a GABA blocking agent. Now GABA, GABA, which stands for GABA Amino butyric acid
Starting point is 02:11:54 is one of the major inhibitory neurotransmitters of the brain. It's kind of like the red... Like the really current sedative. That's it, sort of. Yeah, it's kind of the red light on the traffic light signal. You know, others are green light. Gabber is red light. So by playing around with some sort of clever drugs to manipulate the system, they could prevent the benefit of the kiwi fruit by sort of buggering around with the
Starting point is 02:12:20 Gabber receptor, meaning that perhaps part of the Kiwi Fruit benefit on sleep was mediated by the brain's natural inhibitory neurotransmitter system called the GABA system. And I thought that was kind of, that convinced me a little bit more that maybe there's something here to read into. So to be determined, again, here is the banner. But you know, Tart Charis and Kiwi Fruit, here is the banner. But, you know, cherries and kiwi fruits, the data surprised me. Because in part, I was so preoccupied with being, you know,
Starting point is 02:12:55 I don't know, a bit pure issue about it, and a bit snobby thinking, come on, that's definitely not gonna work well. Comments are compound. I look forward to a day when supplements are no longer called supplements, because at the end of the day, whether or not something has an effect,
Starting point is 02:13:08 whether or not it's a whole kiwi fruit or a derivative kiwi fruit, will depend on the molecular compound. And as you mentioned, this potential mechanism via the GABA system, we both as scientists get excited about mechanism, because when you can trace a mechanism in a pathway, it provides a rationale, a grounding for why
Starting point is 02:13:26 kiwi of all things, or tart cherry of all things might help increase total sleep time. I'd be remiss if I didn't mention or ask about trip-to-fan and serotonin. I can anecdotally say, when I've taken trip-to-fan, the precursor to serotonin or serotonin itself, I have a horrendous night's sleep. I fall asleep very easily and I experience ridiculously vivid dreams.
Starting point is 02:13:57 Neither pleasant nor unpleasant is kind of a mishmash and then I wake up and I experience several days of insomnia that and I've done the positive control and the negative control and all the variations thereof to confirm that at least for me supplementing with serotonergic agents is a bad idea for me. And trip to fan is a common sleep supplement and sleep aid that's discussed. common sleep supplement and sleep aid that's discussed. The normal architecture of sleep involves the release of serotonin, but in a very timed and regulated way. What are your thoughts about serotonin in sleep if you had to kind of put that into a nutshell? And then why supplementing with serotonin and or
Starting point is 02:14:41 its precursor, a tryptophan, might be a good or a bad idea for somebody. I think one of the potential dangers is that based on what's going on in your body, that can change the absorption of natural sort of trip to fan and serotonin uptake within the brain itself. So I'm always thoughtful when you're playing around with that Mother Nature dynamic, as it were. The data as you described
Starting point is 02:15:11 is a little bit all over the map. Some people say that it knocks them out. Other people say just like you do, it has a terrible impact on my sleep. And when I stop, it's pretty bad for a couple of days. It seems to have this lingering after effect. I think what could be happening here is we need serotonin to, just as you described, be modulated in very specific ways during the different stages of sleep. If you look at the firing of the brain epicenters where serotonin is released, and there's a bunch of them in the brainstem.
Starting point is 02:15:49 What you find on the release of serotonin 2, when we're awake, it's usually in high concentrations. As we start to drift off to sleep, it lowers some, but not necessarily dramatically as we're going into non-REM sleep. But then when we go into REM sleep, serotonin is shut off. The other, one of the other neuromodulators, noradrenaline, also shut off. REM sleep is the only time during the 24-hour period where we see noradrenaline and serotonin or norapinephrine completely shut down when I say serotonin, weorepinephrine completely shut down. When I say serotonin, worlds are talking 5-HTP. Sorry, 5-HT. That's just its chemical name here. So whether it speaking about serotonin or 5-HT, it's the same thing. Norepinephrine, noradrenaline,
Starting point is 02:16:35 both of those need to be shut down for you to produce REM sleep. The other one of the other neuromodulators that then ramps up to produce REM sleep is acetylcholine. So these three neuromodulators have this incredible reciprocal dance that they have for you to generate what is called a natural architecture of sleep throughout the night. It's the pushpull again. It's a pushpull again. You know, it's you know, it's chest and back. It's the push pull again. It's a push pull again. It's chest and back. It's whatever you want to think of. That's why I think if you're trying
Starting point is 02:17:10 to increase dramatically drive up your serotonin levels at night, and that sustains throughout the night when you're trying to get into REM sleep, you could be artificially fragmenting REM sleep. Now I don't know the data. I don't think anyone's really got the data. But that's why I would be, you know, if you were to say, Matt, two years' time, that's the data, help me understand the potential mechanism, or let's design some experiments, where would you go first?
Starting point is 02:17:36 I would say, let's look at the disruption of REM sleep, non-REM sleep, reciprocal regulation, because, you know, you need serotonin to be you know up at one time down it another. So I agree with everything you said and I'm personally never taking trip to fan or serotonin again unless there's some clinical reason for that that I would need to do that. I want to ask about some other pro sleep behaviors. But before I do that, let's talk about naps. I love naps. I come from a long history of nappers. My dad always took a nap in the afternoon.
Starting point is 02:18:14 I take a 20 or 30 minute nap, or I do a practice which I took the liberty of coining NSDR non-sleep deep rest. Some sort of just passive laying out there, feet up elevated, sometimes people do you, or I'll do yoga knee draw, I'll do hypnosis, or something of that sort, but 20 or 30 minutes of that has been very beneficial for me to get up from that nap or period of minimal wakefulness, we'll call it,
Starting point is 02:18:40 and go about my day quite well, and also fall asleep just fine. What are the data on NAPs? Do you NAP? And what are your thoughts about keeping NAP short, meaning 20 to 30 minutes versus getting out past 90 minutes, two hours? So for you, personally, NAPs, yay, nay or man, I don't't nap, and I've just never been a habitual nap. Is that because you don't feel sleepy in the afternoon? In order to sleep.
Starting point is 02:19:11 Because sleep. Don't feel sleepy. So you're just harder than that. I wouldn't say, Haudia, I may be less capable of fooling asleep. I'm not dragged into the afternoon. No, no, I don't drag the afternoon. So you don't nap because you don't feel
Starting point is 02:19:26 a need to nap. That's right, yeah. Now, it's not that I am immune to what we call the post-prondial dip in alertness. I definitely feel as though there can be this kind of afternoon low, where I'm not quite as on as I was at 11 o'clock in the morning. And we know the physiology to that, which brings us back to whether we were designed to nap.
Starting point is 02:19:49 So for naps, we've done lots of different studies and other colleagues have done these studies too. Naps can have some really great benefits. We found benefits for cardiovascular health, blood pressure, for example, we found benefits for levels of cortisol, we found benefits for learning in memory, and also emotional regulation. How long are the naps typically in those studies? Anywhere between 20 minutes to 90 minutes. Sometimes we like to use a 90 minute window so that the participant can have a full cycle of sleep, and therefore they get both non-rem and REM sleep within that time period. Then when we wake them up, we usually wait a period of time to get them past what we call sleep inertia, which is that kind of window of groggyness where you say to your better half look,
Starting point is 02:20:33 darling, please don't speak to me for the first hour of drive. Don't anything right now. After the first hour of waking up, I'm just not the best version of myself. So we wait for that time period and then we do some testing. And we've done some testing before and after and we look at the change and that's how we measure what was the benefit of NAPS.
Starting point is 02:20:51 And the reason why we sometimes do 90 minutes so that they get all of those stages of sleep. And then we correlate how much benefit did you get from the NAP and how much of that benefit was explained by what REM sleep you got, what deep sleep you got, what deep sleep you got, what light sleep you got. So that's the only reason that we use that as an experimental tool. What we've also found is that NAPS of as little as 17 minutes can have some quite potent effects on, for example, learning. None of this is novel NASA pioneered this back in
Starting point is 02:21:22 the 1990s. And during the missions, were experimenting with naps for their astronauts. And what they found was that naps of little as 26 minutes improved mission performance by 34% and improved daytime alertness by 50%. And it birthed what was then called the NASA NAP culture throughout all terrestrial NASA staff during that time period. So it's long been known that NAPs can have a benefit. NAPs however can have a double edge sword, there is a dark side to NAPs. And it comes back to our story of a denocene and sleep pressure.
Starting point is 02:22:03 The longer we're awake, the more of that sleep pressure denocene that we build up. But what I didn't tell you is that when we sleep, the brain gets the chance to essentially clear out that a denocene. And after about 16 hours of wakefulness, and then after about eight hours of sleep, eight hours of sleep seems to be able to allow the brain to decrease its adenosine levels back to normal. And so naturally we should start to wake up, which also aligns with your circadian rhythm and those are two separate processes.
Starting point is 02:22:35 But with about 8 hours of good quality sleep, 7 to 9 hours of the average adult, we are free of all of that adenosine. We've evacuated it essentially out of the brain, and we wake up naturally feeling refreshed. The reason that naps can be potentially dangerous is that when you nap, you are essentially opening the valve on the pressure cooker of sleep pressure. And some of that sleepiness is lost by way of the nap. So for some people and not all people,
Starting point is 02:23:07 and you're a great example of this, some people, however, if they are struggling with sleep at night and they nap during the day, it makes their sleep problems even worse. So for people with insomnia, we typically advise against napping. And the advice is if you can nap regularly and you don't struggle with sleep at night, the naps are just fine. But if you do struggle with sleep, stay away
Starting point is 02:23:31 from naps. If you are going to nap, try to limit your naps, try to cut them off a bit like sort of caffeine, maybe eight to 12 hours, maybe not that far off, maybe sort of seven to six hours is a good rule of thumb, try not to nap essentially late in the afternoon. And if you do take a nap and you want to maintain your, you don't want to have that groggyness hang over that can happen after a full night of sleep for the first hour, try to limit it to about 20, 25 minutes, and that way you don't go down into the very deepest stages of sleep, which if I wrench you out of with an alarm, then you just kind of feel, you almost feel worse for the first hour after the nap. I've definitely experienced that if I oversleep.
Starting point is 02:24:17 Certainly if the sun goes down during my nap and I wake up and light overall, lighting conditions have changed, I find it very hard to jolt myself back into the evening and it can screw me up. So I try and keep those naps pretty brief. And I should say, I'm very happy to hear you mention individual differences and why some people might want a nap and other people might not want a nap.
Starting point is 02:24:42 I have a colleague, Leach and Lowe, he'll be familiar to many neurobiologists, but who's a absolutely spectacular scientist, member of the National Academy Howard, who's investigator, just a phenom, and has a ton of energy. But years ago, I learned that he always takes a nap in the afternoon so much so that when he travels
Starting point is 02:25:00 to give seminars at other universities, he will tell his post-lunch, post, whoever it is that he's supposed to meet with. May I have your office for 30 minutes of our, sometimes 30 minute discussion or 60 minute discussion because I like to take a nap and he does that and then gives his, his talks are typically in the afternoon in academic culture. And he describes the, the effect of the nap for him, the short naps in the afternoon being so profound for his productivity. That's actually what inspired me to start feeling okay about my desire to nap. And so I think for me, that was great vindication
Starting point is 02:25:36 for those that might feel guilty about wanting a nap. But I take to heart your note about avoiding naps if you have trouble falling and staying asleep because I think that I have family members who also if they nap, they're a wreck, they can't sleep. Yeah. I think it's just, we've often been very pro sleep, we're sort of the sleep community. So I think it's good to always point out these potential dark sides of any aspect, but you're absolutely right.
Starting point is 02:26:04 No one should feel guilty about getting the sleep that they need. And I think that's been one of the big problems in society. Society has stigmatized sleep with these labels of being slothful or lazy. And we're almost embarrassed, you know, to tell colleagues that we take a nap. I think sleep is a right of human beings. And I therefore think that sleep is a civil right of all human beings. And no one should make you feel unproud of getting the sleep that you need. No, I love that. And it's an important point. I also feel that one of the best ways to beat your competition in any endeavor is to outlive them. So now that we know that sleep can enhance longevity and lack of sleep can shorten
Starting point is 02:26:51 one's life, that's all the justification I need anyway. Can somebody sleep too much? Is it possible to get too much sleep? It's a very good question and there are probably two things to say about it. There is a condition that we call hyposomnia, but that's a mixture of things. It's where people have either a very high sleep need or they are very sleepy during the day and they're typically falling asleep and these can happen in a variety of different clinical contexts. One of the places where we've often seen hyposomnia believed to manifest is in depression. But if you look at some of those studies, it turns out it looks more as though those people are
Starting point is 02:27:39 simply reporting being in bed longer, but not necessarily sleeping longer. And that fits very well with one of the profiles that we know of depression, which is anodonia, you don't get pleasure from normally pleasurable things. So you just don't want to go out into the world, you don't want to interact because you're depressed. So what do you do? You just stay in bed. Blind clothes, watching TV. Right. And that just looks as though, you know, when people say, what time did you go to bed and what time did you get out of bed, the mistake made in that question is,
Starting point is 02:28:10 okay, that's how much time they're sleeping. When you should have said, what time did you fall asleep and what time did you wake up? And the answer could be very different. So that type of somebody from a clinical context, can you sleep too much though? One of the data points that argues, yes, that's possible is when we look at all-cause mortality.
Starting point is 02:28:32 Certainly what you find is that using the sweet spot of seven to nine hours, when you start to drop below seven hours, there is a relationship which suggests that the shorter you sleep, the shorter your life, short sleep in that regard predicts all cause mortality. But it's again not a linear relationship like the one that we've seen with REM sleep. Once you get past nine hours,
Starting point is 02:28:52 the mortality curve stops going down, and then once you get further 10 or 11 hours, it hooks back up again. It's almost like a J-shape, tilted over a little bit, and reversed. So there's this strange hook. What's going on here? Right now, sleep science has at least two non mutually exclusive explanations for this. The first is that if you look at some of those populations, the idea is that whatever was causing them illness
Starting point is 02:29:21 and took their lives was just too much for sleep to deal with. However, we know that when we get sick, one of the things that we do immediately and there's a whole mechanism and inflammatory mechanism, cytokine mediated, when we get sick, we want to sleep more. We just want to kill up in bed and sleep it off. So the argument there is that it's not that sleep
Starting point is 02:29:43 was killing people prematurely. It was that these people were calling on the help of sleep. They were calling on this thing called the swiss army knife of health, that is sleep. But whatever it is that they were facing was just too powerful for sleep to overcome. So it artificially looks as though more sleep leads to a higher risk of death. When sleep was actually responding to the mortality risk and it lost the battle, that's one argument. The second is that we know that sleep quality and poor sleep efficiency is a very strong predictor of all cause mortality. And when you look at people who often report
Starting point is 02:30:25 sleeping long amounts 10 or 11 hours, they typically report having very poor quality sleep. So because their quality of sleep is poor, they just try to sleep longer to try and get some of that back. So again, here now it's poor quality sleep, masking as too much sleep, leading to this artificial hook which looks like mortality. That's a second explanation. A third which is more of a gadunken which is just a kind of like a thought experiment, and I'm of this mentality, I don't know how many other people share this.
Starting point is 02:31:02 I actually think there could be a thing as too much sleep. Physiologically, I think it's possible. But the reason I think that is because it's no different than food, water, or oxygen. Can you overeat? Yes, you can. Can you under eat? Of course. Or light. Light in the early part of the day. Or throughout the day. Wonderful. Light, late in the day. Right. Night, detrimental. By directional. You know, for water, can you overhydrate hyponutri- You mean it can lead, you know, it happened in the 1990s and 2000 with the ecstasy craze. Where governments were saying, you're dehydrating,
Starting point is 02:31:35 you're dancing all night, please drink water. And they drank too much water. They're blood electrolytes when, you know, all over the place and they were having cardiac arrests or stroke. Yeah, people were dying. And they were dying because of excessive hydration. Can you get too much oxygen, hyperoxemia, and it can cause free radical damage, which can be profoundly harmful and kill brain cells?
Starting point is 02:31:58 Can you sleep too much, which is the fifth element of the life equation. Alongside food, water, oxygen. So fourth, I should say, I can't even count. Clearly, I'm sleeping well. Yes, I think there could be that possibility. Are most people in danger of getting too much sleep, oh, contraire, if you look at the data. Right. So, but I don't dismiss that idea. I think it's possible. That's a very thorough and very nuanced and you have very clear answer.
Starting point is 02:32:33 So, I, it's so interesting to think that a lot of the data that out there that talking about being in bed too long that it's just trying to compensate for the actual fragmentation of sleep. So, what I'm coming away with is that it's just trying to compensate for the actual fragmentation of sleep. So what I'm coming away with is that there are many paths to this and both positive and things to avoid, but the idea is to get most nights a similar amount, probably seven to
Starting point is 02:32:58 nine hours somewhere in there, of high quality sleep. That the social sleep quality is going to become. I would hope a phrase that more people think about and learn about and cultivate as a practice. I want to ask about a set of behaviors that I'm at least, I'm aware of at least one company is starting to track in their sleep monitoring device. And that's orgasm. And sex orgasm and masturbation topics that are, you know, are somewhat sensitive, but from the perspective of biology, none of us would be here. We're not for a sperm meat egg in some fashion, either in a dish or in vivo, but what are the data as you know them to be, or maybe your labs even doing
Starting point is 02:33:48 this kind of work and exploration about the role that sex, orgasm, masturbation play in getting to sleep and staying to sleep and sleep quality? Certainly those behaviors and those physiological events have been part of our evolutionary history. What's the story there? What can we say about this in terms of science and their essay practice? Yeah, I mean, it's almost that caricature of, you know, in the movies where, you know, a couple makes love. And then, all of a sudden, you just sort of hear snoring, or you know, it happens with the idea that it's somewhat someogenic, that it's sleep promoting.
Starting point is 02:34:30 Well, the post-organic increase in prolactin is interesting. Thought to be a naturally occurring sedative, though. Presumably has a function in... An oxytocin has that also, that benefit, where you see, you know, a dissipation of the fight or flight branch of the nervous system which has to happen, due to fall asleep. That's why we often see, you know, here at the sleep center, we'll see a phenomenon called wired and tired where people say, look, I am so desperately tired. I just, I'm so, so tired, but I can't fall asleep because I'm too wired.
Starting point is 02:35:05 So your sleep drive, you're, you're desperately tired. It's there, but because you're wired, because you've got too much sympathetic activation, too much cortisol as well, you can't fall asleep. It's a, it's an impressive roadblock to anything like good sleep. And it's one of the principal mechanisms that we now believe stress and physiological activation that is the underlying cause of many forms of insomnia. But coming back to sex, the data is actually quite compelling that both either subjectively assessed sleep quality or objective amount of sleep. Sex that has resulted in orgasm and I think
Starting point is 02:35:48 that latter part that typically needs to happen. I would imagine so. That, you know, so between two mutually exclusive individuals were both beneficial in terms of receiving an orgasm. Yeah, I would say any discussion about sex, we are referring to consensual, age appropriate, species appropriate, context appropriate. Wow, I would never have even gone to the species appropriate. I put species in there because it's the internet and people will come up with a lot of sorts of ideas.
Starting point is 02:36:19 So I think the age appropriate, I think age appropriate, consensual, context appropriate and species appropriate covers all the bases. Yeah, so let appropriate, consensual context appropriate and species appropriate covers all the bases. But if I'm just any, put them in the comment section and we'll be sure to take note. Yeah, no, I think that's really well said,
Starting point is 02:36:33 and important to say. So the data is the, when you look at couples who have orgasm, we've also, however, found benefits of masturbation. And it's not frequently spoken about. We've also, however, found benefits of masturbation. And it's not frequently spoken about. But if you do some surveys, it turns out that people will often use masturbation as a sleep tool if they're struggling with sleep. And I know this sort of sounds almost like a strange conversation or it's a taboo conversation.
Starting point is 02:37:01 But I think we just need to be very open about all this. I started off in science. One of the things I worked on early in my career, not the very first topic, was the topic of early influences of hormones, estrogen and testosterone on sexual development of the brain and body. And when you are weaned in a laboratory like that, regardless of what era you look at sex and its behaviors and its hormones and its physiology as a scientist.
Starting point is 02:37:29 And so I think that's to be clear what we're doing here. We're exploring these behaviors from that perspective. I mean, one thing is for certain, everyone is here because a sperm met an egg, either an addition or an vivo, as we said before. And at least in 2021, there's no way around that fact. And what preceded that is typically this act we call sex, and sometimes, hopefully, I like
Starting point is 02:37:55 to think, orgasm is associated with that sexual activity. Massurvation as one dimension of that is something that I think it can and should be discussed if in fact there are data that relate it to sleep. Yeah, and both of those routes seem to lead to a sleep benefit. Now I'm not saying that it's all about the orgasm, I think as we spoke about with oxytocin, there is some degree of per bonding that if you have a partner and you experience, you know, an intimate loving, you know, relationship that involves that, then you can have hormonal benefits that are sleep promoting that may not necessarily be seen if you're just engaging, you know,
Starting point is 02:38:38 in the solo singular act of masturbation. So what we certainly know now, and I am not someone to take any advice on when it comes to anything relationship wise or sex wise. That's a different episode of podcast certainly and that's not a podcast series that I'm going to be releasing anytime soon. It's going to be mostly about sleep, although I will touch on I'll release a podcast on sleep and sex. But that's the data that we have so far. We also know that it works both ways, though, and it's commonly the same way with sleep. Sleep an exercise, sleep and diet. How you eat can affect how you sleep, how you sleep can affect how you eat, same with exercise, and it turns out it's the same way with sexual behavior too. So here we're talking about whether sex can help with sleep, can sleep help with your
Starting point is 02:39:30 relationship and sex. And the answer is yes it can. Firstly, we know, and we've spoken a little bit about this, that the reproductive hormones are under profound sleep regulation. Both estrogen and testosterone. Estrogen testosterone. Because we hear so often about the testosterone as well. But women who, or I should say anyone
Starting point is 02:39:47 who's interested in having higher levels of estrogen or normal, healthy levels of estrogen, I presume the data show for estrogen, what the data also show, it's at moiety for testosterone. It's testosterone, which is if you get too little or poor quality of sleep, both sex steroid hormones as they're referred to,
Starting point is 02:40:04 testosterone, and estrogen, which are present in both males and females in every variation thereof, little or poor quality of sleep, both sex storied hormones as they're referred to testosterone and chranestrogen, which are present in both males and females and every variation thereof, are going to be diminished below normal healthy levels. Yeah, estrogen, testosterone, FSH in women, a key hormone in the regulation for key for conception, of course. All of these sex hormones seem to become significantly disrupted when sleep becomes of short quantity or poor quality. We also know that in women, sleep disruption can usually lead to menstrual cycle disruption. We know this, particularly from
Starting point is 02:40:40 evidence in shift working women, where they are nighttime shift workers, they struggle with sleep during the day. Often menstruation is disrupted or even becomes impaired. But we also know it works this way not just for sex hormones, but for sex itself. For example, we found that for every one hour of sleep, extra sleep that a woman gets, her interest in becoming sexually intimate with her partner increases by 14%, which is a non-trivial amount. And then the final part of, I think, this equation when it comes to sleep and sex is your relationship itself and there's some great work here
Starting point is 02:41:26 from UC Berkeley by Professor Serena Chen and what she found was that restless nights mean for far more brutal fights in your relationship and they did this in a number of different elegant ways and vice versa as well. I mean not that I've ever had conflict in relationships. I mean, not that I've ever had conflict in relationships. Yeah, me, like, you know, I just, this is a date right now. I've never experienced that at all. So, and they found reliably that sleep would predict higher likelihood of relationship conflict. Secondly, if you got into that conflict,
Starting point is 02:41:59 the chances of you resolving it were significantly lower when the parties had not been sleeping well. Part of the reason is because when you are not well slept, your empathy goes down. So you're not, you're taking more of an abrasive stance with your partner rather than a more agreeable stance with your partner. So at almost every dimension of a human-loving relationship, sleep can have a dramatic impact. I think these are really important things to underscore. One of the most common questions I get because there seems to be a community of people on the internet that are obsessed with this. I don't know who they are because it's all this internet
Starting point is 02:42:43 stuff is shouting into a tunnel and get comments back in written form. It's a very bizarre conversation. So to speak, is whether or not sexual behavior itself lowers or increases testosterone. And I went into the data, which expands many decades actually, both animal studies and human studies. And it seems just to underscore this as long as we're talking about the subject, that it does seem that sexual activity, sex between two people, does seem to increase testosterone in both. There is this question about orgasm or no orgasm, ejaculation, no ejaculation. And indeed, there do seem to be some effects of restricting ejaculation and males as a form of further increasing testosterone. So sex without ejaculation, further increasing testosterone.
Starting point is 02:43:37 But the data are not clean, presumably because organizing these sorts of studies and getting truth in self-reporting is probably hard to get from subjects. But everything sort of points in the direction that provided that the relationship is a healthy one, it's consensual, it's age appropriate, context appropriate, species appropriate, that sex between two individuals does seem to increase the sex-troid hormones, testosterone and estrogen toward healthy ranges. And what I'm hearing now, the sort of gestalt of the discussion we just had is that that too
Starting point is 02:44:12 can promote sleepiness, restful states, and quality sleep. And I think this is an important conversation that just hasn't been held enough. I mean, sooner or later, both in the US and elsewhere, we're going to have to acknowledge that we are biological organisms of some sort and that we have choice in life about all these things from supplementation to sex or no sex, et cetera, but that they have profound effects on our core biology. I mean, it's fascinating to me that the areas of the hypothalamus, the preoptic area, the superoptic areas, those areas,
Starting point is 02:44:47 which the names might not mean anything to anybody besides Matt and I sitting here, but those areas sit cheek to jowl with each other in the hypothalamus and control sleep and sex. The trigger of orgasm, the appetite for food, the appetite for water, for electrolytes. I mean, the hypothalamus is kind of a festival of neurons
Starting point is 02:45:09 with different booths for different, it's just a primitive behavior structure in the brain, but it's the orchestrator of a fast number of our behaviors, disproportionate in terms of its size versus effect. I don't think you can go to this hypothelamic festival without at least seeing all the booths, whether or not you decide to visit them or not. I love that.
Starting point is 02:45:30 I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not.
Starting point is 02:45:38 I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. I'm not. level sensitivity, it's an important one that we're going to hear more about one way or the other. People are certainly thinking about this if not engaging in these sorts of behaviors or avoiding them.
Starting point is 02:45:49 So the more we can understand about the biology, the better. And so thank you for bringing that topic up because for the record, Matt, table it for discussion. I said, we were just like chatting outside and I think we said something about, yeah, sort of sex. I said, yeah, we can go that This is actually interesting. Absolutely I
Starting point is 02:46:09 Want to touch on just two remaining topics one is Are there any unconventional sleep tips or things about sleep that that we've overlooked if we've covered everything great but You know we hear to keep the room cool. We hear, because of this temperature phenomenon, the light aspects, the considerations about alcohol, CBD marijuana, cognitive behavioral, tart cherry fruit, can we perhaps, perhaps please don't put me on the hook
Starting point is 02:46:40 for tart cherries and give it. I was just offering what I know about the days right now. No, and these are considerations, and whether or not people abatch these things, I won't even list them off now because there are too many jokes that one could make. And I have no affiliation with any of these products or good ones.
Starting point is 02:46:55 Well, I'm gonna take out stock in a Kiwi company. No, I'm just kidding. But the question I have is about any unconventional or lesser known things, or maybe you do things or you think about things, just in a purely exploratory way as a scientist, the what if kind of things. Yeah, what if it turns out that, and I hear I've got a blank there for you to fill in, I think beyond the standard, fairer that I've dished out plenty of times of sleep hygiene, of regularity, temperature, darkness,
Starting point is 02:47:33 alcohol caffeine, and we've spoken about all of those. What are some more unconventional tips, I guess? The first one which is unconventional, along the lines of NAPS, if you've had a bad night of sleep, let's say that you're starting to emerge with insomnia and you've had a bad night of sleep, the advice and I learned this from my wonderful colleague Michael Perlis, do nothing. What I mean by that is, don't wake up any later, don't sleep in the following day to try and make up for it, don't NAP during the day, don't wake up any later, don't sleep in the following day to try and make up for it.
Starting point is 02:48:05 Don't nap during the day. Don't consume extra caffeine to wake you up, to try to get you through the day, and don't go to bed any earlier to think that you're going to compensate. And I can explain all of those things, but if you wake up later, you're not going to be sleepy until later the evening. So you're going to go to bed at your normal time and you won't be sleeping. You'll think, well, I just came off a bad night of sleep. And now I still, I can't even get to sleep. And it's my normal time.
Starting point is 02:48:35 It's because you slept in later than you would otherwise. And you reduce the window of a denocene accumulation before your normal bedtime. So don't go, don't wake up any later. Don't use more caffeine for the reasons that are obvious because that's only going to crank you and keep you awake the following night or decrease the probability of a good following night of recovery sleep. Third, I mentioned don't take naps because once again that will just take naps particularly later in the afternoon, I almost liken them to snacking before a main meal.
Starting point is 02:49:09 It just takes your appetite off the edge of that main meal of sleep, so don't do it. And then finally, don't go to bed any earlier. Resist and resist and go to bed at your normal time. What I want to try and do is prevent you from thinking, well, I had such a bad night last night and I normally go to bed at 10, 30. I'm just going to get into bed at 9 o'clock, because last night was just so bad. But that's not your natural bedtime, and it's not aligned with your natural chronotype, because presumably you kind of know something about that, or
Starting point is 02:49:39 a morning type, evening type, and you're trying to sleep in harmony, which is usually how you get best quality sleep. But you go to bed at 9 and my body is not ready to sleep at 9 o'clock. But I'm worried because I had a bad night of sleep last night, so I get into bed and now I'm tossing and turning for the first hour and a half because it's not my natural sleep window, but I just thought it was a good idea. And if I didn't know anything about sleep, I would think all of these same things too, so I'm not finger wagging. But after, if I have a bad night of sleep and I am not immune, just because I know a little bit about sleep, doesn't mean I don't have my bad nights, I do, doesn't mean I haven't had bouts of insomnia in my life, I have. But after a bad night of sleep, I do nothing. I don't do any of those four things.
Starting point is 02:50:26 I think the second tip I would offer in terms of unconventional is have a wind down routine. Many of us think of sleep as if it's like a light switch. That we just jump into bed and when we turn the light out, sleep should arrive in that same way. To the binary, you know, it's on or it's off. Sleep is a physiological process. It's much more like landing a plane. It takes time to gradually descend down onto the terra firmer of what we call good, solid, sleep at night. Find out whatever works for you and it could be light stretching. I usually meditate for about 10 or 15 minutes before bed, some people like reading, try not to watch television in bed.
Starting point is 02:51:11 That's usually advised. It does emit too much light to your own. Too much light to activating. You can listen to a relaxing podcast although we can speak about technology in the bedroom too, but have some kind of a wind down routine. technology in the bedroom too, but have some kind of a wind down routine. It's almost like you wouldn't race into your garage and come to a screeching halt from 60 miles an hour.
Starting point is 02:51:35 You typically down shift your gears and you slow down as you come into the garage. There's the same thing with sleep too. That's the second thing. Have some kind of a wind down routine. Find what works for you. Maybe it's taking a hot bath or a warm shower and then stick to it. Just we do this with kids all the time. We find out what their bedroom, sorry, their bedtime regimen is and then we just stick to it faithfully because we humans are the same way too. The third thing is a myth. Don't count sheep. I was a study
Starting point is 02:52:05 done here at UC Berkeley. I didn't do this today. I wish I did it by my colleague Professor Allison Harvey, and they found that counting sheep actually made it harder to fall asleep. It made matters worse. As a counter, sorry, counter measure to that, what they did find was that taking yourself on some kind of a mental walk. So think of a mental walk. So think about a nice walk that you take in nature or a walk on the beach or even a walk around an environment and visualizing that.
Starting point is 02:52:34 That seemed to be beneficial. The other thing about that idea of shifting focus away from your mind itself, get your mind off itself is a good piece of advice. Catharsis, you can try to write down all of the concerns that you have and do this not right before bed, but usually an hour or two before bed. Some people call it a worry journal. And to me, it's a little bit like closing down all of the emotional tabs on my browser. Because if I shut the computer down and all of those tabs are still open, I'm going to come back in the morning, the computer's red heart, the fans going because it didn't
Starting point is 02:53:17 go to sleep, because it couldn't, because there were too many tabs active and open. I think it's the same way with sleep as well. So try to think about doing that. So just vomit out all of your concerns on the page. I like that. Because my 3 a.m. waking is often associated with me writing down the list of things that I forgot to do that I need to do. And in once I eventually wake up from the later night, second half of the night sleep, that stuff seems much more tractable and reasonable, but it sure would be great to
Starting point is 02:53:45 get that stuff out of the way before sleep. Well, there's also something that I don't think people have spoken about a lot, and I'd like to research it, which is difficulty and anxiety at night in the dark is not the same difficulty and anxiety in the light of day. And when we have those thoughts at night, it comes with a magnitude of rumination and catastrophization that is disproportionate to that which you would describe when you are awake. And I don't know what's going on about the brain and thought and emotion at the time. I've got a bunch of theories as to why. And that's why I like the idea of
Starting point is 02:54:32 closing up, zipping up all of those different components. Just get them out on the page. And it feels, and I at first thought, this just sounds like who it sounds very Berkeley. It's kind of come by are we all hold hands and you know, we'll come at the end of the day. But then the data started coming out, really good studies from good people. And they found that keeping one of those journals decrease the time it takes you to fall asleep by 50% 50.
Starting point is 02:55:00 You know, it's well on par with any pharmaceutical agent. Oh, absolutely. I'm convinced that, well, I've long thought that the worries and concerns and ideas I have at 3-4am, I've learned to not place any stock in them. Because I'm glad that you might decide to eventually look at this in your laboratory because I feel like something is melted away or altered. I suspect it's in the regulation of the autonomic nervous system that it makes sense why I concern at 3.4am ought to evoke more of a panic sense than a concern sense. And certainly that's my experience,
Starting point is 02:55:38 although not I'm fortunate to not suffer from full blown panic attacks, but everything seems worse at 3.4am provided you're awake. We need to look into that because if you look at suicide rates around the 24-hour clock face disproportionately higher rates in those middle sort of night hours. So no, I don't know if that's causative or not, but something, it could just be that that's the time when we're mostly lonely and we're by ourselves and that's the reason. So it's got nothing to do with sleep or the nighttime.
Starting point is 02:56:09 I don't know. So that's the third thing. I think the fourth sort of little tip I would give that's unconventional is remove all clock faces from your bedroom, including your phone, including your phone and resist checking it. Now I know, and I can speak about the phone too, that genie of technology is out the bottle, and it's not going back in any time soon.
Starting point is 02:56:31 So we've got to think of scientists and sleep scientists, you know, as to what we do with, you know, phones in the bedroom. A few years ago, I was a counselor at a summer camp. I worked with at-risk kids and the, there was a phrase that comes to mind here. It's, be a channel, not a damn, because when you try and damn certain kinds of behavior, physically damn certain kinds of behavior, not morally damn, that too, it just creeps over the edge and you get a waterfall. So you have to be channeled. The phone and devices have to be worked with and negotiated, not a waterfall. So you have to be gentle. The phone and devices have to be worked with and negotiated.
Starting point is 02:57:06 That's right. And you know, think about those mindfully too, but clock faces remove all of those because if you are having, you know, a tough night, knowing that it's 3.22 in the morning or it's 4.48 in the morning, does not help you in the slightest. And it's only going to make matters worse than better. So try to remove all clock faces. And I think that's one of those other tips that some people have found helpful. But those would be sort of some slightly unconventional,
Starting point is 02:57:36 I guess, more than your stock fare of here are the five tips for sleep hygiene tonight. So those are terrific sleep tips and several of which, if not all of which, I'm going to incorporate. Matt, this has been an amazing deep dive on sleep and it's positive and negative regulators. I hope it hasn't been too long and I don't know. No, this has been great. Could it down shorten it to the five minutes of meaningful stuff that I have put? Absolutely not. Absolutely not.
Starting point is 02:58:04 It is chalk a block full of valuable takeaways. It's been tremendously fun for me to dissect out this incredible aspect of our lives that we call sleep with a fellow scientist and a fellow public educator. I want to say several things. First of all, we should say where people can find you, although it shouldn't be that difficult these days. You're a very present on the internet. For better, for worse. I think it's wonderful that you're out there.
Starting point is 02:58:32 Look, it's a public health service that you're doing. No one requires you or any other scientists to get out and share this information. My sense of you knowing you a bit and from following your work very closely, both your scientific work and detail and your public facing educational work is that you very much want the best for people. And it's an interesting thing as a scientist or a clinician to know that the certain answers exist, that we don't have all the answers, but that there is a better path,
Starting point is 02:59:04 there are better ways and people can benefit in a myriad of ways. So for that, because I know that to be very genuine in you, um, you want the best for people and you're offering tremendous advice and, um, considerations and people can take it or leave it. I, that's the way I view it. I also want to thank you for taking the time out of your day to, uh, to sit with me here and have this discussion. That's well, I view it. I also want to thank you for taking the time out of your day to sit with me here and have this discussion.
Starting point is 02:59:26 It's a privilege. It's a delight. You and I, I think, were like kind in lots of ways. And I take you as a shining example of how you can effectively connect with the public. And I know that we've had our conversations before we ever sat down, sort of together, about how to think about communicating with the public and the pros and cons of that. And I've just loved your opinions, I've been drinking it all in. And then I think the third thing I'd like to say is, thank you for being such an incredible sleep ambassador, the series that you've released on sleep, the
Starting point is 03:00:05 way that you speak about sleep, the way that you moderate and have championed sleep, it is remarkable. So thank you for just being, you know, a brother in arms in that way. Well, we are. And thanks for those words. 99% of what I discussed there was the work of you and your colleagues in the sleep field. So proper acknowledgement, but thank you. Where can people learn more about what you're doing currently and what's coming next? You're on Twitter. I am on Twitter.
Starting point is 03:00:35 I typically tweet as the sleep diplomat. So it's no, it's just sleep diplomat. Sleep diplomat. Sleep diplomat on Twitter. SleepDiplomat.com website. If you want to learn more about the science that we do here, it's humansleepscience.com. It's the Center for Human Sleep Science. You can pick up a copy of the book.
Starting point is 03:01:01 If you want, it's called Why We Sleep. If you're curious about sleep, that's one path to take. Is there another way of few in the future? I think there may be. I think there are many, many millions of people will be very happy to hear that. I think it's starting to take hold. And then, as we discussed, I am more than kicking around the idea of a short form podcast rather than a long form, not long form because I don't have the mental capacity or the interviewing, just capability that someone like you has.
Starting point is 03:01:36 So it will probably just be monologue short form. So if there is some interest, I'll probably do that as well. So those are the ways that people can find me. But overall, if you're interested in sleep, just listen to Andrew. That's the best thing I can tell. All right. Well, now we're batting back and forth the vector of action, so to speak. But I do hope you'll start a podcast. However, brief or lengthy these episodes turn out to be because I do believe that's a great venue to get information out in the world. And we don't just want to hear more from Matt Walker. I speak for many people.
Starting point is 03:02:13 We need to. The work you're doing is both influential, but more importantly, it is important work. It has the impact that's needed, especially in this day and age, where science and medicine, public health, and the issues of the world, et cetera, are really converging. So I know I speak on behalf of a tremendous number, P1, I just say, thank you for doing the work you do, and for being you.
Starting point is 03:02:37 And thanks for being a good friend. Likewise, too. And by the way, I just going to note that it was nice that the two of us both got the Johnny Cash memo about how to dress today. It seems as though we're both kind of, we got that same memo, which will mean nothing to people who are listening. But if you're watching the video, you'll probably see what I mean. Andrew, thank you for taking this time.
Starting point is 03:03:00 Thank you so much, Matt. Thank you for joining me for my discussion with Dr. Matt Walker. Please also check out his podcast, The Matt Walker Podcast. A link to that podcast can be found in the show notes. If you're enjoying this podcast, please subscribe to us on YouTube. On YouTube, you can also leave us comments and suggestions for future episodes and guests in the comment section. As well, please subscribe to us on Apple and on Spotify. And at Apple, you can leave us up to a five-star review.
Starting point is 03:03:30 Please also check out our sponsors mentioned at the beginning of this episode. Links to those sponsors can be found in the show notes. And as mentioned, at the beginning of today's episode, we are now partnered with Momentus supplements because they make single ingredient formulations that are of the absolute highest quality and they ship international. If you go to livemomentus.com slash huberman, you will find many of the supplements that have been discussed on various episodes of the huberman lab podcast and you will find various protocols related to those supplements.
Starting point is 03:03:57 And last, but certainly not least, thank you for your interest in science. interesting science.

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