#48 – Matthew Walker, Ph.D., on sleep – Part II of III: Heart disease, cancer, sexual function, and the causes of sleep disruption (and tips to correct it)

Foreign. Hey everyone. Welcome to the Peter Attia Drive. I'm your host, Peter Attia. The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful, top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics@peterattiamd.com. Hey everybody. Welcome to this week's episode of the Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about professionally are how to live longer and how to live better. 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Again, the podcast will remain free to all, but my hope is that many of you will find enough value in 1 the podcast itself and 2 the additional content, exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up for a monthly subscription. Welcome back to the three part series on Sleep with Professor Matthew Walker, professor of Neuroscience and Psychology at the University of California, Berkeley, and the Founder and Director of the center for Human Sleep Science. Matthew earned his undergraduate degree and PhD in neurophysiology in London and subsequently became a Professor of Psychiatry at Harvard Medical School before moving to Berkeley. His research examines the impact of sleep on human brain function in healthy and diseased populations. To date, he has published over a hundred scientific studies. He has received numerous funding awards from the National Science Foundation, National Institutes of Health, and he's a Fellow of the National Academy of Sciences. He's the author of the international bestseller why We Sleep, which also happens to be the favorite book of my not yet two year old son. He holds many patents covering various consumer based sleep recordings, sleep tracking and sleep simulation. He's a sleep scientist at Google, where he helps the scientific exploration of sleep in health and disease. He is also an enormous fan of Formula one and my hero, Ayrton Senna. And in the third part of this installment, we actually spend quite a bit of time discussing this. In the second part of this series we discuss sleep and cardiovascular disease. Sleep and how it affects diet, sleep and reproductive function. The risk of deliberate sleep deprivations, sleep and cancer. The lack of sleep within the medical profession. School start times and sleep deprivation, sleep patterns and light, the biochemistry of sleep and naps, the efficacy of various medications on sleep. As a reminder, at the end of this series we're going to take questions for a follow up AMA with Matthew. Asking questions on the AMA forum and listening to the AMA podcast with Matthew along with all AMAs, will only be available to subscribers. So if you haven't signed up yet, you can do so now@peterattiamd.com so without further delay, here is part two of three with Professor Matthew Walker. Okay, there's like literally a hundred more things I want to ask you about. So can you make the case for why cardiovascular disease is worsened by or accelerated by sleep deprivation? And then same question I'm going to ask you in a moment. For cancer, just pick the best like, because again, you could write a book on each of those.

We could go into sort of. But let me just give you one example. For cardiovascular disease, there is a global experiment that is performed on 1.6 billion people across 70 countries twice a year. And it's called Daylight Savings Time. And what we've seen is that in the spring when we lose an hour of sleep, there is a subsequent 24% relative increased risk for heart attacks that following day, 24%. In the fall, when we gain an hour of sleep opportunity, there is a 21% reduction, reduction in heart attacks that follow.

How long has that been known? I mean, I remember the first time I saw that, I was like, that can't be right.

And you know, when you see it bidirectionally like that, it's very diff, you know, that seems like a very robust manipulation that's been known for probably about 10 years. What's also interesting, and I won't get away from cardiovascular disease, don't worry. But just simply to mention that when you look at that same transition, you see the same profile for car accidents, you see the same profile for suicidal attempts and suicide completion as well. What's also interesting, by the way, is that you see it in terms of federal judges handing out harsher sentences. They hand out harsher Sentences on the Monday after that time change in the spring because they're more moody, emotionally irrational, and less sort of empathetically sensitive because of that one hour of lost sleep. And in the fall, more lenient sentences. So I.

And does this effect last for two or three days?

So there is a blast radius to it that you can see it, that it's better, but still worse in the spring, which is where you lose that hour sleep. The effect is still worse on the second day and it's almost recovered by the third day and finally comes back to what looks like a baseline by about day four. So there is a blast radius. And this is, you know, you know.

Why I find this interesting?

One hour of sleep.

Yeah. And here's the other thing I always found amazing about that statistic. In the Northern hemisphere, you would predict the opposite if sleep were irrelevant. Right. Wouldn't you think that gaining that hour of sunlight in the day, in the spring, just the overall anticipation, I mean, there's virtually no one in the Northern hemisphere that isn't happier in April than they are in November. Right. So it's almost like you have all of that positive stuff working against you and you still see the signal you just described.

Yeah. So in the.

It's like a kick in the face.

Yeah. So in the face of birds chirping, sunlight streaming, temperature warming, that one hour of lost sleep will still put you back on your dairy rather quickly in terms of all of these facets. So there's one example for cardiovascular disease. Another one, there was a fascinating study where they took a group of otherwise healthy middle aged adults who had no sign of, of coronary artery disease and then they tracked them for five years and then they looked at how much sleep that they were getting. So again, hands up. This is essentially an associational longitudinal prospect of studying it. You can't derive causality from it. But what you can certainly say is when they started, they had no signs of calcification of the coronary artery. Those people in that study at the end of the five years who were getting five hours of sleep or less had a 2 to 300% increase risk of calcification of the coronary artery, which is the main corridor of life for your heart. If you have a massive coronary, essentially when you hear that colloquially, that's essentially what's happening there. So that you could have that calcium buildup on the basis of being bucketed into insufficient sleep. That tells me that it's not that when you are insufficiently slept, you also are someone who has Calcified arteries. It is saying that if you are insufficiently sleeping, you are increasing your risk for developing that condition. This is about the development of heart.

How hard is it to control that? For some obvious things that would track with that, for example, shift workers or people of lower socioeconomic status who are working three jobs and all the other things that can work against.

So there are exclusion. There are some great exclusion criteria in that city where they prevent those participants from entering the city. They also then added in other factors that you could imagine would lead to that. So they controlled for those things like exercise, bmi, neck circumference, smoking. They even include history of snoring. So they tried to take sleep apnea out of the equation and still that relative risk was significantly larger.

What do you think is the mechanism?

I think the mechanism is probably several folders. I think the first thing that we see when we under sleep people is that they become much more sympathetically nervous system driven. Now that to some people may sound. Oh, that sounds like a good thing. No, you have two branches of your automatic nervous system.

I swear for a moment I thought you would say good, knowing that the listener would understand that they're sympathetic and parasympathetic. But thinking you were going to make a comment about being more high strung is better because. But no, you actually were making a joke. Yeah, I love it. I mean, I think you're so well tuned to this.

I think that's the beauty. My IQ is so low, I'm such a simpleton that I can always revert to the naive state and I don't have to make assumptions. That's the beauty of my idiocy. But no sympathetic nervous system being sort of cranked on your sympathetic nervous system is not a good thing. Your sympathetic nervous system essentially is your fight or flight branch of the nervous system. And what we find is that as soon as you start to under sleep an individual that fight or flight branch of the nervous system starts to ratchet up. When that increases, you start to see. Or perhaps the reason why it increases is that you get a greater amount of adrenaline release. You get a high spiking in levels of cortisol, you get a blunting in growth hormone. And I think probably just the cortisol and the growth hormone alone may set you on a path towards cardiovascular disease. Because we know that those are two factors that lead into that sort of some of that atherosclerotic sort of equation.

And that brings it back to Alzheimer's disease, which is even if you just look at the epidemiologic data, the signal's quite large on the benefits of IGF and growth hormone, more than any other disease in protection for from neurodegeneration. So that may be even in addition to everything you talked about with respect to clearance. You're simply taking away neurotrophic factors that are essential.

There's some data and I don't know how well replicated it is. I just read it in one study where if you look, if you're Apoe4, so this is in terms of your genes, there are some genes that can predispose you to Alzheimer's disease. On this podcast there are wonderful descriptions of going into all of the details of these. But APOE 4 significantly increases your risk for the development of Alzheimer's disease, it appears. But what's interesting is that if you are Apoe4 but you are normatensive, you don't necessarily have an increased risk of Alzheimer's disease. If you are Apoe4 but you are hypertensive, then your Alzheimer's disease risk is far higher. So in other words, there seems to be an interaction, a gene by cardiovascular disease interaction that that leads that genotype to predispose you to Alzheimer's disease. And therefore if you are under sleeping, you are putting yourself on a path towards many new different factors that we are learning regarding cardiovascular disease. Calcification of the arteries is one of them, but we also just see blood pressure spike. We can take someone who is in a lovely state of, you know, normatensive profile and has been and after either one night of total sleep deprivation or one night of short sleep, you know, we can almost start to see it after about reducing sleep by three hours, take someone down to five hours for just one night, you immediately see this spike in the fight or flight nervous system. Blood pressure goes up, you start to see cortisol increase, heart rate starts to increase as well. You know, it's almost as though you've just got a beautiful car engine, you've put it in neutral and you put your foot on the gas pedal and you're just revving the living daylights out of that engine in a fight or flight state. Now if you do that chronically, which is what most people do with insufficient sleep, you know, day after day, week after week, year after year, decade after decade, it's not surprising that, you know, just revving the daylights out of that engine, at some point gaskets are going to start blowing. It's not designed to operate in that high revving state. All of now High revving occasionally just fine. And if you have a beautiful, let's say, you know, Mezca Porsche engine, which loves to go to nine grand, and.

You and I, it's in the GT3.

I had to geek out on cars for a little bit because I'm just so obsessed I had to get it in there. But. But even then, you just can't stay at that rpm, that high RPM for very long. You just know it from listening to the engine. You just know that mechanical badness is happening in neutral when you've got your foot on the gas pedal. Well, that's the same way with chronic sleep deprivation in your nervous system. So I think many of the cardiovascular effects, in fact, I think we're writing a paper right now. I think if there is one central common pathway through which we can understand almost all aspects of the deleterious impact of insufficient sleep, it is through the autonomic nervous system and specifically an excessive leaning on the fight or flight branch of the nervous system, which is to say that your sympathovagal balance is way off and you are far more in that fight or flight sort of aversive state. So I think that to me is where that disease pathology starts and perhaps progresses from that point.

And I think only adding to that, which is probably what you described as sufficient alone. But when you look at what I think are pretty well documented appetitive changes in people under sleep deprivation and more importantly, the inferior fuel partitioning that follows. So the hyperinsulinemia, the impaired glucose disposal, the tendency to probably eat more crap, I mean, I'm at my worst when I am sleep deprived. It is, you know, I just, it's so hard to avoid junk food. Whereas probably the single greatest tool in my arsenal to eat well is to sleep well. I mean, it doesn't sound like that's an obvious thing, but it's amazing when.

You read the data. I mean, it's, it's striking and you know, we can get into that, which is essentially what you've just described is the, the energy balance of an organism, of a human being and both the regulation of energy once you've taken it in, and also the input of the energy and the selection of the energy. How do you eat and how much do you eat? And then secondly, once you've eaten, what does your body do with that food in terms of basic kind of blood sugar control?

And then the fourth thing is where do you access it? So I'm sure, I mean, I'm sure this has been done. I just haven't seen it. But if you look at respiratory quotient of people so sleep deprived versus not, I'm sure RQ must be going up. Right. I'm sure they're absolutely going after the wrong fuel partitioning.

That's exactly what you see.

I'll do what you do. Well, that I always forget to do. Let me explain why that matters. Respiratory quotient going up implies that under the same level of exertion, you would preferentially go after glycogen for ATP as opposed to fat. And so not only is that not what most people want because they'd prefer to burn their fat than burn their glucose, it signals a metabolic inefficiency which lays at the heart of all of this stuff.

And a beautiful example of that is a great study that looked at the efficiency of dieting when you are underslept. And effectively, what they found is that your diet is all for nothing if you're not sleeping well. Because what they found is that when you are underslept, defined as sleeping six hours or less, 70% of the weight that you lose will come from lean muscle mass and not fat.

In other words, which is perfect when your cortisol is high.

That's exactly what you'll see with cortisol. So in other words, your body becomes immensely stingy at giving up its fat. Your body will ruthlessly hold onto its fat when you are underslept and not give it away. Instead, it will. So when you are under slept and you're losing weight, you're losing the thing that you want to keep, which is beautiful muscle definition, and you're holding on to the one thing you're trying to get rid of, which is the blubbery fat.

And it's really everything. It's. The cortisol is working against you. Insulin will work against you. You're going to have more hyperinsulinemia, you will have more catecholamines working against you.

Yeah, we see that with norepinephrine in particular.

Oh, and testosterone will go down. That's going to work against adiposity, getting rid of it.

Yeah. I should note, by the way, that men, and I think we'll come on to this later, but men who are sleeping just five to six hours a night will have a level of testosterone which is that of someone 10 years their senior. So insufficient sleep will age a man by a decade in terms of that critical aspect of wellness and virility. So if you want to sort of be very bravado about insufficient sleep, be careful. I would also Say that by the way, we found it simply associational. But men who are sleeping just five hours a night have significantly smaller testicles than those men who are sleeping seven hours or more.

And I'm sure that in that you would see FSH and LH must be lower. Right?

So we do. So, you know, I'm not trying to make necessarily funny, even though sometimes I'll start talks that way just to sort of get the bravado folks out the way. But you also firstly see that men who are sleeping six hours or less will have fewer sperm, those sperm will have more deformities.

But this is not limited sleep deformities, even genetic. So even aneuploidy in the spleen.

That's correct, yep. And you can see that in rats too, if you do those studies, and those studies have been done with short sleeping rats. But it also transfers to women that you see that women who are sleeping just five to six hours a night will have about a 20% reduction in FSH, which is called follicular stimulating hormone, which essentially is a critical part of the reproductive pathway in terms of getting pregnant. Women who are sleeping that little too typically have about a 30% higher rate of abnormal menstrual cycles. So if you put together a couple that is trying to conceive and that couple is on six hours of sleep, you've got a man who's down on testosterone, down on the amount of sperm that they're producing, the motility of those sperm are reduced, and then the woman, you're down on you. You know, you've got erratic menstrual cycles, you've got fsh, that's down to. From a reproductive standpoint, this is devastation.

And again, it evolutionarily isn't that surprising. It's basically Mother Nature saying if the conditions are not optimized for you to sleep, it's probably not optimal for us to propagate the species at this moment.

And that is probably something that rarely happens.

What happens to FGF 21? Do we know?

I was about to say we don't know. I should say I don't know of any studies that have looked at that.

FTF 21 has such an interesting. It's one of the few places in the brain where you'll see a difference between men and women under a fasted state. So under a fasted state you don't appear to see the same hit in reproductive fitness of a man, but you do see it in the woman. There's actually an anatomic reason for this that I at this moment am forgetting. But it basically has to do with this rise of FGF 21. And, and you'll see basically the inhibition of FSH in the women without it in the men, which again is like, it's this question of if food is scarce, we really don't want a mother to try to nurture another body.

Yeah, maybe that's the biological warning beacon that just says time out on reproductive capacity.

Right now I always get asked, is a ketogenic diet in any way good, bad or indifferent towards fertility? And my answer is I actually have no clue. But just on first principles, it would seem that a ketogenic diet could have one negative side effect on the woman, which is exactly that. Because a ketogenic diet generally does put up FGF21, it could be offset by benefits. So if you took someone who's metabolically ill who is fixed by the ketogenic diet, it could offset it. But all things equal, yeah, I certainly wouldn't recommend fasting for a woman who's trying to conceive. But you've had the luxury of spending a lifetime thinking about this. I'm sort of playing catch up over the past couple of years, by the way.

It's one of the things that you do brilliantly, by the way, from what I listen to on every one of your podcasts. But what I would say in response to your question, though, about that evolutionary question. The reason I suspect it rarely occurs, however, is the following. Human beings are the only species that deliberately deprive themselves of sleep for no apparent reason. You almost never see other organisms undergo sleep deprivation. The only time that you see another species seemingly restrict its sleep is under two conditions. The first is under certain. With certain mammals, after they've given birth, they will deprive themselves of sleep to care for their young. The most obvious example there is in killer whales where the mother will break from what's called the pod, which is the main group. They will go away and, and they will give birth and then they will bring that calf back to the main pod and during that time they will short sleep. The second is under conditions of starvation that when an animal starts to become starved, they will. There is a wake promoting signal where you will actually stay awake longer and it gives the animal the ability to forage in a larger perimeter because presumably the current perimeter is not containing sufficient food. And I think that that's the reason why some people will say, when I undergo, you know, either time restricted feeding or especially when I undergo fasting, the reason that I Feel like I don't need to sleep as much or, you know, and I feel more awake even though I'm sleeping less. And it's great. I actually would be very cautious about doing that for long periods of time. And doing it sort of repetitively for long periods of time is because there are still, you're still suffering the decrements of insufficient sleep. But the reason that you feel awake is because there is a biological mechanism in place that says, oh my goodness, if you're not getting food, we need to keep you awake for a little longer. We're going to sacrifice this thing called sleep for a little bit so that you can go and find more food. So there's a weight promoting mechanism and we know how that works. But the more important point here being made, I think for me is that because human beings are the only species that deliberately deprive itself of sleep and no other species has really done that, it means that Mother Nature throughout the course of evolution has never had to face the challenge of sleep deprivation. So in other words, Mother Nature has never come up with any safety nets for any of our major biological systems. Metabolic, reproductive, cardiovascular, immune, mental health. None of these things have any safe holding. They don't have any sort of crutches when sleep goes away. Why? Because Mother Nature has never been asked to solve that question. Now I'll give you an example.

I use the same argument, by the way, for sitting in chairs, you know, or so many of these things.

Sedentary behavior.

Yeah. That we just do that. We, you could argue if our species could survive another hundred million years, maybe sitting around doing nothing, drinking soda would, we'd figure out a way to make that not so harmful. You know, assuming it interfered with, you know, our capacity to reproduce. If it didn't, then maybe evolution wouldn't take any interest in it.

But I mean, I think it's, it's the reason for me at least, why. An alternative example there in the pro would be, you know, an adipose cell that Mother Nature throughout the course of our life and most species experience times when there was feast and times when there was famine. And so Mother Nature, faced with that challenge of famine, came up with a solution called the fat cell so that we could store caloric credit and then spend it when we needed to when we went into famine. Where is the adipose cell for sleep? Where is the fat cell for sleep? Where is, you know, wouldn't it be lovely if we could store up sleep credit and then spend it? And the answer is there is no such thing. Because there has never been the challenge in the course of evolution to come up with that solution.

Because hibernation is not an example. Right. Hibernation is the opposite. Hibernation basically says it's not giving you credit to sleep less in the summer, it's just taking stock of the fact that there really is nothing for you to eat in the winter.

Correct. And that's really about energy expenditure and essentially energy preservation and torpor and hibernation of different states to sleep itself. But that's always, I think, been something I've thought a lot about that example of the fat cell versus sleep. And it's the reason why people unfortunately think that sleep may be like the bank, that you can accumulate a debt during the week and then you can just sleep it off during the weekend.

What's the name again for that phenomenon of the sort of Monday through Friday short sleeper who binge sleeps on the weekend?

What's called social jet lag.

Social jet lag?

Yeah. Where you sort of essentially it's what I used to term very politically incorrectly as sleep bulimia, which was where you would essentially, you know, purge during the week and then you just binge during the week. It's this real binge purge kind of abstinence syndrome. The reason it's problematic is not just because sleep doesn't work like that and the studies show that that's very deleterious to health, is because it also is terrible torture on your circadian biology because what happens is that you start to wake up, you know, you'll be going to bed at sort of one or, you know, midnight rather than nine, and then waking up at 10:11 on a Saturday and a Sunday. And then come Sunday night, you've got to drag your body clock back by three hours, you know, to get into bed and you repeat it the next weekend. That's essentially like saying to your biology and no different, I'm going to fly back and forth from San Francisco to New York every weekend. Three hour social jet lag difference. That's a hazard ratio impact on your circadian biology.

And as I'm listening to you say this, I'm making the stronger and stronger case for my move to Austin, which in part is driven by just shortening the trips that I have to take to be able to only have to take a one hour time zone delta or never basically having to take more than a two hour time zone delta.

For your lifespan, healthspan for the impact that you can have on this planet and this society during the time that you're here and for the preservation of you in your children's life, I would strongly recommend it.

I'll share with you an interesting example of a patient of mine who has an example of what happens when that system quote, unquote breaks. So this gentleman, I'll try to be as vague as possible so I don't identify him even if he's listening. Not that he would care if I told the story anonymously. Basically worked in the finance sector, but at some point was living on the west coast of the United States, but basically was exclusively involved in, you know, Eastern European markets. So you can imagine what time he had to be waking up to deal with that after several years. And he in part moved from the west coast to the east coast to try to make that gap smaller. But he got to the point where he could Never sleep past 3am it was metaphysically impossible, regardless of what time. If he went to bed early, if he went to bed late, he was up at 3:00am and, and it turned out one of my colleagues, Vic Jain, who's a Stanford trained sleep doc at Northwestern and also someone I just can't wait to interview because he's just so insightful on sleep. You know, he basically did something that you and I had talked about earlier, which was reverse use of melatonin in blue light to phase shift him into the correct time zone. And what humbled me about the story was how long it took to move. And it just gives you that sense of could you imagine forcing that on your system once a week? And I mean, it took months to correctly of course correct. Yeah. Now admittedly it had been in place for a couple of years by the time, you know, I met him. So, you know, you have a little bit more to overcome. But nevertheless, I was blown away at the lengths that Vic had to go to drag him forward by three hours.

For that biology to have been tortured for that long. It's going to take a reset of non trivial magnitude and help from exogenous agents like melatonin, light blue light, regular exercise, exposure to daylight, even manipulations of body temperature, it could take. So there are a whole arsenal of tools in the sleep doc kind of box that we can use to sort of make these manipulations either be it for people with insomnia, be it people with anxiety, be it people with sort of jet lag or what's called circadian phase delay, which is essentially what he was suffering from, which was.

You mentioned temperature. This was something I didn't know until I learned it through this patient's case and through Vic's learning, which was about two hours before the wake up, you see this drop in temperature and like that drop in this guy is occurring at 1am he's getting that drop up and then. And so what you basically were doing was dragging that thing to, you know, 4:00am you had to drag the temperature drop to 4:00am and again, I think it just speaks to the complexity of the situation. And as a general rule, when you mess with really complex, hardwired, evolutionarily sound things, you've got to be careful. You're going to pay the fiddler.

When you fight biology and sleep is one of the most conserved behaviors across all living organisms that we've observed. When you fight that kind of innate hard grained biology, you normally lose and the way that you know that you've lost is disease and sickness, either acute or chronic. You know, at some point a lack of sleep will get you. It may be in your late stages of life, you know, Margaret Thatcher, Ronald Reagan. Examples with Alzheimer's disease could be from a heart attack prematurely when you're 56 years old or it could be a car crash at any moment in time because of a microsleep you will be popped out of the gene pool pretty quickly.

So let's talk about one more thing which I'll we could talk about cardiovascular disease for much longer, but let's talk about cancer and let's talk about when I talk about these diseases with patients, one of the things I try to do is say let's reverse engineer what we think is happening when this disease goes wrong and then back things out. So when it comes to cancer, I say, look, cancer has a bunch of things that have to go wrong. First you have to have a genetic insult. Two, it has to be missed by the immune system. Unfortunately, most of the time our T cells can figure out that cancer is non self, et cetera, et cetera. And you kind of walk through all of these things. So let's talk about the immune system for a moment because we know that if you're not well, I want to let you explain that. Yeah, I'll let you go from there because I was just about to go off on this topic, but tell me about how sleep impacts the immune system and not only how that might impact getting common colds, but how it could impact cancer.

So firstly, what we know is that there are now significant links epidemiologically between sleep and cancer of a variety of forms. Currently that list includes cancer of the bowel, cancer of the prostate and cancer of the breast and then we can step down.

Which are basically three of the top four.

Exactly, yeah. Three of the heavy hitters. Next you can sort of say, okay, what about the causal evidence? Well, firstly, I would say before I describe the causal evidence, that causal evidence is now so strong that recently the world health organization decided to classify any form of nighttime shift work as a probable carcinogen. Their words, not mine. And the proof of evidence that is required by the world health organization to make such a statement Is usually has to be astronomical. And that data is now, I think, very well put in place. I'll just mention one quick causal manipulation study done by a colleague down at ucla. They took a group of healthy adults and they limited them to just four hours of sleep for one single night. And then they looked at a set of cells called natural killer cells. And you can think of natural killer cells like the secret service agents of the immune system in that they're pretty good at identifying dangerous foreign elements, One of which are malignant cancerous cells. They'll inject some things into them and try and destroy them, essentially. So what you want is a pretty virile set of those immune assassins circulating in your body. And what they found is that one night of four hours of sleep reduction led to a 70% drop in natural killer cell activity. That's quite a surprising state of immune deficiency that has happened within one night. So you can step and repeat that and imagine what would be the state of your immune system, Particularly for those critical anti cancer fighting immune cells, after several weeks, if not months of insufficient sleep. That's one aspect which is what is your vulnerability to developing cancer? Because many of us are, you know, we'll have cancer cells emerging in our body every day or so. We need those aspects of our immune system to prevent those cells from becoming the disease that we call cancer.

I mean, that's such an important point. And I'm probably biased because I trained in an immunotherapy lab, But I don't think people necessarily appreciate that we pretty much always have cancer and our immune system is pretty much always protecting us. It's actually the exception when the cancer develops into something clinically.

Correct.

And I've debated, not debated is the wrong question. One of my favorite sort of sitting around dinner discussions with cancer biologists is what is the greater driving force for the obvious age association of cancer? In other words, why does cancer increase nonlinearly as you age? And I offer two hypotheses. Is it three? Actually, is it an increase in the rate of mutagenesis do you experience on a per unit of time basis, a greater insult to the genome? Two, if you assume that that's the same, is it that over time the accumulation and the expression, the phenotype of that becomes more problematic? And or three, is it that our immune system, specifically the adaptive immune system, is weakening and the balance starts tipping in favor of cancer? And you know, I've asked this question of Nobel laureates and future Nobel laureates. Every one of them has said we don't know. They suspect it's all of the above. But they all agree that the weakening of the adaptive immune system is almost assuredly playing a role in why we get cancer more as we age. Because we know many things are working against us when we do that. And so when I HEAR you say NK cells, which, you know, the CD8 cell, the NK cell, the CD4 cell, these are, these are your Green berets and your Navy SEALs of the war against cancer. If you put a hit on those guys, you, you know, you could be taking a 10 year step in the wrong direction. Just as you talked about the gonadal 10 year leap, right, in testosterone.

I mean, I would love to add a 3B hypothesis there, which is that one of the most dramatic changes with age and the most sizable and robust physiological changes in with age that we see is that your sleep gets worse. And sleep is probably one of the most powerful regulators of your immune system. You know, if you want a full arsenal and you want every single weapon in there to be sharp and ready to annihilate sleep is what you need. That data, I think is very clear in terms of the decimation of your immune system with sleep. And that, you know, I just gave one example there too.

And the funny thing is like you give that example and it's not even that dramatic. Like there's no person listening to this who hasn't had a four hour sleep night. That's part and parcel for just being a human being in the civilized world, maybe even in the non civilized world, right? And yet to think about a lifetime of stacking those things and the compounding effect of what does it mean to get 8 hours a night versus 6.25 hours a night? Imagine that. I'm almost amazed it doesn't kill us quicker because to your point, we have adapted a great system to cope with excess nutrients, right? We had a great system and it takes a long time for that to break us down. I think in some ways we're probably so naive in our ability to measure the short term consequences of sleep. I mean not you of course, because this is what you're thinking about day and night. But I think as a medical community we're really shitty at knowing how to measure short term. Like what's really happening in sleep deprivation.

Especially in, you know, in clinics and in healthcare systems.

Yeah. Like in schools. Like we don't really understand how bad sleep deprivation is on a learning child. We clearly don't understand what it's doing on the road. Like we don't understand that this will kill you much faster than bad nutrition, which is clearly going to kill.

You know, if you look at all cause mortality and short sleep, it's not even linear, it's exponential. You know, it really. Sleep will bend that curve of your lifespan in a downward direction which with a dart into the ground when it starts to get short.

I think your argument is so great that it really comes down to the fact that at least we had a system in place to train us for excess nutrients. Now look, we can argue we didn't have a system to train us to consume refined carbohydrates. We didn't have a system that trained to consume massive amounts of polyunsaturated fats or high, high amounts of sucrose, but we still knew how to consume some of these things. And, and there is a dampening effect in nutrition that the, you know, ever present adipocyte can numb and at least for a while blunt that system. But you're right, if we didn't, if it wasn't really until what probably 200 years ago that sleep deprivation could have become common. I mean when do you really think was the tipping point? I know that in the 40s we could compare the 40s to today, but it would almost seem like the light bulb was a pretty big step in the wrong direction. You can not to blame Edison for.

Yeah, but you could go back and you could argue that, you know, Edison with the light bulb and his, his company may have been the starting point. I think it's, it was probably happening even earlier on the basis of social demands. You know, the industrial era I think then starts to compound things. Once we switch from an agrarian society to an industrial society, in my mind that's when stuff really starts.

I mean my history's horrible, but that's about 250 years ago.

Yeah, exactly. Yeah. So I think we've been that that curve to happen.

So it's an evolutionary millisecond, Correct?

Correct. Sounds like a long time blink of an eye. The other aspect of cancer is not just that you increase your risk for developing cancer because you weaken the immune system components that are there to combat against all of those carcinogenic influences cellularly that you've just described, but another study by a colleague at the University of Chicago, David Gozal. He looks at the relationship between sleep loss and cancer in mice. And I'll just give you one example of a study he did. Took a group of mice, inoculated them with some cancer cells on their back, and then gave that cancer a one month period to grow. At the end of the month, he resected the skin, measured the size of the tumor. Half of those mice were allowed to sleep normally, the other half had their sleep restricted. So they just had their sleep kind of top and tail, not total deprivation, just limiting their sleep in the morning and the evening a little bit. What they found is that at the end of that one month, those underslept mice, when they looked at them, the tumor was 200% larger. I mean it was physically distorting the body. And if you were to see these pictures, you would just think, my goodness, I can see a small tiny little sort of dot that is the growth of the cancer in the well slept mice. The others, it just looked like a hideous mass on these underslept mice. Secondly, what they found was that that cancer in those underslept mice had actually metastasized, which is just in some ways a fancy way of saying that it had breached the original origin and started to invade other organs, bone as well as brain. When cancer becomes metastatic, that's when we know things can get really dark and grim in terms of life expectancy.

There are many mechanisms that you could generate or hypothesize could explain that. I'm curious as to how many there were. So one would I think be exactly what we've described, which is this immune weakening. But you could also look at. So hypercorticolemia is going to drive hepatic glucose output, so they create hyperinsulemia.

Did they adrenalectomized the mice and then fed them prior to it. So they controlled the metabolic response. Yeah. And what they did find in terms of they looked a little bit at the mechanism. They found that macrophage M1 cells, those were actually down regulated by a lack of sleep. And what was upregulated was a sort of a rogue version which was called the M2 cells, which seem to have a tumor promotion component to them as well.

So, so they really the. The adrenalectomy is brilliant. What a.

What A clever design, take out the stress response and they limited that. Imagine if you did, and that's the fear is how much worse would it be when it really happens in humans? Because you will have that plus this huge tsunami of a cortisol impact, hypercortisol impact, which is only going to make sense.

So bring this now back to the clinical tragedy here, right? Which is again the weakness of our profession. And I say ours, meaning mine and not yours. You take a patient who's got a diagnosis of cancer, do you think anxiety is going to go up? Hell yes. Right. Do you think, do you think their sleep is gonna deteriorate? On no basis other than the fact that they have this diagnosis and they're often undergoing horrible treatment. Right. It's amazing to me that I can't imagine how many oncologists are thinking through this problem.

Right.

Which is as careful as we are about crafting what the chemotherapy regimen looks like. What the exact. If you go to asco, right? If you go to the largest oncology meeting. I don't know how many papers are being addressed on this topic, do you?

No, and I think they are few and far between with.

If you think about some of the stuff we machinate over in oncology, like exactly who gets the sentinel node biopsy versus this and what if this is an ERPR positive breast cancer versus an ER positive PR negative? We could noodle and machinate on the most minute details, which maybe they matter, maybe they don't, and yet something like this seems so obvious and yet we just seem ill equipped to deal with it. It's almost like you'd say, and it.

Doesn'T surprise me either, by the way, it's not your fault as a medical profession and being part of that profession. What I did was I looked at a retrospective and I looked at medical curriculums across the top 20 first world countries practicing medicine. And what you find is that on average most doctors get about one to two hours of education regarding sleep. So one to two hours regarding a third of the patients lives. That is so anemic in terms of meeting the needs. But the critical part is that 1/3 of their life spent sleeping also makes such a huge difference to their 2/3 of their life awake. That is just to me, unacceptable.

And there's a deeper problem which is in training to be a part of that profession, you enter a culture that is as difficult as the one you described, where, you know, heads of state are chest pounding about how little they sleep. I mean, I'll just pause for a Moment to share another sort of set of stories. So when I started my residency, we were on call every third night. I mean, every third night. You know, I think my record, I think the most sleep I ever got on call in five years was five hours. And that happened once. And it wasn't, of course, straight five hours, but I had accumulated five hours of sleep on a call night. So I think you would average probably two to two and a half hours of sleep every third night. But that's average. So guess what? Lots of those times are 30 minutes or less. So you're on call every third night. So it's my second month on the job. So the way it works is you're basically either on call, post call, or pre call. Those would be your designations. So I come in on a Monday, I am pre call. So it's my day before my call day. So you come in at five in the morning. You would normally leave by about eight o' clock at night or seven o' clock at night. And as we're finishing our rounds that evening, someone, a surgical resident, had failed to show for the ER shift. He got sick. So the chief resident said, you know, hey, we need somebody to stick around tonight to cover the er. So I volunteered because I want to show how tough I am. Like, of course I can do this. So I stick around. I do the ER shift that night. And of course, in the er, you're absolutely not. You don't get one minute of sleep. Obviously, now it's Tuesday now I'm on call. So I'm awake, of course, all day Tuesday and Tuesday night and Wednesday. And I probably slept an hour Tuesday into Wednesday. Now it's Wednesday, I get to go home early, which means 6pm on Wednesday. So I've been up since Monday morning. So this is not like within the realm of the type of sleep deprivation that's gonna kill you. There are lots of people in the life.

I'll come back to that.

Yeah, yeah.

No, it almost did, actually. Yeah.

But, yeah, okay, so I'm driving home.

My point in case.

So I'm driving home. So I have quite a long drive till I have to get to the freeway. It's about 2 miles, but it's like stop signs and street lights. And then I have to get to the freeway and then I've got kind of a hike home. At this point in time, I live kind of north of the hospital. I notice something really odd every time I come to a stoplight or stop sign. I can't keep my foot on the clutch because for some reason I just, I have a habit of like keeping my foot on the clutch and keeping it in first as opposed to just sitting in neutral, which, whatever. So the point is I keep stalling and I'm thinking, God, I've never done this in my life. Like, why can't I even sit here for 27 seconds and maintain my motor control over this thing? So I'm at about the last street, maybe two streets away from before I have to get on the freeway for a 15 minute drive. And in what I can only describe as one of the best, dumbest decisions of my life, I decide I freaking cannot get on this freeway. I'm going to die. So I pull over to the side of this road, Eastern Avenue, and there's this park called Patterson Park. I have no idea what Patterson park is like today, but at the time I knew nothing about it other than it was grassy. It turned out at the time it was like, you know, an open air drug market. And this is now speaks to the second point. So I had really good judgment, which was don't get on the freeway. But then I exercise comically bad judgment, which is I'm going to go take a nap in the park. So I get out of my car, probably didn't even lock it, walked into the park, put my pager on my neck of my scrubs, set the alarm for one hour. It's like 6pm Wake up at 2am in the middle of the park with rat bites on my arms. I mean, this is like the drug infested rat infested park. And just think to myself, what in the hell just happened? I had about 3 of those in residency. The other thing that happened once in residency, same situation every third night call. But I had to take an extra shift in there. And to be clear, I volunteered, right? It wasn't like no one put a gun to my head and said, you have to do this. I volunteered for someone who couldn't take a night of call. So I basically was on the same thing. But now I'm way further into my residency. You know, this was in my like 5th year of training and I think the accumulation of that was devastating. And so now it's two in the morning on that third night and we're operating on a patient. And the way it works in residency is when you're a senior enough resident, you're the operating surgeon, meaning you're the one doing the case. The, the attending surgeon is assisting you. Now this is a very trivial operation we were doing. The only reason in fact, we did it in the middle of the night is just to get the OR time. Like it wasn't even an emergent case. It certainly could have waited a day. It was just removing the gallbladder laparoscopically. So I'm holding the two devices in the trocars and I'm doing the case and the attending is just retracting for me. And I don't know how it happened, but I fell asleep on the patient and face planted directly onto the patient. And again, the only solace you can.

Imagine, the amount of sleep pressure that was necessary to build up for you to, I mean, and I remembered that.

I had had a number of head drops prior.

Exactly. You know, like everyone's like jamming to good music. But no, they're not. It's just like they're falling asleep. Right, right.

And you know, after God knows how many of those, it just turned into bang, your full L position, face first into the patient. Again, only fortunate thing there is in the process I didn't jerk my hand and tear the common bile duct or, you know, an artery that could kill a patient. So what happened? Well, the attending surgeon said, dude, you're too tired, let me do the case. You come and hold this. Like it wasn't even like it was just sort of like this happens and you go stand over there. Now, whereas you think about like if that had happened in an airplane or in some other profession where that's a four alarm fire, that's a, what's going on here? How can this happen?

It is. And the data there we've got is pretty strong. You know, I've lobbied the, the medical association a number of times and I just recently wrote a piece in a journal called the Lancet, which was called a sleep Prescription for Medicine. And I lay out the case for why both for patient and doctor, sleep is, you know, utterly essential but profoundly absent. And firstly, what we know regarding, you know, your surgical experience and that, that story there, we know that if an attending surgeon has slept only six hours in the previous 24, there is 170% higher likelihood that they'll make a major surgical error such as, you know, splicing some kind of major vascular component of the patient. What's also interesting is that when, if a resident has worked a 30 hour shift relative to when they've worked just a 16 hour shift, that resident, after 30 hours of being awake, when they get back in their car and start to drive home just as you did, there is a 178% increased likelihood that they'll get into a car crash, end up back in the same emergency room from which they just came, but now as a patient requiring ER treatment because they got into a crock. The irony is lost on me there. The other point is that we know that one in five medical residents will make a serious medical error during their residency caused by insufficient sleep. One in 20 medical residents will kill a patient because of insufficient sleep. Now, when you realize that there's well over 20,000 medical residents active right now and you think about that statistic, 1 out of 20, and you were to then do the math and lay out the number of bodies in front of you that were preventable deaths, preventable by way of this simple thing called insufficient sleep, I think it is an absolute disgrace. You know, doctors working in the ER, if the residents, if they've worked a 30 hour shift, 460%, I think it is more diagnostic errors, which just stuns me in terms of a number. But what's also interesting is that when you lobby the medical organization and I've tried to do this a while back, and I lay out that compassionate case of medical errors, impact on patients, impact on doctors themselves, there was incredible pushback and resistance, which was, my mind is made up, don't confuse me with the facts.

And I want to just have a mea culpa because there are few people that were more vocally opposed in our residency than me. When this 80 hour work week came in, and my view was not that sleep was good and we needed more of it, I really didn't have a point of view on that. I actually frankly hadn't reflected on that because I obviously didn't know any of the data you shared. My view was the conditions under which we work are horrible. And that's a selection feature. You want people that are willing to opt into that, who are willing to take that much pain to do this. And I had this whole thesis, which I have no idea if it turned out to be true or not, that if you lowered the bar, lowered the pain, you would bring in a broader demographic. Now, regardless of whether that's true or not, it doesn't really matter in the face of those data. In other words, if it is true that back in the day you were just training better physicians because you were attracting people that could persevere more or had whatever make up your thing, it still doesn't change the fact you've got to come up with a new screen for that. You've got to come up with a new filter.

Evidence of the deleterious impact of. Even if you attract, even if it's just a selection bias that you're bringing in these hard knuckle folks who can just jam through with wakefulness in ways that really are just horrific for everyone involved, you still can't get around the fact that they're not going to be performing medicine at its highest. And we know for a fact that you don't need to. So I think the only piece of evidence that favors that type of 30 hour continuous residency type of mentality, the only good argument I've heard is continuity of care, that once you go down to a shorter amount of time, you lose continuity of care with the patient, that you're cycling doctors between patients. But I have to say though, even that I don't believe because when I looked at systematically at the other medical practices, there are places that train wonderful physicians that have a maximum of somewhere between 12 to 16 hours. Places like New Zealand, Sweden and France, they all limit their junior doctors to training on nothing more than those amount of hours. And if you then look at the ranking of the medical systems in terms of how well they're doing, those guys are way up there at the top. So I find it difficult to see a case for arguing for the ability to train doctors with insufficient sleep.

I'll tell you what I think is going on because I agree. I mean, I've been away from it for so long, but I've spoken to a few people who have kept up with the sort of medical education literature and it turns out the 80 hour workweek has not solved the problems that they had wanted. I don't believe that medical errors have necessarily gone down.

Now.

You could argue, well, 80 is not low enough. But I also think a more subtle part of it is in the countries that you mentioned, I suspect that it is the cultural norm of not just the residents, but the people who train those residents because they were trained in that sort of more humane way that you bring a different way of thinking about handing off a patient. It means something different because it's just so ingrained in that's how medicine is practiced. And I think what happened in the United States, and again, this is wild speculation, I don't follow this literature. But just based on what I've seen since, I suspect that when you overnight created a new rule, which I think took place like July 1, 2003, new rule, right overnight. But none of the people that were leading that had trained under those conditions, they didn't necessarily know how to teach under those conditions. They didn't understand, as we said, like what does it mean to hand off a patient after 16 hours? Because in our day you are responsible for everything. I mean you wouldn't dream of doing something like that because you just don't know how to communicate what needs to be done to the next person. I mean so much of it just comes out of that. So I suspect that's a big part of it. And of course, unfortunately that would suggest that this is going to take time, but it still has to change.

But I fear it, that type of mentality is going to die one generation at a time. Because in part there was, you know, it's a bit of an old boys network I think some of it. But you mentioned those things about how do we understand the informational transfer, the propagation from one doctor to the next regarding continuity of the patient who remains. And I think that really is an important point. Part of me though feels as though we've been able to put people on the moon and that was non trivial, but we solved it. I think we can also probably solve continuity of care and protect both patient and doctor alike in terms of their well being and still do it. So I think it's. No, I don't mean cultural, I don't mean to sort of trivialize the problem. And I think what I want to try and do here is, you know, just raise my hands and say that, you know, I really appreciate how hard that is. It's an. It's just like early school start times and the work that I'm doing there to try and lobby for kids to start later. That's not a small thing either because you've got to solve multiple problems. You've got to solve bus unions, bus transportation, you've got parents who need to be in work at a certain time point and you know, starting those times later is going to be non trivial. All of these things are hard problems and it's not as though I'm either ignorant of those and I want to really recognize how hard they are. But what I would also love to do is to try and just make sure that we don't lose sight of the end outcome here. The end outcome in terms of education is our children and making sure that we are not essentially educating our children amnesic by way of their insufficient sleep. And the same is true for our patients and our doctors. Let's keep the target that we have in our crosshair at the end of this process in mind rather than get perhaps distracted by how difficult the problem is. It is difficult And I'm so sympathetic to that. I know it's hard, but there's so much on the line. There is too much on the line for us to be swayed by the difficulty of the problem in terms of the importance of the solution that we must reach.

No, no, no, I don't disagree with anything you've said. I think what I'm trying to do is provide an explanation for why. And it's not an excuse, more of an explanation for why I think the experiment has failed here. And it probably speaks to the need for a greater buy in to the gravity of the problem and therefore a greater emphasis on solving what I agree are quite, in the grand scheme of things, trivial problems. I mean, splitting the atom was hard. Putting a man on the moon, that was hard. Eradicating slavery, that was hard. All of these things have been done.

But I think we will look back with shame, just like you were describing to your family regarding sleep and insufficient sleep. As we look back now with smoking 50 years ago, we will look back in probably 20 years with shame that we were having schools start at 7:30 in the morning. By the way, for schools that start at 7:30 in the morning, buses will start leaving at 5:30 in the morning. That means some kids are having to wake up at 5:15, 5:00 or even earlier, which in my mind is lunacy. And I think the shame will be present when we consider the impact and the impact we already know from the studies. When we delay school start times, what we see is that academic grades improve. We see truancy rates decrease. We see behavioral problems and psychiatric problems also decrease. You see the number of people who drop out of school and drop out of certain classes also decrease. And then finally, shockingly, the life expectancy of students increases. And the reason that it increases is because of car crashes. There's a great study in Teton county in Wyoming. They shifted their school start times from 7:35 in the morning to 8:55 in the morning. And then they looked to see in just this narrow age range of just 16 to 18 years old, what was the change in car accidents and what they found in that following year. Not just that the kids reported getting one hour of extra sleep. There was a 70% drop in car crashes that following year. Now the advent of ABS technology in cars, anti lock brake systems, the that dropped accident rates by 20 to 25%. And it was deemed a revolution by some people. Well, here is a biological feature. Getting enough sleep that will drop accident rates by up to 70%. So when sleep is abundant, minds will flourish. And if our goal as educators truly is to educate and not risk lives in the process, then I fear that we are failing our children in a quite spectacular, spectacular manner with this incessant model of early school start times.

So say a little bit more on this. You and I have talked about this in the past, which is, and I think I even posed the question to you this way, which was all things equal, Matt, if you're trying to pick between three schools for your kids, would you weigh start time in the matrix of decision? And your answer was emphatically yes. Why is this the case? Why is it that do kids just, is there something in their brain as they're developing that it's just a question of they need more sleep and therefore you'll pick it up in the morning, or is there something about they need to sleep to a later time that won't be solved by putting them to bed earlier?

All of the above. So firstly, kids, Even when you're 16, 17, 18, you're still needing nine to 10 hours of sleep because your brain, it doesn't finish developing until it's about 25.

What percentage of 18 year olds in the US do we believe are getting that sleep? Or if it's easier to answer the question, what do we believe is the median duration of sleep for an 18 year old?

About 11%.

11% are achieving the required 89% are.

Not getting sufficient sleep.

And do we have a sense of what that average is? I think the numbers you quoted earlier, I assume were for adults or was that for all comers?

No, that was for adults. For teenagers it's probably, it's down to about seven hours when it should be somewhere between nine to 10 hours. So the bigger deficit, relative deficit, is bigger than it is in adults. What's also striking, by the way, is if you look at parents and you ask them, do you think your teenager is getting sufficient sleep? 72% of them will say, yes, I think my teenager is getting the sleep that they need, yet only 11% of them are getting the necessary sleep. So in other words, there is a mismatch here between the parental and child sleep equation and what that also leads to. Then, because parents believe that their kids are getting enough sleep, there is a parent to child transmission of sleep neglect. And what I mean by that is, you know, the pulling the covers off at the weekend when these kids are sleeping in for two reasons. Firstly, they're sleeping in because naturally their biological circadian rhythm moves forward in time, so they want to Go to bed later and wake up later. It's not their choice, they don't get a choice in that. So it's biological, it's hardwired.

So for a parent listening, what would you say to them if they're brusseling with their kids sleep schedule, what do we think is the most natural time to bed, time to rise for a 16, 17, 18 year old?

I think for 16, 17 you're looking at a 10 hour period, probably from somewhere between 10 to midnight, depending on their chronotype, to then sleeping in until essentially somewhere between 8:30 to 10:30 the following morning. Now the reason that that is actually still too early though is because that would be what would naturally happen if you were to let them sleep like that every single night of the seven days of the week. But we don't, because what we do is during the five days of the school week, we are getting them up way too early. You can even put them to bed at you know, 9 or 10 and say sleep. They can't biologically, so they won't be sleeping as well during the week. So at the weekend they're trying to sleep off a chronic debt that we've saddled them with during the week due to early school start time. So no wonder they've got such a sleep pressure that is forcing them to try and sleep until like 1 or 2 in the afternoon. So then we chastise them for saying you're lazy, get out of bed, you're wasting the day. But it's not their fault, firstly because their biological rhythms, their circadian rhythm wants them to be asleep latent into the morning and into the early afternoon. And secondly, they've got this huge debt of sleep that they're having a rebound from in terms of sleeping, trying to sleep off that debt that the school systems have given them as well. So to me I think we just need to reformulate our notion of how important sleep is in that context.

And you've already alluded to this, that's a hard one to solve. Right, because you're restructuring when a parent goes to work, et cetera, it is non trivial. What would be a middle ground that would be a great compromise. In other words, if a school started at 9am, I feel like when I was in high school we started at.

9:00Am well, ironically, yeah. What's happened is that back in the 60s schools were starting around 9 o' clock and then evermore as we marched on in terms of our quote unquote development in society in the US that time has Actually gone back and back to earlier and earlier start times, I think because it's been squeezed by the sort of the vice grips of, you know, work schedules where parents are having to work longer hours, they are ultimately commuting for longer, so they have to leave the house ever earlier, so they have to put their kids in school ever earlier. And I think many of these kids are just sitting there unabsorbent, like a waterlogged sponge. They're not going to be taking up information. And in fact, if you look at the data regarding delayed school start times and you ask, yes, overall gpa, SAT scores, all of them rocket up. They all improve when you delay school start times. But which classes get the biggest benefit in terms of the grade improvement? It tends to be not the classes in the afternoon where they are finally awake because of their circadian rhythm. It's the classes in the morning where before those classes would be starting at, you know, 8 o', clock, but now are starting at 9:30. When you push them to 9:30, they're doing much better in those classes. And it reaffirms the case that the hit that is going on in terms of the amnesic impact that early school start times are having is really in those morning hours when the brain is not designed to be awake. And it's certainly not designed to be receiving an education. It's designed to be asleep, preparing itself for its education, which should really start at maybe 9 or 10 o' clock in the morning. I mean, the United Kingdom, right now, as we speak at the time of this podcast, there is a bill that's going through that will lobby for a 10am start time, which I think is probably the sweet spot.

And the reality of it is, because someone will say, well, great, what do you want kids to stay in school till 6pm and blah, blah, blah. But my guess is you could probably do less with more if you did it right. In other words, you wouldn't need to spend as much time in school if.

You could cramp, you could more efficiently learn that information. We've done these studies. You absolutely do learn more efficiently when you have had sufficient sleep. So it's a forcing function. Could you compress it? It's like zipping a file. The amount of information that can be stored is much greater. But what's also interesting, let's say that that's not the case. And you say, look, to do all of this staggered system with the bus unions and to make it work out with parents and work schedules, it's going to require More money to figure this out. Well, it turns out that some of that can be cost savings at the back end because kids get released later. There is a time during when kids get kicked out of school if they start early, which is this kind of criminal bewitching hour, which is where the kids are out of school, but the parents are not home yet from work. And when they get together, sometimes for some kids, bad things happen. That's where you see a lot of juvenile crime happen, which is in that sort of twilight hour between, you know, the 3 to 4pm period when they're out of school to the 6 to 7pm period where the parents are finally there and they get home. If you look at the cost of that criminal impact of activity in those hours, and then you say, if we were to start schools later, kids get out later, we'd limit the window of criminal opportunity. The cost savings comes back around and pays for itself, for delayed school start times. So you just need to open up the aperture of your memory, think about the problem, and ultimately you can solve these equations.

My daughter hates when I say this, but I keep saying to her that I think this whole summer vacation thing is ridiculous because it's sort of an artifact of a world when you needed the kids to sort of work in the farm in the summer. But it almost seems like having a shorter day, shorter time in school, more time, in other words, uniform the situation. Right. More time to do extracurricular things, more time to sleep. But just go to school 12 months out of the year. Like go to school, like we work, right? Yeah, that seems to be also culturally a very difficult solution, but conceptually an easier way to approach this as well.

I mean, I love your idea, and I do think that the data supports it empirically right now, which is that you may not necessarily need to just simply take the school day and push it forward in time. You may just need to take the start of school and push it forward in time and hold constant the end of the day. But by way of that sufficient sleep, ultimately you may be able to still gain the same amount of intellectual equity within the minds of those young individuals by way of that sort of later school start time and greater sleep as a consequence.

And it also just seems like something that is so amenable to testing. I mean, it's very easy to do a randomized controlled trial of something like that.

Lots of that stuff that's going on right now, the data just keeps coming out and it goes in no other direction. It's so consistent.

It really Is, is there anything that we as parents can do outside of the obvious, which is choosing, you know, if we have the luxury, Right? A lot of times you don't have the luxury, but if you have the luxury of choosing between schools that have, you know, meaning if you can choose by where you live or if you're putting your kids into private schools or something, the later time, let's assume you don't have that luxury and you got this hand that's dealt to you, which is school starts at 8, 10 and gets out at whatever, 3, 40. What can we do to help the kids get as much sleep as possible, even if it means bucking against what might be their innate circadian rhythm?

I think probably right now the best thing to do is to try and excise technology. And you know, I'm very.

When you say that, can you. Yeah, just say that again? That is such, I mean, that is such a, a hot topic right now. But it's. This is another discussion I had with my daughter, which is, I worry that in 20 years we will look back at the idea of 10 year olds with iPhones, as I worry we will look at it with even a worse lens than this smoking mother. And there's twofold, right? There's the technology piece, which we'll talk about, and then that says nothing about the whole social piece of the influence of social media and stuff like that. So sticking to the first one, you take the technology away completely. You limit light after sundown.

So there's that component which is I think, just the basic impact of light. And this is scales to not just children, it scales to adults too. That we are a dark deprived society in this modern era and we need darkness at night to allow the release of a hormone called melatonin. And that melatonin, as it rises, it will help time the onset of your sleep. And there are great studies that have been done where if you use, let's say an iPad for an hour before bed, firstly you get about a 50% drop in the amount of melatonin that's released. So you lose 50% of the signal of sleep timing. Worse still that melatonin peak, even though it's lower to 50% lower, it will arrive three hours later at night. So it's so mistimed by the perverse impact of the screen. So that would be like you and I living here in California. But our melatonin release is much closer to Hawaii in terms of timing. That's one hour of iPad reading.

Is that true? Also, Matt, for television does Television emit the same.

No, it doesn't. So television less so. But television has another mental impact, especially if you're watching it in bed. That's not a good idea because then your brain associates your bedroom as the place of being awake and watching television, not the place of sleep. And that's a. When you start to form those maladaptive associations, it can be a trigger of insomnia and anxiety. And typically that's one of the recommendations that we have, that you only use the bed if you're struggling with your sleep, for sleep and intimacy. That's it. But to come back to kids, that's the first impact, which is that the light can disturb and disrupt their melatonin significantly. We also found in those studies, by the way, that the one hour of iPad reading before bed reduced the amount of REM sleep time. When people woke up the next day, you have them rate how refreshed by your sleep do you feel? Significantly lower rates of feeling restored and refreshed by their sleep. What was also interesting is that once you stopped that iPad reading, it again had this carryover effect. It had this blast radius where they kept sleeping poorly for another two to three days after that iPad reading. The second component, though, is a mental component. And I think it's the component that may be as if not stronger than the biological component with melatonin, which is firstly that these devices that kids use can cause sleep procrastination. What I mean by that is, and this is just for adults too, you can be there with your phone or your iPad and you can be sleepy and you could fall asleep, no problem at all. But because you got it there, you just think, just check email one more time. Just check Facebook. Let me send that tweet out and I forgot the detergent. Let me go on to Amazon very quickly and I'll just order that and. And then you look up and it's 40 minutes later and now you're 40 minutes short on your sleep. Sleep procrastination is a problem, but for kids, I think the. The two bigger issues are waking up in the middle of the night. There was a survey done that demonstrated that well over 80% of teenagers admit to waking up during the night to check their phones and check social media.

Sorry, say that again.

80%, 8, 0 during the week will wake up at least once to check their devices. So you've got this dependency that is causing this alertness spike to wake you up. And that's a habit that once it builds, is quite difficult to break. The final thing I think even if you were to be diligent and put your phone in airplane mode, what those technologies do is cause what's called anticipatory anxiety. So I think many people have had that experience of having it like an early morning flight and you've got to wake up at 5:30 in the morning and you know it. You set the alarm, but you wake up at 5:28 and you are awake like a bolt.

Matt, I'm glad you brought this up. I have noticed this for my entire life. I sometimes will play the game of can you wake up at 5:28? I'm blown away at the ability to do that now. You can't do it if you're really sleep deprived. At least I can't. So it's not. I can't go to bed at 2am three nights in a row.

You'll oversleep it if you don't have the alarm.

What is that telling us about? It's almost like I've got a CPU with a clock in it.

Like.

No. An actual clock.

No, Correct. That's right.

Because you can do it to a wrong time. You can miss set the clock at the bed by 10 minutes and hit that time versus true time. It's crazy.

And there's a great experiment that I'll tell you about, but that anticipatory anxiety, that airplane example, that's kind of like the extreme version, but a weaker version, but a chronic and I think a very malign sort of version of it happens with our phones. Because most people, the first thing that they do when they wake up in the morning is swipe. And they just unlock this world of anxiety that comes flooding in through their phone, emails, texts, social media. You essentially are training your brain to anticipate that wave of anxiety every morning. And what we've discovered is that when you embed that anticipatory expectation in the morning, the amount of deep sleep that you get at night is less. You end up sleeping in a shallow state and you don't get the same amount of deep sleep. And the greater the anxiety that there is the next morning, the greater the reduction in deep sleep that you have the night before. That's why you'll feel like you've had a pretty rough night of sleep when you're waking up for that early morning flight because you've just had a poor quality of sleep. But the timing thing. So I think to come back to make the point here, so I don't forget, I think for kids, the best recommendation right now is technology. To try and limit it. And I know that's hard because the genie feels like it's out the bottle and it's not going back in anytime soon. And I don't want to be puritanical. I don't want to be puritanical about alcohol or caffeine, about cbd, thc. I don't want to be puritanical about kids getting the sleep or timing of the sleep that they need or can't get. But what I would say is that to try and maximize that sleep in the face of early school start times, which is what we're currently facing right now, taking that technology out the bedroom is probably the single best thing that you can try and do. The other thing that they recently found was a correlation between the use of or having social media in the bedroom and fear of missing out. Because for kids so often, and I understand this, you know, because we were both kids, you could remember that folks were going out, you know, in the afternoon, you wanted to be there, you wanted to hang out. It was fear of missing out fomo. Well, now FOMO plays out on social media and it plays out when you disengage from the parents. It plays out, in other words, in those twilight hours. And so there is good data now showing that fear of missing out is directly related to insufficient sleep at night in teenagers. The way that you can try to help that is to try and limit the devices that give you the ability to have FOMO in the first place. So, but in truth, I don't honestly have a good set of solutions right now for this teenage sleep problem. I think it's going to have to be letting them sleep when biologically they naturally want to sleep again, you fight that biology, it's not going to go your way. It's just not.

Well, Matt, that certainly will scare any parent senseless with respect to electronics. One other question on that that my daughter actually asks me all the time, if she's reading a book in bed with a night light, is that as harmful? A from the standpoint of light, which is actually the question she's asking, and now B would be my question. More broadly, we talked about not watching TV in bed because that's creating kind of a different purpose. Is reading in bed a bad idea and. Or is the, you know, sort of natural white light? Not natural, but, you know, the white light you get from a bulb, where does that rank on the melatonin suppressing scale?

So if you're someone who is struggling with sleep, that you are someone who has sort of insomnia, such that you are finding it difficult to either fall asleep or you wake up at night and you can't get back asleep. So the first is what we call sleep onset insomnia. The other is called sleep maintenance insomnia. You can fall asleep fine, but you can't maintain your sleep. The advice there is even reading should be something that you should forego, that you should read in a different room, wait until you get really sleepy, and then go to bed. That's the advice. And because otherwise, as I mentioned, the brain is this incredibly associative device. And if you lie in bed awake, your brain quickly learns that your bed is the place of wakefulness. I hear this from patients a lot where they'll say, look, I'm sitting on the couch watching television and I'm falling asleep, and then I get into bed and I'm wide awake, and I don't know why. And the answer is because your brain has learned the connection of your bedroom being a trigger for wakefulness, because wakefulness is what you do there. So what you need to do is break that association and get up after 20 minutes, go to a different room in dim light, read a book elsewhere in dim light, and I'll come back to what type of light in a second. And then only when you're sleepy and there's no time limit for this, should you return to bed. And the analogy would be this. You would never sit at a dinner table waiting to get hungry. So why do we lie in bed waiting to get sleepy and you shouldn't? And we need to sort of bring that back. So that's. If you're struggling in terms of light, what I would say is be a bit mindful as to what kind of light it is. If it's an LED light, it's usually enriched in the blue, sort of low frequency of the visible light spectrum. And it's the blue light that is most harmful to melatonin. So light in general, not great for melatonin, it will stamp the brakes on melatonin and it will stop releasing it. So your brain is fooled into thinking it's still daytime, even though it's actually on the clock face nighttime. But of that light, if there is a better form of light, it's the red and the yellow, the very warm kind of colors, the cold blue light that comes from led, that's the more dark, deleterious light, that's the type of light that is more detrimental. So I would say that, you know, you can get these smart light bulbs now that can change the dynamic frequency range of that light in the visible spectrum, make it more kind of warm and yellow in the evening. Definitely favor that. And try to stay away from, you know, light that is LED light, you know, even if it's just going back to a classic light bulb, which typically is warmer in color and low in wattage, that's your best light for reading.

Has the experiment been done when this might not even be ethical today, where subjects are given no restriction on when to sleep, how long to sleep, but they are put in a perpetually light environment?

No, but the opposite.

Well, I know of the opposite.

Yeah, there's two. No, there's one experiment that has kind of been done that is like that, and then there's the other opposite, which is. So the one experiment that's not dissimilar to that actually happened inadvertently, unfortunately, which is with premature babies in the neonatal intensive care unit. What they used to do was they would just leave these fluorescent light bulbs on in the NICU all of the time. And at that point, even though the circadian rhythm isn't especially robust in infants there, you know, awake, they're asleep, they're awake, they're asleep, they still need that signal of light and dark. And what they found is that when they regularized light in the neonatal intensive care unit, in other words, when they gave back darkness at night and gave strong light during the day, firstly, the infant started to sleep better. You saw about a 50% improvement in oxygen saturation in those infants, and they put more weight on within the time period because they were sleeping more regularly. And then finally they left the NICU somewhere between two to two and a half weeks earlier. So that's the only example I know of where you take a condition where you are put under artificial continuous light conditions and then you do the experiment where you try to mimic more Naturally what a 12, 12 hour cycle of light dark would be. And what you see are just biological changes, all for the better. That's the only experiment that I know of in the positive, which is what you're describing. The reverse experiment was done where they essentially took a group of people and they said, you know, what time do you normally go to bed? And they said, normally go to bed. Like, I can't get sleepy until about 11pm and I sleep usually about six, six and a half hours. They took that group of people off. They went to the Sierras here in America, this sort of beautiful mountain range with no electricity whatsoever, no access to artificial light. And firstly, what was dramatic was that these individuals started going to bed around 9 o' clock in the evening. This wasn't necessarily just because they didn't have anything to do. Do they actually rated themselves as feeling sleepier earlier? Why? Because they were getting the signal of darkness at the natural time. Secondly, they went from being, you know, ardent about the fact that they were only six and a half hour sleepers and that's all that they needed to then sleeping a little bit more than nine hours. Now I think this point about going to bed at 9pm is a really important one. Have you ever thought about what the term midnight actually means? It means middle of the solar cycle, it means middle of the night. Whereas now, with the perversity of the industrialized civilization, midnight, and especially now in the digital revolution, means it's maybe the last time to send a few emails. Whereas if you look at hunter gatherer tribes whose way of life hasn't changed for thousands of years, and you ask how do they sleep? As if they are a good indicator, and we think that that's probably a good indicator of how hominids should sleep. They typically go to bed about an hour and a half to two hours after sundown, so around sort of 8:39 o', clock, they usually get about seven, seven and a half hours of sleep at night. And then they have a siesta like nap in the afternoon to make it up to around about a total of nine hours. So I think what has happened with modernity is that we have changed both the amount of sleep that we're getting, we've reduced it, we've changed the timing of sleep so we're getting less sleep and we're getting it at a different time, quote unquote, perhaps a wrong time of night. And finally the nature in which we obtain our sleep has been changed. It seems as though we are designed perhaps to be sleeping biphasically, which is a long bout at night, and then a siesta like nap in the afternoon. A lot of people will ask me about this two phases of sleep thing, but in a very different sense, which was you sleep about four hours, then you wake up, you kind of have a social life, and then you go back to sleep for another four hours. And it's called the two sleeps or first sleep and second sleep. And there's a great book written on this now that definitely happened sometime in human civilization. It seemed to happen around the Dickensian era. But there is nothing in our biology that suggests that we should be sleeping in that way. It seems to have been a social Feature a social pressure.

There was a meal that took place, a large meal that took place between those two, sandwiched between the two four hour sleeps, right?

Correct. Yeah, yeah. And people would, you know, they would have social activities planned, they would write, they would play music, make love. People, you know, it was a real thing, but it was not a biologically defined way of sleeping.

It's amazing.

It's not a natural way of sleeping.

You'd think you'd be, I mean, I guess you could condition yourself to do anything but to wake up after four hours of sleep under any circumstances, generally quite miserable.

It's rough, it's absolutely terrible. So that happened. But I think to come back to the point, it's just that how we are sleeping in modern society is not just about sleeping less, it's about sleeping less, the timing of our sleep and the structure of our sleep. So I think those are the things that have changed.

One of the questions I get asked a lot and I don't know the answer, so I'm hoping you do is one, you sort of touched on it, but the efficacy of naps, and two, the notion that you should or shouldn't nap if you're having sleep issues. Right. So on the second one, I have a slightly stronger point of view and I hope it's not incorrect, which is in that situation, the nap is wrong. You want the adenosine accumulation and you want it to draw your bedtime back earlier. Right. If you're struggling, I'd rather you push through not sleeping and then go to bed at 9 o'. Clock. But to the first question, more broadly speaking, I can't imagine that one cycles through what you described at the outset of our discussion in a 20 minute or a hour long nap. Right. I mean, what actually do you have people nap in the lab as well? You must. Yeah. What does that look like?

So we've done a lot of these studies where we ask, you know, what are the benefits of napping? And we certainly do find them. We find benefits for learning and memory, we find benefits on immune function, we find benefits for things like cardiovascular health in terms of metrics of heart rate variability. We see benefits in terms of lowered systolic blood pressure. All of these things we found benefit by way of a nap. Now when I say nap, you can ask, what do you mean by a nap? And we've played around with that dose, as it were, and we've done sort of, we've tried to do a little bit of a dose response curve with some of these things too. What we found is that you can go down as low as about 20 minutes of a nap and still see some mental health benefits in terms of things like learning and memory. But typically we do a NAP that is 90 minutes because that gives the ability of the brain to go through the full 90 minute cycle so that the brain can go through all of the stages of non REM sleep, stages one through four, and it gets the shot to get to REM sleep. And then we can ask by testing people in brain scanners sort of before and after, and with cognitive tests and then with peripheral body tests, we can ask, what was the benefit of that nap relative to a group that does exactly the same thing? They lie in bed, but we don't let them fall asleep, that they may just kind of passively watch a movie. So they're inert for the same amount of time they're in bed, they get all of the wires on the head. We try to do it as controlled as possible with the only difference between being sleep between those two groups. So you do find benefits to your first point, to your second point, you're absolutely right. In terms of your sleep prescription for your patients, the current recommendation is this. If you are finding it difficult to sleep at night and sleep throughout the night, the recommendation is do not nap during the day. And this helps us when we try to think about the biological mechanisms of how we can sleep actually work. And you mentioned a chemical called adenosine. So from the moment that you and I woke up this morning and everyone listening, the moment that you woke up this morning, a chemical has been building up in your brain called adenosine. The more of it that builds up, the sleepier that you will feel. So it's the sleepiness chemical. And after about 16 hours of accumulation, you should have enough weight of healthy sleepiness. You should have enough adenosine within the brain to have you fall asleep easily and then stay asleep soundly. And then when you're in sleep, the brain actually will clear away that adenosine, removing the sleepiness. And after about eight hours of sleep, you've removed 16 hours of accumulation of adenosine, so that when you wake up in the morning, you feel alert, you feel more awake, and that's the reason that you don't feel as sleepy anymore throughout that following day. Now, the problem with naps is that if you nap in during the day, particularly if you nap in the late afternoon, essentially what you're doing there is acting like a pressure valve on a steam cooker that you're building up all of this great healthy sleepiness, this sleep pressure, and then you nap and you just release some of that sleepiness. So now when it comes to your normal bedtime, you don't feel as sleepy. Why? Because the nap removed some of that sleepiness pressure. It removed some of the adenosine, and you are going to perhaps find it more difficult to fall asleep and stay asleep. Perhaps is the important point. There are some people who can nap. If you can nap regularly and. Or you don't have problems with sleep at night, then naps are just fine. But if you can't nap regularly, and especially if you're struggling with sleep at night, the advice is don't nap. Stay awake, build that healthy sleepiness, build lots of adenosine that gives you the best chance to stay asleep, and then fall under the spell of sleep, under that weight of sleepiness for as long as possible.

You know, it might be oversimplifying, but the way I generally describe sleep to patients is sort of a balancing act between adenosine, cortisol, and melatonin. And you've gotta, like, these three things have to make. They're like an orchestra. You have to have the crescendo of adenosine with the decrescendo of cortisol, and then you have to let melatonin take the brakes off this whole thing. And, you know, even when I just think about myself personally, I am convinced that virtually all of my sleep woes are on the cortisol axis. And the reason I'm hypothesizing that is I can't measure adenosine. It's very complicated to measure. You need a very special type of mass spec to do that, or Mrs. But we can measure melatonin in urine. We can collect urine overnight and measure melatonin levels so we have at least some sense of how much we're making. But because I measure glucose 24 hours a day, and I'm pretty familiar with meal timing and response in many ways, nighttime glucose for me is a proxy for nighttime cortisol. And the association between high nighttime glucose and poor sleep is overwhelming. And I suspect it's that. I suspect it's through this cortisol axis.

There is in some ways a manipulation that we'll speak about in just probably a little while of adenosine. Even though you can't measure it, you can actually manipulate it with something called caffeine. And that can demonstrate to you.

Matt, by the way, we're in America here. I don't think there's a human that doesn't know what caffeine caffeine is. You get everybody's ears perked up, like you're going to mention some new compound you just discovered in the lab yesterday. It's caffeine.

Yeah, yeah, yeah. Somnus squared. No, no, it's called caffeine. But what's interesting regarding cortisol, which really supports your hypothesis right now, the leading underlying mechanism, the leading theory of insomnia essentially comes back to that fight or flight branch of the nervous system that you are in this profound parasympathetic state where that nervous system is cranked too far in sort of the high strength direction. And if you essentially have a cannula and you sample cortisol every 30 minutes across a 24 hour period, you see this, you know, this nice rise during the day where cortisol is helping you stay awake, it's keeping you alert, it's doing all of the things that it needs to do. And then as you start to come towards the nighttime period, cortisol should drop and needs to drop for you to be able to initiate sleep. And in fact, it usually hits its sort of almost its nadir at the point where most people will say, that's my typical bedtime. And it then goes through this awesome sort of downstroke in terms of concentration. And then a few hours before you wake up, cortisol will start to rise. In other words, it's a preparatory hormone that starts to get you ready for wakefulness. If you look at patients with insomnia, however, what you see is that their cortisol starts to come down nicely in the evening, sort of six or seven or eight. So, you know, they could feel just as sleepy as a regular person. But then right before bed, it goes back in the opposite direction, it spikes again and then starts to come down. And then often in the middle of the night, you will see cortisol spike back again when it should be lower still before it starts its rise. Those two cortisol spikes, I think, are the natural biological bookmarks for what we call sleep onset insomnia and sleep maintenance insomnia. So your cortisol spikes just before bed, you can't fall asleep. Sleep onset insomnia cortisol spikes in the middle of the night, you wake up, rolodex of anxiety in brain starts to happen, cortisol spikes, you can't fall back asleep. That's what we call sleep maintenance insomnia. Those are the two principal types of insomnia. I think that's where you can see part of the biological basis. And my guess is that if we were to measure, you know, things like your heart rate variability and we were to decompose them with some mathematical equations that you would know of, things like a fast Fourier transform, you can look at the contribution of the sympathetic versus parasympathetic when you break down the heart rate variability. My guess is that you're going to see that sympathetic, that fight or flight branch of the nervous system getting jacked just before sleep onset and then once again spiking in the middle of the night underlying the cortisol spike, which underlies the awakening, which underlies the syndrome of insomnia.

Yeah. Who do you think in that equation? I mean, I don't want to give everyone a lecture on this topic because you've done a great job explaining what sympathetic is, right, which is autonomic, but it's sort of different from the glucocorticoid regulated pathway. Do you think that the sympathetic is driving the glucocorticoid or the other way around? And the only reason I ask is in a moment I'm going to propose the only two things that I've ever really thought I have in the toolkit to treat that. But the answer to this question might impact that as well.

I honestly don't think we have the evidence to argue which way round that chain of command unfolds. I just genuinely don't know of the evidence. I think both are tenable hypotheses. Both could be independent, so I think they could be non mutually exclusive. So in truth, I don't think I know the evidence in favor. But what's nice is that the fact that we know that they both happen and can be causal contributors means that we've got at least two treatment targets that we can go after, which I think will then play into exactly what you're going to say, which.

Well, I don't know that they're correct. But to me, when we see that pattern, because we do measure nighttime cortisol and we, you know, we measure the metabolites of it and all of these other complicated assays, when we see that high nighttime cortisol, we basically, you know, I mean, we sort of. That's a very hard problem to treat from an, you know, because if you really think about it, we're just dealing with the endocrine system, right? You know, it's a heck of a lot easier to treat thyroid dysfunction and dysfunction of the sex hormones. And I'm not saying that those things are easy, but they are easier than treating the Upper end of the. Like when you have low sympathetic function and low glucocorticoid function, that's actually easier to treat than the opposite. The hardest problem I think in clinical medicine from an endocrine perspective is high sympathetic output. High glucocorticoid output and really it's amenable to behavioral therapy. Right. It really comes down to a change in mindset and a change in routine. We were talking about this earlier. It's like the further I can separate bed from email, the better because for me email is just. I hate email so much. So anytime I'm looking everyone else's agenda for your. Yeah, yeah, yeah. I'm just, I'm just. I have a low level of pissed offedness whenever I'm looking at email. So the further I can separate my pissed offedness from bed, the less my cortisol is.

Can I get that T shirt by the way?

Yeah, yeah, yeah, yeah. And then the second thing which appears to work anecdotally is phosphatidylserine at a high enough dose which generally requires about 400 to 600 milligrams. And again for me the only time I find that that's really necessary is under those jet lag circumstances. You know, when you're trying to put yourself in the time zone of London when you're leaving San Francisco and, and you basically have to make yourself go to bed and it's only 2pm in your brain, but it's late enough there. Slamming yourself with 600 of phosphatidylserine really seems to move the needle both in terms of your glucose response and your cortisol response. What else do you have up your sleeve on that particular problem? Because honestly, I can't think of a more difficult clinical problem than the one you've just described.

I think the glucocorticoid issue is I think is a really tough nut to crack. I think for the sympathetic drive. I do think you're correct that it's behavioral there. I would actually argue meditation. And I looked at this data when I was researching the book. Gosh, this must have been about four years ago now, you know, And I'm. I think I'm a bit of a hard nosed, dyed in the wool scientist. So some of the. When I was reading the studies on meditation and insomnia, I was wondering if it was a bit woo woo and know how to take it seriously. But the data was very compelling in terms of it really does decrease the amount of time it takes someone to fall asleep. The continuity of their sleep is improved. If you look at some of these apps that do it very well and you know, things like headspace or calm, my guess, although I don't know if they've ever released this data, is that if you were to look at their usage statistics, you will already see that people are self medicating their insomnia by way of meditating right before bed. And I think both of those apps are starting to now launch aspects of sleep and sleep health in their portfolio of offerings, rightly so, because they've probably realized that sleep is a huge part of the issue for which people are coming to them to solve. And the clinical data is very supportive of that. So I would say that for driving, it's almost impossible to fall asleep if your autonomic nervous system is pushed in a sympathetic dominant state, in a fight or flight state. And a good example of this is, you know, when you are jet lagged, you can be there. You, you may not have slept on the plane, you can feel that you're tired, you're really tired, but for some reason, you know, your cortisol is now spiking because you're mismatched with your circadian rhythm. You can feel your heart rate and you can just know that your nervous system is cranked and you are tired as tired can be in your eyes and in your mind. But your nervous system, because it's on, on that sort of upward swing will not let you fall asleep. But meditation, I think is a great way to drive a parasympathetic dominance of the nervous system, which is to take you out of the fight or flight branch and more into this quiet, sort of more introspective state. I think that's probably the, the better thing. Now I know it's not from a clinical medical perspective as desirable because it's not a pill that we can take. It's not a dosage, you just have to put in the work to sit there and meditate.

But I think that's the nature of sleep. I mean, I think CBT I has efficacy, but it requires work.

It does.

And changing the way you eat requires work. It's not a pill.

And exercising, same thing.

And I've been asked, this is a totally unrelated topic, but people always say, oh my God, God, please write me a prescription for Metformin because it's going to help me lose weight and blah, blah, blah. And I said, look, let me be clear. I mean, I think Metformin is a really powerful pill. I don't think it's nearly as powerful as an exceptional diet. In other words, metformin superimposed on the world's worst nutrition versus no metformin on exceptional nutrition. I don't think it's any comparison. In the end, molecules that you take intermittently aren't really nearly as potent as molecular changes that occur over a time course. Behaviorally, I mean, that's, I mean I, I wish that weren't true, truthfully.

Yeah, I really do. I'm not anti pharmacology by any means. You know, if we had a good sleeping pill, I would embrace it and I would recommend it. But right now, the sleeping pills on the market, they firstly don't produce naturalistic sleep. Secondly, they've been associated with a significantly higher risk of death and also significantly higher risk of cancer.

I'm glad you mentioned this because this is a great segue to this topic. And going back to my friend Kirk Parsley, I remember another thing he said because I this is again going back to 2011, 2012. My go to travel drug was Ambien. Fortunately, I've never had insomnia, but I empathize greatly with those who do. I've seen enough people with it, but when I needed to sleep, I was gonna take Ambien. And I remember getting hints that this wasn't a great drug when I would, when I worked at McKinsey, I used to have to go from San Francisco to Atlanta every single Monday for a day. And because I was ruthless in my pursuit of not wasting time, rather than like take a Sunday afternoon flight and come back Tuesday, I took a red eye from San Francisco to Atlanta every single Sunday. And as one of my friends put it, that's the pink eye, it ain't the red eye. Like that's a four hour flight, right? You always get the tailwind. So you get about three and a half hours of sleep on a plane. I'd get to Atlanta at 5, pick up a rental car, drive to the gym, do a two hour workout, shave, shower, get to the client, stay there all day, leave at 6:30, get to the airport by 8:30, get the flight back to San Francisco, you're back by whatever, you're home at minute. So it was a 26 hour door to door every single time. And I was using Ambien to make sure I slept on that flight. I would come up with these grisly discoveries, which is I'd find emails I sent that I didn't know I'd sent, and thank God none of them were inappropriate. But you hear these stories of people doing really crazy stuff on Ambien, which.

Is never committed to memory. And it's only when people make the phone call the next morning and they say, what were you going on about last night?

Oh, one of the scariest things I ever saw was I remember looking at my phone and seeing outgoing calls to people that I didn't remember making. So my friend Kirk Parsley is saying, and by the way, that Ambien crap that you take a couple times a month, he said, you know, that's not sleep, right? And I said, what do you mean it's not sleep?

I'm out.

And he just, you know, again, you'll laugh at this because this is exactly the kind of story that you tell so eloquently. He said, you're confusing consciousness and sleep, or lack of consciousness and sleep. If I took a baseball bat and hit you on the head, I could render you completely unconscious laying on the floor for eight hours. Do you think in any way that mimics the restorative process of sleep? I mean, not even close. Right. So, you know, think of Ambien more as a chemical baseball bat to the head than something that's actually promoting what you've just been speaking about for the last little while.

It's such a critical point. Again, I'm not anti pharmacology, and I know some of the people in the drug industries, the scientists, and their goal, their passion is to create drugs that better humanity, and. And they are genuine and authentic about that, and I love that about them. But I also will not accept or speak in public about a drug that clearly doesn't seem to be beneficial for a certain process. And unfortunately, if you look at the evidence firstly, you find absolutely that those drugs are a class of drugs that we call the things like Ambien, sort of, you know, all of these things that you've heard. There are a class of drugs that we call the sedative hypnotics, and sedation is not sleep, but people mistake the former with the latter, and it's not. It's literally just knocking your cortex out. So I'm not going to argue when you take those drugs that you're awake, you're clearly not awake. But to say that you're in naturalistic sleep is an equal fallacy, because if I look at the electrical signature of your sleep when you are on or off Ambien, radically different, for a start, you don't get into the same depth of deep sleep that you get. It's not the same electrical quality of deep sleep. The second Thing that we found is that there does seem to be a higher association with mortality risk. Now we don't know if it's causal. And my guess is that on the strength of the evidence right now, IRB committees, ethics committees that sort of allow you to do certain scientific studies, may not even allow you to try and do those studies because the evidence is already so deleterious. The other finding was this strong association with risk of all forms of cancer, which perplexed me because you would think, well, if I'm taking this drug that helps me sleep more, and sleep is so good for the immune system, including things like natural killer cells and combating sleep, then this drug induced sleep should actually make my cancer risk lower, not higher. And the fact that it is higher, I think tells you that the type of sleep that you're getting is not of this rich, complex, restorative, restful, biologically appropriate sleep. The other thing I would come onto, and these are very difficult studies to get funding for because obviously some of the drug companies, they may not necessarily want some of this information out there. It was the only chapter in the book, by the way, that my publisher brought in a legal team to look at when I was making all of these claims. But I'm just conveying the science. There's nothing controversial about the science. And they ended up feeling legally comfortable with what I wrote. There was this stunning study done by a good friend of mine called Marcus Frank at Penn. And he was looking at basically brain plasticity. How does the brain make connections and strengthen those connections? And those strengthening of connections is the underlying mechanism that we know leads to the long term formation of memories. And it's a very well understood mechanism, this idea of brain plasticity. And there is a model where if you kind of patch the eye of an animal and then you measure the visual cortex, what you see is that once you patch one eye, the brain says, well, we're not going to waste the real estate of that one eye that's no longer doing visual processing. We're going to shift a lot of that over to the other eyes territory and give it even more kind of rich connective fidelity, as it were. So you've got this model of what's called monocular deprivation plasticity, which is a classic model of how the brain rewires itself for things like learning and memory. What he found is that he took a group of animals and he gave them naturalistic sleep and did this kind of monocular deprivation. And sleep, it turns out basically doubles the strengthening of plasticity. Sleep is Wonderful for shifting things and making new connections and really strengthening those neural connections. Sleep is essential for brain plasticity. And it's almost, it's sleep will almost double the strength of the connections relative to if you just keep the animal awake. So sleep, it's not just time that helps the brain rewire itself, it's time with sleep that makes the difference. Then he dosed those animals with Ambien. Now, firstly, the animals slept longer because they were dosed with this sedative hypnotic. And you would think that surely that should improve this strengthening of rewiring in the brain. It did exactly the opposite.

Yeah, I was gonna say. Or at worse, it would make a.

Change from the control if it was quote unquote, naturalistic sleep. What he found was actually a 50% unwiring of the connections that had been laid down before when the animal was awake. In other words, not only had sleep failed to strengthen the connections the Ambien laced or the Ambien induced sleep was doing the opposite. It was weakening connections within the brains. Now what makes me fearful about that is firstly, if you look at the number of people who are using these medications, you know, it took George Lucas, I often say, I think about 40 years with the Star wars franchise to amass about 4 billion in profit. It took Ambien less than 24 months to amass that in terms of profit. So you've got to imagine the number of prescriptions being written are high. Then the fact that the prescription age of these sleep aids is starting to decrease gradually as parents get more concerned about their kids, who may have more anxiety, who are having sleep problems, they're turning to pills. And when you bring that experiment back into the context of pediatric prescriptions of sleep medication, you've got a brain that is developing a brain that needs to wire itself up, strengthen connections, build and mature. It needs to learn, it needs to consolidate. And then you're providing a form of sleep through medication that may actually be unwiring that nervous system and unwiring those memories rather than strengthening them. That frightens me.

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