Combatting the Negative Effects of Sleep Deprivation

In this episode, Dr. David Puder and Dr. Brandon Luu explore the science of sleep deprivation. How missing sleep impacts your brain, metabolism, emotions, and long-term health. Discover evidence-based strategies that can help you protect cognitive performance and recover from sleep loss, including exercise, creatine, caffeine, and bright light therapy. We'll discuss studies showing how even short bouts of high-intensity interval training (HIIT), proper creatine dosing, and morning light exposure can reverse many of the damaging effects of sleep restriction. By listening to this episode, you can earn 1.25 Psychiatry CME Credits. https://www.psychiatrypodcast.com/cme-program Link to blog. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-251-combatting-the-negative-effects-of-sleep-deprivation Link to YouTube video https://youtu.be/WPbIGywn-MI

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:13David Puder?

  Welcome back to the podcast. I am joined today with Brandon Liu. He is an internal medicine doctor in his respiratory fellowship for two years, and we are going to be doing an episode on combating the negative effects of sleep deprivation. Hopefully, this is helpful for you. If you are in medicine, there's pretty much no avoiding some degree of sleep deprivation, whether you're in training and you have to stay up for a large amounts of time at time, or you are going through stressful events in your life and have insomnia and are cognitively impaired the next day. We're going to be talking about,

• 0:58David Puder?

  first, how sleep deprivation impacts the body. Hopefully, this doesn't scare you too much, because we all have sleep deprivation. It's part of human experience, pretty much. But then, we're also going to be talking about how to combat it, how to combat it with things like caffeine, creatine, exercise, and light therapy. So, welcome to the podcast.

• 1:21Speaker 01

  Thanks for having me. Excited to be here.

• 1:23David Puder?

  Yeah, so how about we just start out and give like the basics of sleep deprivation?

• 1:31Speaker 01

  Yeah. So again, yeah, I'm happy to be here. You know, this all started with me just being a bit curious on the evidence of sleep deprivation, as you know, everyone in medicine will go through quite early on, like very extended periods of not being able to sleep. And I was always curious, you know, everyone feels terrible when they don't sleep at night or have been like chronically sleep deprived. But I was really curious, how much does sleep deprivation actually impact us? And what can we actually do about it, if anything? Diving into the literature, it's pretty concerning actually how significantly

• 2:10Speaker 01

  just a single night of sleep deprivation can harm virtually every system in the body. So I think a lot of people have heard the phrase that if you're sleep deprived, it's equivalent to being legally drunk, right? And when you actually look back at the study here, it's this is because they actually took a group of volunteers that volunteered to do a series of cognitive tests after a night of total sleep deprivation. Then they came back later, got drunk, and then did the same cognitive tests. And just one night of sleep deprivation was equivalent to being legally drunk with the blood alcohol concentration of 0.05%.

• 2:55Speaker 01

  And part of the issue here is a lot of the time, people don't realize how impaired they are after just a little bit of sleep deprivation. But this was a beautiful early on study that really demonstrated just how significantly sleep deprivation impairs people's cognition. And what's interesting too is we let a lot of, we'll talk about a couple of cool studies here, but we let a lot of people, you know, after not sleeping overnight, drive home, for example, from the hospital. But of course, you know, it's obviously against the law to drive with a blood alcohol concentration of 0.05%.

• 3:30David Puder?

  And remember, when you drink, the first thing to go is your ability to know how drinking is affecting

• 3:35Speaker 01

  Exactly.

• 3:37David Puder?

  your decision making. And 24 hours of continuous sleep deprivation, it's like a 0.10 BAC. I mean, that's basically five shots, right? Like someone just took five shots of alcohol.

• 3:52Speaker 01

  It's incredible. And, you know, they didn't measure in the study, but I think a lot of people realize, you know, the self insight really dissolves away the more tired or drunk you are.

• 4:03David Puder?

  You know, I have this awareness of this because when I'm more sleep deprived, whether I'm like, you know, kids are up in the middle of the night and I have to take care of them. Like the other night, my son had a nightmare and he comes in and then I'm trying to get him down and then I have to go back in and end up sleeping next to him because he was so scared. And so my sleep was wrecked, right? And so I played chess. My chess score was not, I was not doing well. My like elo dropped, you know, and so it's like your cognitive function, just from one night, right? I'm not sleeping well.

• 4:37Speaker 01

  Yeah, it's crazy how fragile we are with one night of sleep deprivation.

• 4:43David Puder?

  Yeah.

• 4:44Speaker 01

  And you know, so the next question I had too was, you know, thinking more on the cognitive side of things, you know, through residency, every about four days on average, my first year, I was doing a 26 hour straight shift where, you know, sometimes you might get a little sleep, but a lot of the times, none. And then the question is like, what do you do the next day, right? Because I still had to get some work done, study, you know, medical students will be doing the exact same thing and have exams coming up. And so the next question I had was, you know, if you really, you know, sit down, grind, try to memorize things, how much of a difference does it actually make when you're sleep deprived? Right? And Matt Walker, who is

• 5:27Speaker 01

  a very famous sleep expert, wrote a very beautiful paper on this, actually. And the takeaway is that sleep deprivation is very, very bad for learning. So in one particular study, people stayed up for 36 hours, so pretty extreme sleep deprivation. And then they were asked to memorize a series of words, right? So they had positive, negative words that people tend to associate, remember better, and then neutral words. People who were sleep deprived remembered 40% less than those who had slept. So, you know, if you're severely sleep deprived, you really, the last thing you should probably be doing is putting your time towards memorizing things.

• 6:12David Puder?

  Yeah, and it's like, how do you study? Some students are just naive to this thing that like optimizing your sleep is actually optimizing your chances of doing well on a test. So in any step preparation, you know, it's it's paramount to get eight hours of sleep every night to get good sleep. Yeah, it's good.

• 6:33Speaker 01

  Exactly. And you hear about people pulling all nighters and the evidence very clearly says that you should you should not do that. Just, you know, sleep as much as you can, prioritize studying when you're not sleep deprived, and it'll it'll be better in the long run.

• 6:48David Puder?

  Wow. And then this, this, this is probably more common, right? Because this one study that looked at people who get two weeks of six hours per night of sleep. Talk about that one.

• 7:03Speaker 01

  Exactly. So that is so then the next question is, you know, so most people aren't staying up for 24 hours straight, right? Most of the time, people have, you know, busy things with work, kids, they're not sleeping a ton every night. And what's interesting is sleeping just six hours a night directly being compared to one night of total sleep deprivation was equivalent in one study. And of course, you know, in the studies, it's it's dose dependent, right? The less you sleep, the longer you're sleep deprived, the worse your cognition is going to be. But, you know, going through all these studies before with one night of sleep deprivation hurts cognition so bad, you can, it, there's the same effect with just slightly reducing your sleep every night for over a chronic period.

• 7:48David Puder?

  Yeah. Okay. So let's talk about what is happening in the body, like biologically, when someone is acutely sleep deprived.

• 7:58Speaker 01

  Yeah. So there's also several metabolic and other physiologic effects. So you can really just go through every single body system and you'll find a significant amount of evidence on harm with sleep deprivation. So people also, I think intuitively recognize that when you're not sleeping well, you tend to get sick more often. And there are studies even from the 90s showing that certain immune cells, like natural killer cells, which are supposed to fight off infections as the interior body, are reduced by up to 28%.

• 8:33Speaker 01

  From a metabolism perspective, the other thing that, you know, I realized a lot when I was sleep deprived quite a bit was I was making very poor food choices. You know, I'd be way more likely to order something and overeat and get a dessert and eat more of it. And there's metabolic evidence to support this where if you took a group of healthy young men and just gave them two nights of four hours of sleep deprivation, their leptin decreased by 18% and ghrelin increased by 28%. And so these are your hunger hormones where ghrelin, you know, I remember it from the step exams, ghre makes you more hungry. So that's increasing and then leptin, your satiety or fullness hormone is also decreasing.

• 9:17Speaker 01

  So it's a perfect recipe for overeating and making bad food choices.

• 9:23David Puder?

  Right. And you can see how chronically this would cause your weight to increase and so on and so forth. Yeah.

• 9:31Speaker 01

  Exactly. And we also have a lot of retrospective data, um, looking at cohorts, people that sleep less, they have a higher risk of all sorts of diseases, right? They have a higher risk of becoming obese, getting type 2 diabetes, blood pressure goes up. They have higher risks of cardiovascular disease, even cancer.

• 9:54Speaker 01

  So overall, you know, it'd be nice to have long-term preventive studies on what we can do about this. But for now, based on the evidence, the best thing you can do is try to prioritize your sleep as much as possible.

• 10:08David Puder?

  Yeah. And I think there's a chronic impact is what a lot of these things are talking about, like this chronic impact of sleep deprivation that goes on for years and years. I'm even thinking about the studies on physicians. Physician suicide rates in residency are actually lower than the, than the general population. But for people who are in their 60s, it's higher. And I've been, I've been curious about that data. Why is it so much higher after a life of doing, you know, medicine? And sleep deprivation could be part of that because it's just part of the life of a doctor to have some degree of sleep deprivation. And so I think that's that's part of our passion behind doing this topic today is like,

• 10:53David Puder?

  okay, what can we do to ameliorate it? What can we do to improve it? How can we prioritize it? It really is the um, sleep is like the new status symbol of choice, right? That we should be aspiring towards.

• 11:07Speaker 01

  Exactly, exactly. And that's, yeah, exactly what you said is, you know, people dedicate their lives to medicine and it's, you know, such a great field, but also just with the culture, it's a lot of the times it's something that you just, you know, you just fight through it because everyone else does. And there hasn't been much of an emphasis that I've seen at least on, you know, what, what can we do about the people that are being sleep deprived, right? I know there's implementation of night flood systems and such, but there's really no avoiding sleep deprivation. So what, what exactly should people be doing to kind of try to offset these negative effects?

• 11:43David Puder?

  Yeah, okay. Interestingly, it's not just when someone is like, someone craving more fatty foods, more, you know, more high carbohydrate foods, but it's actually how the body is processing those high carbohydrate foods. Why don't you talk about that study?

• 12:02Speaker 01

  Yes, yeah. So there's a lot of evidence on processing carbs, higher blood sugar after sleep deprivation. And that's probably from a variety of mechanisms, probably more of a shift to a kind of sympathetic or fight or flight mode after a night of sleep deprivation. And then also a lot of hormonal changes with circadian rhythms being dysfunctional. But, you know, just to put this in terms of numbers, healthy people, sleep deprived or not sleep deprived, given a high carb meal, right? When you're sleep deprived, it takes 40% longer to clear the glucose. And it takes a lot more insulin secretion to bring that down.

• 12:47Speaker 01

  And so it kind of mimics, you know, in this study, what the author's kind of called a, an early diabetic state. Where, you know, you have, you have relative insulin resistance, where you need to increase your insulin, which has a lot of downstream effects elsewhere in the body. And your glucose will be higher for longer. So terrible, terrible recipe for glucose.

• 13:08David Puder?

  I, I've, I've seen this in the, the IOP partial we used to, I used to run. We'd get patients referred from endocrine because they had out of control diabetes. They could not control it with, with any amount of the medications. And when someone is chronically psychologically stressed and sleep deprived, it, it will be almost impossible to control your glucose, right? And you can see that in the numbers here and you can imagine what that would, how that would play out, right? If someone's on insulin, they're sleep deprived, they're going to spike higher levels because the stress cortisol and the, you know, that fight and flight system. So really interesting. What about the, um, brain health, emotional regulation, amygdala reactivity?

• 13:54David Puder?

  How does that change?

• 13:56Speaker 01

  Yeah, this is another thing I think a lot of people also can reflect on when they're sleep deprived, where it's, it can be a lot harder to contain and regulate emotions. So, uh, researchers actually sought to characterize this. So they did FMRI, uh, looking at people's amygdalas after sleep deprivation, and then exposing them to negative stimuli. And their amygdala after 35 hours of sleep deprivation was 60% more reactive to negative stimuli. And, uh, you know, this is a common thing you see in the hospital a lot or in other fields where people are sleep deprived. People are more likely to, you know, get upset, get into arguments, um, be harder to self-regulate.

• 14:39David Puder?

  You know, and this is, I'll do couples therapy sometimes and I'll, you know, the I'll have once in a while, I'll have a couple that they will be like, we will not go to bed until we figure this out.

• 14:51Speaker 01

  Yeah.

• 14:51David Puder?

  We will argue half the night, right? And, and I'll be like, wait a minute, like, let's, let's talk about this, like, the more and more sleep deprived you get, the more emotionally reactive you're gonna get. How about we like, pause an argument? And then say, why don't we bring this to therapy, right? After we've slept well, right? And, and that could be a big win for, for a couple that does that, right? It's like, under no conditions does it make sense to have a middle of the night, sleep deprived argument? When you could have a well rested one and your amygdala is gonna work better. So.

• 15:32Speaker 01

  That's a good point. I do hear that a lot, actually. I didn't, I didn't include this study in the show notes, but it also helps, sleeping helps solve problems, right? Even without people knowing it. So if you give people a, a task, like a hidden, a task with a hidden rule that people are, are supposed to find to speed up how they can solve it. If you keep people awake that whole time, like, I think something like 20% will figure out the hidden rule, but if you let people sleep, in the same amount of time people are trying to do this test, a significant amount more wake up and solve this hidden rule problem.

• 16:12Speaker 01

  So it just goes to show, if you sleep, your brain is still working on problems and you do not need to stay awake all night if you can help it.

• 16:23David Puder?

  Yeah, unless, unless your brain, like mine, wakes me up in the middle of the night to think, to, to think about problems, to think about patients, it's very common for that to happen. And, and one of the biggest wins I've had recently is if I wake up and I'm thinking about a patient, you know, I wish them well and I, I pray for them, you know, like, I just, I just think positive things for them, I wish them well, and I kind of let that awakening do that and it's changed the meaning of it, you know, like, it's changed the meaning of it for me a little bit from, from being like, oh gosh, why am I awake? I don't wanna be awake, to like, okay, I'm gonna, I'm gonna utilize this opportunity. So, okay, let's get into exercise and sleep deprivation.

• 17:10Speaker 01

  Let's do it.

• 17:10David Puder?

  Let's do it.

• 17:12Speaker 01

  Yeah, this is a pretty much the the best thing you can do if you're sleep deprived.

• 17:16David Puder?

  Like in in the midst of the sleep deprivation or like to to be ready for the sleep deprivation? Or in what context?

• 17:23Speaker 01

  So that's exactly the thing. So the more you exercise beforehand and the more fit you are, the more it will protect you when you get sleep deprived. And the more sleep deprived you are, doing exercise right before an important task will help significantly improve how you perform. So one of the the first studies I wanted to go over was this very interesting one, where they took two groups of healthy young people. And they did an eight day study period, right? So first two days were, you know, they let everyone be in bed for eight hours. And then they broke people into three groups. So normal sleep, you know, sleep at home.

• 18:07Speaker 01

  Sleep restriction, where for five days straight, they were only allowed to sleep for four hours at a time.

• 18:15Speaker 01

  And then sleep restriction and exercise, where still only allowed to sleep for four hours at a time. But the middle three days, so for example, you know, this is a weekday or throughout the work week, Tuesday, Wednesday, Thursday, they had to do high intensity interval training. And it wasn't the most, you know, time intensive. It was about 10 intervals of 60 seconds at your peak, resting for 75 seconds. So you can do that in less than 30 minutes easily with a warm up and cool down. And then they did a series of tests to see glucose tolerance and how mitochondria were functioning and amplitude of diurnal rhythms, which is a measure of how well circadian rhythms are functioning. Because you're supposed to get nice and warm during during the day, early in the morning,

• 18:59Speaker 01

  and then cool down at night. And it was pretty interesting. So, you know, as we've seen in several other studies, sleep deprivation causes a kind of acute phase of a diabetes looking state, where you have increased glucose, you require more insulin to bring that glucose down. It takes longer. And sleep restriction group, their glucose, of course, with the oral glucose challenge test increased significantly more than the people that were sleeping regularly. But just doing those three days of high intensity interval training during that work week, almost completely negated the effect of higher glucose at the end of the week.

• 19:44Speaker 01

  There was also improved mitochondrial respiration, so your mitochondria are working better. But it didn't really seem to make a big impact on circadian rhythms, at least on the way they measured it. But this, you know, this was one of the first studies I found early in my residency, like, what can I do to help, you know, reverse all these negative metabolic effects? And I actually wore one of those Dexcon or Libre 2s and was monitoring my blood sugar. And I did notice, interestingly, the mornings after I was sleep deprived, I'd have much larger glucose spikes. But if I exercised more during those weeks, it really blunted it and it kept it normal. So if you are sleep deprived, exercising is probably the last thing you're going to

• 20:27Speaker 01

  want to do and it's going to feel terrible when you start, but I promise it's one of the best things you can do for just your overall health, but also to fight through a period of sleep deprivation.

• 20:36David Puder?

  That's, this, this is, this is really interesting. I mean, it almost like negates some of the impact of the sleep deprivation to do the exercise. I notice this is, this strenuous exercise, 90% is very hard. I'll go and I'll

• 20:51Speaker 01

  Really hard.

• 20:52David Puder?

  I'll go do sprints up a hill near my house in Florida. It's like an overpass, so I run up to the top of the overpass, I walk down. And this is, 90% is very hard.

• 21:03Speaker 01

  It is.

• 21:04David Puder?

  That's like very, and 10 sets, 10 sets of that.

• 21:09Speaker 01

  Yeah.

• 21:10David Puder?

  That's intense. That's intense. And think about like as well, this is a young population. So it's even more important to know about this as we get into our 40s, you know, and 50s, it's like so much more important. It's like sleep deprivation is going to be even a bigger impactor.

• 21:28Speaker 01

  Yeah.

• 21:31Speaker 01

  And I guess I should say, just from a practicality standpoint, like I do a lot of running and sprints and stuff too, but when I'm very sleep deprived, I'm more likely to get on the bike because I feel like I'll be less likely to get injured. But it's a lot of balancing the risks and benefits there because sprinting at 90% when you're sleep deprived on a hill, you're probably a little more likely to roll your ankle or miss a little hole or something. So just be mindful of that.

• 21:58David Puder?

  So once again, the compared to the control, this, the people that just had the sleep deprivation, what happened to their mitochondrial related mRNA?

• 22:08Speaker 01

  So their mitochondrial respiration, like a function of how efficient or well their mitochondria were working worsened with sleep deprivation.

• 22:17David Puder?

  And then?

• 22:18Speaker 01

  Probably from an kind of inflammatory state is my thought. And that significantly improved almost back to baseline with the exercise.

• 22:27David Puder?

  Okay, that's very convincing.

• 22:29Speaker 01

  Yeah.

• 22:30David Puder?

  Because like, this is a very sort of common circumstance of like, four hours a night for a period of a week or whatnot. This is very.

• 22:40Speaker 01

  Exactly. Yeah. You just have a tough week and you just have to, you know, find the time 30 minutes, three times that week and you will, you will reap the rewards.

• 22:51David Puder?

  Okay. Let's get, let's keep going. Study number two.

• 22:55Speaker 01

  Yeah. I wanted to go through this one as well. It's very similar, but this one shows a bit more of a, of the preventive effect that I talked about. So they took 11 physically active men, healthy guys, and underwent 24 hours of sleep deprivation in one of two circumstances. So one group, again, high intensity interval training, the other group, nothing. And so this was two weeks before. So for example, if, if, for example, in two weeks, you're going to have to stay awake for 24 hours on a Friday night and Friday during the day. This means you do a Monday, Wednesday, Friday session one week, Monday,

• 23:36Speaker 01

  Wednesday, Friday session the next week. This one, they did a little less intensity training, six sessions, or sorry, sorry, eight to 10, eight to 12 intervals. Actually, it was about the same, very similar, 60 seconds max effort and then 75 seconds recovery. So again, another thing you can do in less than 30 minutes.

• 23:58Speaker 01

  And when you look, this study actually measured insulin, which was very helpful. So you can see sleep deprivation caused a pretty much a state of insulin resistance, increased glucose levels, significantly increased fatty acids as well. And for the group that did exercise before the sleep deprivation, so it wasn't, you know, the day of sleep, like the day after or anything, this is just you're getting physically fit and doing a lot of hit leading up to the episode. Their insulin resistance came back exactly to baseline in this rested sleep condition. But improved mitochondrial function, it didn't completely reverse fatty acid increase, but it did reduce it a bit.

• 24:43Speaker 01

  So this is all the more reason that the more fit you are walking into a, you know, unknown day of sleep deprivation or not being able to sleep your regular amount, the better off you'll be.

• 24:55David Puder?

  Wow. It's dark, the difference with the high intensity interval training, how that prepares your brain for that insult.

• 25:05Speaker 01

  Exactly.

• 25:06David Puder?

  And so I think this is why it's like paramount to have a regimen, you know, that we do on a regular basis. And if it's like Dr. Peter, I can't, I can't do this by myself. I don't have the willpower. It's like find a group. You know, there's lots of different types of groups that you can meet with that put you through a high intensity interval training. And if, if you're completely unexercised, then start somewhere, you know? Doesn't matter where you start. Okay, let's go to the immediate cognitive boost of exercise on sleep deprivation.

• 25:44Speaker 01

  Yeah. So this was, so the other question I had after this was, you know, I'm sleep deprived so much, or I was during my residency and the days that I didn't sleep, what can I do to, you know, if I need to get some work done or need to perform well, like what can I do? And we'll, we'll talk about creatine a little bit, but this was a very cool exercise study. Where they took students, sleep deprived them for 24 hours, similar to what a lot of residents do. And then they gave a series of cognitive tests. But beforehand, they got them to exercise for 20 minutes. And this was 20 minutes of, you know, moderate cycling. They cited a 60% VO2 max. So you're working like you're not going all out, but you're working pretty hard.

• 26:29Speaker 01

  You'd be feeling a burn during those 20 minutes for sure.

• 26:34Speaker 01

  It now, just the 20 minutes of moderate cycling did significantly improve cognitive performance. It did not reverse it back to baseline. You know, for example, so reaction time dropped about 14% when you were sleep deprived for 24 hours. Exercising for 20 minutes reduced it to about a 7% drop from rested state.

• 26:55David Puder?

  So it cut about half of the the damage.

• 26:58Speaker 01

  Exactly, exactly. So it's you're like, you know, everyone kind of knows you're not going to get back to exactly where you were with, you know, not sleeping for 24 hours, but this this helps. So if you have a meeting, if you have to do something, getting on the bike or just doing a light jog for 20 minutes, it will help you. But it won't fix the sleep deprivation. The other neat thing is that they also measured cerebral blood flow in a lot in some of these studies. And the thought is that

• 27:30Speaker 01

  when you're sleep deprived, you have kind of a relative low oxygen state in the brain. And whether that's from, you know, basal constriction, inflammatory state from not being able to remove all the waste products. We know that exercise significantly improves cerebral blood flow. So the mechanism here is potentially that when you exercise, you're pushing a lot more blood through your brain. You're maybe helping remove some of the waste products your brain didn't remove the night before. And that's getting more oxygen to the places that need it if you're going to do something cognitively demanding.

• 28:04David Puder?

  Very cool. Okay, what about handling multiple stressors? Tell me about.

• 28:09Speaker 01

  Yeah, this was a, this was also a cool study. So they, this goes along with a theory that, you know, in a sleep deprived state, it's, it's kind of in a state of lower oxygen delivery to the brain. So they wanted to challenge people with sleep deprivation and hypoxia, where they gave people a low oxygen environment. And then they exercised them.

• 28:33David Puder?

  Which is torture, by the way.

• 28:35Speaker 01

  Torture. It's, I hope these, these volunteers got compensated well, because it was, it was probably horrible. But so, yeah, they did, they essentially took, they did two groups, uh, partial sleep deprivation, so three nights of four hours of sleep, or one night of not sleeping at all. And then they made them hypoxic. So essentially, I think it was 11% oxygen. Atmosphere is typically 21%, depending where you are. So it was, it was like being very high altitude. And then 20 minutes cycling, but 50% VO2 max, after all this episode of sleep deprivation. And then, um, in both groups, you know, one had exercise, one didn't.

• 29:18Speaker 01

  And they measured how people did on cognitive performance. In this study, it, it actually showed a pretty significant and impressive effect of improving cognitive performance with just the exercise beforehand, almost completely reversing some of the tests on reaction time and executive function. Again, not all tests came back to normal. Uh, there was obviously still some performance below baseline, but there was, was a pretty significant improvement in many of the cognitive domains with exercise. And that's just 20 minutes, and it's under a hypoxic environment. So even more evidence that, you know, the more stressors you have, the more exercise is going to help

• 30:03Speaker 01

  prevent, uh, the negative effects from that.

• 30:06David Puder?

  So just, just to give you an idea, 11%, oxygen is like being up 17,000 feet. So for those of you who have done any mountaineering, that's what that experience is like. And then, as I say, this, this is torture to be, you know, it's torture to be sleep deprived. It's like, it is not fun to be forced to be without sleep. And, uh, yeah.

• 30:31Speaker 01

  No, I thank all the people that did these studies because I, I think, and then to control it a lot, like sometimes, I don't know about this study, but they're not allowed to, you know, watch TV or use screens and stuff.

• 30:41David Puder?

  Do you know I've been a part of one of these studies?

• 30:44Speaker 01

  Oh, really?

• 30:44David Puder?

  Yeah, I actually was a part of a sleep deprivation study while I was a resident. And they wouldn't let me sleep at night, like if I had an opportunity to sleep, you know? So normally you'd be on call and if you could sleep for an hour, you would, you know, take a little cat nap. But you were supposed to not do that. And then I took a cognitive test afterwards and I, I was like totally aware that I was awful at it. And then I barely drove successfully home, which now in retrospect, I don't know if I would drive myself home if I was that tired. But yeah.

• 31:14Speaker 01

  Exactly. The, did, uh, we should include that study. Was it published?

• 31:19David Puder?

  We should, I don't know, I don't know, like, you know, it's like you get, I, well, I don't know where the study is published, but that would be interesting. Yeah, maybe we'll add that to the, the write-up.

• 31:29Speaker 01

  Yeah.

• 31:31David Puder?

  Okay, so do we want to phase shift to creatine?

• 31:37Speaker 01

  Let's do it.

• 31:38David Puder?

  Okay. And just for those of you who don't know, Brandon was actually part of my creatine team that produced that amazing creatine episode. If you haven't listened to that full thing, go back and listen to it.

• 31:49Speaker 01

  Yeah, no, that was a, that was a fun podcast, especially learning about all the effects on, on depression that, um, I know you guys are, are working on and Nick Fabiano also is doing a lot of work on. Yeah, I definitely want to stick more to the, the sleep deprivation side of things where there's a lot of interesting evidence, and I know we, we covered it a little bit in that episode, but I want to start with one of my favorite creatine studies, which essentially looks at when people are acutely sleep deprived, you know, you can't sleep all night, 21 hours of sleep deprivation in this study. They received like a massive, like what you can call like a bolus of creatine. So most people take five grams a day. I know there's a lot of talk about taking 10 grams a day now.

• 32:33Speaker 01

  This was 0.35 grams per kilogram. So for, you know, an average sized, you know, man, that's probably 25, 30 grams of creatine. Right, that's six scoops.

• 32:47David Puder?

  How many grams did you have this morning?

• 32:49Speaker 01

  I had 10.

• 32:50David Puder?

  I had 10 also.

• 32:52Speaker 01

  But I slept well, so.

• 32:55David Puder?

  But, but if you're taking 10 every day, do you really, I don't know if you need to take 20 or 25 or 30 grams like acutely.

• 33:02Speaker 01

  That's, yeah, so that's the thing is I don't know exactly what to do practically from the, the study, right? Because it's, i- i- if you're creatine naive, yeah, maybe. But I will maybe bump up to 10 grams in the morning and five grams at night if I haven't slept. But I feel like that's enough.

• 33:19David Puder?

  Okay, let's, let's, let's take us through the study.

• 33:23Speaker 01

  Yeah, so, uh, sleep deprived, massive dose of creatine right before they went under, uh, the, the sleep deprivation overnight. They took it in the evening. And they actually were measuring people's, uh, creatine stores. So they, they noticed that there was a significant increase in, in brain creatine.

• 33:45Speaker 01

  And of course overnight, they were giving people a series of cognitive tests. I think over like kind of midnight, 3am, 6am, throughout that episode of sleep deprivation. And not surprisingly, most measures of cognitive performance significantly declined with sleep deprivation. But what was really interesting is the group that received this very high dose of creatine significantly improved in most aspects of their cognition. It almost completely reversed a lot of the effects of sleep deprivation. And, you know, this is really relevant because, you know, for people that, you know, you, you have to stay up overnight

• 34:27Speaker 01

  and, and you know, your cognition is going to decline, taking a large dose of creatine is, you know, an evidence-based way to improve a lot of your, your markers of cognitive performance.

• 34:39Speaker 01

  And the way to time it, particularly in the study is they, so there's a really nice graph that's been shared, we'll include it in the show notes, but so this was pooled across all three time points, not just at the end of the night comparatively, but the maximum effect seemed to occur four hours after the creatine was took and the benefits were there for the nine hours measured. So, you know, it's 9pm, you know, you have to do something at midnight. What I would do is take another five grams at night. If I didn't have creatine before, I'd probably take the high dose right beforehand. But, you know, this is one of the, the studies that really convinced me on, on using creatine when I'm sleep deprived.

• 35:21David Puder?

  Yeah, it's incredible. It's incredible how, how it impacts, just one dose impacts. Yeah. And I've had a patient who like one day when I looked a little bit more sleepy, he was like, Dr. Peter, have you taken your creatine this morning?

• 35:38David Puder?

  So, yeah, take your creatine. And maybe we should put a caveat, if you have bipolar, probably not. I would, I would probably not take creatine if you have a history of bipolar.

• 35:50Speaker 01

  Yeah. Well, yeah. What are your, what are your thoughts on the data there for, you know, converting to a state of, of mania with, with creatine use?

• 35:57David Puder?

  You know, there's a couple of cases, like in, in these studies where they've looked at bipolar, there's a couple of people who, who seem to have more manic symptoms. And so I, I tend to not give it to that population. I think we need bigger studies to fully assess it, you know?

• 36:14Speaker 01

  Yeah.

• 36:14David Puder?

  But at this point, it's too much of a risk. If someone has true bipolar, not going to do it.

• 36:22Speaker 01

  Okay.

• 36:22David Puder?

  Do you have an opinion?

• 36:24Speaker 01

  Um, not in the psychiatric parts of things, but I guess just as a caveat, if you have chronic kidney disease would be one of the main things that I would check with your doctor before, because they can, taking a lot of creatine can falsely elevate your creatinine. It doesn't seem to cause kidney damage, but you know, if you have a lot of medical conditions, best to check with your doctor first.

• 36:45David Puder?

  It can, it can be confusing to your medical doctor, right? Because, but there are long five-year, six-year studies. It doesn't seem to increase risk of renal disease. I haven't seen any of those studies. Have you?

• 36:55Speaker 01

  No, no, I'm not worried, no, I'm not too worried about that. But it can, if you take a lot, mess up some of the lab work that we, that we use. So it could, it could definitely confuse your doctors.

• 37:06David Puder?

  Okay, so take me through some of the other studies looking at creatine and sleep deprivation.

• 37:11Speaker 01

  Yeah. Another, you know, kind of original study that really looked at this in 2006, did a more traditional creatine load. So, you know, this all comes back to, you know, the gym where, you know, the guys will tell you to take 20 grams of creatine for a week and massively saturate your creatine stores, which works. So what this study did is they took healthy adults. They gave one group a placebo, the other group, they loaded with creatine, 20 grams for seven days. So the thought is that you're building up creatine stores. Then they sleep deprived a group for 24 hours. And then they did a series of cognitive tests.

• 37:57Speaker 01

  Of course, with sleep deprivation, it harmed all sorts of things like working memory, reaction time. People were obviously more fatigued. After the 24 hours, they started to see an effect with executive function, where, for example, in the random movement generation test, people in the creatine group performed better. People that took creatine actually reported less fatigue. And then they had better reaction times in the creatine group. And, you know, this is one of the first studies demonstrating creatine can help preserve cognitive function in episodes of sleep deprivation. I'll talk about the mechanism a little more in that when we go over the next study, but, um, you know, it seems like-

• 38:40David Puder?

  I think it's worth highlighting just from this study, it's the executive function, that frontal brain capacity to think, right? That's so important that gets impacted with the sleep deprivation. And it's that, it's that part of the tests that was improved, which is so important for the work we do as physicians, as mental health professionals.

• 39:05Speaker 01

  Hundred percent. So I definitely, you know, this is obviously potentially placebo, but you know, when I took more creatine overnight versus the nights I forgot when I was, you know, working all night, I did feel like I was able to keep my thoughts a bit better organized, manage things better, keep a cooler head and stuff. So, and again, for something so low risk and easy to take and cheap, it just kind of makes sense if you're going to be sleep deprived to at least try creatine in addition to exercise.

• 39:35David Puder?

  You know, how do you take your creatine? Cause I have a new, I have a new method that I think works the best. I have a new method.

• 39:42Speaker 01

  I just stir it in water like the original way.

• 39:46David Puder?

  Okay. I, I, um, I put it in hot water.

• 39:50Speaker 01

  Hmm.

• 39:51David Puder?

  It dissolves better and it causes less GI side effects.

• 39:55Speaker 01

  Interesting.

• 39:56David Puder?

  Yeah. So yeah, I think it really does absorb better. I think it breaks down into smaller pieces. So then it absorbs better into my system. So you'll have to try that.

• 40:07Speaker 01

  I know some people will put it in their coffee. Um, there was a bit of concern about that, but I'm, I'm less concerned now looking a little more into it.

• 40:16David Puder?

  What was the concern?

• 40:18Speaker 01

  It was that caffeine could blunt the uptake of creatine. But yeah, I've been meaning to try to put it in my coffee as well, but I also get a little nervous about like how hot it is, you know, could it break down at all? But, um, I have to look into that a bit more. I also, I think it's important to talk about the mechanism here where what really seems to be the key is that creatine helps in stressful circumstances. So in an average person, an average day, um, you know, creatine is not going to make you significantly smarter. But when you're stressed and under sleep deprivation or exercising significantly, creatine will significantly help. And the reason here is that, um, it all comes back

• 41:01Speaker 01

  down to energy currency in the body where creatine is able to rapidly donate a phosphate group to ADP, adenosine diphosphate to create adenosine triphosphate, which is

• 41:14Speaker 01

  The most effective fuel are energy currency in the body. So when you're sleep deprived, you're highly stressed, your body's inflamed, and you're running out of energy, creatine is key here. When you're really pushing your limits to create more ATP, to do more, you know, cognitively demanding tasks or exercise. And so this was beautifully demonstrated by one study, where they actually got people to undergo significantly hypoxic effects. Again, 10% of FiO2 were, you know, atmospheric was 21%.

• 41:56Speaker 01

  So these people were equivalent of very, very high altitude. And then what else they did is that they made these people, under hypoxic conditions, do a series of cognitive tests. And this was over 90 minutes. So their oxygen saturations did drop, you know, I think up to 20%. It was, it was pretty significant. And, you know, there's a beautiful figure here, you know, markers of attention, executive function, flexibility, all decreased in the hypoxic condition. But if you loaded these people with creatine, 20 grams a day for seven days before, it actually prevented a lot of the decline of all of these domains.

• 42:41Speaker 01

  You know, executive function cognitive flexibility actually increased relative to baseline, compared to decreasing in the hypoxic group. So this kind of beautifully demonstrates, you know, you're starving people of oxygen. You don't have enough energy currency in the body. But if you're loaded with creatine, you can dig into those stores to really improve cognitive performance in the moment.

• 43:07David Puder?

  Fascinating. Yeah, I think this is a really important study as well. Thank you for bringing this to our attention.

• 43:15David Puder?

  I also looked up, does creatine break down in temperature? And I don't think it would break down in coffee.

• 43:22Speaker 01

  No.

• 43:22David Puder?

  Like that level of temperature.

• 43:24Speaker 01

  I'm gonna try it then.

• 43:25David Puder?

  So, yeah. It's, it's stable even at like higher temperature for multiple years in the powder form. And then maybe depending on the pH of the beverage over days, like a small percentage might degrade. But I think if you're putting it in like 160 degree water to help dissolve it, you're probably fine.

• 43:53Speaker 01

  Right.

• 43:54David Puder?

  That's my thought.

• 43:55Speaker 01

  Yeah, I'll have to try that.

• 43:57David Puder?

  Okay.

• 43:59David Puder?

  Let's, uh, let's keep going.

• 44:01Speaker 01

  Wanted to go over one last quick study just about, you know, people ask, you know, how much creatine should I take every day? We both take 10 grams a day. And I think partially because of this one study as well as others, but they actually measured in one study, the, the frontal lobe creatine stores with different dosages of creatine. But this was, you know, as a caveat, it was adolescent females with treatment resistant depression, definitely a certain subgroup. But what was interesting is giving two to four grams of creatine a day increased brain phosphocreatine by about 4%. But when you cross, cross that threshold and give them

• 44:42Speaker 01

  10 grams a day, their creatine increased to 9% or by 9%. So no adverse effects were reported. You know, multiple studies have found creatine is relatively safe up to, you know, doses greater than 10 grams. And when it comes to cognitive performance, potentially depression, what really matters is, is, you know, increasing those stories so that when you're under stress, you can rapidly increase your energy. So I take 10 grams partially because of the study, but we certainly need more, more data on this.

• 45:18David Puder?

  Right. Yep. So you think about creatine donates a phosphate group to generate ATP. And so this, this can be sustaining for neuronal function during metabolic stress. This is, this is the value, this is one of the values. Also, it potentially therefore improves mitochondrial function and reduces reactive oxygen species, especially under conditions of hypoxia, high stress, right? Because reactive oxygen species are not good. So if you have that extra phosphate group that can get donated to regenerate ATP, not

• 45:58David Puder?

  only does it help muscles, but it also helps the brain function better. And then through that, it helps preserve frontal parietal network activity, essential for executive tasks and working memory. Like this is so important for that frontal lobe. And so that's why we're looking at the study that looks at what percentage in the frontal lobe is present. And so 9% is probably better than 4%. 20 years from now, we may look back at this and have a lot more studies, but there's no big creatine funding these studies. So they may need, hopefully the pod, my podcast can get to a place in the future where we

• 46:42David Puder?

  can like group fund some studies for Brandon to do, like next level.

• 46:47Speaker 01

  That'd be amazing. And then we have all these sleep deprived residents that we can perform studies on.

• 46:54David Puder?

  Do we, is this your, is this a part of your personality? What is this sadism coming out? Like, I'm gonna.

• 47:02Speaker 01

  No, but yeah, it's, it's, it's pretty amazing. And again, it's such a low hanging fruit, right? Like we've talked about before, it's easy to take, it's low risk, and there's all this, this evidence of benefit and in these stressful conditions.

• 47:16David Puder?

  So I had a patient just today ask me, Dr. Peter, how much creatine, I mean, how much caffeine is too much? How much, what's the optimum dose for cognitive function? This is a person that, you know, does computer programming, does like stuff like that all day long. How do I optimize my brain function with caffeine? So we're going to talk about caffeine and sleep deprivation.

• 47:44Speaker 01

  Yeah, this is something that I think everyone is kind of familiar with. You know, you don't, you don't get a good sleep, you have a large coffee.

• 47:53Speaker 01

  There, there was a very cool meta-analysis that really broke down the effects. And of course, it's dose-dependent. I was, what I was really surprised by was how high some of these studies went with their caffeine dosing. So, you know, there's evidence that, I wouldn't recommend this, by going up to 600mg of caffeine provides the largest benefit of, of cognition. Which for reference is like, you know, a typical cup of coffee is maybe 100mg, 200mg, maybe if you get a large one. So this is like two large Starbucks coffees that you'd just be slamming. So most of the time it was pills, but caffeine, you know, if you're sleep deprived, is also one of the best things you can do.

• 48:38Speaker 01

  Keeping in mind that it will impact sleep if you take too much too late in the afternoon or in the evening. But it really improves, in a dose-dependent fashion, cognitive performance, improves reaction time, improves accuracy, executive function, reaction time. It actually significantly speeds up how fast you process information and the accuracy of that information that you process. And then for driving, it actually, you know, not that we would ever endorse people driving when they're, they're sleep deprived, but you know, sometimes there's not much of a choice if you're slightly sleep deprived. And it actually improves, to a significant degree, people's control of cars.

• 49:21Speaker 01

  So if they look at how often people are, they call it like lateral vehicular control, but how often you're kind of swerving, crossing lines, significantly better with caffeine, as well as longitudinal control. So speeding up, staying at the same speed, not tailgating too much, also improves. So with that said, you know, I drink coffee every morning, even after I haven't slept and need to go to bed, because otherwise I'll go into withdrawal and be miserable and, and get a headache and not be able to sleep. But if you are sleep deprived, a large cup of coffee, if you can handle it, will probably help most domains here cognitive function.

• 50:03David Puder?

  Yeah, so it's really like in a lot of the studies, it's like weight specific. It's like how they think about the dosing. It's three to six milligrams per kilogram. And, you know, so a hundred kilogram person like myself, 600 milligrams, it sounds like a lot.

• 50:21David Puder?

  I usually probably don't drink that much. Three, maybe two cups in the morning, you know?

• 50:27Speaker 01

  Yeah, yeah, exactly.

• 50:28David Puder?

  But then I think a lot of my patients, it's like, okay, how much can they drink before they get anxious? Jittery, don't feel good. You know, what's the optimum for performance? You know, a cup, a cup of coffee is like, what? Almost maybe 100 milligrams. So you could do four cups of coffee. But then, yeah, it does it affect sleep? Because then you, you can get in this bad cycle of if you drink too much, then you're, then you end up being sleep deprived because of the caffeine, right?

• 50:57Speaker 01

  Exactly, exactly.

• 50:59David Puder?

  This is where it's very person specific. So it's like, what is the right answer for every patient? I can't tell you that. It's like, how, how does coffee impact them? Also, where they get their coffee, right? Because if, if they're Starbucks, I think is a little bit stronger caffeine wise.

• 51:14Speaker 01

  Way, way stronger, yeah. Which I guess could be advantageous if you want a good dose of caffeine. But, but like you said, the, yeah, it, I think it requires a lot of self experimentation with, I typically aim for like, maybe 300 milligrams, like I'll have.

• 51:33David Puder?

  That's one, that's one grande. That's, you know, 16 ounce at Starbucks is 310 milligrams of caffeine.

• 51:41Speaker 01

  I think they, I don't know if this is true. Someone told me they put, they add caffeine to their coffees, but I don't, I don't wanna, I'll have to look into this because the, the caffeine content at Starbucks, when I look it up, seems to be pretty high compared to other things.

• 51:56David Puder?

  Let's see. They have the two X caffeine, homebrew lines that they do add caffeine to.

• 52:06David Puder?

  But the typical in-store brewed.

• 52:10David Puder?

  I think it's it's not, but then do they genetically modify it? Right? That's my question is like, has has coffee been genetically modified?

• 52:19Speaker 01

  Maybe they just make it a lot stronger because when I compare that to some other shops, it's definitely like a good, strong cup of coffee.

• 52:27David Puder?

  I do. I do like pour over and that's that's probably high in caffeine, too, because it's like very potent, a lot of a lot of beans per the amount of water I put through.

• 52:39Speaker 01

  But even an espresso shot is, you know, typically under 100 milligrams caffeine. Right? So for some of these studies, it's equivalent of doing like six espresso shots at once, which is a lot.

• 52:51David Puder?

  Yeah, okay, so we'll keep going. But yes, Starbucks probably is higher amounts of caffeine, not to promote Starbucks, but.

• 53:02Speaker 01

  So the other thing, a very low hanging fruit that that makes a lot of physiologic sense is bright light therapy. So, you know, when you wake up in the morning, you look at the sun, it sends all sorts of signals to your brain saying time to wake up, increased cortisol. And we have evidence, actually, very interesting, that after sleep deprivation, bright light therapy improves cognitive performance. So one was comparing 18 healthy young subjects, sleep deprived them for 24 hours, and they gave them three different interventions and they did these a week apart. You know, traditional 10,000 lux, white light boxed, whatever, and you kind of use this for

• 53:43Speaker 01

  seasonal affective disorder. Is there, there might be a new name for that, but winter depression kind of thing. And then they gave them 2,000 lux blue enriched light glasses. So that was the Luminet device, which are blue light glasses that you can wear around if you don't want the box versus compared to just a dim light setting.

• 54:04Speaker 01

  And so what they did was sleep deprived them all night, gave them a series of cognitive tests. And then in two of the groups, they gave them light therapy at 5:00 AM and then tested them at 7:00 AM. And with just bright light therapy versus being in the dark, there was a significant improvement in sustained attention. So they had a task where, you know, they had people stare at a computer screen. When they saw something flash up, they had to click it or notify that. And they were about 200 milliseconds faster. And then also, they made them do mental math, which is also pretty mean after 24 hours of sleep

• 54:43Speaker 01

  deprivation. And in the light therapy group, scores were preserved, but dropped 25% in the controlled dim light group. So and then that people also felt a little less sleepy as well. So for something pretty, you know, low risk, easy to get, bright light therapy, if you haven't slept much overnight, if you already have one of those depression labs, this is probably going to help your cognitive performance. And I always use my bright light therapy in the morning, even in the summers, because I tend to be an early riser and, you know, helps with resetting your circadian rhythm, but also there's evidence on cognitive performance as well now.

• 55:27David Puder?

  So one of the the common mistakes I'll have patients make is they will not put the 10,000 lux box close enough to their face. So just to give you an idea, if you put, if you put a 10,000 lux box, like 40 centimeters away versus 60 centimeters, you go, you about half the amount of lux that get into your, get into your eyes, actually. So getting it like a foot and a half from your face is actually where I recommend it. Okay, foot and half. So it's not enough to sit two or three feet away. Like, you're

• 56:07David Puder?

  gonna have, you're just not going to get the impact of it. You're gonna have to. So take that into consideration when you talk to patients about this, when you consider doing it yourself, you have to sit very close.

• 56:21Speaker 01

  And for for your patients with depression, do you tell them to exclusively use it in the morning? Or just kind of anytime they can?

• 56:29David Puder?

  I think it makes the most sense to me to use it first thing in the morning, you know, when they're having a when they're having their cup of coffee, when they're kind of waking up, right? Like, get right, get right there, 20 minutes, 30 minutes, right? Especially people that have this kind of seasonal downness, right? This kind of like period during the winter where we're heading into right now. You know, if you have more of a depressogenic experience during the winter, you should consider this for yourself. And now you should consider it based off the study if you have some degree of sleep deprivation. Right?

• 57:06Speaker 01

  Exactly, exactly.

• 57:09David Puder?

  For sleep deprivation, do you think it matters when they use it?

• 57:13Speaker 01

  So that's the thing, right? Because if you need to perform in the morning, it makes sense based on this study. You know, if you have to do something at 7:00 AM, two hours before your bright light kind of wakes you up. But it's a bit challenging with if you want to sleep after, because it might have a negative effect on sleeping after a full day of sleep deprivation. So I think there's a little bit of nuance there. I personally, there's no great study to support this, but if I'm awake for 24 hours, I'll just go to bed right when I get home. And then when I wake up after two, three hours at midday, then I'll have bright light, which might be shifting my circadian rhythm a bit.

• 57:53Speaker 01

  But it's, I find it really does help wake me up at that, at that time in the afternoon. So what's probably more important is getting bright light the next day, very early in the morning to help reset your rhythm then.

• 58:09Speaker 01

  So that's what I do.

• 58:10David Puder?

  Great, I think it's good. I think getting outside, getting out, getting exercise. I mean, that's another sort of intervention, right? Of just getting into nature, getting the natural light. You know, that can also be vital. But this, this is probably a higher dose than that, right?

• 58:31Speaker 01

  Probably equivalent, actually, but um yeah, yeah, honestly, just getting outside. Side, um, I'll usually go for a run or do my high intensity interval training after I wake up too. So yeah, just getting sunlight is probably one of the best things you can do after being sleep deprived. There's another really interesting study I wanted to go over to another bright light intervention study. And this was on driving safety, which, you know, we talked about before is, you know, if you haven't slept at all, it's a terrible idea to drive.

• 59:03Speaker 01

  So what this study did is they took nineteen healthy adults, they were kind of typically age twenty-three, and did three different conditions for them. So they sleep deprived them in total dim light. And then afterwards, they received forty-five minutes of bright light therapy. So this wasn't typical, like ten thousand lux, it was fifty-six hundred lux. Or they just continued in dim light sessions. And in the, the, you know, kind of controlled rested condition, these people, you know, got to sleep at home, did their bright light in the morning while they were drinking their coffee, and then all groups did driving tests.

• 59:44Speaker 01

  And these were simulators, you know, forty-five minute kind of what they call like very high, uh, realistic, uh, driving simulator. And what was pretty profound is, you know, this was a small study, nineteen adults, but five out of nineteen, so that's twenty-six percent, uh, got into a terminal accident in the sleep deprivation and dim light group. That means that, you know, they flipped their car, they did something that would potentially kill them. And that's a huge percentage there.

• 1:00:19Speaker 01

  But when they put them in a bright light condition, there were zero terminal accidents or crashes reported.

• 1:00:27Speaker 01

  And throughout the, you know, monitoring for minor incidents and such, there was consistently significant improvement in the bright light condition, which makes sense because it's, you know, if you're in total darkness and you're sleep deprived, you're probably not going to be as cognitively alert and aroused. Whereas if you give that bright light, it's going to kind of tell your body to wake up, release more cortisol, be more sharp and focused. But what was, what was interesting is that the bright light group actually didn't have, in the study, any reported changes in sleepiness. So even if you're doing this and not really feeling like there's much of a difference, there, there might be.

• 1:01:09Speaker 01

  But that was, I was really surprised by this study with just the significant difference in, you know, at least, you know, it's a simulated environment, of course. Not that many people in real life tend to get an accident as far as I'm aware, but comparing the two groups is significantly more mistakes that can, that can really cost people their lives.

• 1:01:29David Puder?

  Yeah, that's, that's impressive. And I'm, I'm, I'm like, I did look it up about like, does natural sunlight, how much lux is that? And it is higher than a lightbox, especially if it's a bright sunny morning, right? Early morning, sun low indirect is like 1,000 to five, or 1,000 to 5,000 lux. But a bright morning, clear sky, no direct sun is 10,000 to 30,000 lux. And if you're having direct sunlight, that's 40,000 to 100,000 lux. I mean, that's way more than you're going to get from a lightbox. So interesting.

• 1:02:11Speaker 01

  Yeah, I should caveat, there's, there's no replacement for the sun, for sure. Bright sunny day, definitely get out there. This is more for conditions where like it's overnight or it's a dark day or it's the middle of winter kind of thing. But yeah, that's a really good point is, yeah, there's no replacing the sun.

• 1:02:27David Puder?

  So I think that's why this study that you just talked about makes sense because it's like, yeah, if it's sunny out, there's going to be less accidents.

• 1:02:35Speaker 01

  Yeah.

• 1:02:35David Puder?

  Very interesting.

• 1:02:37Speaker 01

  Yeah.

• 1:02:38David Puder?

  And so if it's dark out and people have been drinking, your mother's probably right, be careful.

• 1:02:44Speaker 01

  Yes. Yeah.

• 1:02:47Speaker 01

  And I guess one question is, you know, what do you do about this? There are some bright light devices that you can put in your car, actually. So if you're, for example, driving overnight, I have like a thing that attaches to my dashboard. That's that's high intensity blue light to kind of keep me awake.

• 1:03:06David Puder?

  Wow, okay.

• 1:03:08Speaker 01

  Yeah, there's, there's tons of them out there and stuff, but it's something to consider because, you know, I do a lot of like long distance driving, especially from where I'm from. So that's one thing that I found pretty helpful.

• 1:03:21David Puder?

  Great. Okay. Well, this has been really good. I, um, yeah, I think, I think we will kind of wrap it up unless was there other stuff we wanted to go through nicotine? Oh, I guess there are more things that we talked.

• 1:03:34Speaker 01

  No, those were I removed a couple because I wanted to keep it more focused. We could, we could talk about nicotine a little bit if you want, but it's not the strongest evidence.

• 1:03:44David Puder?

  Give me like the, the short, the short pitch on nicotine.

• 1:03:51Speaker 01

  So there is minimal animal evidence that nicotine improves sleep deprivation induced learning and memory impairment. And so there's a couple pretty interesting studies in mice, at least where, you know, and for mice, they usually do these, you know, maze tests to see how fast they learn, how many mistakes they make, how well they can remember to go back to where the food was. And there were a few studies where they, you know, sleep deprived these rats for 24 hours, up to 48 hours even. And they saw all sorts of, you know, of course, negative biomarker effects. So BDNF, which a lot of people call miracle

• 1:04:32Speaker 01

  growth for the brain significantly reduces in mice. In one study, they gave the mice nicotine and it actually reversed BDNF back to normal. So then the question was, could nicotine actually improve cognitive performance under sleep deprivation?

• 1:04:51Speaker 01

  And quite amazingly, actually, giving nicotine to sleep deprived mice for up to 48 hours reduced their amount of mistakes back to baseline. So, you know, mice were, for example, at 24 hours, they're making four errors in this kind of test. With nicotine, on average, they were making 0.5 errors. So like a massive improvement in memory and learning. I think we definitely need more data and evidence. There's, there's some, you know, emerging interesting data on nicotine not smoked. You know, these are like transdermal or oral on cognition in general, like even in people with Alzheimer's, there's some

• 1:05:33Speaker 01

  emerging evidence that improves cognition and memory. And there's also a lot of mechanistic data. So, you know, I'm a pretty self experiment kind of guy. So I, a couple nights when I was sleep deprived, did try low doses of nicotine, like not the kind of zin patches, the zin poaches that a lot of people use that are really high dose, like the lowest two milligram gum that you could find. Personally, I found it, it would actually woke me up and made me feel sharper than, than anything else I've ever tried. But it's also, you have to be careful because it's very addictive substance. It increases blood pressure. But

• 1:06:16Speaker 01

  I think for sleep deprivation, it has, it's early, but it has a lot of interesting potential. And I would love to see a human trial on it.

• 1:06:25David Puder?

  We should, we should have also talked about dark chocolate.

• 1:06:28Speaker 01

  Hmm.

• 1:06:29David Puder?

  And green tea.

• 1:06:30Speaker 01

  Yeah.

• 1:06:32David Puder?

  Maybe we'll put some of that in the, the handout. So you can go to psychiatrypodcast.com and see that. Also modafinil, we may include that in the handout. So go over to psychiatrypodcast.com. All these handouts are for free. Say hi to me, send me a message if any of this is helpful. And Brandon, I think we'll wrap it up there. Do you have any sort of summative statements or kind of like last? Reflections in summary.

• 1:07:01Speaker 01

  I think we've gone over most of it, but you know, definitely, sleep deprivation is a normal part of life for everyone. There's really no getting around it. And when you're sleep deprived, I hope that this podcast helped kind of give you some tools and outline some things you can do to actually make a significant improvement. So don't forget to exercise, consider taking your creatine, get your bright light therapy. Very simple things that you could be doing anyways, just to significantly improve your health and prevent a lot of the negative effects of sleep deprivation.

• 1:07:35David Puder?

  Awesome. So good to have you on. I've enjoyed, you know, our developing work together, writing papers and getting to know you. And great to have a friend in Canada.

• 1:07:47Speaker 01

  Yeah, it's always a good time. Thank you, David.

• 1:07:50David Puder?

  All right. Take care.