Combatting the Negative Effects of Sleep Deprivation

[Music] 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 amount 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 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. Thanks for having me. Excited to be here. Yeah, so how about we just start out and give the basics of sleep deprivation? Yeah. So again, yeah, I'm happy to be here. This all started with me just being a bit curious on the evidence of sleep deprivation as ever an in medicine will go through quite early on, like very extended periods of not being able to sleep. And I was always curious, everyone feels terrible when they don't sleep in the air 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 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 a blood alcohol concentration of 0.05%. 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 after not sleeping overnight drive home, for example, from the hospital. But of course, it's obviously against law to drive with a blood alcohol concentration of 0.05%. And remember, when you drink, the first thing to go is your ability to know how drinking is affecting your decision making. And 24 hours of continuous sleep deprivation, it's like a 0.10 B.A.C. I mean, that's basically five shots, right? Like someone just took five shots of alcohol. It's incredible. And they didn't measure in the study, but I think a lot of people realize the self-insight really dissolves away the more tired or drunk you are. 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 for one night, right? I've not sleeped well. It's crazy how fragile we are with one night of sleep deprivation. Yeah. And you know, so the next question I had to 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 a very famous sleep expert, wrote a very beautiful paper on this actually. And the takeaway is that sleep, 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 the 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. Yeah. And this is 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 paramount to get eight hours of sleep every night to get good sleep. Yeah, that's good. Exactly. And you hear what 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. 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. 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 at time 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, the, in the studies, it's, it's dose dependent, right? The less you sleep, the longer you 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. Yeah. Okay. So let's talk about what is happening in the body, like biologically, when someone is acutely sleep deprived. 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 the harm with sleep deprivation. So people also, I think intuitively recognized 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 they enter your body or reduce by up to 28%. 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 out over the eats 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, they're leptin decreased by 18% and grellen increased by 28%. And so these are your hunger hormones where grellen, you know, I remember it from the step exam, skirr makes you more hungry. So that's increasing. And then leptin, your satiety or fullness hormone is also decreasing. So it's a perfect recipe for overeating and making bad food choices. Right, and you can see how chronically this would cause your weight to increase and so on and so forth. Yeah. Exactly. And we also have a lot of retrospective data 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. So overall, you know, it'd be nice to have long term preventive studies on what we can 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. Yeah, and I think there's a chronic impact. It's 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. Physicians, suicide rates and residency are actually lower than the general population. But for people who are in their 60s, it's higher. And 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 part of our passion behind doing this topic today is like, okay, how can we do to ameliorate it? What can we do to improve it? How can we prioritize it? It really is the sleep is like the new status symbol of choice, right? That we should be aspiring towards. Exactly, exactly. And that's 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 can we do about the people that are being sleep deprived, right? I know there's implementation of night float systems and such, but there's really no avoiding sleep deprivation. So what exactly should people be doing to kind of try to offset these negative effects? Yeah. Okay. Interestingly, it's not just when someone is like create 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? 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. And so it kind of mimics, you know, in this study what the author's kind of called an early diabetic state where, you know, 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. I've seen this in 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 any amount of the medications. And when someone is chronically, psychologically stressed and sleep deprived, it will be almost impossible to control your glucose, right? And you can see that in the numbers here and you can imagine how that would play out, right? If someone's on insulin, they're sleep deprived, they're going to spike higher levels because they're stressed cortisol and you know, that fight and flight system. So really interesting. What about the brain health, emotional regulation, amygdala reactivity? How does that change? Yeah, this is another thing I think a lot of people also can reflect on when they're sleep deprived. It can be a lot harder to contain and regulate emotions. So researchers actually sought to characterize this. So they did FMRI looking at people's amygdala's 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 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 get upset, get into arguments, be harder to self-regulate. You know, and this is, I'll do couples therapy sometimes and I'll, you know, 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. Yeah. We will argue half the night, right? And I'll be like, wait a minute. Let's talk about this. The more and more sleep deprived you get, the more emotionally reactive you're going to 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 that could be a big win 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 MIGDLA is going to work better? So that's a good point. I do hear that a lot actually. I didn't include the study in the show notes, but it also helped, the sleeping helps solve problems, right? Even without people knowing it. So if you give people a task, like a hidden task with a hidden rule that people are supposed to find to speed up how they can solve it, if you keep people awake that whole time, it's not 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. 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. Yeah, unless your brain, like mine wakes me up in the middle of the night to think about problems, to think about patients, it's very common for that to happen. 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 pray for them, you know, like 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 being like, oh gosh, why am I awake? I don't want to be awake to like, okay, I'm going to utilize this opportunity. So okay, let's get into exercise and sleep deprivation. Let's do it. Let's do it. Yeah, this is pretty much the best thing you can do if you're sleep deprived. Like in the midst of the sleep deprivation or like to be ready for the sleep deprivation or in what context. 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 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 where, 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, sleep restriction, where for five days straight, they were only allowed to sleep for four hours at a time 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 week day 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 might a contraire of a 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 the day or early in the morning 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 their 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. There was also improved mitochondrial respiration. So you're mitochondria 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? do to help, you know, reverse all these negative metabolic effects. And I actually wore one of those DEXCOM or Libre twos 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 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. That's 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 really 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. So that's like very and intense sets. Ten sets of that. Yeah. Yeah. 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. Yeah. And I guess I should say just from a practicality standpoint, like I do a lot of running in 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 in 90% when you 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. So once again, the compared to the control, the people that just have the sleep deprivation. What happened to their mitochondrial related mRNA? So their mitochondrial respiration, like a function of how efficient or well their mitochondrial working, worsened with sleep deprivation. And then probably from an kind of inflammatory state is my thought. And that significantly improved almost back to baseline with the exercise. Okay. That's very convincing. 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. Exactly. Yeah. You just have a tough week and you just have to find the time 30 minutes, three times that week. And you will reap the rewards. Okay. Let's keep going. Study number two. Yeah. I wanted to go through this one as well. It's very similar. But this one shows a bit more 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 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, 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. And when you look, this study actually measured insulin, which is very helpful. So you can see sleep deprivation caused a pretty much a state of insulin resistance increased glucose level 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 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. 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. Well, it's stark the difference with the high intensity interval training. How that prepares your brain for that insult. Exactly. 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. Pewter, 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 a lot to different types of groups that you can meet with that put you through a high intensity interval training. And 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 and on sleep deprivation. 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 while like what can I do and what we'll talk about creating 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 they cited a 60% VO2 max. So you're working like you're not going all out, but you're working pretty hard. You'd be feeling a burden during those 20 minutes for sure. 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 rest at state. So cut about half of the damage. Exactly. Exactly. So 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 anything is that they also measured cerebral blood flow in some of these studies. And the thought is that when your sleep deprived, you have kind of a relative low oxygen state in the brain. And whether that's from, you know, viso constriction and 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 needed if you're going to do something cognitively demanding. Very cool. Okay. What about handling multiple stressors? Tell me about yeah, this was this was also a cool study. So they this goes along with the theory that, you know, in sleep deprived state, it's it's kind of an 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, which is torture, by the way, torture. It's I hope these are these volunteers got compensated well because it was probably horrible. But so yeah, they did, they essentially took they did two groups, partial sleep deprivation, so three nights to 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 at 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 in both groups, you know, one had exercise, one didn't, and they measured how people did on cognitive performance. In this study, it actually showed us 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. 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 exercises are going to help prevent the negative effects from that. So 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 is torture to be sleep deprived. It's like it is not fun to be forced to be without sleep. And yeah. Yeah. No, I think all the people that did these studies, because I think it, and then to control it a lot, like sometimes, I don't know about this study, but they're not a lot to watch TV or use screens and stuff. Do you know I've been a part of one of these studies? Oh, really? 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 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. Exactly. We should include that study. And it was a published? We should. I don't know. You know, it's like you get, well, I don't know where the study is published, but that would be interesting. Yeah. Maybe we'll add that to the write up. Yeah. Okay. So do we want to face shift to creating? Let's do it. Okay. And just for those of you who don't know Brandon was actually part of my creating team that produced that amazing creating episode. If you haven't listened to that full thing, go back and listen to it. Yeah. No, that was a, that was a fun podcast, especially learning about all the effects on depression that I know you guys are working on and Nick Fabiano also is doing a lot of work on. Yeah. I definitely want to stick more to the sleep deprivation side of things where there's a lot of interesting evidence. And I know 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 bullness 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. 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. That's six scoops. How many grams did you have this morning? I had 10. I had 10 also. But I slept well. 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? Yeah, so that's the thing is I don't know exactly what to do practically from this study, right? Because 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. Let's take us to the study. Yeah. So sleep deprived, massive dose of creatine, right before they went under the sleep deprivation overnight. They took it in the evening. And they actually were measuring people's creatine stores. So they noticed that there was a significant increase in in brain creatine. And of course, overnight they were giving people a series of cognitive tests. I think over like kind of midnight, 3 AM, 6 AM 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 this is really relevant because for people that you have to stay up overnight and you know your cognition is going to decline. Taking a large dose of creatine is an evidence-based way to improve a lot of your markers of cognitive performance. And the way to time it, particularly in the study, is they, so there's a really nice graph that's been shared. So this was pulled 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 9 PM. 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 would probably take the high dose rate beforehand. But you know, this is one of the studies that really convinced me on using creatine when I'm sleep deprived. Yeah, it's incredible. It's incredible 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 asleep, he was like, "Dr. Peter, have you taken your creatine this morning?" Oh, amazing. So, yeah, take your creatine and maybe we should put a caveat. If you have bipolar, probably not. I would probably not take creatine if you have history of bipolar. Yeah. What are your thoughts on the data there for converting to the state of Mania with creatine use? You know, there's a couple of cases like in these studies where they've looked up bipolar, there's a couple people who seem to have more manned. They have more manic symptoms. And so, I tend to not give it to that population. I think we need bigger studies to fully assess it, you know. But at this point, it's too much of a risk. If someone has true bipolar, not going to do it. Okay. Do you have an opinion? Not in the psychiatric parts of things, but I guess just as a caveat, if you have chronic kidney disease, there's a lot of main things that I would check with your doctor before, because they can take a lot of creatine, can falsely elevate your creatinine. It doesn't seem to cause kidney damage, but if you have a lot of medical conditions, best to check with your doctor first. It can be confusing to your medical doctor, right? But there are long five years, six years studies. It doesn't seem to increase risk of renal disease. I haven't seen any of those studies, have you? No, no, I'm not too worried about that. It can, if you take a lot, mess up some of the lab work that we use. So it could definitely confuse your doctors. Okay. So, take me through some of the other studies looking at creatine and sleep deprivation. Yeah. Another, you know, the 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 of 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 group for 24 hours. And then they did a series of cognitive tests. 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 tests, people in the creatine group performed better. People that to creatine actually supported 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 than that when we go over the next study, but I think it's worth highlighting just from the study is 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 part of the tests that was improved, which is so important for the work we do as physicians, as mental health professionals. 100%. 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 working all night, I did feel like I was able to keep my thoughts a bit better organized. And then I was able to do that. better. I think it breaks down into smaller pieces so then it absorbs better into my system. So, you have to try that. I know some people will put it in their coffee. There was a bit of concern about that, but I'm less concerned now looking a little more into it. What was the concern? It was like caffeine could blunt the uptake of protein. But yeah, I've been waiting to try to put it in my coffee as well, but I also get a little nervous about how hot it is. It could have break down at all, but I have to look into that a bit more. 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, creatine's not going to make you significantly smarter, but when you're stressed and under-sleeped deprivation or exercising significantly, creatine will significantly help. And the reason here is that it all comes back down to energy currency in the body, where creatine is able to rapidly donate a phosphate group to ADP, adenosine dye phosphate, to create adenosine triphosphate, which is the most effective fuel or 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, or, you know, atmospheric is 21%. 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. I think up to 20%, 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. 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, that 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. Fascinating. Yeah, I think this is a really important study as well. Thank you for bringing this to our attention. I also looked up, does creatine break down in temperature? And I don't think it would break down in coffee. No, like that level of temperature. I'm going to try it then. So, yeah, 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 in like 160 degree water to help dissolve it, you're probably fun. Right. That's my thought. Yeah, I'll have to try that. Okay. Let's keep going. I 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 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 phospho creatine by about 4%. When you cross that threshold and give them 10 grams a day, they're creatine increased to 9%, or by 9%. So, no adverse effects were reported, you know, multiple studies have been creatines relatively safe up to, you know, dose was greater than 10 grams. And when it comes to cognitive performance, potentially depression, what really matters is, is, you know, increasing those stores, so that when you're under stress, you can rapidly increase your energy. So, I take 10 grams partially because of this study, but we certainly need more data on this. Right. Yeah. So, you think about creatine donates a phosphate group to generate ATP. And so, this can be sustaining for neuronal function during metabolic stress. 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 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 tax 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%, it's 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, my podcast can get to a place in the future where we can, like, group fund some studies for Brandon to do, like next level. That would be amazing. And then we have all these sleep deprived residents that we can perform studies on. Do we? Is this your thing, Michael? Is this a part of your personality? What is this sadism coming out? Like, I'm going to. No, but yeah, 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 evidence of benefit in these stressful conditions. So, I had a patient just today asked me, "Talk to a computer, how much creativity, I mean, how much caffeine is too much? How much, how much the optimum dose for cognitive function is the person that, you know, does computer programming does 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. Yeah, this is something that I think everyone is kind of familiar with. You know, you don't get a good sleep, you have a large coffee. There was a very cool net 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 600 milligrams of caffeine provides the largest benefit of cognition, which for references like, you know, a typical cup of coffee is maybe 100 milligrams, 200 milligrams, maybe if you get a large one. So, this is like two large Starbucks coffees that you 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. 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. And 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 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 of people's control of cars. So, if they look at how often people are, they call it like lateral vehicular control, but how often you're kind of swarving 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 get ahead, it cannot 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. 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 100 kilogram person like myself, 600 milligrams, sounds like a lot. I usually probably don't drink that much. Three, maybe two cups in the morning, you know? Yeah, yeah, exactly. But then I think a lot of my patients, it's like, okay, how much can they drink before they get anxious? Gittery. Don't feel good. You know, what's the optimum for performance? You know, 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 can get in this bad cycle of if you drink too much. Then you end up being sleep deprived because of the caffeine, right? Exactly. Exactly. 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 does coffee impact them? Also where they get their coffee, right? Because if they're Starbucks, I think it's a little bit stronger caffeine-wise. Way stronger. Yeah. Which I guess could be advantageous if you want a good dose of caffeine. But like you said, yeah, I think it requires a lot of self experimentation with the caffeine. I typically aim for like maybe 300 milligrams. Like I'll have that's one that's one grand day. That's you know, 16 ounce at Starbucks is 310 milligrams of caffeine. I think they I don't know if this is true. Someone told me they put the ad caffeine to their coffees, but I don't want to I'll have to look into this because the caffeine content at Starbucks when I look it up seems to be pretty high compared to other things. Let's see. They have the 2x caffeine home brew lines that they do add caffeine to. But the typical in store brewed, I think it's it's not, but then do they genetically modify it, right? That's my question. It's like has has coffee been genetically modified. 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. 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. But even in espresso shot is you know typically under 100 milligrams caffeine, right? So for some of these studies, it's the equivalent of doing like six espresso shots at once, which is a lot. Yeah. So we'll keep going, but yes Starbucks probably is higher amounts of caffeine not to promote Starbucks, but. So the other thing a very low hanging fruit 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, increase 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 locks, white light box, whatever one you kind of use is for seasonal effective disorder. Is there there might be a new name for that, but winter depression kind of thing. And then they gave them 2000 locks, blue enriched light glasses. So that was the lumenet 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. 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 like therapy at 5 a.m. and then test them at 7 a.m. 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 a mental math, which is also pretty mean after 24 hours of sleep deprivation. And in the light therapy group, scores were preserved, but dropped 25% in the control dim light group. So and then 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. So one of 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 foot and half. So it's not enough to sit two or three feet away. Like you're going to have a, you're just not going to get the impact of it. You're going to 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. And for your patients with depression, do you tell them to exclusively use it in the morning or just kind of any time they can? 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 is 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? Exactly. Exactly. For sleep deprivation, do you think it matters when they use it? 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 a.m., 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. But it's, I find it really does help wake me up 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. So that's what I do. Great. I think it's good. I think getting outside, getting out, getting exercise, I mean, that's another sort of intervention, right? I've just getting into nature, getting the natural light, you know, that can also be vital. But this is probably a higher dose than that, right? Probably equivalent, actually, but yeah, yeah, honestly, just getting outside, so I'd usually go for a run or do my high intensity interval training after a wake up to. 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 want it 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. So what this study did is they took 19 healthy adults. They were kind of typically age 23 and did three different conditions for them. So they sleep deprived them in total dim light. And then afterwards they received 45 minutes of bright light therapy. So this wasn't typical like 10,000 lux, it was 5,600 lux, or they just continued in dim light sessions. And in the, you know, kind of control 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. And these were simulators, you know, 45 minute kind of what they call like very high realistic driving simulator. And what was pretty profound is, you know, this was a small study 19 adults, but. Five out of 19, so that's 26% got into a terminal accident in the sleep deprivation in dim light group. That means they flipped their car, they did something that would potentially kill them. And that's a huge percentage there. But when they put them in a bright light condition, there were zero terminal accidents or crashes reported. And throughout the 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 your 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 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 might be. But that was a, 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 really cost people their lives. Yeah, that's impressive. And I'm like, I did look it up about like, does natural sunlight, how much luck is that? And it is higher than a light box, especially if it's a bright sunny morning, right? Early morning, sun low indirect is like 1000 to five or 1000 to 5000 looks, but a bright morning clear sky. No direct sun is 10,000 to 30,000 looks. And if you're having direct sunlight, that's 40,000 to 100,000 looks. I mean, that's way more. Yeah, then you're going to get from a light box. So interesting. Yeah, I should caveat, 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. 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. Yeah, very interesting. Yeah. And so if it's dark out and people have been drinking, your mother's probably right, be careful. Yes. Yeah. 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. Wow. Okay. 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 for where I'm from. So that's one thing that I found pretty helpful. 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 talk. 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, um, give me the strongest evidence, give me like the, the short, the short pitch on nicotine. So there is minimal animal evidence that nicotine improves sleep deprivation induced learning and memory impairment. And so there's a couple of pretty interesting studies in mice, at least where, you know, and for mice, they usually do these, um, you know, mace 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, go for the brain, significantly reduces in mice. In one study, they gave the mice nicotine and actually reversed BDNF back to normal. So then the question was, could nicotine actually improve cognitive performance under sleep deprivation. And quite amazingly actually giving nicotine to sleep deprived mice for up to 48 hours, reduce 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 urging 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, 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 that increases blood pressure. But 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. We should we should have also talked about dark chocolate. And green tea. Yeah. Maybe we'll put some of that in the hand out so you can go to psychiatry podcast.com and see that also Modaphanil. We may include that in the handout. So go over to psychiatry podcast.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? 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 you know, 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 green teen, get your bright light therapy. And very simple things that you know, you could be doing anyways, just to significantly improve your health and prevent a lot of the negative effects of sleep deprivation. Awesome. So good to have you on. I've enjoyed a TIDR developing work together, writing papers and getting to know you and great type of friend in Canada. Yeah, it's always a good time. Thank you, David. All right, take care. [Music]