Janette Rodrigues: Welcome to GW Integrative Medicine, the podcast about disease prevention and health promotion from the Office of Integrative Medicine and Health at the George Washington University School of Medicine and Health Sciences.
Dr. Leigh Frame: I'm Dr. Leigh Frame, director of the Integrative Medicine Programs here at GW.
Janette Rodrigues: And I'm Janette Rodrigues, the office's administrative director. Today, we're talking about sleep deprivation in glymphatics with Vivek Jain, MD, Associate Professor of Medicine in the division of Pulmonary Critical Care and Sleep Medicine here at GW, and the director of the GW Center for Sleep Disorders.
Dr. Leigh Frame: Dr. Jain is a graduate from the All India Institute of Medical Sciences in New Delhi, India. He did his residency in internal medicine and fellowship in pulmonology and critical care medicine at the University of Missouri Hospital and Clinics in Columbia, Missouri.
Janette Rodrigues: Dr. Jain's research on various aspects of sleep disorders have been published in more than dozens of peer reviewed scholarly journals and numerous books. He lectures nationally and internationally on the topics of obstructive sleep apnea and heart disease.
Dr. Leigh Frame: Welcome to GW Integrative Medicine, Vivek or welcome back.
Dr. Vivek Jain: Oh, thank you. Well, thank you Leigh, and thank you Janette for having me back.
Dr. Leigh Frame: Absolutely. We are very glad to have you back. Sleep's such an important topic, and I think this topic is going to be extra interesting because I don't think most people are going to even know what it is. So maybe we'll start there. What is the glymphatic system, and how is it changing sleep medicine?
Dr. Vivek Jain: So glymphatics is something that was recently discovered, so that's why there's not much known about it. We think about lymphatics, which I guess most of the audience would be familiar with, which is a drainage system all over a body that helps remove waste, whether it be infectious stuff, inflammatory stuff, cancer cells, and so we heard about lymph nodes getting big. We've never really understood that there's a similar system in the brain that will allow removal of waste products. And it was in 2012 that researchers discovered this process happening inside the brain. So glymphatic is a take on the lymphatic system, but the gl or the gly-part comes from the glial cells that are involved in helping remove this waste product.
So what essentially happens in a brain, which is constantly active, is that the metabolism of each nerve cell produces waste products, byproducts, that if not removed in a timely manner, they'll start accumulating and so which makes sense except that it hadn't been discovered. And these glial cells, which are specialized neuronal cells, pump this waste material that accumulates in the cells after metabolic activity into the CSF or the cerebral spinal fluid and flush it out, so to say, out of the system, across the blood-brain barrier. So it is important.
And how is it changing sleep medicine? I think it helps. We've known for years that various forms of sleep disorders, and specifically sleep deprivation or insufficient sleep, can cause various disorders or health effects, one being memory issues. So we know that sleep's important for memory, and when one is sleep deprived, it does affect memory. And so one can extrapolate that into the long term and say perhaps insufficient sleep can lead to say dementia, be a risk factor for dementia in the future.
So one of the waste products that accumulates as a result of the normal day-to-day activity in all our brain cells is a protein called beta amyloid. And so it's one of the many proteins along with something else called the tau proteins that needs to be removed from the brain cells and not be allowed to stay there. And so normal sleep, good amount of sleep helps us do that. But if we don't flush it out and it accumulates in the body, then it causes these depositions in the brain cells, which we know from other studies done in dementia, one of the causes or one of the pathological biomarkers, so to say of dementia or cognitive problems is the accumulation of things like the beta amyloid proteins and tau proteins inside the brain cells. So it's like an extension. So if I sleep well, I don't allow those bad proteins to accumulate in the brain cells. But if I don't sleep well and they accumulate, that could be one of the reasons for development of dementia in the future.
Dr. Leigh Frame: That is so important. And I think we've talked in our previous episode about how people often don't prioritize sleep. And I hope that the glymphatic system will be maybe a real motivating factor for people to prioritize sleep because we're not in a good position to be able to prevent or treat many of these cognitive disorders at this time. And if you could simply get more higher quality sleep to prevent it, that's something we can do.
Dr. Vivek Jain: That is so true because once these proteins start accumulating, you're right, there is no turning back. There is no... One of the, I guess the problems with dementia treatment is we know that it's due to, in most cases, due to the accumulation of these bad players, the proteins, but we don't know how to get rid of those proteins once they've accumulated in a very large amount. And so you're right that it is almost like prevention is better than because we don't have a cure.
Dr. Leigh Frame: Right. Absolutely.
Janette Rodrigues: Sleep and the brain, these two areas of study are just endlessly fascinating. So how do glymphatics relate to sleep deprivation?
Dr. Vivek Jain: Yes. So what is understood after we discovered the glymphatic system was that what pumps this, and it's like a pump, so all these, just like a blood vessel. So something inside the brain is going to have this pump action to remove this waste material. And so if one studies the physiology of sleep, so during deep sleep, the cells in the brain are fired in a very synchronized manner. And so when they're firing in this synchronized manner, they create a force which is thought to create the proportion waves that then allows that waste material to move through the intracellular fluid in the brain and into something called the cerebral spinal fluid across the blood-brain barrier. So that is the key that this pumping action is required. And people have also felt that the supine position, of course, most humans don't sleep standing up. We do sometimes sleep sitting up, but that supine position also facilitates this pumping action and the movement of this fluid removing the bad proteins.
Dr. Leigh Frame: So just a quick clarification for those in our audience that are not familiar with the supine position, what does that mean?
Dr. Vivek Jain: Sleeping on the back or sleeping in the flat position. You can be sleeping on the sides. You can be on the back. You can be prone, sleeping on your stomach, but the idea is that you're not upright. You are horizontal.
Dr. Leigh Frame: That makes sense. That way, it's not trying to force it in some sort of direction against the flow of gravity.
Dr. Vivek Jain: Right, right. I mean, that might be the simplest explanation, but yeah, that could be. You're right. Absolutely.
Dr. Leigh Frame: So obviously glymphatics is really important for the brain. Sleep is really important for the brain. So how does all of this come together, and how does sleep deprivation affect mood?
Dr. Vivek Jain: Yeah, excellent question. Certainly again, people have only recently started realizing the connection between good sleep and other mental and also physical health issues. Many very years ago and very early on, almost 40, 50 years ago, one of the antidepressants that was used used to make the patient sleep deprived. So believe it or not, if somebody has a bipolar disorder or a manic depressive disorder and the treatment, if they come into the clinic with severe depression, the treatment offered was don't let that person sleep. And they will shift that spectrum from being depressed to being manic.
Now, a lot of people who have bipolar disorder or major depression or manic depressive disorder are not usually bipolar, they could just be unipolar or depressed. In that situation, obviously, the connection between sleep and treatment of depression is not that clear. In fact, the opposite is true that if one is sleep deprived, it can actually lead to symptoms like fatigue and irritability, things that can be misdiagnosed as depression or exacerbation of depression. So it's almost like if I don't have the tendency to become manic then, and I'm just depressed, or even other mood disorders, including things like anxiety or schizophrenia, they tend to get worse with sleep deprivation. So we know that that relationship is more in the direction of sleep deprivation causing worsening of the mood issues rather than sleep deprivation being used as a treatment for depression and causing manic episodes.
Dr. Leigh Frame: So what else do we need to know about sleep deprivation and its consequences on health?
Dr. Vivek Jain:
So for the audience, I think we've talked obviously about the connection between sleep deprivation and future risk for dementia. There are other aspects. So the independent effects of sleep deprivation on even things like weight gain and obesity, so there were lots of studies were done, especially in Belgium and also from the University of Chicago that very specifically looked at the relationship between what happens when a community and an individual is sleep deprived. And they very clearly found that even both at the individual level and at the community level, if one is not getting enough amount of sleep, they're more likely to gain weight or also more likely to find it harder to lose weight. So if somebody comes to say to the weight loss clinic and is having a hard time, following a good diet, doing some exercise but not getting enough sleep, they will find it harder to lose weight.
The same group of researchers many years ago also found the relationship between sleep deprivation and development of diabetes or insulin resistance. And that was fascinating to us because in their initial experimental paradigm, what they found was that even you take a healthy sleeper, somebody who says that they sleep eight hours or more and follow regular schedules, they have no problems staying awake during the daytime; they're healthy, normal sleepers, and then you collect these individuals, both men and women, and you say, "You know what? I'm going to divide you into two groups and one group, I'm going to make you sleep only four hours a night for five nights, and the other group can continue sleeping just like they normally sleep." And even after five nights of sleep deprivation, what we call as an acute sleep deprivation experimental model, these 100% of these individuals who were in the sleep deprivation group compared to the people who were allowed to sleep normally, developed signs of insulin resistance and what we call as diabetes within five nights of sleep deprivation.
And then, of course, they were recovered and allowed to sleep more for five nights following the sleep deprivation, and fortunately obviously, they all recovered, but this was the first idea that my God, sleep deprivation that we all know, we all are guilty of from time to time, can have acute effects, not just chronic effects. In a general population, acute sleep deprivation is rare. Somebody's on call, somebody's a police officer, somebody's a firefighter, somebody's on duty-
Dr. Leigh Frame: A shift worker.
Dr. Vivek Jain: Shift workers. But most of us get what we call as an opportunity to recover sleep. As I say, one night I'm sleep deprived, obviously we know we are sleepy the following day, and we recover sleep. Most of us can. Now what is the other interesting finding amongst after doing research is that there is this more common condition called chronic partial sleep deprivation in which we never ever ever recover from a sleep debt.
So what is a sleep debt? So if say most people they say require seven to eight hours of sleep, and just for the audience, I think one way of looking at understanding how much sleep one needs is in a very simplistic way to say, "If I'm on vacation and I get X amount of sleep, I feel good." What is that X amount of sleep? Because most of us during our day-to-day lives are a very fatigued and sleepy society because we're not really... We have many things that we think are causing our fatigue and sleepiness, but vacation is the right time to understand what my own specific individual sleep needs are.
So if I meet those sleep needs on a regular basis, which for most individuals is seven to eight hours per night, I'll be healthy for the most part. Now if I, for whatever reason, got say six hours of sleep tonight, that means one or say one and a half hours less than what I needed tonight for whatever reason, then the recovery models have shown that I have to recover that deficit within the next two nights. So if I have a two hour sleep deficit tonight for whatever reason, I should sleep maybe nine hours on the two following nights or 10 hours and eight hours on the two subsequent nights to recover from that sleep debt right away.
Dr. Leigh Frame: So we can't store it all up for the weekend is what you're telling us?
Dr. Vivek Jain: Absolutely not. And that's what most of us do is that we store it out for the weekend. We sleep extra on the weekends to make up, but that model doesn't work. And that's why the more real life situation is chronic partial sleep deprivation. So there's this so-called the Tale of Two Epidemics where we've known that over the past 20 years as a society, we have even over 30 years as a society, we've become more sleep deprived, chronically sleep deprived, not just acutely, and we are becoming bigger. And all these chronic disease states are flaring up, including metabolic disorders, diabetes, heart disease, and all of these now have been individually linked to sleep deprivation in one way or the other. Cancer is another thing which has now been linked to chronic partial sleep deprivation.
There's a very interesting group of researchers looking at the immune system and sleep deprivation. And so we all talk about how autoimmune diseases, lupus, rheumatoid dermatological diseases are starting to increase. And the question really is why is that? Is it just maybe environmental or maybe intrinsic to our body physiology? And so some group of researchers are showing the connection between inflammation and sleep deprivation. Also a very simple example and which we all should be aware of, for example, I go get a flu shot. And for whatever reason after getting the flu shot, I do not sleep well that night because I have work to do or something to catch up with, and I get less than my requisite amount of sleep. Research has clearly shown that my immune response to that flu shot in generating antibodies is going to be much, much less if I do not get good sleep after getting a vaccination.
Dr. Leigh Frame:
That really puts it in perspective. There's so many important things that you need sleep for, not the least of which is disease prevention, but in my mind, that's health promotion. We're trying to allow the body to educate its own immune system, so if it is exposed to a disease, it will not succumb to it.
Dr. Vivek Jain: Right. And so sleeper is like our fifth vital sign in a way. We need it.
Dr. Leigh Frame: I love that. So obviously, there's a lot of different health outcomes, negative health outcomes from sleep deprivation. What role, if any, does glymphatics play in that or do we not know yet?
Dr. Vivek Jain: We do not know yet. The only big players where we do know for sure is the development of dementia in a sleep deprived individual. So that's both animal experiments and some human studies are showing the clear relationship between accumulation of these beta amyloid proteins, tau proteins, and risk for cognitive dysfunction. And obviously, you can extrapolate that to dementia in sleep deprived individuals. It's very difficult to do retrospective studies if somebody's already developed dementia or cognitive dysfunction. How far back do we go in life and say, "How much sleep were you getting 30 years ago when you were 15 years old?"
Dr. Leigh Frame: Right. Oh, that would be the best study if we could follow people, get all information about sleep diet, all their exposures, have the ultimate study. We could possibly figure out some of these more complex diseases like dementia that we really haven't done very well with studying.
Dr. Vivek Jain: I think one place where this is going to probably become easier to do if privacy rules and laws can be regulated and just my personal opinion, so to the audience, I don't want you to go out there and say, "Oh my God, what is Dr. Jain talking about?" But with all these smart watches and all these variables, we are collecting so much data on patients' habits. And if you can remove the identifiers from each individual data point and just collect that information and say, "Hey, you know, young kids are wearing wearables. Adults are wearing wearables. Same individual is wearing a wearable. All this data is available for years and years and years, potentially, now and into the future." If one can just say, "I want my data from my wearable to become a part of a medical record," I mean, it'll be a great study.
Dr. Leigh Frame: Yeah.
Dr. Vivek Jain: I mean, I had a simple, one of the wearables recently... Patients bring this to us nowadays, and there's no way to make it a part of a medical record. It's just sad.
Dr. Leigh Frame: Yet, there's no way yet.
Dr. Vivek Jain: No way yet, correct.
Janette Rodrigues: Let's keep our fingers crossed everybody. So how do you increase glymphatic flow?
Dr. Vivek Jain: Get more sleep, short answer, seriously. Yeah.
Janette Rodrigues: Plain and simple.
Dr. Vivek Jain: And sleep in a supine position. Don't have your... Again, most people sleep flat or semi elevated with the head up, but that's okay. It's the sleep. Again, going back to experiments done by association between sleep and memory. It's not just the type of sleep like REM versus non-REM. Just sleep itself has been shown to have a very positive effect on recall and memory. And so one doesn't have to really say, "Oh, I don't have deep sleep or REM sleep. I don't dream. Maybe I don't get enough good sleep." Not true, just any sleep.
Janette Rodrigues: So give us your top three or four sleep hygiene tips for patients and also for clinicians to share with their patients.
Dr. Vivek Jain: Be cognizant of the need for sleep. Consider it to be an important, as a Leigh pointed out, a preventive health measure, not just diet and exercise, but emphasize just the need for sleep. And a simple questionnaire, how much sleep do you get during the weekdays? How much sleep do you get on the weekends? Are your routines constant? Are they variable? Because it's not just the amount of sleep, but that amount of sleep according to a certain fixed or a semi-fixed schedule is more important. There's some concept called social jet lag where again, most of us are guilty of this in the modern society where we sleep from a certain time to a certain time during the weekdays and a different time to a different time on the weekends, and every hour difference between the weekdays and the weekends has an independent effect on health, cardiovascular health independent of the amount of sleep.
So sleep tip would be get adequate amounts of sleep according to a more or less fixed schedule. Three would be if you do end up losing sleep for whatever reason one night, then make up for that sleep within the next two nights, and don't wait till the weekend. Other effects of, for example, noisy environment, lighted environments, on lymphatic flow is obviously a hot area of research. If I read in bed, and then take eight hours of sleep, is my glymphatic flow the same as if I was sleeping in a darker environment? That is unknown at present, but it makes sense to most of us that our sleep quality is not as good if we've exposed ourself to light in bed like electronics or Kindles and iPads.
Janette Rodrigues: And how about eating at night?
Dr. Vivek Jain: Eating at night within two hours of bedtime is not, again, a good idea for most of us because it does disturb sleep because food sits in the stomach and doesn't get emptied out into the intestines. It's a cool, quiet, dark bedroom environment, not going from the computer to the bedroom. Maybe just relaxing, giving some winding down time before bedtime, seven to eight hours of sleep for most of us, according to a fixed schedule. Again, alcohol disrupts sleep, nicotine disrupts sleep, caffeine close to bedtime disrupts sleep when most people. So all these things would be good sleep habits, and will definitely improve glymphatic flow and theoretically, prevent dementia in the future.
Janette Rodrigues: And what's your opinion on having a TV in the bedroom?
Dr. Vivek Jain: Again, if it's used as a relaxing agent or a distracting agent, it's a different story. Most of us don't use it for that reason. In fact, we get stimulated by that light, and the noise, and the content that we watch. Very few people I've come across, at least in the clinic, will say, "Oh, I use it as a source of white noise." It's not true. Most of us are actually catching up on because we've never had a chance to catch up. And so laying down in bed, and catching up on the news, and catching up on programs that we've missed or recorded on the DVR. So we are not relaxed watching that TV, most of us. So it's definitely not a good thing to have.
Dr. Leigh Frame: Well, that is good to know, and I know we aren't all always perfect, but it seems like most of these things are small little tweaks that we can make to improve. And like you're saying, even if you don't get a great night's sleep one night, well then you have the next two nights to make up for it. So those next two nights, you really have to prioritize not watching the TV in bed, giving yourself the time to wind down, avoiding alcohol and caffeine, those type of things.
Dr. Vivek Jain: Exactly. And just start with one low hanging fruit, and then develop that into good habit, and then start developing a second habit, which becomes part of the nature. And then that's how we get to the end of the journey.
Dr. Leigh Frame: Love it. So what do you see coming down the pipeline in terms of research? What are you excited about hearing about in the future?
Dr. Vivek Jain: I think, again, the question about what improves glymphatic flow. I mean, are there going to be medications out there in the future? Again, is it going to be a substitute for sleep? So we know that sleep causes glymphatic flow and therefore removal of all the bad proteins and the bad players. And so if somebody says, "You know what? I don't have the opportunity to sleep, but I don't want to develop dementia in the future, so what choice do I have here?" Is that going to be something really powerful?
Obviously people, I don't want the audience to take a message from here and say, "Listen, okay doc, give me a sleeping pill. Let me just get knocked out, and even if I get knocked out for six hours, I'll have enough glymphatic flow to..." That's not true. Again, nobody knows, but theoretically speaking, we know that none of the sleep aids that we use currently cause what we call as deep sleep or REM sleep. In fact, most of them deprive us of what we call as a real sleep. So natural sleep is the best and how can we use a pharmaceutical agent in the future to replicate natural sleep? Who knows, maybe coming down the pipeline. It's not there yet.
Dr. Leigh Frame: But something that could certainly be interesting. It makes you wonder that the complexity of sleep, is it possible to replace it? Perhaps you could have a pill that would help with glymphatic flow, but it wouldn't necessarily get all the other elements of sleep.
Dr. Vivek Jain: That's a great point, Leigh. You're absolutely right. And so it's a complicated process. It's not just one thing leading to another, and what other players get left behind is what we don't know.
Dr. Leigh Frame: Right, exactly. Well, there's certainly going to be more for us to talk about, and when there is more research out there, we'd love to have you back again, but that is all the time we have for today. Thank you so much for joining us, Vivek.
Dr. Vivek Jain: Oh, no. Thanks again for having me, and I'll be delighted to come back again. Thanks again.
Janette Rodrigues: This is the GW Integrative Medicine Podcast from the GW Office of Integrative Medicine and Health.
Dr. Leigh Frame: I'm Dr. Leigh Frame.
Janette Rodrigues: And I'm Janette Rodrigues. Thanks for listening.
Dr. Leigh Frame and Janette Rodrigues: Thanks for listening.
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