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My conversation with Matthew Walker, PhD on faculty at UC Berkeley where he is a professor of neuroscience and psychology, the founder and director of the Center for Human Sleep Science, and has a long history of seminal contributions on sleep science and health. Audio File (also downloadable at Apple Podcast and Spotify)“Sleep is a non-negotiablebiological state required for the maintenance of human life . . . our needsfor sleep parallel those for air, food, and water.”—Grandner and FernandezEric Topol (00:07):Hello, it's Eric Topol with Ground Truths, and I am really delighted to welcome Matt Walker, who I believe has had more impact on sleep health than anyone I know. It's reflected by the fact that he is a Professor at UC Berkeley, heads up the center that he originated for Human Sleep Science. He wrote a remarkable book back in 2017, Why We Sleep, and also we'll link to that as well as the TED Talk of 2019. Sleep is Your Superpower with 24 million views. That's a lot of views here.Matt Walker:Striking, isn't it?Eric Topol:Wow. I think does reflect the kind of impact, you were onto the sleep story sooner, earlier than anyone I know. And what I wanted to do today was get to the updates because you taught us a lot back then and a lot of things have been happening in these years since. You're on it, of course, I think you have a podcast Sleep Diplomat, and you're obviously continued working on the science of sleep. But maybe the first thing I'd ask you about is in the last few years, what do you think has been, are there been any real changes or breakthroughs in the field?What Is New?Matt Walker (01:27):Yeah, I think there has been changes, and maybe we'll speak about one of them, which is the emergence of this brain cleansing system called the glymphatic system, but spreading that aside for potential future discussion. I would say that there are maybe at least two fascinating areas. The first is the broader impact of sleep on much more complex human social interactions. We think of sleep at maybe the level of the cell or systems or whole scale biology or even the entire organism. We forget that a lack of sleep, or at least the evidence suggests a lack of sleep will dislocate each other, one from the other. And there's been some great work by Dr. Eti Ben Simon for example, demonstrating that when you are sleep deprived, you become more asocial. So you basically become socially repellent. You want to withdraw, you become lonely. And what's also fascinating is that other people, even they don't know that you sleep deprived, they rate you as being less socially sort of attractive to engage with.Matt Walker (02:35):And after interacting with you, the sleep deprived individual, even though they don't know you're sleep deprived, they themselves walk away feeling more lonely themselves. So there is a social loneliness contagion that happens that a sleep deprived lonely individual can have almost a viral knock on effect that causes loneliness in another well-rested individual. And then that work spanned out and it started to demonstrate that another impact of a lack of sleep socially is that we stop wanting to help other people. And you think, well, helping behavior that's not really very impactful. Try to tell me of any major civilization that has not risen up through human cooperation and helping. There just isn't one. Human cooperative behavior is one of our innate traits as homo sapiens. And what they discovered is that when you are insufficiently slept, firstly, you don't wish to help other people. And you can see that at the individual level.Matt Walker (03:41):You can see it in groups. And then there was a great study again by Dr. Eti Ben Simon that demonstrated this at a national level because what she did was she looked at this wonderful manipulation of one hour of sleep that happens twice a year to 1.6 billion people. It's called daylight savings time at spring. Yeah, when you lose one hour of sleep opportunity. She looked at donations across the nation and sure enough, there was this big dent in donation giving in the sleepy Monday and Tuesday after the clock change. Because of that sleep, we become less willing to empathetically and selflessly help other individuals. And so, to me I think it's just a fascinating area. And then the other area I think is great, and I'm sorry I'm racing forward because I get so excited. But this work now looking at what we call genetic short sleepers and sort of idiots like me have been out there touting the importance of somewhere between seven to nine hours of sleep.Matt Walker (04:48):And once you get less than that, and we'll perhaps speak about that, you can see biological changes. But there is a subset of individuals who, and we've identified at least two different genes. One of them is what we call the DEC2 gene. And it seems to allow individuals to sleep about five hours, maybe even a little bit less and show no impairment whatsoever. Now we haven't tracked these individuals across the lifespan to truly understand does it lead to a higher mortality risk. But so far, they don't implode like you perhaps or I would do when you are limited to this anemic diet of five hours of sleep. They hang in there just fine. And I think philosophically what that tells me, and by the way, for people who are listening thinking, gosh, I think I'm probably one of those people. Statistically, I think you are more likely to be struck by lightning in your lifetime than you are to have the DEC2 gene. Think about what tells us, Eric. It tells us that there is a moment in biology in the evolution of this thing called the sleep physiological need that has changed such that mother nature has found a genetic way to ZIP file sleep.Matt Walker (06:14):You can essentially compress sleep from seven to nine hour need, down to five to six hour need. To me, that is absolutely fascinating. So now the race is on, what are the mechanisms that control this? How do we understand them? I'm sure much to my chagrin, society would like to then say, okay, is there a pill that I can take to basically ZIP file my own sleep and then it becomes an arms race in my mind, which is then all of a sudden six hours becomes the new eight hours and then everyone is saying, well, six hours is my need. Well I'll go to four hours and then it's this arms race of de-escalation of sleep. Anyway, I'm going on and on, does that help give you a sense of two of the what I feel the more fascinating areas?Eric Topol (07:01):Absolutely. When I saw the other recent report on the short sleep gene variant and thought about what the potential of that would be with respect to potential drug development or could you imagine genome editing early in life that you don't need any sleep? I mean crazy stuff.Matt Walker (07:19):It was amazing.Glymphatics and Deep Sleepfor more, see previous Ground Truths on this topic Eric Topol (07:22):No, the mechanism of course we have to work out and also what you mentioned regarding the social and the behavior engagement, all that sort of thing, it was just fascinating stuff. Now we touched on one thing early on to come back to the glymphatics these channels to get rid of the waste metabolites from the brain each night that might be considered toxic metabolites. We've learned a lot about those and of course there's some controversy about it. What are your thoughts?Matt Walker (07:55):Yeah, I think there's really quite comprehensive evidence suggesting that the brain has this cleansing system like the body has one the lymphatic system, the brain has one the glymphatic system named after these glial cells that make it up. And I think there's been evidence from multiple groups across multiple different species types, from mouse models all the way up to human models suggesting that there is a state dependent control of the brain cleansing system, which is a fancy way of saying if you are awake in light NREM, deep NREM or perhaps you're just quiet and you are resting in your wakefulness, the glymphatic system is not switched on at the same rate across all of those different brain states. And I think the overwhelming evidence so far using different techniques in different species from different groups is that sleep is a preferential time. It's not an exclusive time, it's a preferential time when that brain cleansing system kicks into gear because as some people have, I think argued, and you could say it's hyperbolic, but wakefulness is low level from a biochemicals perspective, it's low level brain damage and sleep is therefore your sanitary salvation that combat that biochemical cascade.Matt Walker (09:15):So in other words, a better way of putting it would be, sleep is the price that you pay for wakefulness in some ways. And I think there was a recent controversial study that came out in 2022 or 2023, and they actually suggested quite the opposite. They said using their specific imaging methods, they found that the sort of clearance, the amount of cerebral spinal fluid, which is what washes through the brain to cleanse the toxins, the rate of that flow of cerebral spinal fluid was highest during wakefulness and lowest during deep NREM sleep, the exact opposite of what others have found. Now, I think the defendants of the glymphatic sleep dependent hypothesis pushed back and said, well, if you look at the imaging methods. Firstly, they're nonstandard. Secondly, they were measuring the cerebral spinal flow in an artificial way because they were actually perfusing solutions through the brain rather than naturally letting it flow and therefore the artificial forcing of fluid changed the prototypical result you would get.Matt Walker (10:27):And they also argued that the essentially kind of the sampling rate, so how quickly are you taking snapshots of the cerebral spinal fluid flow. Those were different and they were probably missing some of the sleep dependent slow oscillations that seemed to sort of drive that pulsatile flow. Honestly, I think that paper was still very well done, and I still think there is right now, I would still cleave to the majority of overwhelming evidence considering it's not just from one group in one species, but across multiple species, multiple groups. And I think it's nevertheless a weight of burden that has pushed back. And my sense right now, I used to think and cleaves to the notion that it was a sleep expressly selective process. Now I don't think that that's the case anymore. I think that the glymphatic system is a dynamic system, but it's always looking for the opportunity to go into cleansing mode. And you can kind of go into almost like a low battery mode when you are awake, but in quiet rest. And I think that can drive some already early clearance from the brain and then when you go into sleep, it's like powering your phone off entirely. It truly gets the chance to cleanse and reboot the biochemical system. But I think it's really interesting. I think there's a lot of work still yet to be done. It's not quite as case closed as we used to think.Eric Topol (12:03):Yeah, I mean first of all, it's great that you straighten out the controversy because that's exactly what I was referring to. And secondly, as you also pointed out, the weight of the evidence is that it's a sleep dependent phenomena, particularly during flow wave deep sleep is at least what I've seen.Matt Walker (12:21):Yes.Eric Topol (12:22):What's also interesting, your point about it being dynamic, which fascinating, there was a paper in my field of cardiology, people with atrial fibrillation had less active glymphatic, less clearance which was really interesting. And then the other finding that's also noteworthy was that Ambien made things worse. What do you think about that?We Are An Embodied OrganismMatt Walker (12:45):I think it's really interesting, and just to come back to your point about the AFib paper, what we know is that this cleansing system in the brain does seem to track the big slow brainwaves of deep slow wave sleep, but it's not only tracking the big slow brainwaves. If anything, there's something to do with the cardiorespiratory cycle, the respiration rate and the cardiac signal that may actually sink with the brainwaves. And it's essentially a cardiorespiratory neurophysiological coupling, which is a lot of ways, which is to say heart, lungs and brain coupled together. And it's the coupling of the cardiorespiratory slow oscillations that drive these pulsatile fluid mechanical, it's literally a hydro mechanical, hydro meaning cerebral spinal fluid push and pull in and out of the system drawing those metabolites out. So ago, if you have a disrupted either cardiac or respiratory or neurophysiological signal, no wonder the glymphatic system isn't going to work as efficiently.Matt Walker (14:00):I think that's a beautiful demonstration of the hemineglect that people like me who study sleep largely from the neck upwards would miss. But if you think about sleep is not just for the brain, it's for the body and it's not just for the body, it's for the brain. And we're an embodied organism. We study the organism in silos, neurology, psychiatry, cardiology, respiratory, but they all interact. And so, I think what's lovely about your example is the reminder that if you don't study the body in this study of the glymphatic system, you could miss out a profound explanation that possibly accounts for the head scratching, I don't know why we're getting this result. So that's a long way to come back to it. But the same group that was the pioneer in the discovery of the glymphatic system led by Maiken Nedergaard at the University of Rochester.In SUPER AGERS, p. 57. SRI-sleep regulatory indexSleep MedicationsMatt Walker (15:01):She has gone on to then look to say, well, if this is a sleep dependent process of brain cleansing during deep sleep, what about sleeping pills because so many people are either taking or are addicted to sleeping pills. And we've gone through, we're in the era of web 3.0 with sleeping pills, we started off web 1.0 which were the benzos, the kind of temazepam, diazepam, lorazepam. Then we went to web 2.0, which was sort of the Ambien (zolpidem), Lunesta, Sonata. And what was common about those two classes of drugs is that they both went after something called the GABA receptor in the brain, which is this major inhibitory receptor in the brain. And essentially, they were called sedative hypnotics because they sedated your cortex. And when you take an Ambien and not going to argue you're awake. You're clearly not awake, but to argue you're a naturalistic sleep, if you look at this, physiology is an equal fallacy.Matt Walker (16:01):They made this interesting experimental hypothesis that when you take Ambien, you sleep longer and based on how you score deep sleep, it would seem as though Ambien increases the amount of minutes that you spend in deep sleep. But if you look at the electrical signature during that “increased deep sleep” it's not the same. Ambien takes a big bite. There's a big dent out of the very slowest of the slow brainwaves, and it's the slowest of the slow brainwaves that drive the glymphatic system. So what they found was that when you take Ambien or you give mice Ambien. Yes, they sleep longer, they seem to have more deep sleep, but the brain cleansing mechanism seem to be reduced by anywhere between 30-40%, which is counterintuitive. If you are sleeping more and you're getting more deep sleep and the glymphatic system is active during deep sleep, you should get greater cleansing of the brain.Matt Walker (17:05):Here they found, yes, the drug increased sleep, particularly deep sleep, but it empowered the cleansing of the brain system. Now, have we got evidence of that in humans yet? No, we don't. I don't think it's far away though, because there was a counter study that brings us onto web 3.0. There's a new class of sleep medications. It's the first class of medications that have actually been publicly advocating for, they're called the DORAs drugs, and they are a class of drugs and there's three of them that are FDA approved right now. DORA stands for dual orexin receptor antagonists, which means that these drugs go in there and they block the action of a chemical called orexin. What is orexin? Orexin is the volume button for wakefulness. It dials at wakefulness, but these drugs come into your system and unlike the sedative sort of baseball bat to the cortex, which is Ambien, these drugs are much more elegant.Matt Walker (18:11):They go down towards the brainstem and they just dial down the volume on wakefulness and then they step back, and they allow the antithesis of wakefulness to come in its place, which is this thing called naturalistic sleep. And people sleep longer. So as a scientist, you and I perhaps skeptics would then say, well, so you increase sleep, and I have four words for you. Yes, and so what. Just because you increase sleep, it doesn't mean that it's functional sleep. It could just be like the old notion of junk DNA, that it's epiphenomenal sleep. It's not functional sleep. There was a study out of WashU and they took 85-year olds and above and they gave them one of these DORAs drugs. It's a drug called Belsomra, it's a play on good sleep or beautiful sleep, chemical named suvorexant and randomized placebo control. What they found is that when they took the drug, yes, these older adults slept longer, they had more deep sleep, but then what they did was clever. Before and after the night of sleep, they drew blood because we can now measure markers of β-amyloid and tau protein circulating in the bloodstream, which are these two markers of Alzheimer's disease.Matt Walker (19:28):Why is that relevant to the glymphatic system? It's relevant because two of the pieces of metabolic detritus that the cleansing system washes away at night, β-amyloid and tau. I'm sure enough of what they found was that not only did the adults sleep longer with these sleeping medications, they also had a greater clearance of β-amyloid and tau within the bloodstream. So this was the exact opposite of the Ambien study, which was where they were seeing an impairment in the glymphatic activity. Here in humans was a study with the web 3.0 sleep medications. Suvorexant, not only did it increase sleep, but it seemed to increase. Well, the assumption was that it was increasing glymphatic clearance because at least as the end outcome product, there was greater clearance of β-amyloid and tau protein in the blood. It wasn't just junk sleep, it was functional sleep. So for the first time I'd seen a sleeping medication that increased sleep more naturalistically, but that increased sleep made you the organism function better the next day as a consequence. Does that make any sense?Eric Topol (20:38):Absolutely. And it's interesting that we may have a sleep medicine finally or a class that actually is doing what is desired. This is one of the other things I was going to ask you about is that as you pointed out, this is an interaction throughout the organism, throughout the human being, and we've seen studies about how sleep disrupts metabolism and through that of course, and even separately, can take down our immune system or disrupt that as well. And so, one of the questions I guess is your thoughts about these other effects because you mentioned of course the potential of looking at things like p-Tau217 markers or other markers that would denote the status of your ultimate risk for moving on to Alzheimer's disease. But there's these other factors that also play a role with lack of adequate sleep and perhaps particularly sleep quality. I wonder if you could just comment about this because there's so many different systems of the body that are integrated here, and so the sanitary effect that you just described with the ability to potentially see less, at least biomarkers for what would be considered risks to ultimately develop Alzheimer's, there's also these other very important effects when we talk about high quality sleep, I guess, right? And maybe you could comment about that.Matt Walker (22:21):Yeah, I think quantity is what we've been talking about in some ways, but quality has also come onto the radar as absolutely essential. And what we find is that the quality of your sleep is as if not more predictive of both all-cause mortality, cardiovascular mortality, metabolic mortality, and in some regards, cancer mortality as well. And when I say quality of sleep, what we're really referring to here is at least one of two things. One is the continuity of your sleep. So you could be sleeping for eight and a half hours according to your sleep tracker, but maybe you are getting eight and a half hours by spending ten hours of time in bed because you are awake so much throughout the night and your sleep is very sort of punctured and littered with all of these awakenings across the night. That's sufficient quantity of sleep eight and a half hours, but it's poor quality of sleep because you are spending too much time awake.Matt Walker (23:30):And so, our measure of quality of sleep typically is what we call sleep efficiency. Of the time that you are in bed, what percent of that time are you asleep? And we like to see some measure of at least 85% or above because once you get less than 85% in terms of your sleep quality or your sleep efficiency, then you start to see many of these unfolding system-wide impairments. You seem to have high risk of diabetes, high risk obesity, high risk, as we said, cardiovascular disease. Also, hormonal changes both in men and in women. We see upstairs in the brain with poor quality of sleep, much more so than quantity of sleep. Poor quality of sleep is a more powerful predictor of mood disturbances and psychiatric conditions. And in fact, I think if you look at the data, at least in my center in the past 23 years, we've not been able to discover a single psychiatric condition in which sleep is normal, which to me is a stunning revelation. And what that tells us is that in many of those conditions they do seem to be getting not too bad of quantity of sleep. What is the marker of psychiatric sleep disturbance is not short quantity, it's poor quality of sleep. So I think it's a wonderful important point that I don't think we pay enough attention to, which is the quality.Eric Topol (25:05):Yes. And the other thing that you've emphasized, and I just want to reiterate to people listening or watching that is the regularity story, just like you said with quality. The data and I'll put the figure in that shows the link between regularity and cardiovascular, neurodegenerative, cancer, that regularity thing. A lot of people don't understand how important that is as well.Matt Walker (25:30):Stunning study from data from the UK Biobank, and this is across thousands and thousands of individuals and they tracked quantity and they tracked regularity and they split people up into the quartiles, those who were most regular and those who were least regular. And as you'll see in those sort of the figure that you flash up, those people who were in the upper quartile of regularity, de-risk all-cause mortality, cancer mortality, cardiovascular mortality, it was stunning. And then they did a cute little experiment of a statistical test where they took quantity because they had it in these individuals and regularity and they kind of put them in the same statistical bucket and did a sort of a Coke Pepsi challenge to see which one won out. And what it seemed to be was that regularity almost beat out quantity in terms of predicting all-cause mortality. Now that's not to say that you can get away with saying, well, I sleep four hours a night, but I sleep very regularly, consistently four hours a night. No, you need both, but regularity. I was someone who based on my remarkably vanilla and pedestrian personality, I've always been quite regular in my regard. But goodness me, even when I read that paper, I thought I'm doubling down on regularity. It's so important. That tells us, I think something that is in some ways a story not about sleep. It's a story about your circadian rhythm.Matt Walker (27:02):We speak a lot, or I speak a lot about sleep, and I think I've probably done a mis service to the other aspect of the sleep wake rhythmicity, which is called your 24 hours circadian rhythm. Now your sleep pressure, the drive to sleep is independent of your circadian rhythm, but they often work beautifully in harmony with each other, and you fall asleep, and you stay asleep. But I think the circadian system is critical because, excuse me, and what the circadian rhythm also regulates, sneezing right at the inopportune moment when you are recording a podcast. But nevertheless, what that tells me is that when you feed your brain signals of wake sleep consistency, which is to say wake, sleep, timing, regularity, there is something about feeding the brain signals of regularity that anchor your 24-hour circadian rhythm and as a consequence, it improves the quantity and the quality of your sleep. They're intertwined.What About Sleep Trackers?Eric Topol (28:09):That's a terrific explanation for what I think a lot of people don't appreciate it's importance. Now, last topic about tracking. Now we understand how important sleep is. It is the superpower I am with you on that really brought that to light in so many ways. But of course, now we can track it with rings with smart watches and we get these readouts things like efficiency as part of the Oura score and other rings and deep sleep or NREM, REM, the works, you can see your awake times that you didn't know you're awake and the whole bit. Do you recommend for people that aren't getting great sleep quality beyond that they should try to establish a regular schedule that they should track to try to improve it and of course how would they improve it? Or are these things like having a cold mattress temperature that is controlled? What are the tricks that you would suggest for trying to improve your sleep through tracking? Or do you think tracking shouldn't be done?Matt Walker (29:16):Oh gosh, it's such a wonderful question and as with wonderful questions, the answer is usually it's complicated and I have to be careful because for someone who's currently wearing three different sleep trackers, it's going to be hard for me to answer this question completely in the negative. And there are three different sleep trackers. But I would say that for the most part, I like the idea of sleep tracking if you are sleeping well, meaning if as long as you're not suffering from insomnia. The reason is because sleep unlike those two other critical of health, which is diet and exercise, is very difficult to subjectively estimate. So if I were to ask you, Eric, how many times have you worked out in the past week, you'd be able to tell me how cleanly or how poorly have you been eating in the past week. You could tell me.Matt Walker (30:09):But if I was to say to you, Eric, how much deep sleep did you get last Tuesday? And if you don't have a sleep tracker, you'd say, I don't know. And so, there's something useful about tracking, especially a non-conscious process that I think is meaningful to many. And often medicine we say what gets measured gets managed, and there is that trite sort of statement. I do think that that's still true for sleep. So many people I've spoken to have, for example, markedly reduced the amount of alcohol consumption because they've been seeing the huge impact that the alcohol consumption in the evening has on their ring smart ring data as a consequence. So overall, I think they're pretty good. When people ask me what's the best sleep tracker, I usually say it's the one that you wear most frequently because if I come up with a band, headband, chest straps, all sorts of different things and it's a hundred percent accurate, but after three uses of it, you stop using it, that's a useless sleep tracker. So I like to think about sleep trackers that are low friction and no friction. When we go to sleep, we take things off, we don't put things on. That's why I liked things like the ring. For example, I think that's a non-intrusive way. I think the mattress may be as if not better because it's a completely friction less device. You don't have to remember to charge it. You don't have to put it on, you just fall into bed, and it tracks your sleep.Matt Walker (31:40):One form factor, I like to think about sleep trackers is the form factor itself. But then the other is accuracy. And I think right now if you look at the data, probably Oura is winning the ring kind of wars. If you look at all wristband wars, I think it's probably the most accurate relative to something like Fitbit or Apple Watch or the Whoop Band. But they're all pretty close. I think Oura is probably the leader in class right now at least. Keep in mind that I used to be an advisor for Oura. I want to make that very clear. So take what I say with a grain of salt in that regard. I think to your question, well, I'll come back to mattresses in just one second.Matt Walker (32:34):For people who are struggling with sleep, I think you've got to be very, very careful with sleep trackers because they can have the counterproductive effect where I gave you the example of alcohol or eating too late. And these sleep trackers help you modify your behaviors to improve your sleep. Well, there are places where these trackers can actually do you a disservice. When you get so hyper focused on your data and your data not looking good each and every day, it becomes a self-fulfilling prophecy of a negative spiral. And we now have a condition in sleep medicine called orthosomnia. So ortho in medicine typically means straightened. So you've heard of orthodontic straightening teeth, orthopedic straightening bones, orthosomnia is about getting so obsessed with getting your sleep perfect and your sleep straight that it causes an insomnia like syndrome. Now, I don't know, I think the press has made more of this than there is.Matt Walker (33:30):It probably is about 5-7% of the population. I would say at that moment in time, do one of two things. Either take the ring off entirely and just say, I'm going to get my sea legs back underneath me, get some cognitive behavioral therapy for insomnia. And when I'm confident I'll put the ring back on. Or don't throw the baby out with the bath water, keep wearing the ring. Try to say to yourself only on let's say a Sunday afternoon, will I open up the app and look historically what's been happening during the past week so that you keep getting your data, but you don't get the angiogenic daily sort of repetition of reinforcement of I'm not sleeping well. I should also note by the way that I think sleep trackers are not a substitute for either a sleep recording laboratory, but also, they're not a substitute for ultimately telling you entirely how good your sleep is.Matt Walker (34:24):Don't forget, you should always keep in mind how do I feel the next day? Because I think a lot of people will see their readiness score as 92 and they feel miserable. They just feel rough. And then another day, my readiness score was 62 and I just went out and I just ran my fastest five mile that I've done in the past six months. So don't forget that subjective sense of sleep is just as important as objective measures of sleep. The final thing I would say to your point about the mattresses, I actually do think that they are a really great vehicle for sleep augmentation because these smart mattresses, they're filled with sensors, things like Eight Sleep, and they will assess your physiology, they will track your sleep just like a sleep tracking ring. But what's also good is that because they can manipulate temperature and your sleep is so thermoregulatory sensitive that they create this kind, it's almost like this bent arc of thermal story throughout the night because you have to warm up at the surface to cool down at the core to fall asleep, then you have to stay cool to stay asleep, then you have to warm up to wake up and they take you through that natural change.Matt Walker (35:41):But they do it intelligently because they're measuring your sleep minute to minute. And then they're saying, I'm tweaking temperature a little bit. Has sleep improved? Has it become worse? Oh, it's become better. Let's lean into that. Let's get them even colder. Oh, wait a second, it's getting worse. Let's warm it back up a little bit. It's like a staircase method, like a Richter shock. And gradually they find your sweet spot and I think that is a really elegant system. And now they're measuring snoring. Snoring perturbations, and they can augment the bed and raise the angle of the bed up just a little bit so that the gravity doesn't have as much of a hold on your airway because when you're lying on your back, the airway wants to collapse down to gravity, and when you raise back up again, it will change that. And so, I think that there's lots of new advantages in, I think mattress technology that we'll see coming out into the future. I think it's a great vehicle for sleep augmentation.Eric Topol (36:37):That's terrific. Well, this has been for me, very educational, as I would've predicted, if anybody's up on everything in this area, it would be you. So thank you, Matt. It's a really brilliant discussion, really enlightening. We could talk some more hours, but I think we've encapsulated some of the big things. And before we finish up, is there anything else you wanted to say?Matt Walker (37:05):No, I think just to thank you for both your work in general in terms of science communication, your offer here specifically to allow me to try to be a very poorly communicated voice of sleep, and also just what you've done in general for I think the accuracy of science communication out into the public. Please never stop, continue to be a shining light for all of us. You are remarkable. Thank you, Eric.Eric Topol (37:31):Oh, you're very kind. And I look forward to the next chance we get to visit in person. It's been too long, Matt. And all the best to you. Thanks for joining today.************************************************A quick pollI cover much about sleep and healthy aging in SUPER AGERS, which has been on the NYT Bestseller list for 3 weeks. I'm very grateful to many of you for being one of the book's readers.And thanks for reading and subscribing to Ground Truths.If you found this interesting please share it!That makes the work involved in putting these together especially worthwhile.All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years Get full access to Ground Truths at erictopol.substack.com/subscribe

 You're at the end of your rope, so you head to the pharmacy for the help you so desperately need to sleep. But wait, you aren't sure if it's safe, if it works, and if there's a better way.  Stay tuned to learn about the benefits, side effects, and risk of sleep aids.   I'm Dr.Vickie Petz Kasper. If you're ready to take control of your health, you're in the right  place. I'll give you practical steps to start your own journey toward better health because healthy looks great on you.  This is episode 159, Sleeping Pills and Potions. What works and what doesn't. You know that poor sleep is associated with heart disease, cancer, diabetes, obesity, immune dysfunction, high blood pressure, anxiety, depression, fatigue, irritability, and good grief, I could go on and on. So, taking something to help you sleep sounds like a good idea, right?  Today, we'll discuss what you need to know before you go and get a prescription, supplement, or over the counter sleeping aid. Look, we have to sleep. Our very lives and health depend on it. But the struggle is real. Insomnia is one of the most common symptoms people go to the doctor or health care provider for treatment.   And what if I told you that good sleep is possible without medications? Well, it is. In fact, the first line treatment recommended to treat insomnia is not medication. The standard recommendation for managing insomnia is to eliminate things that go bump in the night and keep you awake.  Or, to treat underlying diseases that disrupt sleep. It's not recommended to start with behavioral therapy or medications until these other things are maximized. Ha! But good luck with that. If you go to your primary care provider and you don't get a prescription, I'll buy you a cup of coffee and we can both stay awake.  And, if you think you need to see a specialist, then you'll probably get to spend the night in a sleep lab hotel hooked up to a bunch of wires and you may get answers, like, a CPAP, and that's important if you have sleep apnea, but if not, you might not even hear from them. No wonder you're looking for a good solution to sleep.  And though medications are not the first line recommendation, that is the topic of today's episode. So let's get to it. We're going to start with prescription medications, then we'll talk about over the counter medications and wrap up with supplements.  There are three classes of drugs approved to treat insomnia. Benzodiazepine receptor agonist, histamine receptor antagonist, and melatonin receptor agonist. Listening to all that medical jargon may be sufficient to put you to sleep. But wait, let me explain. You'll understand more after we go to mini medical school today and learn about receptors.  These are made up of proteins and they receive chemical signals that produce a response.  Let me give you this analogy. You've got a lamp sitting on an end table, but it's not plugged in, so there's no light. And when you stick those two prongs into the socket, behold, now you can sit and read. And that's kind of how a receptor works. The plug fits into the plug in. So an agonist is like the plug. It fits. It turns it on. It lets the electricity flow.  But, if you had a toddler in the house, you might want to plug in one of those little plastic things so he doesn't stick a butter knife in there and get shocked. So that would be an antagonist.  Okay, now wake up and pay attention. We've got three classes of drugs to look at. Benzo receptor agonist and melatonin agonist. That plug in and histamine receptor antagonist that block the plugin. And then there's another category called other. We'll just call that the clapper, you know, clap, clap. And the light comes on, clap, clap, and the light goes off.  There are eight drugs in the benzodiazepine receptor agonist family. And the first five are about my age, you know, born in the 60s. They are Estazolam, which is Prosom, Florazepam, which is Dalmane, Quamazepam, which is Doral, Temazepam, which is Restoril and Triazolam, which is Halcion. Now the millennials aren't benzos, but they're still benzo receptor agonist. And you know, this generation got way more complicated spelling their kids' names, so I'm probably gonna have to sound them out like a first grade teacher on the first day of school.  Eszopiclone is Lunesta, Zaleplon is Sonata. Zolpidem is Ambien.  Those older drugs are crankier and cause more dependence although Restoril is the nicest in the category. There are other benzos which are technically prescribed for anxiety and  some people do use them to help them sleep. Do they work? Here's what the data says for the old guys. They help you fall asleep faster. A whole whopping 10 minutes faster. And they increase total sleep time by half an hour to an hour. That's it.  What about risk? Well, they make you sleepy, which is kind of the point, but also they can make you dizzy, which can make you fall if you get up and go to the bathroom during the night. And if you mix them with opioids, the reaction can be fatal.   Now, the younger guys function about as well as the older ones, but they have shorter half lives, so their effects don't wear out their welcome so much with daytime grogginess. And they aren't so deadly when socializing with opioids. But rarely, they do some bizarre things like compel you to shop or gamble in the middle of the night. All for 10 minutes faster to go to sleep and half hour to an hour longer sleeping.  Okay, clap on, clap off, let's talk about the other drugs.  These are dual orexin receptor antagonists.  Affectionately known as D O R A or Dora.  The first one is Suvarexant, which is called Belsomra. The next one is Derodorexant, which sounds a lot like deodorant to me, and that's exactly what I'm gonna call it because the brand name is Quviviq. And finally, there is Limboxerant, which has a really cool brand name, Dayvigo.  What? You've never heard of any of these? Well, that's probably because they're slightly less effective than the other drugs. They help you go to sleep seven minutes faster. But the main side effect is sleepiness, and people generally say they slept better. The next topic in pharmacology class in mini medical school is the histamine antagonist. You know, the little plastic thing that goes in the wall socket so your toddler doesn't.  Doxepin is a tricyclic antidepressant that functions this way, and even in low doses it causes the desirable effect of drowsiness. So, it's approved for the treatment of drowsiness deficit.  Unfortunately, there are some drugs it doesn't play nice with. But, it does increase sleep time by Drum roll please! 25 to 30 minutes. Womp, womp, womp. And, it helps people stay asleep toward the end of the sleep cycle.    And I think this underscores why one size does not fit all and prescriptions should be customized for individual needs.  The last class of drugs approved for the treatment of insomnia makes a lot of sense.  Ramelteon is a melatonin receptor agonist and the brand name Rosarem, get it? REM, R E M, as in rapid eye movement sleep. It's got a good mechanism of action, a good name. Problem is, it doesn't work any better than placebo. So, you can skip the potential for fatigue, nausea, and worsening of liver disease and just take a sugar pill.  So, am I saying it doesn't work at all? Of course not. Why would it be approved if it didn't work? Well, it's not in Europe, but it does work to lengthen sleep time by a grand total of seven minutes. And I don't know about you, but it's going to take more than seven minutes to get rid of the bags under these eyes.  So that's the gamut of drugs approved for the treatment of insomnia in the United States. But wait, there's more. Just because the FDA doesn't approve something for a particular indication, that doesn't mean that doctors can't prescribe it. And sometimes, off label prescribing is a really good thing, though it's a set up for a knock down, drag out fight with your insurance company for coverage. In addition to using the antidepressant Doxepin, many doctors prescribe other antidepressants for sleep. Things like Amitriptyline and Trazodone, even though the American Academy of Sleep Medicine advises against it because of side effects and no data showing that it works. Now, I always recommend that you consult with your health care provider regarding your medications. Always, always, always.  But, I also recommend that they consult with up to date society recommendations and guidelines. That's just fair. And while they're at it, they should look at the potential adverse reactions. So, now maybe you've decided to skip the copay and just help yourself to the sleep aid aisle of the pharmacy. You could even ask the pharmacist to guide you, and I recommend that. There are two over the counter medications approved to treat insomnia. They are diphenhydramine, commonly known as Benadryl, and doxalamine, commonly known as Unisom. Side note, over the counter medications are regulated  FDA, And both of these drugs are histamine blockers. Therefore, all of the fun side effects that come with that, like dry mouth, GI distress, dizziness, trouble emptying your bladder, and of course, sedation, which is the desired side effect. These medications are often combined with things like Advil or Tylenol with an added P. M. at the end, so you know what's in store for you. And here's what's in store for diphenhydramine. 8 less minutes to fall asleep and 12 more minutes of sleep. And for doxylamine, there's no data available. That's it. That's what we've got. So, maybe now you've decided just to take matters into your own hands and look for a supplement. And because you've listened to my previous podcast episode about dementia, you're gonna skip right over the Prevagen, right? Promise me. Now, in the supplement section, you're going to walk in understanding that claims, concentrations, and ingredients are not guaranteed. They're not regulated. They are, generally speaking, considered safe and ineffective. You heard that right. Safe. And ineffective. But what about melatonin? You swear it works, but does it?  Maybe. It is sedating in about 10 percent of people and in everyone else, it shifts the sleep phase. So, there is a place for that such as jet lag, and I have an episode on jet lag in the show notes.  But even though it may help you drift off to sleep, it probably isn't going to help you stay asleep. The half life is less than an hour, and in some people it causes stomach cramps, irritability, and even depression. It's best used in combination with other things that regulate your circadian rhythm. More to come on that. But a big one is light. And so this probably would be a great time to tell you about some exciting news I have for you. I have an upcoming series of live webinars to talk about six hidden things that keep you tossing and turning at night.   And soon you'll have access to an online course called Unlock the Secret to Sleep, your personal sleep solution. I have been working so hard on this for so long that I cannot wait to share it with you.  I want to help you reset your sleep and get your Z's. Now there are other supplements labeled as sleep aids and most of them again are safe and probably not effective. The exceptions on safety are kava and valerian root. Both of those have been associated with liver damage. Now it's rare, but it's very serious. Other things you might find on this aisle are chamomile, Glycine, Gryphonia, Hops,  , Kava, L theanine, Lavender, , Passionflower, Nightshade, Skullcap, Strymonium, Tryptophan, , and Wild Jujube Seeds.  They're all equally effective and work every bit as well as a sugar pill, but hey, sugar pills can have powerful placebo effects. And one last thing I want to mention, and that is cannabis. Bottom line is there's not enough research to say one way or another, whether it works. It does have the potential for addiction and it's not legal everywhere. So there's that.  But also it's a problem that if you quit, you'll likely experience sleep disturbances that can last for several months.     The bottom line is, I want you to know that you shouldn't have to choose between serious health consequences of poor sleep and the side effects and risk of sleeping pills and potions.  If you suffer from insomnia, I do encourage you not to stop any medications without medical supervision and to have an honest conversation with your doctor. And if they want access to my resources, just give them my email address. I'm happy to share and they're 100 percent legit, but if good sleep eludes you, I want you to know while there's no magic pill for perfect sleep, there is a proven path to natural, restorative rest that can transform your life. Imagine waking up energized, focused, and ready to tackle your day without relying on sleeping pills or potions.  Are you tired of tossing and turning at night? Desperately wishing for deep, restful sleep?  I'm hosting two exclusive live webinars where I'll share my evidence based approach to achieving consistent quality sleep. Join me on March 3rd or March 5th to discover how to fall asleep naturally. and wake up refreshed, practical strategies to boost your energy and mental clarity, and solutions to common sleep challenges that keep you awake at night.  Plus you'll get a chance to ask your most pressing sleep questions during a live Q& A session. So don't miss this opportunity. To revolutionize your sleep. Click the link in the show notes to save your spot now. Registration is required. And make sure you're on my email list to receive exclusive pre webinar insights and special bonuses. Your journey to better sleep starts here. Sign up right now and let's transform your nights and supercharge your days.  Because good sleep is crucial for good health and healthy looks great on you.   RESOURCES: FREE, live sleep masterclass registration Jet Lag Does Prevagen work? Why doctors prescribe a pill Meet Aunt Edna - Your holiday survival stress guide

Join Matt today as he explores the fascinating intersection of sleep, metabolism, and weight management, delving into the science of dual orexin receptor antagonists (DORAs). This episode dissects a groundbreaking study on suvorexant (Belsomra), an FDA-approved insomnia medication, and its potential to enhance fat burning during sleep. Matt unpacks the role of orexin, a neuropeptide crucial for wakefulness, and explains how DORAs work by targeting orexin receptors to promote natural sleep. This preliminary research, conducted on healthy young men, reveals suvorexant's intriguing ability to not only improve sleep quality, but also increase fat oxidation while preserving muscle mass. While these initial findings are promising, Matt emphasizes the importance of cautious optimism and the need for further research in more diverse groups. He explores the implications for weight management and metabolic health, highlighting the potential of suvorexant as a novel approach to weight loss. However, Matt underscores that a holistic approach, including diet, exercise, and good sleep hygiene, remains essential for long-term success. Tune in today to gain valuable insights into the complex relationship between sleep and metabolism, and how scientific advancements may pave the way for innovative solutions in weight management.Please note that Matt is not a medical doctor, and none of the content in this podcast should be considered medical advice in any way, shape, or form, nor prescriptive in any way.Are sleep troubles keeping you up at night? Matt used to be a skeptic about meditation, but 7 years ago, he tried it using a fantastic meditation app called ‘Calm', and it transformed his sleep! Now, he meditates for 10 minutes before bedtime every night! He's also partnered with Calm who have been generous enough to offer his podcast listeners an exclusive 40% discount on their premium subscription! All you have to do is go to calm.com/mattwalker and take advantage of this incredible deal! Head on over now and improve your sleep today!Another great sponsor of the show is AG1, a comprehensive nutritional drink trusted by thousands worldwide, including Matt! For nearly four years and counting, he has relied on AG1 to fuel his post-workout routine with its powerhouse blend of over 75 essential minerals, vitamins, probiotics, and prebiotics, meticulously crafted to support your daily nutritional needs. AG1 is registered and approved by the Therapeutic Goods Administration, boasting GMP badges for quality assurance. As a special offer for our listeners, when you try AG1, you'll receive a complimentary one-year supply of both Vitamin D and K2, and with your first subscription, you'll also receive five free AG1 travel packs! Visit AG1 to explore AG1's range of offerings and claim your exclusive offer.As always, if you have thoughts or feedback you'd like to share, please reach out to Matt on Instagram.Matt: Instagram @drmattwalker or on X @sleepdiplomat

Join us for our first episode on the orexin antagonists! We will be briefly discussing: Suvorexant, brand-name Belsomra, Lemborexant, brand-name Dayvigo, and Daridorexant, brand-name Quviviq.

Dr. Mindy answers questions about the Heat, MRI results, kidney stones, too much milk, tight knees, Belsomra, Holden update, ADHD, stomach bug, always being tired, elbow pain, head moles, low resting heart rate, IV drips and lower back pain.See omnystudio.com/listener for privacy information.

Coronavirus outbreak is very scary because of Chinese Lunar New Year migration; The mechanism and problems of the sleep aid Suvorexant, brand name Belsomra; Email with a variety of topics: dead space in the lung, asthma and microbiome, healthy oils; Coronary calcium score and coronary artery disease -- Caller has a very high level; Chronotherapy addresses the best times to take meds and progressive resetting of sleep time for insomnia; Don’t take anti-inflammatories at night after surgery; Slow wave sleep is important to cleanup brain cell waste like beta amyloid

Coronavirus outbreak is very scary because of Chinese Lunar New Year migration; The mechanism and problems of the sleep aid Suvorexant, brand name Belsomra; Email with a variety of topics: dead space in the lung, asthma and microbiome, healthy oils; Coronary calcium score and coronary artery disease -- Caller has a very high level; Chronotherapy addresses the best times to take meds and progressive resetting of sleep time for insomnia; Don't take anti-inflammatories at night after surgery; Slow wave sleep is important to cleanup brain cell waste like beta amyloid

The Centers for Disease Control and Prevention has called insufficient sleep a public health epidemic. And yet, many of the commonly prescribed medications are not helping most patients. In this interview, John Neustadt, ND, explains why an integrative approach to treating insomnia provides a much more effective alternative to commonly used sleep medications.   About the Expert John Neustadt, ND, received his naturopathic doctorate from Bastyr University. He was founder and medical director of Montana Integrative Medicine and founder and president of Nutritional Biochemistry, Inc. (NBI) and NBI Pharmaceuticals. He’s a medical expert for TAP Integrative, a nonprofit organization educating doctors about integrative medicine. He has published more than 100 research reviews and was recognized by Elsevier as a Top Ten Cited Author for his work. Neustadt’s books include A Revolution in Health through Nutritional Biochemistry and the textbook Foundations and Applications of Medical Biochemistry in Clinical Practice. Neustadt is an editor of the textbook Laboratory Evaluations for Integrative and Functional Medicine (2d Edition). He was the first naturopathic doctor ever voted Best Doctor among all physicians in his area. Neustadt received 15 Orphan Drug Designation by the US Food and Drug Administration for the use of natural products for the potential treatment of rare diseases. About the Sponsor Nutritional Biochemistry, Inc. (NBI) formulates and manufactures products that give results. Started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed to help his patients and family, NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and actually shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study, or use entirely different nutrients that weren’t supported by the research. Neustadt’s latest creation is Sleep Relief. NBI’s Sleep Relief is a breakthrough in sleep technology. Its bi-phasic, time-release technology delivers NBI’s proprietary formula with clinically validated nutrients in two stages—a quick-release first stage and a slow-release second stage to help you gently fall asleep, stay asleep and wake refreshed and ready for your day. NBI's Osteo-K delivers the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80%. NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality. NBI is a name you can trust. But don’t take our word for it. Spend some time on our website, learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Thank you so much for joining me. Today, our topic is the integrative approach to insomnia. During this interview, we will learn that insomnia is a significant problem for many patients that can have far reaching physical, mental and emotional health ramifications. We will also learn how to successfully treat this condition by using a combination of diet, lifestyle recommendations, and dietary supplements. My expert guest today is Dr. John Neustadt. Dr. Neustadt received his naturopathic doctorate from Bastyr University and he was the founder and medical director of Montana Integrative Health. Before we begin, I'd like to thank the sponsor of this topic who is Nutritional Biochemistry Incorporated, or NBI, manufacturers of high-quality dietary supplements for health care professionals. Dr. Neustadt, thank you so much for joining me today. John Neustadt, ND: Thank you for having me on. Gazella: Well, so the Centers of Disease Control and Prevention calls lack of sleep a public health epidemic. Now, that seems pretty significant so today we're going to talk specifically about insomnia. How common is insomnia in particular? Neustadt: Well, the CDC is absolutely correct. It is a public health epidemic. Up to 80% of people struggle at some point with what's considered transient insomnia, less than two weeks of duration and insomnia effects 10 to 15 percent of the general population. In primary care settings, it's estimated that up to almost 70 percent of primary care patients have insomnia so it is incredibly common. Gazella: Oh, yeah that is. So how does lack of sleep impact a patient's overall health from like a physical, mental, emotional standpoint? Neustadt: It has devastating impacts. There are two ways to think of it. One is short-term impacts and the other are the long-term impacts. So, short term it can impact decreased job performance, impact social and family life by creating greater fatigue. I mean, just you're more tired during the day. Decreased mood and depression, increases in anxiety and stress. Decreased vigor and just not being able to cope with the demands of daily life and be able to complete tasks. That's only short term. Devastating just in the short term. But in the long term, it can be a killer. There, if people are sleeping an average of less than six hours per night, it can increase the ... or decrease the quality of life at the same magnitude of a similar condition such as congestive heart failure and major depressive disorder. It's an early symptom for Alzheimer's Disease and Parkinson's Disease and Huntington's Disease and there's a sweet spot for sleeping of about eight hours. That research shows is the healthiest, and if you're sleeping less than six, or longer than nine hours, it increases your risk for diabetes, metabolic syndrome, and death and, in fact, for metabolic syndrome, there's a 45 percent increase in risk compared to people who are sleeping seven to eight hours a night. Gazella: Wow, so yeah, so this is a very important topic for clinicians to have on their radar. So, when you're evaluating a patient with a sleep disorder such as insomnia, how do you approach the work up? Neustadt: Well, insomnia's really a qualitative diagnosis. It's how are they ... how do they feel that they're sleeping? How do they feel that it's impacting their health? Now the DSM official diagnosis, there is a quantitative or a couple of quantitative aspects to that and that is it's occurring at least three nights per week, and present for at least three months. So understand the difference between transient insomnia, less than two weeks, versus the diagnosis, official diagnosis, needs to be going on for greater than three months. So there's a huge discrepancy there and in time periods and clinically it's important to be aware of that because these detrimental and dangerous effects of insomnia and sleep deprivation definitely are occurring in shorter than three months period of time. They're happening pretty quickly if someone's not getting enough sleep and even over a few days the short term consequences. And so what I ask people about is how many hours, on average, do they think they're sleeping a night? Do they have any difficulty with falling asleep or staying asleep called sleep phase delay or sleep phase advance? Are they waking refreshed in the morning? What's going on with them psychosocially? Are there any stresses going on at work or in relationships or financially that's increasing their anxiety and could be impacting their sleep? Are they are risk for any hormonal abnormalities or imbalances because the research is clear that low estrogen, low or high testosterone, elevated TSH, those are all things that can create insomnia. Abnormal progesterone, as well. And then looking at medications because there are some medications that can impact sleep, as well. Gazella: Yeah, let's talk about the medications that can impact sleep. What are some of those medications that can impact sleep? Neustadt: Well, prednisone, that can cause hyper-arousal, or can cause somebody to not sleep, not be able to fall asleep, or have fragmented sleep. Beta-blockers, very common heart medications, can decrease melatonin production. So we know what the mechanism of action ... their interaction of sleep is they decrease melatonin and can cause poor sleep. Some antidepressants, actually, can cause poor sleep. Antidepressants can, depending on the antidepressants, can either cause somebody to not be able to sleep enough or can cause hypersomnolence, somebody to be sleeping too much. So looking at those, looking up ... it's very easy to look up whatever medication they're taking quickly and see, besides the ones that I mentioned, could it be potentially interfering and impacting with their sleep. Gazella: So I've been hearing about hyperarousal, or the hyperarousal hypothesis, which I find quite fascinating. What is the hyperarousal hypothesis and how can it affect what is recommended to patients? Neustadt: Great question. So the hyperarousal hypothesis I like to refer to as "wired-but-tired." And it occurs to people typically who are under a lot of stress, they have elevated cortisol, and when they end up trying to fall asleep they just can't turn their mind off, or even if their mind isn't racing, they just can't calm down. Their body can't relax and settle into sleep. They're staring at the ceiling, it can cause fragmented sleep. And that wired-but-tired, again, typically occurs in people who are under chronic stress. Gazella: Yeah. And you know the other day when you and I were talking as it related to the hyperarousal hypothesis, you were telling me about something else that was new to me and it was called social jet lag. Talk a little bit about social jet lag and the research associated with social jet lag. Neustadt: I'm so happy you brought this up because I love this as well. Fitbit, that maker of the wearable tracking devices, and tracking people's sleep as well, they had access, because of their users, to over six billion data points of sleep. And they looked at those. And they looked at the data and determined that the biggest predictor of healthy sleep, restful sleep, is going to bed at about the same time every night. Basically training our body that it's bedtime, getting that routine. Social jet lag occurs when people are going to bed at about the same time every night during the week but then the weekend comes. Friday night they go out, hang out with friends, stay out late. Saturday night maybe do the same thing, and then Sunday comes around and they try to go to bed again at their weekday, or their work week time, and they can't fall asleep. And essentially what they've done is it's as if they've flown to another time zone and their body thinks that it's not time to go to sleep yet. And they've induced their own jet lag called social jet lag. And so one of the things that Fitbit found, and I think one of the most impactful things, is showing that getting that regular bedtime, being in that routine, going to bed at about the same time every night is one of the best things people can do for improving their sleep. Gazella: And even on the weekend, and I'll tell, you, when you put this on my radar I, of course, had to do a little research and there's a lot of studies on this that actually show that the physical effects that you talked about with sleep deprivation earlier also occur with this social jet lag. So I think it's really important for clinicians to be aware of that. So thank you for bringing this to my attention. So now doctors often prescribe benzodiazepine or benzodiazepine-like drugs to help patients sleep. What are some of the potential risks of these particular medications? Neustadt: Well, the potential risks are very well documented and they increase risk for falling, dizziness, light-headedness, those risks are increased in people who are 60 years or older because their ability to metabolize the drug tends to decrease. And so because it increases the risk for falls and dizziness and light-headedness, it then increases the risk for fall-related injuries, such as osteoporotic fractures, such as concussions, such as death, even. But even beyond those risks associated with increased risks for falling, the research has shown that cancer risk is actually increased in people who take over about 132 doses of benzodiazepine a year. So that's even ... that's less than half of a year worth. And in fact some of these risks are increased with very small and limited exposure. So you know from half a dose to 18 doses per year, the hazard risk for death is increased 3.6 times. 18 to 132 doses, the hazard risk for death increased 4.43 times in a study that looked at this. And for greater than 132 doses, it increases 5.32 times. That's 532 percent greater than somebody not taking these medications for death. And the research has shown to actually get one benefit, the number needed to treat, to have one patient benefit is 13 patients. But the number to treat to create harm is only 6 patients. Gazella: Yeah, that's problematic. So what about the newer class of medications, like the orexin receptor antagonist Belsomra? Neustadt: Belsomra came on the market in 2015, it's a schedule 4 drug and it's a CNS depressant. So, like other CNS depressants, like benzodiazepine, it can have similar adverse effects. Some of the benzodiazepine drugs like Lunesta or Ambien can also cause, like Belsomra, can cause daytime impairment including impaired driving skills, risk of falling asleep while driving, abnormal thinking and behavioral changes are part of the adverse events spectrum, including amnesia, anxiety, hallucinations, other neuropsychiatric symptoms, even complex behaviors like sleep-driving. I mean, you're driving while not fully awake, after taking the hypnotic. Or other complex behaviors have been documented, like preparing and eating food, making phone calls, or even having sex, without remembering it. And so the drug has some serious risks, including worsening of depression and suicidal ideation, and the benefits of that, it can increase ... or the benefits of the medication, because all medication, it's a risk-reward calculation ... it can decrease sleep latency, that is, the amount of time to fall asleep by about eight to 10 minutes and increase sleep duration by 17 to 20 minutes. So at the most beneficial end of that, maybe it's 30 extra minutes of sleep. But you get all of those risks associated with it. Gazella: And are patients getting good sleep when they're on these prescription and over-counter medications? Are they getting good quality sleep? Neustadt: Well, you raise a great point. That's one of the problems with all of these medications is they tend to increase sleep duration, sleep quantity, but they're not increasing sleep quality. They're not getting patients into that deep, restorative phrases of sleep, the slow-wave sleep, phase 3 and into phase 4, to get that good, restorative sleep. So the quantity of the sleep may be increased but the quality has not been shown to be increased. Gazella: So you've made a pretty compelling case that a more integrated, holistic approach is needed. And integrative practitioners often recommend melatonin for insomnia with their patients. Can you talk a little bit about melatonin and why for some patients, many even many patients, it may not be enough? Neustadt: Melatonin is one of the first things I find that people with whom I speak, they've tried. They've reached for that. If they're going to try a natural product, they've reached for the melatonin, you know, first, almost universally. The challenge with melatonin is that it's got a very short half life, 40 to 50 minutes. And so while melatonin is considered a circadian modulator, meaning it helps the body recognize day from night, and it is a natural hormone, a natural product that our body uses to help us fall asleep, it's not really used for sleep maintenance. And so when somebody takes melatonin to help them fall asleep, because it's got such a short half life, well 50 percent of the melatonin is eliminated from the body in less than an hour, so let's just be generous and say an hour for easy calculations. So common doses out there is a 3 mg dose. So in an hour, they've got a one and a half milligrams left. An hour later they've got .75 milligrams left. And on down. And so 3, 4 hours later, essentially most of that melatonin is out of their body and they wake up again. I hear so often people who take melatonin, they end up waking up in the middle of the night, still. And so what do they do? Well, they might need more melatonin. And so they keep taking higher and higher doses until they're sleeping through the night and then they wake up feeling drugged in the morning. Groggy, hungover and it takes them hours to actually feel fully awake. So the natural rhythm of melatonin in our body is that the rise in melatonin occurs around 10 PM and then it peaks at about 2 AM in the morning, and it declines at approximately 6 AM, it's declined back to baseline. And that makes sense because that's sort of the rhythm of when we start to fall asleep and when our body then starts to wake up. Of course melatonin is balanced with other hormones as well that the body is producing during sleep, but the immediate release of melatonin that people are taking is not mimicking the body's cycle of melatonin production during the night. And it's also not a complete solution because it's not dealing with the other phases of sleep, we're looking at the other hormones in sleep, GABA for example. Or the other variables that can impact sleep such as poor blood sugar. When blood sugar can drop, hormones are secreted like cortisol and epinephrine to increase the body's blood sugar and we wake up. And so that's why melatonin for a lot of people doesn't work, because it's just not a complete enough solution. Gazella: I think that's a really good point, that it's not a complete solution for many people and that's why you use such an integrative approach. So I'd like to really dig into your integrative approach, I'd like to talk about dietary supplements, diet, and other lifestyle factors. So as long as we're talking about melatonin, let's keep on that subject and talk about dietary supplements. Are there specific dietary supplements that you use in your clinical practice specifically for insomnia? Neustadt: There are and it depends typically on the clinical picture. So for example if somebody has muscle aches or tight muscles that's keeping them from sleeping, magnesium can help, that can be a gentle muscle relaxant. If there's some anxiety that may keep them from sleep, well, glycine is an amino acid that's also an inhibitory neurotransmitter, that can be helpful. GABA also an inhibitory neurotransmitter used in the body available as a dietary supplement. That can be helpful. Botanical extracts such as alphianine increases alpha-wave production in the brain which is associated with calming, alert calmness. Then there are some sedative botanicals that can be helpful such as hops or skullcap, also called Scutellaria. And others. So that's part of it and for potential, looking at decreasing the response to stress, I like using, if they're under a lot of stress, some adaptogenic herbs like ashwagandha, or jujube, magnolia bark extract. If there is vaso ... if there's an issue with hot flashes and perimenopause, pine back extract. There's a clinical trial on that showing that it improved sleep quality and sleep quantity. And so I typically, you know, this monotherapy approach of one symptom, 1 pill, it really doesn't work when we're looking at complex pathologies like insomnia or many other chronic issues. And so I tend to like products that combine those different nutrients shown in clinical trials to work that target the underlying pathology, the underlying biochemical pathways at work and sleep and affected by insomnia in a time release or a biphasic time release delivery system because it more closely mimics the body's natural rhythm of the 2 major categories of your sleep. One is helping somebody fall asleep, you know how do we do that, and the other, over ... you know, the subsequent 6, 7 hours later after they've fallen asleep, how do we help them stay asleep? And so that's how I conceptualize it and that's the overall approach with dietary supplements when they're indicated. Gazella: So before I move on to diet, I know that you helped formulate and create a specific sleep supplement. I want you to tell me the name of that supplement but I also want you to tell me why you created it, because let's face it, there are a lot of sleep supplements in the market. So why did you want to create the supplement that you created? Neustadt: So the name of the product is NBI's, my company, NBI's Sleep Relief is the name of the product. And I created it for a couple reasons. One, just like all the products that I've created in NBI and formulated, I couldn't find the combination of nutrients or the dose and form of nutrients in a product shown in clinical trials to actually work. And I personally suffered from insomnia for years and years. And I tried a lot of different things. It wasn't helping me. I'd work with a lot of my patients trying to different things, having to dispense different bottles of products, in addition of course to working with diet and lifestyle and other psychosocial factors involved. And I couldn't find something that worked consistently. And so I started digging into the sleep research, the pathophysiology of sleep, the clinical trials, what are the underlying mechanisms affecting sleep. And after over a year of research and formulating and working, trying over a dozen different combinations and doses, that's when I created Sleep Relief. Gazella: Okay perfect, Sleep Relief. So now let's talk a little bit about diet. What are some of the things that you recommend to your patients when it comes to sleep, associated with diet that may not be on the radar of some practitioners? Neustadt: So one of the big things that I see over and over is a lot of people have, may have acid reflux and they don't know about it. And because maybe it's not ... maybe they have a cough when they lay down, maybe they are just not aware that that's going on. And so evaluating for that because that can wake people up. The other thing that I find with diet that's very important, and with acid reflux, you know, that can be diet related. There are 5 most common foods that can contribute to that and interrupt sleep, that's raw garlic and onion, chocolate, coffee, and citrus. Although other things can do it for other people. An infection can do that, H. Pylori can cause that as well. And then if they have a hernia, a hiatal hernia, that can cause it as well. So looking at that, looking at those underlying potential causes if that is involved. The other thing is poor blood sugar control which I already mentioned. And one of the things I like to ask that can indicate if they might have poor blood sugar control is if they get that afternoon, postprandial tiredness. You know, about 3, 4 o'clock in the afternoon, a couple hours after lunch do they just get that energy slump. And that can be an indication that they're having a little bit of blood sugar control issues. Or are they waking up at the same time every night. Both of those questions can give clues. And if that does seem to be involved, one thing that I love to try with patients ... it doesn't work very often but when it does, it's really a home run, and that is ask them to eat 8 to 10 grams of protein before bed. Protein's one of the best ways to regulate blood sugar. And so if they do that and it stabilizes their blood sugar and they then are sleeping through the night, well, again, it's a home run. I mean, there are no pills, no powders, it's just natural doing it with food and it also opens the door for even more discussions with helping them understand how they can improve their diet during the day to help, to eat, to promote ... to help them understand how they can eat, changes they can make to eat, the promote their health for the rest of their life. Gazella: Yeah, those are some great suggestions when it comes to diet. Now let's talk a little bit about lifestyle. What are some things that may not be on the radar of some practitioners when it comes to lifestyle aspects? Neustadt: So we talked about going to sleep at about the same time every night, that's really important. The other thing is ... and most practitioners, or hopefully all of them have heard of sleep hygiene. The research shows that about the 69 to 70 degrees for most people is the ideal temperature for sleep. Some people who, if they're in a relationship with their partner, they may like different temperatures may be most comfortable for them. So there are wonderful things out there now, it's call the ChiliPad, that you can get, it's a pad you can put on your bed, where you can control the temperature on each side of the bed. So that can be really helpful. Stress of course is a big issue in our society, a lot of people are under chronic stress, so anything that we can do to help people decrease their stress or better deal with stress is really important. And a fantastic study came out recently that showed that a lot of the impact of stress is not the actual event happening to us, it's how we view it. So if people view stress as a good thing, meaning "I gotta learn something from it and what can I take from this," the health impacts from stress are mitigated. If somebody sees a stressful event and they're internalizing it and they're not seeing it as a growth opportunity, then it magnifies the negative stress impacts. So, A) getting them to just understand that mindset is really important, just when it comes to stress happening, and then what can they do to have more control over those events that may be causing them stress to decrease that stress. And that could mean creating healthy boundaries for themselves. That could mean doing any yoga or mind-body techniques. You know there's lots of things that we can offer to patients that can be incredibly, incredibly helpful. Gazella: Yeah, I would agree. And now your approach focuses on diet, lifestyle, and dietary supplements. How important is it to focus on all 3? So some practitioners might be really focused on the person's diet, or some might be looking at their stress level, and some might be focused on just melatonin. Why is it so important to look at this from an integrative standpoint? Neustadt: Well I think if we want to do the best job we possibly can for our patients and give them the best results, looking at it through a more integrative approach is important. And I like the approach of trying dietary supplements to give people benefit quickly. So if somebody is sleep deprived, it's gonna increase their tendency to reach for those comfort foods. I think we've probably all experienced that. And especially because what happens with insomnia and sleep deprivation, it decreases mood. It can cause depression. And sugary foods, for example, when we reach for those, it can increase our serotonin production and temporarily lift mood. But it causes this rollercoaster of insulin and blood sugar that's hard to get off of. So just getting people sleep can help improve their mood. So I like the dietary supplement approach for triage to get them feeling better so they can make healthier decisions, have a more present mindset, be more proactive instead of reactive, while I'm working with them also on improving their diet. Transitioning to a healthier way of eating, which, the research has shown, unambiguously is the Mediterranean pattern of eating. And also stress reduction and exercise and those things as well. Gazella: Yeah, I mean that all makes a lot of sense. And this is a very important topic and I want to thank you, Dr. Neustadt for a very interesting conversation and once again, I'd also thank today's sponsor, Nutritional Biochemistry Incorporated, or NBI. Thanks again, Dr. Neustadt, for joining me. Neustadt: Thank you for the opportunity. Gazella: Have a great day. Neustadt: Thank you. Gazella: I'd like to remind readers of the Natural Medicine Journal that we now offer free continuing education credits for naturopathic physicians. Our list of podcasts and research guides that have free CE credits is growing. For more information, just click the Continuing Education tab at the top of our Natural Medicine Journal website.

Orexin is a 'master controller' of the sleep wake control system. It stimulates the wake-promoting system and stabilises the switching between wake and sleep. The unique role of orexin makes it an attractive target for manipulating sleep. Blocking orexin has been shown to be an effective strategy in insomnia, and drugs that block orexin, like suvorexant (Belsomra), are now available. Orexin replacement will also play a key role in managing narcolepsy in the future. Dr Moira Junge (Health Psychologist) and Dr David Cunnington (Sleep Physician) host the monthly podcast, Sleep Talk, talking all things sleep. Leave a review and subscribe via iTunes Audio Timeline: 00:00 - 01:25 Introduction 01:25 - 07:43 What's news in sleep? 01:25 - 02:53 SCN2a gene mutation / sleep for carers 02:53 - 04:14 Sleep in Australians - Sleep Health Foundation research 04:14 - 05:17 World Sleep Day - Sleep Health Foundation campaign 05:17 - 07:13 Melatonin - TGA registration 07:13 - 07:43 Sleep walking research 07:43 -  36:44 Theme - Orexin & Suvorexant 07:43 - 12:07 Sleep wake regulation and role of orexin 12:07 - 25:51 Guest interview - Daniel Hoyer: Orexin 25:51 - 34:05 Clinical use of suvorexant (Belsomra) 34:05 - 36:44 Orexin replacement in narcolepsy 36:44 - 37:56 Clinical tip of the month - Map sleep symptoms to brain systems 37:56 - 37:58 Pick of the month: 37:56 - 40:35 Moira - Insomniac City - Book 40:35 - 44:46 David - Sleep in Primitive Societies - journal article 44:46 - 46:52 What's coming up in sleep? Next episode: April 3rd 2017 - Headaches and Sleep Links mentioned in the podcast: SCN2a gene mutation Australian Sleep Health Survey Sleep Health Foundation - Swap screen time for sleep time Melatonin - TGA registration in Australia Melatonin for sleep - SleepHub post Sleep walking research Prof Daniel Hoyer - Key research publications Suvorexant (Belsomra) approval - FDA (United States) Suvorexant (Belsomra) - US Consumer Reports Suvorexant (Belsomra) - The New Daily on Belsomra in Australia Consumer Medicine Information on Belsomra - Australia Medication for Insomnia - SleepHub post Cognitive Behavioural Therapy for Insomnia - SleepHub post Medication for narcolepsy - SleepHub post Neurological Regulation of Sleep - Nature paper by Saper et al Suvorexant - SleepHub post Orexin - SleepHub post Assessing Sleep Disorders - Video Insomniac City - Book Sleep in Primitive Societies - American Journal of Human Biology Sleep Down Under 2017 meeting - Auckland Oct 25-28 Sleep 2017 meeting - Boston June 3-7 World Sleep Congress 2017 - Prague October 7-11

In this episode, we discuss suvarexant (Belsomra), the first dual orexin receptor antagonist approved in the United States for the treatment of insomnia.

In this show we shot the shit for a while, talked about a show called Neon Joe, Rob's racist delusion of a Papa John's commercial, watched a commercial for a sleeping pill called Belsomra with some sweet side effects, and Opie completely losing his mind and being a colossal piece of shit to Co host and comedian Jim Norton. We interviewed Comedian Adam Heath Avitable, Freematik from the animated sci-fi/horror comicbook series Dark Moon, Comedian Anthony Ennis, Gamer Juls, Legendary DJ Steve Porter, and our good friend Ricky. It was a great show!

1 - More on Yes Means Yes. 2 - Joe has a hot take on the dem debate; #AuntFromHell; Belsomra advert names many possible side effects. 3 - The News with Marshall Phillips. 4 - OSHA whistleblower fired.

8 AM - 1 - More on Yes Means Yes. 2 - Joe has a hot take on the dem debate; #AuntFromHell; Belsomra advert names many possible side effects. 3 - The News with Marshall Phillips. 4 - OSHA whistleblower fired.