Dr. Craig Heller on Cool Hands and Temperature Regulation for Better Performance and Sleep



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Katie: Hello and welcome to ďThe Wellness Mama Podcast.Ē Iím Katie from wellnessmama.com and wellnesse.com, thatís wellness with an E on the end. And this episode is a lot about temperature, sleep, learning, and a lot more. This is an exciting one for me. Iím here with Dr. Craig Heller, who is a doctor at Yale. He received his PhD from Yale in 1970. He did a post-doctorate fellowship at the Scripps Institution of Oceanography. He joined Stanford University in 1972, where he is now the Lorry Lokey Business Wire Professor of Biology and Human Biology. Heís held many positions at Stanford. And heís done a lot of research focused on the neurobiology of sleep, circadian rhythms and thermoregulation, including on things like mammalian hibernation, and temperature controls. And this is one of the reasons I wanted to have him on today, to talk about a fascinatingÖthe Stanford cool mitt study.

And we go deep on a lot of these topics, including how he got into heat exchange research, the fascinating way that the brain regulates body temperature and how this can be used to our benefit for athletic performance, for sleep. He talks about the astounding study where they had someone go from 180 pull-ups over setsÖin sets of 10, 10 sets, to 618 by adding a cooling protocol, and he gives some guidelines for how we can all experiment with this in our own lives.

We talk a lot about temperature regulation and sleep hygiene, ways to improve sleep that can be beneficial to your children as well. We talk about light and circadian rhythms, and so much more. He was such a fun interview for me. I have followed his work for a long time, and heís able to give some really practical applications for some of his really fascinating areas of research. I know that you will enjoy this interview. I certainly did, and Iím excited to apply some of his ideas to my own experimentation with athletic performance and also sleep. So without further ado, letís join Dr. Heller. Dr. Heller, welcome. And thanks so, much for being here.

Craig: Well, my pleasure. Thanks for inviting me.

Katie: Iím very excited to chat with you. I have followed your work and have so, many directions I want to go today. But before we jump into the science side, I have notes in my show notes about some amazing things that you have done. And I have to hear a little bit about swimming at the North Pole and the fact that you did a thousand pushups on your 60th birthday. Thatís incredible.

Craig: You got my deepest secrets there. No, the trip to the North Pole was a Stanford alumni trip in which I was the faculty host and the speaker, and my daughter and I always had a pact that whenever we took a hike and we came to a new lake, we had to jump in. It didnít matter what time of year. So, when I had the chance to go to the North Pole, I immediately called her up and said, okay, this is our chance. Weíve got to take a swim at the North Pole. And we did.

Katie: Thatís amazing. The farthest north Iíve been is the Lapland area of Finland. And we did the sauna and then got in theÖit was 24-degree water, but moving water. So, it wasnít frozen. And that is definitely the coldest Iíve ever experienced. It was next level.

Craig: Itís quite a shock. But zero is zero. No, freezing is freezing. So, whether youíre in the Sierra, Nevada, where we hike a lot, or at the North Pole, itís pretty much the same cold exposure.

Katie: Thatís a good point. And itís a good segue because weíre gonna talk quite a bit about cold today and, in particular, some of your research around this. I feel like thereís some base terms we can define and then delve into the specifics of what you found. But Iíd love to hear how you got into thisÖkind of youíve discovered a unique heat exchange property with certain areas of skin. So, maybe walk us into how you got into that research.

Craig: Well, it sort of came from a challenge or a bet that a lot of my work had to do with how the brain regulates body temperature and that of course was work with animals, including hibernators. And one day a friend who is an anesthesiologist challenged my colleague and I and said, ďWell, you think, you know, so, much about temperature regulation. I bet you couldnít solve a problem we have in the recovery room.Ē ďWell, whatís that?Ē Well, patients come into recovery very cold, theyíre hypothermic, and it takes them and it takes the nurses hours to get them to stop shivering and they rip stitches, they even break teeth and the beds are practically jumping up and down with the shivering. I said to my friend, you know, ďWell, thatís a trivial problem.Ē Well, no, itís not a trivial problem. Itís a very difficult problem because when youíre hypothermic in anesthesia and youíre coming out of anesthesia, you are very cold and you constrict all of your blood vessels.

You keep the blood in the core of your body, and therefore, itís hard to get heat across the skin. So, if you use hot blankets, if you use radiant heaters, itís very hard to rewarm these patients. So, we got the idea that, ďWell, we could put an arm or a leg into a chamber with a negative pressure, a vacuum, that would pull blood into that arm or leg. And then we could heat that arm or leg and that would then send heat to the rest of the body.Ē So, my colleague, Dennis Gron, he built an apparatus to try this. He took it over to the recovery room and, well, in the first patient, there was no shivering. It was like 8 to 10 minutes and the patient was back up to normal. And we couldnít understand why this was unbelievably successful.

And just to make a long story short, we eventually found out that it had only had to do with the hand, not the whole arm. And then we came to the realization that what we were dealing with was a mammalian adaptation for heat loss. If you are a mammal, you have fur. Weíre unusual mammals. If you have a fur coat, itís great in the wintertime, but if you canít take it off in the summer, thatís a problem. So, mammals can have problems dissipating heat in the summer. So, the only areas of their body that donít have fur are the pads of the feet, the tongue, the nose, the ears, and in primates, the upper part of the face.

And what we discoveredÖ We didnít discover it, but in the old anatomical literature, there are special blood vessels in these non-hairy skin areas. And those blood vessels were totally not understood as to what they were for. And what they are is theyíre shunts between the arteries and the veins. Normally, the blood goes from arteries through capillaries to veins, and capillaries are high resistance. So, what this shunt does is it bypasses the resistance so you can send large volumes of blood through these skin areas and, therefore, dissipate heat. So, you can tell right away, when you shake someoneís hand what his or her thermal status is. You couldnít tell that if you touched his or her arm. So, we discovered this rather general mammalian adaptation for dissipating heat. And we were just using it in reverse to warm the patients in the recovery room.

Katie: And this is so fascinating to me. Just out of curiosity, why are patients so cold coming out of anesthesia? Is this a side effect of the anesthesia itself and then the body having to re-regulate?

Craig: Well, when youíre under anesthesia, youíre totally vasodilated. I mean, thereís no constriction of the blood vessels. And also, operating rooms are generally cold so the surgeons and the nurses donít sweat. And also, theyíre not clothed and maybe theyíre being irrigated with fluids. So, itís very common for body temperature to drop during anesthesia.

Katie: That makes sense. Okay. And so, I may butcher the pronunciation of this, but from what Iíve read, these are the glabrous regions of skin, the hands and the face?

Craig: Yes. Right. Itís essentially non-hairy skin. Now we think we donít have hairy skin, but we do. There are hair follicles in all of our skin, except these particular areas. So, weíre unusual mammals, but we have the same anatomical structures.

Katie: And theyíre unique because the blood can go straight fromÖ They basically skip the capillaries, it can go straight from veins to arteries?

Craig: Thatís right. Goes actually from arteries to veins.

Katie: Arteries to veins. Got it.

Craig: Yeah. And then that cool blood goes right back to the heart, and from the heart, it goes out to the muscles that are working. Okay? So, youíre cooling the muscles from the inside out rather from the outside in.

Katie: And so, with anesthesia, you guys found this innate ability to warm, but on the other side of this equation, it has some really cool implications because of its ability to actually cool, from what I understand? And I know thereís some amazing research on this, but, essentially, I guess my top-level understanding is itís that heat of the muscles thatís one of the limiting factors during exercise, it kind of leads to that feedback mechanism and tells us to stop and that we can kind of use this same thing to our advantage in the other direction?

Craig: Youíre good. Thatís a great explanation. Yeah. Absolutely. Another feature of being mammals is we have a high body temperature. So, weíre up around 37 degrees, thatís centigrade or 98.6 Fahrenheit. And when we exercise, our temperature goes up. And we donít have a lot of scope. If we get up to 40 degrees, 39 or 40 degrees centigrade or 100, 101 degrees Fahrenheit, weíre in trouble. That definitely is a danger zone for humans. And thatís called hyperthermia. So, itís very easy with heavy exercise, and especially in the hot environmentÖ Think of ultra-marathoners in Death Valley, you know, they are really, really taking it to the limit and challenging their bodies. So, if you can get that heat out of the body, the muscles can keep on working. And we discovered that because we were interested in seeing what the right parameters were for extracting heat.

In other words, what should the temperature be? What should the vacuum be? What should be the flow rate? And so forth. We had a research assistant who was a gym rat, and he would go to the gym at night after work. And so, we said to him, ďWhy donít you do your workout here in the lab, and thatíll raise your body temperature, and then weíll see what are the best parameters for extracting that heat.Ē So, he was doing pull-ups. He was doing 10 sets of pull-ups to muscle failure with three-minute rests. And then at the end of that series of 10 pull-ups, we would measure his temperature and apply our prototype devices to extract the heat. And one day after we extracted the heat, he went back to the pull-up bar and did the same number of pull-ups as in his first set and we said, ďHoly crow, what does that mean? The fatigue is gone.Ē And it had to do with the temperature of the muscle. Thatís what we discovered. So, we then started cooling him after every other set of pull-ups, and his performance plateaued to a certain extent. So, he increased his work volume dramatically from one day to the next.

Katie: And I got to read a summary of that study, and it was really astounding to me because this was not a small, just like marginal improvement. This was a drastic difference in performance even without a lot of rest days in between or any of the normal things you would think would be necessary.

Craig: So, just to give you the numbers, in that one particular initial discovery, when we started cooling him after every other set of pull-ups, he went from a total of 180 pull-ups, which is already amazing, to 618 pull-ups in 10 sets. Itís remarkable.

Katie: That really, really is astounding. Thatís almost whatÖalmost a 4X inference, which really speaks to essentially understanding that itís not necessarily the muscle strength that is the limiting factor in these workouts, itís that heat. And from what we can tell in the data, is this a safe way to actually manipulate that, like cooling the body actually lets the body safely perform at that level?

Craig: Right. You cannot lower the body temperatureÖwhy this techniqueÖ These vessels will shut down if it gets too cold. Thatís why putting your hand in a bucket of ice water wonít work. It just shuts down the heat loss. So, itís safe, from that regard, you canít induce hypothermia. So, the danger is that if you get to too high levels of performance, you actually start doing damage to your tendons and ligaments. So, itís good to have coaches and trainers to protect against that. But thatís at the high end.

Katie: And probably most of us in normal everyday exertion are not hitting the upper limits of athletic ability. This is just a really amazing tool. And I would guess also, has just important implications to understand for the more extreme cases as well. Like, for instance, someone whoís hypothermic, you found, you can warm them. If someone is having maybe heat stroke, I would guess the same is true, the most effective way to cool them is to cool the hands, feet, and face, but not overcool it. So, not ice water but cool water?

Craig: Absolutely. You have it. And although this is for athletic trainingÖ So, you mentioned increasing strength. Well, thatís for sure. What happens is that when you increase your workout, you increase your work volume, the result is a conditioning effect. This reaching of 618 pull-ups, that was over a period of maybe six weeksÖsix to eight weeks. But what you see is you see each day, you are able to do a little bit more and then the rest periods between bouts of exercise, thatís when you get the hypertrophy of the muscle, the improved conditioning. So, you definitely have effect. I had a group of freshman women who were doing an experiment that was part of a seminar they were in. So, we had them doing pushups. And some of these freshman women, not athletes, they got to over 800 pushups. And they came in one day and they said, ďDr. Heller, you cost us a lot of money.Ē Why? ďWe had a formal dance this weekend. We all had to buy new sleeveless dresses.Ē

Katie: Thatís so funny. And Iím curious, do we have any best practices based on the research youíve done of the best ways to incorporate this? I work with some athletes in increasing their athletic performance, Iím also personally on a journey of getting stronger and weightlifting, and then I have kids who are athletes. So, it makes me curious of, how can we use this in our own lives? Like, are there best practices for how long, or what temperature, or what that protocol looks like?

Craig: Yes, there are. First of all, you could checkÖ Weíre just coming out with a new device that will be available thatís now in sort of beta testing in a number of athletic teams, and with athletes, and with firefighters, and with military special forces. But you can check it out at the website, coolmitt.com, C-O-O-L-M-I-T-T.com. And that gives you an idea of what is available now or will soon be available and how itís best used.

But temperature is critical. So, for athletes or people that are working out regularly, we sort of set the temperature between 12 and 15 degrees centigrade, temperature of the water. But, for some people, thatís too cold. So, an example is weíve worked with a lot of multiple sclerosis patients. And individuals with multiple sclerosis can be very temperature-sensitive. If the temperature goes up a little bit, either the room temperature, the outdoor temperature, or the body temperatures, their symptoms are exacerbated. And with these individuals, the cooling greatly reduces their symptoms. They can go back to normal functioning and not have to stay in air-conditioned places. But, for them, if you cool their palm or surfaces, these palms of the hands, below about 23 degrees centigrade, then they will vasoconstrict. So, for these individuals usually about 20 degrees was a good temperature.

Katie: Okay. So, kind of a rudimentary way to experiment with this sounds like it would be to have cool water in that temperature range and a cooler or something and try putting the hands in between sets or sprints or workouts?

Craig: So, thatís essentially like tap water. Okay? Let me go back to something you mentioned about safety. I think this is really an important issue because every year there are high school athletes that go into heatstroke in the late summer, early fall, with athletic practices. Now, in every single school, you have defibrillators, but how many students get heart attacks? None. But many, many go into heat illness or heat stroke every year. And there are even fatalities due to heatstroke as a consequence of practice..not competition, but practice.

So, I think worrying about ways of rapidly cooling those individuals is very important. Now, the recommendation for National Collegiate Athletic Association is immersion in cold water. And that absolutely works. Thatís fine if you immerse the whole body in cold water, but you donít necessarily have cold water tub available every place. Whereas, if you attack the glabrous skin, you can apply it immediately. Even at first contact with the patient, you can apply it and it will bring them back.

Katie: Yeah. And a couple of follow-ups related to this, just from a percentage perspective, I think about like, when you look at any other substance that we can use for athletic performance, even steroids, youíre not getting this kind of improvements. And this is a safe, non-invasive, non-injectable, non-supplement temperature regulation, and youíre not even talking about extreme temperature. So, even before this is more mainstream adopted, which I agree with you, this should be in schools, itís a thing I feel like as individuals and parents, we can implement to help our kids and to help ourselves with training.

Craig: Yeah. Absolutely. And you put your finger right on the critical button, people are willing to try all sorts of things that are not good for them. Performance-enhancing drugs, theyíre absolutely bad news. And this actually is much more efficacious than performance-enhancing drugs. Now, you mentioned weight lifting, and weíre talking about that sort of strength conditioning, but itís also true for endurance sports. Now, with the current devices that weíve built, we canít take them outdoors and use them continuously. We can use them episodically. But we are in the process of designing and building wearable systems. And this will be very important, for example, for firefighters. And also, we got onto this because we got emails from Ebola workers in Sierra Leone. They said, you know, ďWe have to take care of these patients, and we go into the hot zone in our PPE, personal protective equipment, and we canít be in there for more than 15, 20 minutes. So, isnít there something you can do?Ē So, that set us on the track of trying to build wearable systems.

Katie: Yeah. I can see so many potential uses, and Iím really excited to keep following the work youíre doing in this. I also have just anecdotally noticed, in myself, the same is true in extreme cold as well. Not in the operating room, but I love doing cold plunges sometimes for athletic recovery, and Iíve found that itís my hands and my feet that limit how long I can get in there. And when I wear scuba gloves, like neoprene socks and gloves, I can get so much more muscle benefit without feeling as cold and without hitting that shiver point as rapidly.

Craig: Right. So, I bet when you come out, in a couple of minutes, you start shivering. Yeah. So, whatís happening is youíre losing heat from all of your peripheral tissue, your legs, your arms, and so forth. And then when you get out, your body starts sending blood back into those limbs and it comes back into the core of your body cold. And then thatís when you see the intense shivering.

Katie: That makes sense. And, obviously, weíve gotten to delve into the athletic and performance benefits of this, but thereís so much more related to temperature than just athletic performance. And I know youíve done research in other areas as well and that thereís some crossover here into the sleep world, which I think will be a good segue. I know Iím a big fan of sleeping with a chili pad, which cools my sleep environment. And thereís to be some well-established data on sleep temperature affecting things like deep sleep, for instance, and sleep duration and number of wake-ups. But letís just start broad and talk a little bit about your sleep research as well.

Craig: Well, the sleep research is quite varied. And long time ago, we did research on temperature and sleep, and what happens to our regulation of body temperature during sleep. Most recently, my sleep research has to do with the role of sleep and circadian rhythms in learning in memory. And specifically, weíre working on down syndrome, which is a condition thatís very, veryÖitís the most common genetic cause of cognitive intellectual disability. And so, weíve been working in that area. But going back to temperature, one of the interesting things that was our first discovery was that, you know, we have two sleep states. We have REM sleep, rapid eye movement sleep, which is one we have vivid dreams and nightmares. Okay? And then we have non-rapid eye movement sleep, which is about 80% of our sleep.

And one of the interesting things we found a long time ago was that during REM sleep, we donít regulate our body temperature. The internal thermostat is turned off. That is just a side comment. During non-REM sleep, we do regulate our body temperature, but at a lower level than during wake. So, the thermostat in the brain is set to a lower level when you go to sleep. Now, if you go to sleep and youíre feeling cool in the evening, which is likely, youíll pull on lots of covers. Okay? And 15 minutes later, you wake up sweating because whatís happened is you insulated yourself to the temperature of your bodyÖto your regulated temperature before sleep, your thermostat gets set down and now youíre too hot.

So, itís true that a cool environment is much better for sleeping. And the reason for that ties these two areas of research together. What happens when youíre too hot in bed? You stick out your hands or you stick out your feet from under the covers, right? So, if youíre in a warm environment, that doesnít help. But if youíre in a cool environment, that makes it possible to come back into the regulated temperature that your brain is telling you you should be at.

Katie: That makes sense. And Iíve read how thereís thatÖmammals have that adaptation of that our body temperature does tend to go up, I think a little bit, during sleep, which Iíve heard it explained, it came from sleeping on the ground and the temperature on the ground would bring your body temperature down, so we developed that adaptation to heat the body. But now weíre sleeping in these temperature-controlled environments, and like you said, we get hot in the middle of the night.

Craig: Well, yeah. In general, temperature goes down with sleep. It goes down with the circadian timing of sleep as well. It comes back up and it starts coming back up in the morning before you wake up. Okay? So, temperatures generally lower late in the day than around noon, but then when you go to sleep, it takes a further dip. Thereís a company that I have been an advisor for called Eight Sleep, and they make a bed which is temperature-controlled. But, in addition, you can program it to a temperature cycle that best matches your bodyís settings. Okay? And recently, the San Francisco 49ers bought those beds for all of their players, and they love them. They say theyíre getting much better sleep.

Katie: Having experimented with the temperature regulation at night, I will say it spoils you though. Now when I travel, I miss being able to be cool at night. But from understanding this, would it be logical to then assume that if someone wore just the cool mitt during sleep, it would have a similar or even potentially bigger effect, or would you not want to wear that during sleep?

Craig: I think it would have an effect. I donít necessarily know that it would be bigger. The other thing is just cooling before you go to sleep. So, if you used it before sleep so it got rid of any excess heat load that you haveÖ Letís say you did a workout in the evening, youíre going to go to bed with an extra heat load. So, if you could take that heat load away, it would facilitate your sleep.

Katie: That makes sense. Iíve noticed, and I donít think most people want to do this, but if I get in the cold plunge like an hour or so before bedtime, my deep sleep numbers improve, which makes sense, in light of what you just said, but I feel like most people arenít gonna be gung-ho about jumping into cold water right before bed. So, this might be an easier, gentler approach.

Craig: Yeah. Right. I think so.

Katie: And I think sleep is a big issue for moms, especially with kids at various ages and what comes along with that. So, based on your research, what are some of these practical things we can pull that might be tips to help improve sleep quality and duration based on what youíre seeing in the research?

Craig: Well, there has been a big sea change in the sleep medicine world in the last decade or so. And 20 years ago, the big thing were sleeping pills, all sorts of different kinds of sleeping pills. And many of them are still available now and are used and are actually prescribed for people who have serious problems. But those drugs have problems as well. You become acclimated to them, and therefore the doses have to go up, have to go up, have to go up. And they have side effects, okay? So, what has happened in the sleep medicine world in the last 10, 15 years, has been the rise of behavioral therapy, cognitive-behavioral therapy. And thatís used to improve sleep hygiene. So, sleep hygiene sounds like a strange concept, but it is. Itís what you can do to improve the quality of your sleep.

And there are easy things such as have a scheduled bedtime. Donít just work until you feel as if you donít want to work anymore and then go to bed. You know, donít do that. Have a scheduled bedtime. And donít work, or donít do things that you would normally be doing during the day for the hour or hour and a half, two hours before bedtime. Okay? One of the critical things is not to use computers because computers have a lot of blue light. And what blue light does is, in the evening, exposure to blue light phase-delays your circadian system. So, it makes you react as if itís not as late as it really is. Okay? So, you donít want to phase-delay your circadian system. You want your circadian clock to favor sleep at the right time.

Another thing is just maintain a specific sleep environment, and this is called contextual conditioning, so that you only associate the bedroom with sleep and sex. Thatís it, you know? Not work, you donít use your bedroom as an office. Now, for people who live in efficiency apartments, that might be difficult, but there are ways you can do it in setting up the room. And, of course, the critical thing is your own behavior. Turn off the computer an hour before bed. Donít try to be thinking right up until bedtime and then expect your brainís gonna shut off and go to sleep.

Katie: And Iíve noticed that light manipulation in the morning also seems to have a big influence on sleep patterns as well. And I tell people this a lot, itís a freeÖseems so simple, and it has such a profound impact, just going outside. Even if itís a cloudy day, just going outside when you wake up, starts that clock.

Craig: Oh, yeah. Outside light, even on a cloudy day is hundredsÖno, thousands of times brighter than your inside light. We donít realize it because our eyes rapidly adjust to the light level. But when you go outside, you get much, much greater visual stimulation, light stimulation. And early morning light, along with exercise, is great for keeping your circadian clock synchronized. Your circadian clock is not running at exactly 24 hours. So, some people are early, theyíre larks, and other people are owls, they tend to run later every day. But one of the ways you keep your clock in sync with the real world is that light exposure in the morning.

Katie: And youíve also, from my reading, done some work specific to insomnia. And this is a problem I hear from more and more people who are seeming to experience insomnia. Do you have any insomnia-specific recommendations?

Craig: I am not an expert on insomnia at all. And the primary treatments or the recommended treatments for insomnia are the cognitive behavioral therapy, setting up a pattern of sleep so that you expect to sleep, youíre ready for sleep, youíre in the right place for sleep every day. Now, for people who are really, really, you know, terrible insomniacs, there are protocols that are used. So, one of the things that is used is a protocol in which the individuals are only allowed to be in bed for, letís say, six hours or seven hours. Okay?

And so, day after day, theyíre only allowed to be in bed for six hours. So, theyíre gonna get a sleep debt. Theyíre going to get, you know, pressure for sleep. Okay. So, then allow them seven hours. Okay. So, eventually, get to a point where when you go to bed, you are tuned to sleep. So, it seems counterproductive to deprive someone of sleep who has insomnia, but thatís a way of getting their system back in sync with the way it should be functioning.

Katie: That makes sense. I hadnít thought about that approach.

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You also mentioned REM sleep being the time of dreams and nightmares. And this is actually a breakfast conversation recently at my house that I would love to be able to explain to my kids better, but why do we dream? Whatís happening to our brains during your dream states?

Craig: Well, when we are in REM sleep, we are paralyzed. Thereís inhibition of all of the commands going out to our muscles. So, the supposed rationale for this, the evolutionary rationale, is that it prevents us from acting out our dreams. Okay? So, acting out dreams is not sleepwalking. Sleepwalking occurs in non-REM sleep. But acting out dreams for someone who has REM sleep disorder, they can injure themselves or their sleeping partners because of violent movements. They can get up from bed and start to run and run into something. They can do something very violent, like break furniture or put their head through a wall. Itís incredible what people can do with REM behavior disorder. So, to prevent that, or the reason we donít do that is our muscles are essentially paralyzed during REM sleep.

And that also applies to some of the sensory input. So, whatís happening in the brain during REM sleep is the brain is reactivated. So, if you look at the electroencophilic REM, the EEG, the EEG of REM sleep looks very similar to wakefulness because the cortex of the brain, the thinking cap of the brain, is reactivated. Okay? So, that reactivation is independent of any feedback from muscles and any sensory input. So, itís like putting the brain in neutral. It can just freely associate. And thatís why we get theseÖwhat seem to be reasonable dreams when weíre dreaming, but then when we wake up, we realize how bizarre they were. Theyíre just totally unrealistic. But they may have components of things that were on our minds before we went to sleep, things that happened the day before. But itís a process, I think, of free association of information in the brain, not constrained by sensory feedback from muscles and joints and from eyes and ears, and so forth.

Katie: And I donít know if this is true, you can confirm or deny for me, but Iíve read that sometimes when youíre falling asleep and you have that experience of like jolting for a second, that that is the body kind of testing to see if you are going into that state of paralysis. Is that right or is that urban myth?

Craig: Itís probably a myth. And the reason is that except in certain pathological conditions, we donít go into REM sleep immediately from wakefulness. We always enter sleep through non-REM sleep and then afterÖ Well, when we go to bed after about maybe 60 minutes, weíll have our first REM episode. Okay? And then it cycles throughout the night, about five cycles of non-REM, REM, non-REM, REM. And much more REM late in the night, a much deeper non-REM early in the night. So, what youíre thinking about or talking about is probably this drowsy state or what we call stage one non-REM sleep in which there is still some association with wakeful experience. And all of a sudden, you may realize youíre falling asleep and then you have some brief arousal that you go back up to wakefulness. So, itís that tricky stage between wakefulness and sleep that is not stable, and that can result inÖ Another thing it results in is a big word, hypnagogic hallucinations. So, itís once again, sort of like a dreamlike condition, but itís not REM sleep.

Katie: Okay. Thatís helpful to understand. And Iíd love to talk a little bit more about sleep stages. And maybe now that things like Oura rings and trackers have gotten more popular, people have more data related to their sleep. Iíve read that deep sleep is a reparative state of the body and that itís an important thing to make sure that weíre getting enough deep sleep. Iíve noticed in my own life, like I said, cool seems to help deep sleep as well as not eating too close to bedtime, getting morning sunlight. But is that a correct understanding, that we should be prioritizing this deep restfulness, and what are some of the ways we can hopefully lead to better-quality sleep?

Craig: Yeah. Well, you just mentioned something very interesting, and that is not eating too late. That has another effect, and that is weight gain. That the same number of calories eaten late has a much bigger effect on body weight than eaten earlier. So, to maintain body weight, even with no diet or what have you, if you take late eaters and you put them on a more reasonable schedule, like eating at 5:00 or 6:00 in the evening, you know, 6:00, 7:00 in the evening, they will lose weight even without imposing any dietary restrictions. So, thatís maybe not what you were thinking, but there are lots of healthÖ Well, let me just say this. First of all, we spend one-third of our lives sleeping, but we donít know why. So, I canít give you any definitive answer.

I can give you answers that are partial, in other words, ideas about what sleep functions are and why we know that or why we think that, but thereís no one who can say sleep is for this particular function. It probably has many functions. And we now are understanding that the evolution of sleep is much deeper than we thought previously because our primary way of studying sleep has been the electroencephalogram. The electroencephalogram is only good for mammals and birds that have a cerebral cortex. Okay? So, it wasnít useful for studying turtles, and fish, and snakes, and lizards, and other things.

But now weíre beginning to use different metrics for identifying sleep and characteristics of sleep. And it seems the farther back we go in the evolutionary history, the more evidence we find for sleep-like states. Now, whether they serve the same function in all animals, we donít know. So, weíre pretty much limited to studyingÖ For functional studies, we pretty much limited to mammals, but thereís more and more studies being done on other species such as fruit flies, zebrafish. And these are now popular models for studying sleep.

Katie: Yeah. And shorter lifespan makes them easier to study. Thatís really fascinating aboutÖ I know thereís research behind that of not eating close to bedtime and I know itís not as socially fun or easy to adapt often to our normal lifestyle, but I do notice the most difference when I stop eating by even like 4:00 or 5:00 in the afternoon. And when it comes to like time-restricted feeding, doing that earlier in the day, whichÖ it seems like physiologically our bodies are designed to absorb and break down calories earlier in the day anyway, and we have that longer digestive period where we think weíre fasting, but we still have food in our body. And so, giving time for that before sleep. And I feel like any discussion on sleep and temperature, I would be remiss not to ask, and I have a note to ask you about hibernation and bears. I know, totally a deviation, but Iím so curious just to hear a little bit about that.

Craig: Oh, yeah. So, Iíve done a lot of work in my career on hibernators, but almost all small hibernators, because you can maintain them in the lab. So, ground squirrels and chipmunks, and hamsters, and so forth. And weíve done a lot to show that hibernation is really an evolutionary extension of sleep. That downward regulation of body temperature during sleep is exaggerated in hibernators. And the other thing which is not exaggerated but dampened is the circadian system. Because the circadian system functions to wake us up, it supports alertness rather than sleep. So, there are animals that go into toper on a daily basis, so their circadian system is still waking them up at the end of the sleep phase. But in other animals that are true hibernators, they will go into toper for many days, maybe seven, eight days.

So, what we found in those animals is that the circadian system is dampened way, way, way down. So, in some of them, it still continues to function and may actually be what brings them out of hibernation every seven days or so. But the question was always, what about bears? You know, people have argued whether bears hibernate or not. So, sure, they disappear in the winter, they go into their winter dens, but there was some evidence that they were still fairly warm. They werenít really in deep hibernation. So, quite a few years ago, some colleagues and I decided we were gonna answer this question. And one of my colleagues, Brian Barnes, was at University of Alaska where bears are common. So, what we did is we built a facility at University of Alaska where we could keep bears over winter, and we could instrument them with EEG and EMG. So, electroencephalogram, electromyogram, electrooculogram, body temperature, metabolism, and so forth and so on, and study them all winter long.

And itís true that theyÖ Where did the bears come from? Thereís a ďthree strikes youíre outĒ law in Alaska that if a bear is a problem bear and it comes into a community, it will be trapped and taken away and released. Well, itís collared then, so they know whoís who. And if the bear comes back three times then itís eliminated, itís euthanized. So, we asked the Alaska Fish and Game to let us have a couple of those bears each winter. So, over the years, weíve studied 18 bears. And this is an enormous, enormous amount of data because, you know, EEG is something which is being collected on a frequency of less than a second, you know, many times per second. So, you can imagine the amount of recordings, the data files. So, weíre analyzing all of that now.

But what we found is the bears do go into toper, but they go down only to about 32, 33 degrees body temperature. They do not have these periodic arousals during the winter like the small hibernators do every 5, 6, 7 days, they come out of hibernation and go back in again. The other thing thatís interesting is that the small hibernators, as they enter hibernation, they lose REM sleep. They have then almost continuous what seems to be continuous with non-REM sleep. And the bears have REM and non-REM sleep during hibernation. And the other thing is that they lose their circadian rhythms. During the hibernation season, they no longer have a circadian rhythm and in the spring, that begins to come back. So, these are the sorts of things weíre learning about the bears.

Katie: Thatís so fascinating and probably very fun research to get to do. That sounds exciting.

Craig: Yeah. And it could have very important medical applications later on because in the induction of hypothermia, could be a valuable procedure to be able to use on stroke victims, heart attack victims, people who have had traumatic injuries. But thereís a lot we donít know about how the human body functions at low temperature. So, if we find out how the bears, another big mammal, how the bears have adapted to function at a lower temperature, that could have medical applications.

Katie: Well, Iím excited to keep following your research on that. And a few questions I wanna make sure we have time to get through, you mentioned your research on learning and memory, and I would love to just hear what the goal is with that and the current state of what youíre looking at related to learning and memory.

Craig: Well, we came to this because of a graduate student of a colleague. His name is Fabian Fernandez. Heís now a professor at University of Arizona and he started investigating learning and memory in a mouse model of down syndrome. And the mouse model has severe learning deficits just like humans with down syndrome do. And Fabian came up with the idea thatÖ And we think about the nervous system almost as a puppet master pulling strings, you know, the neuron fires, and the muscle twitches. And what Fabian said is we tend to think about the nervous system too much in terms of excitation, but what about inhibition? You know, inhibition is very important. So, the brain has to have a balance of excitation/inhibition. So, he thought maybe itís the inhibition which is too high.

So, the first thing we did is we did studies of sleep and circadian rhythms in these mice and we found there were no dramatic differences in sleep. And actually, their circadian rhythms were stronger. So, we knew that sleep and circadian rhythms are involved in learning and memory, but they didnít seem to be the problem with the down syndrome model mice. And what Fabian discovered is that if he enhanced inhibition in the brainÖ There are certain neurotransmitters, the chemicals that communicate between neurons. There are certain neurotransmitters which are inhibitory. So, he used drugs which mimic the activity of those neurotransmitters. And lo and behold, the learning was normalized. These animals that had severe learning disability were now functioning like their littermates who didnít have the condition.

And then the most remarkable thing in this research was that a short-term treatment with these drugs resulted in a very long-term normalization. So, it wasnít just, you know, you take the pill and you get an effect. No. The short-term treatment, two weeks of daily doses with the drug normalized the behavior for months. So, it changed the way the brain was functioning. So, our challenge has been, first of all, doing as much characterization of these drug effects as possible to be able to move it to the clinic, but also, to understand what is changed in the brain. And thatís pretty complicated neurophysiology, which I donít think I could describe.

Katie: Thatís really exciting though. What else is in the future of research for you? Like I said, I follow your research, so, Iím excited to hear.

Craig: Well, we are studying now another gene, which is triplicated in Down syndrome. And this gene, its name is USP 16. So, itís not United Parcel Service, but itís USP 16. And what this gene does is itís very much involved in determining whenÖ Youíve heard of stem cells, cells that can develop into any kind of different cell. So, what this gene does is it plays a role in determining whether the stem cells differentiate when they divide or whether they produce another stem cell. So, thatís called renewal. So, are they keeping up the population of stem cells or are they going down the pathway to differentiation? And the triplication of this gene in down syndrome model mice has a big effect on development. So, the brains are smaller probably because the neural stem cells have differentiated rather than maintained themselves. Bone cells are affected.

So, the down syndrome mice have a much higher level of osteoporosis-like symptoms, and that is improved by eliminating this particular triplication. The other approach weíre taking is looking at theÖ Thereís another gene which is very critical, which is triplicated and thatís whatís called the amyloid precursor protein gene. Itís very much involved in Alzheimerís disease. And individuals with down syndrome have early-onset Alzheimerís, so weíre studying what the benefit is by normalizing the APP gene in these animals. So, thatís the sort of thing weíre doing. In the case of the human performance, we continue to study the role of temperature in muscle function. And one of the things weíre discovering now is that the production of lactate by muscle is temperature-dependent. So, we know thereís the myth that muscle failure, muscle fatigue, is caused by lactic acid.

Well, itís really more correctly lactate, which is produced, not lactic acid. But we know now that lactate does not cause fatigue. You can actually elevate blood lactate levels and it doesnít have an effect on performance, but if you have extreme performance, you get a rise in blood lactate. So, could it be that lactate does not cause fatigue, but fatigue causes lactate? And what is it about the chemistry, the energy chemistry in the muscle, that results in that elevation of lactate? What we find is that the lactate threshold, the threshold of activity that you start seeing rise of lactate in the blood is a function of body temperature.

That if we start people exercising in low body temperature, they go a lot longer before they start showing this increase in lactate. If they start at a high body temperature, lactate comes up very quickly. So, weíre studying essentially what the significance of that is. So, itís clearly a biomarker of fatigue, and if we could use that as a biomarker, we could perhaps improve conditioning protocols. We could design conditioning protocols that didnít cause fatigue so rapidly.

Katie: Well, that circles back to where our conversation started. Iím very excited to continue following that work and also to experiment with this myself just anecdotally as I try to get stronger and lift weights, and with my kids as athletes. Like I said, Iíve followed your work for a while, and itís an absolute honor to get to hear more about it today. A couple of last wrap-up questions. The first being, if there is a book or a number of books that have profoundly impacted your life, and if so, what they are and why?

Craig: Well, I read very widely. So I canít say any one book, but I tend to like to read novels because they tell me about conditions of the world, conditions of life, that are not in my experience. So, it broadens my knowledge of whatís happening in nature and in the world. I like to read books about incredible human performances like Arctic exploration or something that is just, you know, amazing because that I enjoy learning about what the real limits are or arenít for human performance. And then, perhaps, this is not what you might expect to hear. One of the books thatís had a huge impact on my life is my own book. I have a textbook with other authors called ďLife: The Science of Biology.Ē So, weíre now going into our 13th edition. So, why does this have such a big impact on me? It forces me, every few years, to update myself in my field broadly. So, if I hadnít had that book to worry about, I probably wouldíve narrowed, narrowed, narrowed my work and my interests and fallen way behind in understanding other areas of my field, in general.

Katie: That is definitely a new recommendation. Iíll make sure thatís linked as well if I can find it online andÖ

Craig: Iíll always keep up.

Katie: I love that. Where can people follow you and your work if they wanna keep learning more from you or see your research?

Craig: Well, thatís a good question. I donít know. I am not very good at keeping up a website, but we are building a website now for our down research work and itís essentially the Down Syndrome Research Center at Stanford. So, that can be pulled up. And CoolMitt site is going to be posting all of our work. It posts already the work that weíve done. So, you can access the scientific papers, the studies that weíve done through that particular access.

Katie: Iíll make sure thatís linked in the show notes. For you guys listening, wellnessmama.fm. And, perhaps, we can do another round one day with some updates and research as things go along. And then, lastly, any parting advice for the audience today that could be related to anything weíve talked about or entirely unrelated life advice?

Craig: Sure. One bit of advice I give my students is follow your interests. Donít let other people tell you what you should be doing. Follow your interests because itís when you are interested in what youíre doing, youíll do your best work. So then you might ask, ďWhat restrictions should be put on that?Ē And that reminds me advice that I always gave my daughter when she was growing up and she hated it. And this came from the musical, ďHair,Ē this old musical of hippie days. And the quote from the musical was, ďDo whatever you wanna do, be whatever you wanna be, just so long as you donít hurt anybody.Ē

Katie: I love it.

Craig: I thought that was very good advice. And the other advice Iíd give you is sleep well. Sleep is important. There are three pillars to health, diet, exercise, and sleep. And we tend to be pretty good about our diet and pretty religious about our exercise, but weíre always ready to sacrifice sleep when thereís something else we think we should be doing. And thatís not good.

Katie: Well, thatís a perfect place to wrap up. Thank you for sharing your time today and for all the work that youíre doing. This was such a fun conversation, and Iím very grateful to you for being here.

Craig: Thanks. I enjoyed it. And I love talking with you. You are really a very good questioner. You understand what weíre talking about. Thanks.

Katie: Thank you. And thanks, as always, to all of you for listening, sharing your most valuable resources, your time, your energy, and your attention with us today. Weíre both so grateful that you did. And I hope that you will join me again on the next episode of the ďWellnessMama Podcast.Ē

If youíre enjoying these interviews, would you please take two minutes to leave a rating or review on iTunes for me? Doing this helps more people to find the podcast, which means even more moms and families could benefit from the information. I really appreciate your time, and thanks as always for listening.


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