ending-jet-lag circadian biology podcast

A New Product to Significantly Reduce Jet Lag – Interview with Stanford Professor, Jamie Zeitzer

air-travel-jet lag circadian biology

Technology is the cause of most modern health issues, but it can also be a key part of the solution. As a sleep scientist, I’ve been pleased to see that several early iterations of digital wearables have tackled sleep. However, while devices can influence behavior, they do not affect sleep itself. That is, until now.

In this show, I speak with Dr. Jamie Zeitzer, who is an Assistant Professor in the Department of Psychiatry & Behavioral Sciences at Stanford, and also at the VA Aging Clinical Research Center of Stanford. Jamie has over 50 publications related to sleep and circadian biology, and he’s also my primary mentor at Stanford in my own research on eating behavior and alertness. Much of Jamie’s current work aims to better understand human photoreception not involved with vision.

In his research on light and the timing of biological rhythms, he noticed something curious: brief flashes of light have a greater ability to adjust body clock timing than continuous light exposure.

For instance, let’s say you wanted to adjust your body clock to wake up earlier than you typically do in the coming days (a common scenario for those who travel across time zones). In order to make this adjustment, on the morning before you leave, you could wake up at 4:00am, turn on the room light and go back to sleep. This technique can adjust your clock by about 35 minutes, which means that if you typically awake at 7:30am, you could naturally wake up tomorrow around 6:55am (and the timing of all your other body processes would shift accordingly, too).

On the other hand, if you were to get 2 millisecond flash of light every 10 seconds starting at 4:00am (instead of laying in a room with the light on) – something Jamie’s research has demonstrated you can sleep through –  you could advance your clock by about 120 minutes – over 3x more than continuous light.

What does this mean? Well, one thing it means is that it would be a heck of a lot easier to be up and ready before your typical natural wake time in those moments when you have an early start to your day (e.g., early plane flight). The ability to affect your body timing in this manner is more than a mere luxury; it’s also about personal safety and performance. None of us want to be on the road with sleepy drivers, and likewise, no one wants to have to perform at a time when you’re too sleepy to keep your eyes open. This is pretty exciting technology!


On SoundcloudiTunes, Google PlayStitcher, and YouTube

No More Jet Lag?

The benefits of a technology like this are immediately obvious. Who needs to adjust their clock regularly? Well, the most obvious group of people are those who travel across time zones regularly. Being able to implement this technique would significantly alleviate the negative effects of jet lag.

Personally, it’s not uncommon for me to have to travel from San Francisco to New York for work meetings. On more than one occasion, I’ve had to present at 8am NYC time the day after I arrived. In order to be dressed and ready, and to travel to where I’m headed for that day, I would need to wake up 90 minutes prior, which equates to having to get up 4 hours earlier than my normal wake time. These are tough conditions to perform under, and yet, many people do it, some week after week.

LumosTechLumosTech sleep mask

Thankfully, a group of people, including Stanford graduate students, have developed a sleep mask with LED lights to help travelers implement Jamie’s light technology. The company is called LumosTech, and they are already taking orders that they aim to fulfill early in 2017. Please note, neither Jamie or myself have any commercial interest in the company, but both of us are excited to see the technology come to market so that it can help people. Essentially, this wearable device and its accompanying app will help you adjust to any new time zone that you’re traveling to (and back) much faster than if you were just to let natural forces like light help you synchronize to your new time zone once you arrive. 

Other groups of people can benefit, too. Teenagers naturally have a delay in the timing of their circadian rhythms, which makes them want to go to bed later. They still need more sleep than adults, however, because they’re still growing. This natural phenomenon is exacerbated by screen usage before bed. In fact, new research from Kings College London, published in JAMA Pediatrics, reviewed data from 125,000 children aged 6-19 and found that engaging with a device within 90 minutes of going to sleep was associated with an increased likelihood of inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. There’s a lot of disturbing things that result from young kids not getting enough sleep, including showing clear symptoms of ADHD. A device like LumosTech could help counteract the light at night from screens to keep circadian rhythm timing where you want it. And as we all know, we will have to counteract screen usage rather than prevent it, so that’s another reason I’m optimistic about this device.

Color Tint


In  the meantime – and since this feature recently came out from Apple in their latest update of iOS 10 – I’ll take this opportunity to mention that you can now go beyond “Night Shift” mode to filter blue light from your Apple device before bed (hat tip to Kevin Cottrell of Fitfluential for point this out to me). This is important because, again, light at night is going to shift your rhythm to a later time, so modifying your light exposure at night is another opportunity to affect clock timing. Color Tint allows you to create a dark mode for your phone, and triggering it is easy. Here’s how to set it up:

Step 1: Set the color tint

Settings app → General → Accessibility → Display Accommodations → Enable ‘Color Filters’ → slide Hue and Intensity to the max level.

Step 2: Set the trigger

Settings app → General → Accessibility → scroll to the bottom of the page → select “Color Filters” on a triple-click of the home button to turn on and off.

So, before the LumosTech mask comes out – and even when it does – use this setting if you’re using your phone 90 minutes before bed. That will help reduce the impact of the light emitted from the device on your circadian rhythms.



Jamie Zeitzer: You could basically have an exposure to these light flashes before you leave and then if you’re taking a night flight you could have a wearable device and wear it on the plane receiving these light flashes and it’s going to adapt your system such that when you land in Italy your circadian system is already adapted to Italy. Your brain is there and your body just landed.

Speaker 1:

Human OS, learn, master, achieve.
Dan Pardi: Jame Zeitzer welcome to Human OS radio thanks for joining us.
Jamie Zeitzer: Thank you for having me.
Dan Pardi: Obviously Jamie and I know each other quite well. Jamie is one of my mentors in my PhD and let’s be honest, am I one of your best students?
Jamie Zeitzer: I have to say, the best graduate student I’ve ever had.
Dan Pardi: Over 50?

Jamie Zeitzer:

Only graduate student, but that’s a different issue but amongst them you are both the best and worst is quite impressive.
Dan Pardi: Let’s talk a little bit about your background and how you kind of got into sciences overall and what you pursued. Then we can talk a little bit more about what you do today and some other current research.
Jamie Zeitzer:


Sure, well I started in college, I went to Vassar which is a small liberal arts college in New York. When I got there I thought, I was either going to be a biology major, an english major, or a major in medieval studies. I ended up doing a biology major figuring that later that would perhaps better pay the bills but I took as few sciences as possible at that point. Mainly just took courses in the humanities, that was good and it was a lot of fun. I enjoyed that very much.
Dan Pardi: You could’ve been a writer for Game of Thrones right now, you realize that?
Jamie Zeitzer:


I know it was a path but I have to say, my writing skills, I have the uncanny ability to write incredibility long indecipherable sentences that are grammatically correct. I’m not sure how that translates to television.
Dan Pardi: Perhaps this is the better path to pursue then.
Jamie Zeitzer:[00:02:30]


I think it might have been. I have to say that even in the humanities I was attracted to courses in which we didn’t discuss what the authors meant, we discussed what the authors actually wrote. That was a plus for me. Then I went to Harvard for graduate school. There I didn’t know exactly what I wanted to go I got a PhD in neurobiology, it was a large program lots of different opportunities. I knew I wanted to go something more on the behavioral side of things and the first lab I went into of course it was a molecular biology lab and I didn’t particularly like the approach. The lab was fantastic and the people were amazing but doing molecular biology was not my thing. The lab was that of Steven Reppert and he does amongst other things a lot of circadian biology work. That got me interested in circadian biology which I had never heard of prior to that. Then I took a class which was for grad students and advanced undergraduates and that was on circadian rhythms. That was co-taught and one of the professors was Chuck Czeisler who ended up being my PhD advisor. One of my classmates ended up becoming my wife. It was a successful class I have to say.
Dan Pardi: I didn’t know that little fact.
Jamie Zeitzer: Yes, I was not her TA I was in the class together.
Dan Pardi: Okay so it was all…
Jamie Zeitzer:


It was all above board. Yeah and then I joined Chuck’s lab and several years later I ended up his PhD in neurobiology focusing on circadian rhythms. I followed my wife to the Los Angeles area where she was in medical school at the time and did a two year stunt in a neurology lab looking at how the brain changes with epilepsy and sleep. Then I spent five years up at Stanford as a post-doc working on a primate model of sleep and then I’ve started my own lab and it’s been fun.

Dan Pardi:

Did you get the chance to work with Robert Sapolsky working with the primates during your post-grad work?
Jamie Zeitzer:


I did not actually. I know Robert I’ve been on some committees with him. I have an incredible amount of respect for him I think he’s an amazing person and a fantastic researcher and professor. One of the best lecturers I’ve heard on campus. IN fact, I’m kind of jealous that he’s so supremely talented. We didn’t work together on these I was mainly developing a model that was more laboratory based, monitoring behaviors that can be associated with sleep. We were doing very non-invasive kinds of work, similar to what Robert does in terms of basically just acquiring blood samples, CSF samples, things like that. No terminal experiments in the monkeys. Unfortunately I didn’t have a chance to work directly with him on this project which is unfortunate but he’s done some pretty amazing stuff with the primates in Africa in looking at the social structures and things like that.
Dan Pardi:


I’ve actually brought him up on the show before with David Samson. Calling David Samson the new generation of Robert Sapolsky just because he’ll go and live with primates for a while and study their behaviors which I definitely admire people that can put themselves into the environment of their subjects so thoroughly.
Jamie Zeitzer: Oh yes you’ve got to understand what they are living in.
Dan Pardi:


Totally, so over the course of that you had studied circadian biology which Chuck Czeisler at Harvard, and for anybody who is not aware of Dr. Czeisler he is one of the luminaries of circadian biology in the field. He’s definitely done a ton to advance the research in that space so it’s a great lineage that you’ve been apart of there. Then you continued to work with mostly circadian biology work at Stanford in your post-grad and continue today.
Jamie Zeitzer:


Yeah it was a bit peripatetic, I did some stuff in sleep, some stuff in circadian, working with humans which I’m back to working with now. I started working with humans and I took side trips in mice, rats, monkeys, cats, hamsters, fish. I’m kind of an equal opportunity researcher. Mainly using different species to answer specific questions when appropriate. That’s why we developed the monkey model was because we were particularly looking at hyper-kreton which is a peptide that’s found in the brain but not in the blood. We were working with squirrel monkeys which are very nice monkeys. They are from South America and they are one of the few mammalian species besides humans that consolidate sleep into a single nighttime period, at least have the capacity to do so. That made us looking at them as a model was very interesting especially because we think hyper-kretin we think is involved in that consolidation process.

Dan Pardi:

Describe what consolidation means for somebody who’s unfamiliar with that term.
Jamie Zeitzer: Sure so basically if you look at most mammals you might call them nocturnal or diurnal, some are even called crepuscular. Which means basically having maximum amount of activity during dawn and dusk.
Dan Pardi: Coyotes.
Jamie Zeitzer:




Yeah or even the house cat. House cats basically can be active dawn and dusk mainly but the rest of the day it’s kind of random whether or not they are awake or asleep. If you look out in the wild a lot of predators have that kind of activity figuring that they can optimize finding prey at the dawn and dusk transitions. When you look at non-crepuscular species so nocturnal or diurnal you basically find is that they can change the patterns of their sleep and wake. If you look at for example a mouse, a mouse in general is nocturnal but if you provide them with various kinds of stimuli they will change their pattern. There are certain mice where if you reduce the amount of food they have they will actually become much more day active. There are other times where you can introduce stressors and their timing of their wake will become much more consolidated so when they are awake it becomes much more continuous and when they are asleep it becomes much more continuous. There are various environmental pressures that you can apply. Their system is saying, “Well I’m mainly night active or I’m mainly day active but given the right circumstances and the right environmental or internal pressures, I’ll change my pattern”.




This is not really what humans do. Humans are volitional in the sense we can choose to be awake or asleep or at least try to be asleep at different times of day. I mean, we’ve had plenty of people in my laboratory were you pay them a few hundred dollars and they will gladly stay up all night. Our sleep and wake system doesn’t work in the same way in the sense that we have a period during the day time that we’re kind of programmed to be awake for a continuous stretch of time and that we have the capacity to be awake for 16 hours without any sort of environmental stimulation. If you bring someone into a laboratory you don’t tell them what time it is and you don’t give them anything fun to do it’s just boring, no sensory stimulation, nothing like that and their not sleep deprived. If that’s the situation, you’ll find that people will stay up for about 16 hours continuously before spontaneously wanting to do to sleep. When they sleep they will sleep for about eight hours. Again, this is without knowing what time it is. This is unusual in the mammalian world. Again, only humans and some new world or South American species of primates will do this.

Dan Pardi:


Yeah it was interesting a couple years ago that history professor from Virginia Tech Roger Ekirch was looking at historical texts and he kept noticing this idea of a first and second sleep or that’s what he called it. Period where they go to bed, they wake up in the middle of the night, they are up for a few hours during that time they tell stories, have sex, things like that and then they go back to bed for a second extended period. What people postulated on that probably falsely is that that is the natural human way of sleeping. The way I interpret it is that it was another way that humans can sleep that is probably natural as well and probably related to the seasons. If it’s longer dark periods then you might fall asleep earlier and have that bifurcated sleep. What are your thoughts on that idea?
Jamie Zeitzer:



I agree I thought Dr. Ekirch was a very interesting set of ideas looking at that. I agree with you that it’s more related to the capacity of the human system to be flexible than it is related to kind of a pre-programmed default system. I don’t know what the default is but I think it is another possibility. I agree that it’s mainly due to if you were living in the middle ages and you had access to fire , you weren’t wealthy, you didn’t have a lot of candles. When the sun goes down you’re going to go to sleep. Even if you look at etymology, you look at the word midnight. Midnight is the middle of the night. It’s not the time you go to sleep, it’s the time that was in the middle of everything. When you look at that, we don’t have the capacity to sleep from, especially the further away from the Northern Hemisphere where it can get quite cold at night, we don’t have the capacity to sleep for 12 hours or from sun down to sun up, we just don’t have that much sleep in us. If that’s going to be the case where you’re going try to go to sleep early, you’re going to have to wake up in the middle of the night to do something.


Again, it makes more sense to kind of wake up in the middle of the night and have an extended period of wakefulness in the middle of the night to kind of bifurcate that sleep as you as opposed to trying to sleep for 10 or 12 hours and just waking up and having several minutes of sleep periodically
Dan Pardi:



We see naps are another way that sleep is bifurcated certainly in many populations throughout the world. Interesting speaking with Dr. Jerry Siegel at UCLA one of my first interview for Human OS he was talking about the three hunter gather groups that he looked at in Bolivia and Africa. Saying that he really didn’t notice much sleep time at all. Less than 2% of the population slept even though they didn’t sleep very long, different times of day. Then talking with David Samson he reported to me that in a soon to be published paper of hunter-gathers in a different part of Africa that most of them did sleep. Again, it shows that flexibility verses saying it’s natural to do it one way and not the other.
Jamie Zeitzer:



Right and I think that the careful thing here is this word natural that people throw around when referring to sleep patterns and the question is are there costs or benefits with sleeping in particular ways when we obviously have the capacity to sleep in various ways. If you’re only sleeping say four hours at night and then having multiple naps during the day or if you’re bifurcating sleep at night, or if you’re having eight hours of sleep at night. What are the costs and benefits of each of these things knowing that we have the capacity to do it but what are the consequences of doing that. That’s something that I think we’re struggling with in trying to understand better. It’s in general the consequences of sleep is something that we don’t describe well to the public.


Even when we describe it it’s somewhat problematic because for the most part it ends up being a time use issue. Where it’s not that people don’t want to sleep and feel well rested, and that they don’t understand that it might contribute to their health in the long term it’s that they make decisions saying, “Well I understand that but I’d like to spend time with my family or friends or I’ve got work to do”. Then the question is when you’re substituting sleep for another activity, what are the costs and benefits of doing that.
Dan Pardi:


Yeah and I remember when David Dinges came from the University of Pennsylvania and talked and said that even just kind of repeating what you just said. Is that people will always defend their own personal times. As work times extend and as driving times extend people are still going to take a couple hour period to even do things that you might not consider super valuable, just sit on the couch, watch television. You need that personal time and when you have less of it you need to make it up somewhere.
Jamie Zeitzer:




That’s right and this is what I think we need to get a better understanding of is how that time is used and when is it better or worse. For example, is it better to spend that extra hour getting work done at night or would it be more productive to get that hour of sleep and increase the productivity in your next day because you’re not as tired.


Dan Pardi:



It’s funny because I talk about the consequences of making that choice regularly to skip sleep and to do work. I call this modern day shift work where people come home, they spend time with family, family goes to bed and then they spend another couple of hours doing work. One of the reasons why is you’re probably getting bombarded by e-mails and distractions less during that period so if you have to do some work that required deeper thinking it’s easier to get that sort of work done and there might just not be enough time to do it the next day. There are real consequences to it, but I even personally choose to do that on occasion when the situation calls for it. I need to basically make the sacrifice but I know what sacrifice I’m making.
Jamie Zeitzer:


Right and these are important kinds of decisions that people make and I think it’s our jobs as scientists and ones that we don’t necessarily do very well all the time is to let people makes those as informed decisions. You make this as an informed decision knowing the field quite well. I think a lot of individuals make it and don’t understand what the consequences are of their decisions both in the short or long term.
Dan Pardi: Let’s say I go to bed three or four hours later than I usually do, but if I sleep as long as I usually do and that sleep is going to be just as good as, I got eight hours or I got seven hours, whatever I usually get. Let’s say you usually sleep from midnight to eight but you went to be from three to 11, same amount of time is that sleep as good as it was if you were sleeping during that regular phase where you usually sleep?
Jamie Zeitzer:



It’s a good question. We don’t know the answer. We know that the sleep is different but we don’t know if it’s as good because we don’t know how to evaluate sleep quality. People use the term quite loosely both in public forum and in scientific literature, it’s a very poorly defined word. We’ve been doing a lot of work on this issue of sleep quality and I’ve thinking about this quite a bit and I think the only kind of sleep quality that we have a handle on is sleep quality from the subjective perspective. Basically if you wake up in the morning and I say, “Dan how’d you sleep?” You’ll have an answer and it can be good or bad but regardless of what happened during your sleep that’s how you feel about your sleep. That’s the only aspect of sleep quality in the moment that we can really understand.
[00:16:00] We actually just did a large analysis of 1500 people where their sleep was recorded. This was using polysomnography which is kind of all these electrode on your head and asked all these questionnaires and poked and probed and then associated that information with how they claim their sleep was from a subjective personal perspective. We found out is that all the stuff that we’re recording, the signal might be there but it’s not something that we standardily can derive from those data. Basically all the stuff that will happen in the sleep lab tells us very very little about sleep from a subjective or personal perspective.
Dan Pardi: That’s so interesting.
Jamie Zeitzer:


I really think that going forward, that’s the first frontier to capture. If we can identify what makes someone say if they had a good or a bad night, once we identify what that is then we can proceed and try to change that.
Dan Pardi: Do you think that has to do with the resolution of current sleep measurement? So polysomnography in a sleep lab, if you had greater resolution with something like MRI or something? Do you think that that signal is there but we are just above it right now?
Jamie Zeitzer:



I think that the signal might be there, I think the resolution is good. I think that much of it rests of historical accidents I would say. When we look at sleep we tend to group it into 20 or 30 seconds at a time. Then say, what happened during this 20 or 30 seconds. Then we can stage it. The typical way to stage it is to say you’re in non-REM or REM sleep. REM being rapid eye movement sleep where your body is basically paralyzed and you’re brain, the activity is very similar to what occurs during wake. Then in non-REM, it’s a time when you have a lot of synchrony between groups of neurons. Then non-REM can be divided into different stages, one, two, and three and there are different kind of characteristics in each of those stages. THere’s no 30 second time constant in the brain. This 30 seconds was used because it’s what looked good on a piece of paper when this stuff was being recorded, it was easy to understand. I’m not sure if that’s the appropriate way to describe or quantity what’s going on in sleep.



here are various other techniques and we actually did something called power spectrum analysis where you basically look at where the oscillations in the brain, at the speed of these oscillations. When you look at it that way, it actually much to our surprise and our disappoint really didn’t contribute either but I think that there are other signals in there that we might be able to detect. I think it’s important going forward. Then similarly when you look at sleep functions, if you look for example how good is sleep working with consolidating memory or how good is sleep working to restore energy in the brain or how good is sleep working to clear cellular debris out of the brain. All of these things are functions of sleep that I would say are equally if not more so important than the personal subjective quality of sleep and we have no idea how to capture that part and to say whether or not these are happening more effectively or less effectively in people.
Dan Pardi: Could you give us a general description of circadian biology and circadian rhythms?
Jamie Zeitzer:



Sure so circadian rhythms are near 24 hours rhythms. These are ubiquitous in nature. Every living organism that has been studied on the planet earth has a circadian rhythm. This goes from humans all the way down to single cell organisms that don’t have a nucleus. Everything has a circadian rhythm so it’s an absolutely fundamental part of evolution and life. Again they are these 24 hour rhythms, it’s an internal clock and this internal clock can do several things. One of the things is that is coordinates different cellular events or different physiological events, different things going on in the body depending on how large an organism you are in time. It makes sure things happen at the same time. It also synchronizes what’s happening with internal time to external time. At least in modern days what it means is if you travel and all of a sudden your body ends up in a new time zone and you start going on a different sleep wake schedule, this internal clock will synchronize with the external light dark cycle that you’re on.



The other thing that it does that’s really of critical importance is that because it’s able to keep track of time, it allows for predictive physiology. It allows the body to anticipate the things that are going to occur and then respond prior to their occurrence. For example, one of the things that is the timing of which is strongly controlled by a circadian clock is the timing of cortisol production. Cortisol production does lots of things but one of the main things that it does is it frees up glucose for you to use. It actually starts to rise, cortisol has kind of a sinusoidal rhythm and it’s lowest during the night and starts to rise a couple of hours before your anticipated wake time. Basically what it does is it’s anticipating when you’re going to wake up and it starts to free up glucose in anticipation of that event. You need lots of glucose when you wake up to control blood pressure amongst other things. Instead of responding to waking up it’s predicting that you’re going to wake up. This is an example of this predictable physiology.
[00:21:00][00:21:30] There are some classical studies in bees showing that they can basically know when different flowers are going to be open and ready to have their pollen take at different times of day. The bees know what time of day it is so they can get there just as these flowers are opening as opposed to waiting for the flower to open, sensing the flower is open, and then heading to the flower. It’s a very important thing. One of the other things that it does that’s kind of critical is in this timing of things it allows for much more precise control of energy. Basically you don’t waste energy by making things that are unnecessary at particular times of day. For example, if you’re suppose to be awake during the day and asleep at night and there are various proteins that might be very useful for being active and awake during the day, no need to waste energy and make them at night
Dan Pardi: Right.
Jamie Zeitzer:


Again, I think one of the reasons it’s so ubiquitous in nature is it has to do with that energetic aspect. It can really help save a considerable amount of energy.
Dan Pardi: Okay so to rephrase, the internal circadian system is coordinating with external timing and then part of that process is to anticipate a certain type of physiological activity at different times of day and behaviors and then kind of prepare the body to be able to act accordingly to whatever the needs are of that time of day.
Cool so what are the signals that our circadian systems responds most strongly too?

Jamie Zeitzer:

The circadian system remains synchronized with the outside world basically responds to light. There are some other signals but they are much much less potent in terms of being like a 100 fold less important than light. Light exposure is anything you can see. Anything you can see can impact your circadian clock. For the most part we get normal kinds of light exposure. Room lighting, outdoor lighting, this is called integrated and determines with some other internal factors the timing of your clock.

Dan Pardi:

Light comes into the eye, it goes back to master clock. What is that?
Jamie Zeitzer:


Light comes into the eyes and interacts with both the standard rods and cons that you use for vision for seeing images as well as a special group of cells in the back of the eye that we actually didn’t know about until about 15 years ago. These specialized cells also can detect the light. The combination of the rods and cons and these specialized cells which are called intrinsically photosensitive retinal ganglion cells. These kind of send information to the brain, to lots of different areas of the brain including the circadian clock. They also send this information to other areas of the brain that control things like hormone production, pupil size, how alert you’re feeling. There are other functions of this light signal but when it sends it back to the circadian clock, the circadian clock is located in the nucleus called the suprachiasmatic nucleus. It’s a very small group of neurons there are about 10000 neurons on both sides of the brain.


In this small group of neurons this is where the circadian clock is located. Each one of these neurons can act as a clock independently but what happens is that these 20000 neurons in total all fire synchronously together or are highly coordinated and have kind of a singular clock output. That’s where all of this action is occurring, the SCN or the suprachiasmatic nucleus is in the hypothalamus of the brain and is located as the name would indicate above the optic chiasm which is basically where the nerve fibers from the retina going to the thalamus cross and it’s located just above that crossing or above the chiasmatic chiasm.
Dan Pardi: These 20000 neurons are firing synchronously and what is the output of the circadian clock to affect physiology throughout our body?
Jamie Zeitzer:



They have a rhythmic firing output. They fire high at some times of the day and low at other times of the day. This nucleus basically innervates lots of other nuclei which then transmits the information to basically all parts of the brain and body. That’s some of which we understand, some of which we don’t. Some of the pathways are well worked out, others not so much. If you look at most aspects of brain function or body function there’s going to be an aspect of circadian rhythms. When you look at most body tissue, if you look at lung tissue or liver tissue or immune cells or skin cells, these all have clocks in them. They are not circadian clocks, but they do run at 24 hours. They are synchronized to each other and with the rest of the body through signals from the suprachiasmatic nucleus.
Dan Pardi: When you said they are not circadian clocks does mean that they are not controlling the circadian rhythm but they are basically in control by the circadian system?
Jamie Zeitzer: Right, basically they don’t have the ability to be autonomous and synchronize to the outside world without the suprachiasmatic nucleus.

Dan Pardi:


Okay so let’s talk about a real world example then, you brought it up a little bit earlier, jet lag. This is a really common example to help people understand how circadian rhythm’s work. One I often share is let’s say you and I hopped on a flight, we went to Italy. As soon as we landed our biology would still be synchronized with San Francisco time because that’s where we are but over the course of several days as our bodies were exposed to the different light signals and behavioral rhythms then they timing of our own internal clock would then shift. That is again mostly probably through taking in light. How long can that take? What is it about nine time zones that a person is going across to go from here to mid Europe?
Jamie Zeitzer:


Something like that. In general without doing much it takes about a day per time zone. The flight to Italy sounds quite nice, well I should say the flight doesn’t sound nice, being in Italy sounds much nicer. Yeah that would take about nine days to adjust. There are ways to accelerate that adjustment and basically it’s getting light in the new time zone as rapidly as possible. That’s the general rule of thumb but there are fancier ways of getting light and avoiding light at particular times in order to accelerate that process.
Dan Pardi: Really controlling your light even though it feels counter to what your body is used to, it helps you adjust faster.
Jamie Zeitzer: It does.
Dan Pardi: Under doing everything right, it still takes about a day per time zone? That’s still nine days or so to full adjust?

Jamie Zeitzer:

Again if you avoid light at particular times and get light at other times you can probably do it in half that amount of time.
Dan Pardi: Are there ways to accelerate the shifting of time zone even faster?
Jamie Zeitzer:[00:28:00]


Sure so it’s something that is pervasive in modern society and it’s not just in jet lag, when thinking about traveling long distances but it’s also in what you mentioned before which is on some nights you decide to stay up later. When thinking about circadian system and again there are lots of different areas the circadian system influences but the one of the easiest to understand I think is how it influences sleep. The circadian system works in concert with another system which is referred to as a homeostatic system. A homeostatic system for sleep, we don’t know where it is or what it is but what we do know is it’s intuitive in the sense that the longer you’ve been awake the more tired you get. The more sleep you get the less tired you become. It’s kind of an appetitive process. This system interacts with the circadian system to create the sleep-wake patterns that we observe. The circadian system has a very strong signal that starts in the afternoon and builds up throughout the evening to promote wakefulness. You can think about it as when you wake up in the morning as the day goes along you build up more and more pressure to go to sleep because you’ve been awake longer and longer. Then in about the middle of the afternoon when you’ve built up enough pressure that you could go to sleep, the circadian system says, “No, no, no let’s stay awake”.





The circadian system building strength to counter the building strength of the homeostatic pressure for sleep, allowing you to stay awake for 16 hours. You have a very strong drive to stay awake in those hours just prior to normally going to sleep. Anyway, that’s kind of background for this. The reason I mentioned that is because when you decide on a given night to stay up later than you might normally, by exposing yourself to light when you’re doing your work you’ve actually dragged your circadian system to a later time point. Then when on the next night when you want to go to sleep, you’re now trying to go to sleep when your circadian system is telling you to be awake.
Dan Pardi: Right.
Jamie Zeitzer:


Then it becomes difficult to go back to your old schedule. People have described this as kind of a social jet lag which usually they are describing more on weekday verses weekend shifts but it also happens within the week in a lot of working people. One can argue that this is not good but the point is that this is modern society and it’s going to be hard to turn back the clock on this. Getting then to your question then about how can we accelerate this adjustment, we’re talking about light exposure and how that adjusts circadian timing. Light exposure can adjust circadian timing in a way that is dependent on when the light is given. In general light given at the beginning of the night just prior to when you go to sleep or in those first few hours after when you’d normally be asleep delays the circadian rhythm. What that means is that things that would occur today after begin delayed are going to occur later tomorrow.
[00:30:30] If you normally go to sleep at 11 and you experience light that will delay your system, your system is then want to go to sleep at let’s say, 12 the next day.
Dan Pardi:


So you stay up late one night doing work, because nobody works in the dark or most people don’t then you are getting light exposure and that light exposure at a time when you usually are not exposed to light gives your circadian clock more of a day time signal and the body is trying to adjust to it. It shifts the clock, that means your alertness rhythms are off the next day. They start later and they end later, that throws you off. If you had to do this and you didn’t want your clock to shift, what would you do at night when you’re working and then is there anything else that you could do to minimize shifting even if you have to stay up late?
Jamie Zeitzer:


Sure there are kind of two strategies that are generally successful in this way and they both revolve around light exposure. The first is to understand the light that you are getting at night is viewed by the circadian clock in a relative way. It’s saying, how bright is this compared to the light that you’ve gotten during the day time. If you go out and get a lot of light during the day it will minimize the impact of that night at night. The other way to do it is to play with the spectral or the color content of the light that you’re getting at night. This is proved very popular amongst many people at least in the Bay Area where they use a program like Aflux or I believe Apple is now integrated this into their current operating system.
Dan Pardi: Night-shift.

Jamie Zeitzer:

Yeah, where they can basically change the spectral output of your device to kind of minimize the short of the blue wavelengths that are coming out of it. The blue wavelengths are interesting because they don’t contribute very much to high acuity vision or that precision vision that you need for reading. They do have a very strong effect on the circadian clock. By dropping out those wavelengths you can still have good vision to see things and you minimize the impact of that light on your circadian rhythms.

Dan Pardi:

I think a lot of people are aware of that. You can minimize the impact of light at night by pulling out the blue light and you can do that by filtering it either a program like f.lux or the program light night-shift or you can wear blue filtering lens.
Jamie Zeitzer: Sure.
Dan Pardi: It doesn’t obviate the entire effect because there are other receptors in the eye that are also responding to light intensity so you also want to keep the light basically as dim as possible, is that right as well?
Jamie Zeitzer:



I think so. In general, the light isn’t particularly bright from a screen, it looks bright especially in a room which is dark. A light from a computer screen can look quite intense, in actuality, it’s not that bright. I usually have much more caution for content and activity rather than light. What are you using your electronics for late at night, yes the light is going to have an impact but also if you’re up and you’re doing things that are going to increase your stress level, make you anxious, make you depressed, these are going to impact your ability to then fall asleep. It’s an important consideration in thinking about what you do in the evening prior to bedtime and how that’s going to impact your ability to sleep. This is a bit independent of the circadian system but will eventually impact it. There’s no blanket kind of statement that one can make because different people response in different ways.




For example, I don’t check e-mail in the evening because generally the only e-mails that I get in the evening are ones that are going to be stressful and say things like, “Now that you’re home and can’t do anything about this here’s this e-mail and tomorrow morning you can deal with it”. I don’t have to look at that e-mail at eight o’clock at night, I can look at it at seven o’clock in the morning and it won’t disrupt my sleep. For other people though, checking their e-mail is very relaxing because then they know, “Okay, I’ve done everything that I needed to do today and my table is clear” Then they can go to sleep much better. It very much depends on what you’re doing, the content of what you’re doing, and how that’s going to impact your sleep. Sometimes the light that you’re getting even if it’s dim is going to impact your circadian system. It has a direct effect as well of learning your brain, making it more difficult to fall asleep but that might be off set by the comfort that you’re receiving from checking on your e-mail. It’s not the best strategy but it’s one that many people do utilize.
Dan Pardi:


I think that’s a really important point is that you can think about the inputs but people are individuals, they perceive things differently, you gave a great example. You like to say, “Hey I’m going to shut it off now because in the morning is when I can deal about it so I’ll just hit the ground running”. Other people like to feel on top of what’s there and that’s stress relieving so it’s how you perceive things. Cool, so going back to the circadian system, you said there was two strategies. One which is looking at light at night and then is there anything else you can do to also prevent the shifting if you’re getting again, light at night?
Jamie Zeitzer:



Sure so the other thing to do is to compensate that light with other light, strategically place lighting. As I mentioned light early in the night will delay, light in the morning prior to waking up and when you wake up will cause an advance of cause things to happen earlier. For example if you’re travelling from California to New York, that early morning light in New York is going to push things earlier which is what you want to do when you’re travelling from west to east. Now the inconvenient part about that is the brain and circadian clock is most sensitive to light when you’re normally asleep. One strategy that people have used is to change your sleep wake timing and for example you get up early and you get exposed to light when you need the light but that kind of truncates sleep and it’s a difficult thing to do. You can do it and people do but it isn’t the easiest strategy. Whenever you’re asking people to change their sleep patterns even if it has direct benefits it’s often problematic in getting to do this consistently.
[00:36:30] We’ve been working on something which is a bit of an alternative strategy which is giving light to people while they are asleep and this has been something that people have played around with since the early 90’s. Dan [inaudible 00:36:26] lab did several studies looking at his, he’s a professor down in San Diego and did some very interesting things. It never really took off because I think there’s a lot of concern that if you’re applying continuous light for several hours while people are sleeping, one is it going to wake them up and even if it doesn’t wake them up, everyone wakes up spontaneously multiple times a night and if you were to wake up spontaneously and all of a sudden you’ve got this incredibly bright light shining down on your eyes, that might not be the most conducive thing to sleep.



We’ve been doing a series of experiments for the past eight or nine years where we are looking at very brief light flashes and the capacity of these light flashes to induce changes in circadian timing. There are about the length of a camera flash so it’s about two milliseconds in length and we can give various kinds of sequences of these flashes. For a variety of reasons, none of which we are totally sure of but I think the best bet is what’s happening is, when you get a light flash and then say you wait 10 seconds, 20 seconds, until the next light flash, these IPRGC’s these special cells in the retina that project the circadian clock have a very unusual physiology and when you hit them with a light flash and then take the light away, they continue to respond as if the light were still there. So at least from the perspective of these cells, we’re giving continuous light exposure but in actuality it’s just a very brief flash of light happening every 10 seconds or so. What we found is that not only can we do this during sleep without it interfering with people’s sleep but it actually is much more potent, it’s a much strong stimulus then continuous light.




We can talk about the various reasons why we think that it’s stronger but it’s two or three folds stronger than continuous light and you can give it during sleep when people’s circadian systems are most sensitive. The idea here is that you would be able to for example, you’re taking that nice trip to Italy, you could basically have an exposure to these light flashes before you leave and then if you’re taking a night flight you could have a wearable device and wear it on the plane receiving these light flashes and it’s going to adapt your system such that when you land in Italy your circadian system is already adapted to Italy. Your brain is there and your body just landed. This is nice and I think this is something which is going to be very important going forward in terms of things that are convenient things for businesses, for travelers. Also convenient and useful for athletes who are doing a lot of flights and travel around the country and around the world.


Also it will have a much greater impact on the sleep regulation that we spoke of earlier where people have much more random sleep schedules and they can make their sleep worse by going to sleep later on one night and then trying to go to sleep earlier the next night. This device can basically compensate by if you stay up late but you want to go to sleep regularly the next night it can provide the off setting light while you’re sleeping. Before you wake up it would give you light and this would off set the light that you received by staying up late that night.
Dan Pardi: Without causing you to truncate your sleep and get five hours verses …
Jamie Zeitzer: Exactly, you don’t have to change your sleep pattern at all this would just occur during sleep without impacting your sleep.
Dan Pardi:


Let’s do a crystal clear scenario. I’ll give you a example of something that I’ve experienced pretty regularly. I’m going to New York, I’m going to give a presentation at a company or a VC fund and I’m presenting at 8:00am. New York, three hours later, that’s different time. I’m actually having to present and get up at a time where physiologically I’m most sleepy across the day. Being in San Francisco how would I use this technology to then help myself feel more alert when I arrive in New York. I have to present at 8:00am which is 5:00am my time.
Jamie Zeitzer: Sure for example let’s just say you’re going to fly out on Thursday morning, arrive Thursday afternoon and then give that presentation Friday morning. I’m reasonable?
Dan Pardi: Yup.

Jamie Zeitzer:

On Wednesday overnight you would get exposed to light flashes that would help you basically shift your circadian system from California to New York.
Dan Pardi: Starting at what time would I start to get the flashes?
Jamie Zeitzer: About two hours before your normal wake time.
Dan Pardi: Okay, so not three, even though that’s the time zone, you want to do it gradually?
Jamie Zeitzer: Well it’s not that it’s that we can get basically a very large change by just doing two hours prior to you waking up.
Dan Pardi: So I usually wake up at seven?

Jamie Zeitzer:

Right so between five and seven on Wednesday you’d get the light flashes. Your brain is going to start then shifting to New York time at that point. Then Thursday night you’re probably going to have to get up early to get to that airport and it’s going to be easy to do that because your brain is already in New York or pretty close to New York at that point.
Dan Pardi: Yeah.
Jamie Zeitzer: Then you’re going to get on the plane. Your plane might be leaving SFO at 8:00am so you’ve got to get there at six and you’re waking up at five but five o’clock already that’s okay because in your brain it’s not five, in your brain it’s eight.

Dan Pardi:

Have you looked at how disruptive the light flashes are compared to continuous light?
Jamie Zeitzer:[00:42:00] We haven’t compared continuous light during sleep, we have searched quite a lot to whether the light flashes are disruptive and I have to say they can be disruptive. Some people are very sensitive to external light in any sort of light they receive is going to be disruptive to their sleep. This is definitely the minority of people. In all of the people that we’ve tested in the laboratory and in the real world, in general we have fairly high acceptance. We actually just completed a trial in teenagers where what we are trying to do with them is enable them to go to sleep at an earlier time so we give them this light stimulation late in the night prior to waking up to move their system to an early time so that way when clock time in California is one o’clock, their brains are already going to be ready for sleep. Their brains are going to be thinking it’s already three or four o’clock in the morning.

Dan Pardi:

That’s really exciting to me. Teenagers undergo what the call delayed sleep phase syndrome so they want to stay up later and wake up later. Because they are still growing they still need a lot of sleep, nine hours in bed, schools start early. You have this condition where they have more alertness later in the night, they have to get up for school early in the morning, because of the natural amount of sleep that they need a lot of them are chronically sleep deprived.
Jamie Zeitzer:



That’s right so we’ve been able to basically get them an extra 40 minutes of sleep per night using this. When we started this I have to say I went in a bit naively thinking that they actually wanted to go to sleep earlier. We had to convince then that going to sleep earlier was actually an okay thing to to. The first thing we did was basically just piss them off because we just gave them a system that made them get tired earlier but not go to sleep earlier. Then we worked with them to try to convince them that it was actually okay to go to sleep earlier. Now we’re getting fairly consistently an extra 40 minutes of sleep and this is a system that we’re constantly optimizing. I was a bit disappointed that it was only 40. I was hoping that they would get closer to two hours but hopefully in the next iteration we’ll get even more from that.
Dan Pardi: So it sounds like pairing this sort of technology with some education is better than the technology by itself.
Jamie Zeitzer:




In teenagers definitely so because there’s going to be the motivation factor. One of the things that I like about this, at least for the business traveler, or the athlete, or just the general adult who has an erratic sleep schedule is that it’s a passive technology. You don’t have to do anything except tell the system when you want to get up or where you’re going to be traveling to and it will figure out the rest. You don’t change your sleep schedule, it will change it for you. It applies the light during your sleep, you don’t have to change anything about that. One of the things we’ve been doing these kinds of light based therapies for many years and our compliance is always an issue. The standard light therapy for someone who wants to go to sleep at an earlier clock hour would be to get up earlier and to sit in front of a very bright light for a couple of hours. No one wants to do that. This is not something that people really want to do.
There have been some clever adaptations in different populations. I’ve seen both for in older individuals where you want to get them extra light and in kids when you want get specifically time light, they’ve actually flipped large computer screens horizontally and made them into a table that people can play on. Older people can play mahjong on it and it gives them extra light from below so where they are looking at. Or they do it as a table for kids and they can do drawing on the table.
Dan Pardi: Right.

Jamie Zeitzer:

All that light is then coming right up into their eyes and it’s a much more effective strategy then say putting it on a table and say, “You’ve got to look at this light continuously for a couple of hours for it to have an effect”.
Dan Pardi: Right it may be effective but not practical.
Jamie Zeitzer:


That’s right and so that’s why I think something these flashes during sleep is in fact more effective then the continuous light and exceedingly practical. We’ve been working with a group of students who are looking to commercialize it. I don’t have any financial interest in this but I do have personal interest in it because they basically want to turn this into a wearable device and I think that’s one useful form factor. Some people don’t like wearing things on their face so hopefully they will be coming out with a beside lamp form factor as well. It’s very exciting seeing something that has been a long time process in the lab move out into the real world and actually help people.
Dan Pardi:


So I’ve been very interested in quantified self technologies for a while and I’m interested both in the education to help people to understand the real benefits and understand sleep better so they have more motivation to modify their behavior. Then also the wearable technologies that can monitor how you’re sleeping which can help promote the right set of behaviors. To me this technology is the first tech that can really modify your sleep verses your behaviors around sleep and that’s exciting to me.


Jamie Zeitzer:



I have a bias but I agree. Monitoring sleep is very tricky because it gets back to the original question of why are we monitoring sleep? What is the information that we’re getting from that monitoring and can it be used to improve your sleep? Right now most of the devices that I’ve seen that are out there have very generic feedback to the user that’s not very specific. It takes in the user information and says, “You slept seven hours last night, try for more”. Some are more environmentally aware of saying they’ve got light sensors saying, “lights coming in perhaps this is disturbing your sleep”. But most of them don’t integrate the component of asking the person what they felt their sleep was like.
[00:47:30] Again as you know, there is a wide variety of how much sleep people need and so saying seven hours is sufficient or insufficient is not very telling. In fact when we looked at this large cohort we saw that the total amount of sleep time had almost no impact on how people say the sleep quality. That’s at a group level. It’s basically saying sleeping five hours doesn’t have any inherent meaning. If you normally sleep six hours and are sleeping five, that’s a little truncation. If you’re only sleeping nine hours and you sleep five, that’s a big truncation. A lot of the stuff has to be really contextualized within the individual to see how it’s impacting that specific individual.
Dan Pardi: I’m curious too, when was the question how well did you sleep asked?
Jamie Zeitzer: It was the morning that they woke up after the sleep recording.
Dan Pardi: Within an hour?


Jamie Zeitzer: A few minutes.
Dan Pardi:


That’s a confound to because sleep inertia, I know some people don’t really become alert until an hour or later after they sleep. They got a great night sleep, they feel sleepy but then they have a different quality of alertness over the course of the day then if they got let’s say five hours. They might feel similar to five minutes after they woke up then they did when they got eight hours but they do feel differently an hour and later for the rest of the day.
Jamie Zeitzer:


That’s definitely true. There’s the time push of sleep inertia there’s also looking at changes in day time alertness, and so I’ve seen that with different aspects of sleep. How alert are you at four in the afternoon may very well be impacted by the kind of sleep that you received. That eight hours might not be equal eight hours for everyone. Again all these things have impact and really speaks to the universal impact of sleep on pretty much all functions in the body.
Dan Pardi:



Right well that’s really exciting I think that often times you can see technology overreaching, misused, even the less sophisticated technologies that are around now I think have a place when they are viewed correctly but seeing this it feels to me like it’s a true advancement. Not only could you use it if you are regularly traveling across time zones to be more alert both where you are going both also when you return. You could also use it for the “social jet lag” which is staying up several hours later, being exposed to light then when you usually do. You’re not traveling time zones but essentially you’re promoting that through your behaviors and also for teenagers that have delayed sleep phase and even adults that have that as well. The tendency to have delayed sleep phase where you get this light exposure, these pulses of light earlier in the morning and it helps them feel more alert during the day and sleepier at more reasonable times in the evening. Tons of application, definitely athletes like you mentioned, very exciting stuff.
Jamie Zeitzer:


Yeah I think so. I’m very excited about it, we’ve got a lot of work to do to optimize it. The thing we’d like to get to eventually is to get large enough changes. Right now we know that we can get a two to three hour change in circadian timing in a single night, I think we can get much larger changes. If we can get much larger changes then we can capture shift-workers and that to me would be a really important advancement. Shift-workers you’ve got people who sometimes by choice but many times by economic necessity are forced into working odd shifts and on their off days they want to spend time with friends and family. Right now we don’t have the capacity to switch people 12 hours in a single day. If we could do that I think that again would be extremely helpful.

Dan Pardi:


So much of shift work is absolutely necessary work for our society. Police, fire, emergency first responders. If this technology could help with that as well that has a major positive impact on society.

Jamie Zeitzer: I think so and this is really where we are going with this and that’s what I’d like to see is that kind of impact and that kind of change.
Dan Pardi: What is the name of the company that is commercialization the technology?
Jamie Zeitzer: They are called Lumos Tech.
Dan Pardi: Lumos Tech.
Jamie Zeitzer:


Yeah they were Stanford-based post-docs, some have left some are still here and they were just part of a program that tried to commercialize things that were invented at Stanford and this technology was invented by a colleague of mine who did some work in mice. I’m out of the financial loop for that but to me it’s far more important to see this thing be done right and be done in a way that can impact society.
Dan Pardi: I love that about Stanford. There’s an entrepreneurial spirit of silicon valley is certainly influenced Stanford in so they are thinking how can we use the technologies that we are discovering here to benefit the world in some way and I think that’s how it should be. I think that’s great.

Jamie Zeitzer:

Yeah I think so. It’s a definite plus I think
Dan Pardi: Well this is phenomenal information Jamie, thanks for joining us on Human OS and talking to us about the circadian system and now soon to be available hopefully. Actually do you know when this might his the market?
Jamie Zeitzer: Thanks for having me. That I don’t know, hopefully this year. They are still doing beta testing and optimizing stuff like that.
Dan Pardi: Okay so it’s not available now but maybe within the year.
Jamie Zeitzer: I’m hoping so. I think hopefully within less than a year.
Dan Pardi: Thanks again Jamie and I appreciate having you on.
Jamie Zeitzer: All right, I’m sure I’ll talk to you soon.
Dan Pardi: Definitely.


Thanks for listening and come visit us soon at humanos.me

  • Artur Domin

    On the different approach to this problem it seems that you can apply light through the ears 🙂 I listened about it on a podcast. Commercial product is already available. It has scientific basis and has quite a numer of positive testimonials. You can read more in this paper.


    Light can also be used to treat Alzheimers disease. There is Radiolab podcast about it


    and related paper in Nature


    • danpardi

      Hi @arturdomin:disqus, yes, the the people at Human Charger, who make the light-in-the-ear device sent me one to try. I honestly haven’t had a great chance to experiment with it as I haven’t been traveling much recently, but I look forward to giving it a try in the future. The data are compelling and surprising, as for the life of me, I cannot figure out the mechanism for how this could work. And yes, the effects of light on human physiology are robust. Thanks for the links!