Circadian science

The Future of Circadian Rhythms in Healthcare (It’s more than just sleep!)

Sleep is heavily influenced by your circadian rhythms, but it’s not the only function in your body that falls into that category. In fact, circadian rhythms govern almost every process our body carries out over the day, including metabolism, immune response, DNA repair, and physical performance.

One topic that’s been getting a lot of buzz lately is the influence of circadian rhythms on how effective treatments are and how many side effects you experience while on that treatment. It turns out that taking a medication at 7am or taking that same medication at 6pm might mean you experience dramatically reduced side effects—or dramatically larger benefits. This is the idea behind “chronomedicine.”

While many of the drugs and treatments with known time-of-day effects are related to cancer, such as chemotherapy, the field is still mapping all the potential conditions out there that can benefit from timing. The fact that 80% of drugs act on targets that oscillate over the course of the day suggests that the potential could be pretty huge. We can also include preventative care in our scope: in a study published in 2016, researchers found that people who received influenza vaccines between 9am and 11am had higher levels of anti-flu antibodies one month later than people who received vaccines between 3pm and 5pm.

The effects of timing have implications on how we even measure the effectiveness of drugs. In a study from 2020, researchers from Harvard Medical School found that some preventative stroke strategies may have failed in humans because the rats they were initially tested on are nocturnal. Since rats are inactive during the day and active at night, they respond differently to treatments given during the day than humans would.

Difficulties with applying this knowledge are twofold. The first is the challenge of being able to accurately estimate a person’s circadian rhythms. While most people’s circadian rhythms have roughly adapted to the 24 hour cycle of day and night, our individual rhythms can vary significantly from one another. Across people who work during the day, circadian rhythms can vary by as much as 7 hours from person to person. If you work night shifts, that variance could be up to 24 hours. So if circadian rhythms are so variable, how can we give accurate circadian recommendations?

We built Shift to make this a possibility. Regular readers already know that Shift works by estimating your circadian rhythms through your phone and wearable data. From there we can help you change your circadian rhythms to better suit the sleep schedule you’d like to be on—whether that means helping you adjust faster to your next three night shifts or optimizing your schedule so you can finally get more than 4 hrs of sleep after a grueling shift. 

By estimating a person’s circadian rhythms in this way, we have made circadian estimations available to everyone with a smartphone. We hope that in the future you’ll be timing treatments and medications with our algorithms for tracking body clock time, which are 3x more accurate that methods based on wall clock time or bedtime.

Okay, but what’s the other challenge with taking chronomedicine into the real world? Adherence. The second difficulty often cited with chronomedicine is the fact that patients must adhere to these recommendations about their circadian rhythms to get the benefits. The thinking by some experts is that since people have enough trouble remembering to adhere to treatment plans without timing recommendations, the additional complexity of intentionally timing them is too much of an ask. 

We believe in patients’ desire to improve their outcomes and reduce their side effects, just like how shift workers desire to improve their sleep and prevent lasting health detriments. We even think that the fact that our recommendations are dynamic—that they change daily in response to the signal from the user’s devices and inputs—holds potential to improve engagement and increase adherence to treatment plans. That’s why we’re so focused on making sure Shift is built for the user. We are putting the science of technology into the hands of everyday people.

We’re starting with sleep and following circadian science to the expanse of human health. Follow our journey by subscribing HERE.

Circadian science Interviews Technology

Interview With Bharath A.

Thanks so much for joining us this morning! Could you tell us a little bit about yourself and your research interests?

I am currently a theoretical and computational chronobiologist. I work in the area of circadian clocks. My PhD was in the field of wireless communications with a focus on designing new technology to provide higher rates of data transfer between phones and data stations. In a sense, cellular technology and chronobiology are connected because your cellphone’s functions depend heavily on oscillators. There is a lot to do with oscillators, amplitude, and phases, which transitions into circadian clocks and circadian rhythms. After completing my PhD in electrical engineering in the US, I relocated to Germany and explored my interest in biology, ultimately combining my knowledge of biology and engineering at a theoretical biology institute. Now, I have my one small group here at Humboldt University in Berlin.

You’ve done a lot—from blood tests for circadian rhythms to pure modeling work. What is the direction you’re most excited about in your current research? 

I am most interested in circadian medicine, (or chronomedicine). We began looking at how rhythms were generated, starting with the negative feedback loop, which was awarded the Nobel prize in 2017. In the late ‘90s and early 2000s, all the clock genes were found, and then we moved into using kinds of massive sequencing technology. We started to look at initial clock outputs, which include all the transcriptomes, and peripheral clocks in all the different tissues.

Through proteomics and metabolomics, we now have a very good idea of how rhythms and clock outputs are generated. We have also started looking at how these outputs couple with different physiological processes and how they mediate the interaction between clocks, immunity, metabolism etc. It really does seem to affect almost everything. So, I think the next natural step is to look at how we can leverage this understanding to help people improve their health. I am taking the more computational and theoretical angle, including blood tests, towards improving people’s health through circadian medicine. 

I am also involved in clinical studies that explore what has already been done in mice, although human clocks, of course, are more heterogeneous. I tend to focus on the molecular outputs of the human clock. We are trying to map out how different clocks look in peripheral tissues of specific patient groups or subpopulations. We are also currently trying to associate these data with other clinical parameters. 

I started at Arcascope about a year ago, and that’s when I learned about circadian rhythms and how it affects you day-to-day. I’m still learning, but I find the field of chronomedicine very exciting. 

What we are talking about is cutting edge in terms of medication. Even simple things, such as timing—whether to consume medicine during the day or night—have a huge impact. For example, my colleagues discovered this in a patient’s case of rheumatoid arthritis. 

The symptoms of rheumatoid arthritis are strongest early in the morning, with certain markers ascending really early in the morning, around 4:00 or 5:00 AM. So they took the standard medication, formulated a delayed-release form, and asked patients to take it at night so that the medication was released when the disease symptoms were at their highest rate. It was a very, very simple chrono-solution. I think it was published in Lancet, around eight or ten years ago in the early days of chronomedicine. Some very simple things, such as timing medication, can improve the efficacy of medicines that already exist. 

How has your work on biological rhythms changed the way you live your life day to day?

I will divide this into two parts of my life: before kids and after kids. After having kids and experiencing the coronavirus pandemic, things have become more chaotic. I have always had a fairly regular circadian lifestyle. Most of my life, I could survive with maybe six or seven hours of regular-quality sleep. I would go to bed at 9:00 PM and wake up at around 5:30 AM. And only after University, I started staying up later, typically going to bed at 11:00 PM and waking up in the morning around 6:00 AM.

I never slept in much because I was always awake once the sun was out. And now with kids, I try to work when they are asleep. So I end up staying up a lot later than I should. I know that I should not eat at night, but I still do it even though I know it’s wrong, so I will try to change that.

In fact, the funny thing was that after we created this blood test, we did the blood test on ourselves. At the time when my son was an infant, we had really crazy sleep/wake schedules. Still, when I did the blood test to determine my chronotype, it was actually the most consistent measurement of all the people we had tested. We tested at three different days and my chronotype estimate was within ten minutes of each other. So, objectively my chronotype looks pretty stable in spite of changing seasons and having to endure a crazy sleep/wake schedule.

Olivia, Arcascope’s CEO, is actually working on a blog post about how sleep regularity could be more important than sleep duration. 

Yes, possibly. As a chronologist, we do not really know how long it takes before one starts feeling the negative effects of an irregular sleep schedule. At the moment, I’m not living a chronologically good lifestyle based on what we know. At a recent meeting, we had a discussion on the effects of living against your clock and it is still unclear. 

So we talk about correlations, which is all we have. We do not really know whether it’s a consequence, which way the causality goes or whether it is bidirectional. So, it is hard to say. Essentially if we change the balance, we change the likelihood that something can go wrong.

For example, Satchin Panda, the author of The Circadian Code, discusses fasting, and emphasizes that a 12-hour fasting period at night is very important. That is one very simple takeaway from his work. I tried fasting for the longest time but it is hard, especially if you stay up quite late after dinner, then it’s hard to fast. I realize my kids can fast because they end up sleeping for 12 hours. Although, I personally know scientists in his lab who have been regularly fasting for quite some time.

And that’s an interesting thought too, is if you do eat outside of your optimal meal window, what exactly does that do?

At this point, we do not know. I do know about [timing and] caloric restriction from Joe Takahashi. It is not just about when you eat, but also how much you eat. Also, if you have a long fasting window, you probably eat less throughout the day; on average, you eat less if you have a longer fasting period. This means that for the larger part of your wake time you are not eating.

As the former public outreach fellow for SRBR, what did you learn from the experience?

The biggest takeaway is that this field, initially narrow, is now really broad. We focus on how our rhythms are generated and the outputs of the clock. Now, since we are at the point where we are looking at interactions with other systems, you can pick any other aspect of physiology and apply a clock angle. There are people working on that interface, looking at immune clocks, microbiome clocks, cancer clocks, metabolism clocks and endocrinology clocks. 

From a personal perspective, I think that this broad field is challenging because I am not a biologist with the background information that one needs to understand a lot of this. I have to know about clocks, but I have to understand some background in these other fields as well, and being in this position forced me to keep abreast of everything in these interfaces.

Through networking, I met a lot of people. I was the fellow at the beginning of the coronavirus pandemic, so I was networking while everything was digital, including our SRBR conference, which was hosted online in 2020.

It was actually surprising, people didn’t really have any baseline ideas about how this was going to work. And it worked quite well. At that point, people were quite wired and they were kind of happy to put up with anything to still function in the sciences.

One of the rewarding things, which I found out after the fact, is that a lot of people found the content produced from SRBR, which helped people create or maintain some sort of connection with the outside world since they could not travel to meetings. Everybody was more active; there were a lot of PhD students and postdocs.

How do you think we can communicate our results better as a field in general?

This is something that is close to my heart. As an SRBR public outreach fellow, my true goal was to do public outreach, although we also did a lot of “in-reach”. We did a lot of outreach within the chrono-community, which is important to other scientists who are less aware of chronobiology, similar to when you entered the industry and you were less aware of how much clocks impact other fields. 

One example was the Daylight Savings Time (DST) laws during my time as the public outreach fellow. We had a town hall and still, in spite of so much science being out there, we did not get the result that we wanted. In a sense, we got the exact opposite result. Of course, that is not purely because of the science, but communicating science is also important from that perspective. As scientists, communication is also important, since the science must be seen in the context of lifestyle, society and general health. I think we have to become better at talking to all kinds of different people. 

Sometimes that comes with being less preachy about the sciences. In the DST example, we realize that people may have other reasons for wanting something different. Everything is not just about the things that we, as chronologists, care about.

And then there are methods of communicating science. Twitter is now becoming a standard tool for communicating science at the technical level, and we are quite active on Twitter. Nowadays, I think Twitter, at least in the chronobiology field, is here to stay. If we want to reach other audiences, we obviously have to go beyond just Twitter, such as videos and visuals on TikTok.

I struggle with using videos and visuals to tell a story about chronobiology. Our research is publicly funded: the taxpayer basically funds our research. This means that we have an obligation to report our findings back to the public and help them understand and lead better lives. Scientists, who are good at writing papers, have to communicate better with the public by creating content for social media, such as this very interview, but generating content takes a lot of time and effort. 

And of course, scientists are busy people who have lots of tasks on their plates. There is a group of people who are convinced that the pluses outweigh the minuses, and that they should generate content. But then there are people who would like to generate content, but they just do not have any bandwidth or they do not really know how to do it. That’s the bottleneck, really.

I think postdocs and PhD students are much more familiar with these tools. Some of them are creative and they already generate content. Actually, during SRBR, we did this trainee session on why public outreach is important on social media and how people can get involved. 

We asked others in the chrono-community, “How has being on social media helped your science?” This question presented an interesting opportunity to network among a community of friends who maintained connections and continued to ask questions during the pandemic.

So it sounds like there are a lot of pros to being online.

One must concede that while social media is great, there are some negatives and some people do not use social media. Just talking to an audience on social media platforms is not sufficient, and one has to look at other ways to reach other groups of people, such as speaking in different spaces. If you are senior, maybe you can get interviewed by a magazine or a newspaper, for example, the New York Times. 

So a recent example is John Hogenesch’s article, which was published in the New York Times about a month ago. It is a whole write-up on health and circadian medicine, arguing the case for why we should do it.

I wanted to take the last few minutes to ask if you had any work of yours that we haven’t touched on yet that you would like to highlight.

One recent controversial (not so in my opinion) practice is the use of Venn diagrams in circadian biology studies because it tends to overestimate the impact of all interventions on the circadian clock. This study was published last year which has had a very broad impact, not just in chronobiology but in all kinds of omics studies. One of my passions is teaching. I host trainee sessions where I teach people about the analysis of circadian rhythms, and have taught at two summer schools and three trainee days. I do this regularly to help people analyze circadian rhythms, and in the end, do the science correctly.

Circadian science Shift Work

Running the numbers on health care shift workers

At Arcascope, we’re focused on helping shift workers get more sleep and feel better with circadian-specific interventions. In particular, we’ve spoken to a lot of shift workers in the healthcare industry about their experiences working nights. 

A lot of the lessons we’ve learned are echoed in this recent survey we ran with 218 nurses who work night shifts (both rotating and fixed nights). Here’s a tour of what we found:

Increased risk of error 

A full 65.1% of nurses we surveyed either agreed with or strongly agreed with the statement “Being tired on night shift makes me more likely to make a mistake.” More than a quarter said they strongly agreed with the sentiment, compared to less than 5% who said they strongly disagreed.

Heightened turnover risk 

Nearly half of the nurses—49.5%— said they’ve thought about leaving their current job for reasons specifically related to working night shift. 

When we asked them what made them want to quit, the number one cited reason was sleep loss. 

Negative effects on health and wellbeing 

More than half of the nurses in the survey, 53.7%, said they agreed with the statement “Working the night shift has negatively impacted my health and wellbeing,” with only 5% strongly disagreeing. 

This lines up with a past survey we conducted, where we asked nurses who work the night shift what symptoms they found most disruptive. The table below summarizes what we heard then: in general, feeling exhausted and not being able to fall asleep and stay asleep are major pain points for these workers.

Absenteeism…or presenteeism? 

38.5% of nurses working the night shift surveyed said they agreed with the statement “I’ve missed work because of health problems due to shift work (e.g. sleep loss, fatigue, etc.).” That said, 50% said they disagreed or strongly disagreed with the statement. 

On the one hand, society needs critical workers like night shift nurses in order to function. On the other, given the risks of fatigue and error that come with lost sleep, it may be that there are people showing up to work who are putting themselves at risk by getting behind the wheel to drive in. 

Interestingly, our population for this survey skewed a bit older, with 45-60 being the largest age group represented. 

This is interesting in part because the pain points we found here agree with the literature: You don’t tend to see shift workers being better at handling the night as they get older. Studies have found that night shift workers who are older tend to follow less adaptive sleep strategies, possibly because they have a harder time sleeping in. 

If you’re a nurse struggling with shift work, or a health system looking for a solution to get your people sleeping more, we want our app Shift to lend you a hand. Reach out to get on our pilot waitlist. 

Circadian science Shift Work

Feeling Flat

Over and over again, I’ve heard shift workers say something like the following: 

“I have no rhythms.” 

“It’s just a constant experience of bleh.”

“I get off shift, and more than tired, I just feel… flat.”

Ah,” I think when I hear this. “The amplitudes of their circadian rhythms have been squashed.” To steal an analogy from an older blog post, it’s like they’re rocking back and forth just a little bit on a swing at the park, instead of getting some nice height and momentum. It’s like they’re a yo-yo that’s only making it a fraction of the way back up to your hand. Or experiencing one of those dud bounces on a trampoline, where you only go up a few inches while the friend next to you goes flying. 

There are lots of ways of talking about this idea of lost amplitude.

You can think of the amplitude of an average daily activity profile, where you visualize a person’s normal day by taking the average of what they do over multiple days. For somebody with an irregular schedule, the amplitude (or maximum height) of this profile is going to be lower than for somebody with a super regular schedule: An irregular person’s periods of high activity will get canceled out by periods of low activity, whereas somebody who’s super regular will have all their high activity happening at roughly the same time. 

You can also think of amplitude in terms of the brain’s suprachiasmatic nucleus, or SCN, where the core timekeeping of your body’s daily rhythms occurs. If all the neurons in the SCN are like “Yes! It’s daytime!” they’ll send a clearer, stronger signal to the rest of your body, whereas if half of them are like “It’s day!” and the other half are like “No, it’s night!” the signal will be… not so clear. Kind of muddled, really. A dud bounce. 

I was thinking about circadian amplitude as I made my way through this recent paper from Zhang et al. in eBioMedicine. In this paper, the authors track the temperature and activity patterns of both day and night shift healthcare workers, and look at the ways in which they differ from one another.

For instance, the probability of a day worker resting at different times of the day in their dataset looked a little something like this: 

While the same plot for night shift workers looked like this: 

The black dashed average line for night shift workers maxes out around 0.6, while the same line for day workers hits ~0.9. In other words, we see a lower amplitude of the probability of resting (and a much more chaotic picture overall of night shift activity overall).

This is that “average daily activity profile” I mentioned above. But the authors also looked at patterns in chest temperature over the course of the day, finding 24-hour rhythms in 70% of the day shift workers and only 48% of the night shift workers. 

What’s that mean? Well, it could reflect the fact that temperature and activity are correlated—you move a bunch, your temperature goes up—so the story we see in activity could simply be making itself known through temperature as well. But it could also be capturing a bit of the SCN discord I brought up earlier. Your body’s clock contributes its own 24-hr pattern to your daily temperature profile, so a flatter signal coming from your brain could make for a flatter body temperature pattern too. 

I’ve written elsewhere about how more amplitude—or a clearer difference between night and day—seems to be linked to lots of good things, like lower cardiovascular disease. One nice thing about amplitude? It’s not fixed over your lifetime: it can change, dynamically, with your actions. Our app Shift isn’t just aimed at shifting the time of your body’s clock: we also want to help you to boost amplitude as well. Want to give it a shot, for yourself or your employees? Reach out at inquiries@arcascope.com

Thanks to the authors of Digital circadian and sleep health in individual hospital shift workers: A cross sectional telemonitoring study for an enjoyable read!

Lighting Sleeping troubles

Book & Article of the Month (June – July)

If you follow us on social media, you already know what we picked for our monthly reading material. For those who don’t, don’t worry: we’re also highlighting them here, on the blog. Let’s dive in, with…

June’s article of the month

Interindividual variability in neurobehavioral response to sleep loss: A comprehensive review

We picked this article because we think the kind of math we do at Arcascope—coupling biophysics with machine learning—is going to be clutch for capturing inter-individual effects in real world data.

And this is important, because (drumroll):

The big differences from person to person in how they handle sleep loss can make it a challenge to predict an individual’s fatigue risk level. That’s why we need new and sophisticated models to track fatigue—including models that take into account the dynamic, constantly shifting nature of the human circadian clock.

There are other reasons to care about inter-individual differences. Quoth the authors:

“Individual variability in response to countermeasures with different pharmacological targets suggests it may be possible to personalize the selection of countermeasures against the effects of sleep loss using information about genetic variants of implicated receptors.”

In other words, the fact that caffeine and other stimulants work differently for different people means that someday we could be recommending when to drink coffee based on your genes.

We completely agree with the authors that “Research should strive toward a systems approach to the study of interindividual vulnerability to sleep loss in which behavioral, neurobiological, and genetic data are integrated in a larger framework delineating the relationships between genes, proteins, and their functional consequences with observable alterations in cognitive functioning and behavior.”

July’s book of the month

In July, we went in a different direction, reading

Wild Nights: How Taming Sleep Created Our Restless World by Benjamin Reiss.

We really enjoyed this tour of sleep through the lens of history, literature, and society, featuring quotes like:

Did the switches go on because people wanted to stay up later, or did people stay up later because the switches went on?

Light at night has definitely changed the way we live, and most of us aren’t in a rush to go back to 1878 levels of illumination. But the growing evidence that light at night can disrupt your health in a whole host of ways should have us all asking: What can we do differently?

The good news is that there are a lot more ways of improving your circadian health than just keeping the switches off in the evening.

One of the other quotes that stood out to us:

In this age of connection, people might take classes on the other side of the world when it’s 3am in their home time zone. Or they might check their phone at night and be jolted awake by news.

This puts our body clocks, which track the light around us, in conflict with the things that demand our attention, which are running round-the-clock.

We also liked the call-out to how sleep deprivation has had massive, society-level impacts throughout history:

“Sleep deprivation has been blamed for such high-profile industrial and transportation accidents as the Chernobyl nuclear meltdown, the Exxon Valdez oil spill, and the Challenger space shuttle disaster, as well as less spectacular but more systemic problems such as loss of worker productivity, impaired memory, and increased health and emotional problems.”

History has shown that sleep deprivation is not a topic that should be taken lightly. Yet it can still be dismissed as nothing more than just “feeling tired”. We want to change that. With our app, Shift, we are giving people the tools they need to fight sleep deprivation and finally take the “tired” out of their life.

Circadian science Technology

Visualizing MESA: Part 2

We’ve already looked at the Multi-Ethnic Study of Atherosclerosis (MESA) dataset—an absolute treasure trove of sleep data, available from the NSRR at sleepdata.org—once, through the lens of sleep duration. But what about other dimensions of sleep health? After all, sleep regularity may be just as important as sleep duration in a number of contexts.

We once again teamed up with Ryan Rezai, a data scientist and student at the University of Waterloo, to visualize some MESA data. Once again, all the plots below were made by Ryan to highlight some intriguing trends in the MESA dataset. As always, we think there’s a lot of value in looking for pictures that can help you grapple with the complexity of multifaceted, complex phenomena like sleep.

Let’s start with the basics:

First we need to define sleep irregularity. We can do this in a number of ways. In the plots below, we’ve defined it in the ways MESA does—as either the standard deviation in total sleep duration (sd24hrsleep5) or the standard deviation in bed time (sdinbedtime5). 

So how does sleep irregularity, as defined above, relate to Epworth Sleepiness Scale self-reports (ESS) in the dataset? Like this: 

Looking at this, I feel pretty confident that there’s a trend here! As sleep irregularity increases, so does ESS, up until you get up to pretty profound variability in sleep regularity (180 minutes = 3 hrs standard deviation—you might be a shift worker at that point).

It’s even more remarkable when you look back at sleep duration and ESS (see last blog):

Not only does sleep regularity seem to have a clearer trend with ESS than sleep duration, it also seems to have a slightly higher amplitude effect, as shown on the y-axis. Right off the bat, this is a clue that we might be wanting to pay more attention to sleep regularity when we talk about the experience of sleepiness.

If we look at both bedtime irregularity and sleep duration simultaneously, we can notice something else interesting: 

Namely, that even for people sleeping quite a long time (e.g. 500 minutes), greater bedtime irregularity is linked to greater feelings of subjective sleepiness. 

What might be going on here?

We know a person’s subjective experience of sleepiness doesn’t always line up with how restricted their sleep has actually been. For instance, people on four hours of sleep a night tend to get worse and worse at reaction time tests, while their subjective sleepiness grows for a while but eventually levels off. Maybe irregularity makes people more reliably aware of just how sleepy and impaired they are because their irregularity means they’re more likely to be awake during periods of time when melatonin is at a high concentration in their body. Or maybe irregularity is having a dampening effect on their body’s circadian rhythms, making them more likely to feel exhausted and flat. There’s plenty of work to be done here in the future, but I’ll take off my Hat of Speculation now.

Beyond sleepiness

These 3-D sleep plots can be used to visualize more than just ESS. Take, for instance, this plot of total apneas over the course of the night as a function of sleep duration and sleep regularity: 

Ok, wow! That’s a clear picture, albeit perhaps not a surprising one in some ways. After all, you’d expect a longer duration of sleep to mean more opportunities for apneas. That said, it is interesting how, once you get above about 300 minutes of sleep (5 hours) or so, holding sleep duration fixed and increasing irregularity seems to correlate with increased apneas. 

Something similar appears to hold for sleep irregularity, sleep duration, and apneas per hour, with more sleep irregularity linked to a higher rate of apneas—at least when you ignore people sleeping around 200 minutes a night (which, to be clear, is probably not that many people):

Sleep irregularity and heart rate

Lastly, we might be interested in how sleep irregularity correlates with heart rate. After all, recent research has shown the risk of a cardiovascular event is more than twice as high in irregular sleepers as it is in regular sleepers. When we look at the irregularity in sleep duration, it sure looks like there might be something going on with average heart rate and irregularity in how long you sleep:

This trend also seems to hold when you look at the correlation between bedtime irregularity and average heart rate:

For both of these plots, the standard error is smallest between 0 and 180 minutes of standard deviation in sleep irregularity—and like we noted earlier, three hours standard deviation in sleep irregularity is a lot! (What’s going on when the standard deviation of bedtime irregularity is around 300 minutes? I sure as heck don’t know. But since that’s a standard deviation of five hours in sleep irregularity, odds are good that that’s not the typical sleeper.)

On the whole, it seems pretty clear: People who care about their overall sleep health shouldn’t sleep on sleep regularity.

With thanks to these resources:

Zhang GQ, Cui L, Mueller R, Tao S, Kim M, Rueschman M, Mariani S, Mobley D, Redline S. The National Sleep Research Resource: towards a sleep data commons. J Am Med Inform Assoc. 2018 Oct 1;25(10):1351-1358. doi: 10.1093/jamia/ocy064. PMID: 29860441; PMCID: PMC6188513.

Chen X, Wang R, Zee P, Lutsey PL, Javaheri S, Alcántara C, Jackson CL, Williams MA, Redline S. Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015 Jun 1;38(6):877-88. doi: 10.5665/sleep.4732. PMID: 25409106; PMCID: PMC4434554.

The Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Ancillary study was funded by NIH-NHLBI Association of Sleep Disorders with Cardiovascular Health Across Ethnic Groups (RO1 HL098433). MESA is supported by NHLBI funded contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by cooperative agreements UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 funded by NCATS. The National Sleep Research Resource was supported by the National Heart, Lung, and Blood Institute (R24 HL114473, 75N92019R002).

Circadian science Shift Work

A space for shift workers, Pt. 2

Here again is our blog feature where we look on the internet for what folks are saying about their shift work, and try to speak to their experiences with the power of circadian science.

First up: 

Reddit User:
My shift is usually 7pm-3:15am. when i get off work i shower, eat, and watch some Netflix until i fall asleep around 5am, but then i’ll only sleep until around lunch when my body naturally wakes me up and i can’t go back to sleep. i end up spending the rest of the day anxious and anticipating going into work and feeling like i can’t do anything productive because i’ll be too tired to perform at my job. i’m a card dealer so i need to be alert and focused during my shift to count cards and do the mental math for payouts.

Sometimes i can squeeze in a nap in the afternoon but it can make me more groggy when i wake up. i’ve tried forcing myself to stay up a little longer after i get home from work but i’ll still wake up around noon and then i’m stuck with less sleep than if i had passed out right when i got home.

Any advice? i get so much anxiety about sleeping through my alarms or being so tired at work i pay someone wrong and it’s overwhelming sometimes. i want to try to keep this job for at least a year so i can pay off my debt and student loan but it’s becoming mentally draining

Our Take:

Reddit user, you’re not alone. Many shift workers experience the exact same thing you do—waking up after only a short time sleeping, post-shift. What you’re describing sounds like your body’s circadian clock swinging to wake you up after you’ve drained your homeostatic build-up, or sleep hunger, from working the night shift. In other words, your body clock is still pretty well adjusted to a day schedule, so it’s trying to wake you up to match the day. By the time noon rolls around, it thinks your circadian sleep window has passed.

The good news is that you can shift your body’s clock, so that your circadian sleep window happens when you want it to (like in the hours after your shift, instead of during your shift). Might make life a little easier, huh? You may be thinking to yourself that the process of “shifting your clock” sounds complicated, and you really don’t have time to add more to your plate. Well, here are two pieces of good news for you.

First, while understanding your unique circadian clock is complex, with a lot of moving parts, we’ve been working on a way to make it simple: simply hook our app up to the data collected from your phone (and wearables, if you own one). Living a circadian-aware life is something that anyone can accomplish, whether you work day shifts, night shifts, or somewhere in between. 

Second, it’s not about “the time it takes” to fix your clock— it’s about “the time” itself. Your normal activities throughout the day like eating, exercising, and looking at screens are all sending signals to your clock. When you start timing these activities correctly, the signals can help shift your circadian sleep window to where you want it to be. So what we’re really trying to say is, it’s not so much about the what of your day, it’s about the when of it.

Oh, and that grogginess you feel after a nap in the afternoon? That’s called sleep inertia, and it can be worse at some times vs. others. We can warn you when sleep inertia’s likely to be worse by tracking your body clock’s time.

There are a lot of things we’ve learned about what can help shift workers adjust to their schedules. If you’re looking for where to start, that’s where our app, Shift, comes in.

Reddit User:
I’ve been doing overnights for almost 3 years now (22:15-0645). It’s been decent for the most part, but the one thing I’ve consistently had an issue with is staying asleep. I’ll get off work, come home, eat breakfast, and be asleep by 08:45. I have no trouble at all falling asleep, but I wake up around 14:00 all the time. I was wondering if you guys have had similar problems? What did you do to stay asleep? Ideally I’d like to sleep until 15:45, as that would give me 7 hours of rest. Thanks for any help.

Our take:

Once again, this sounds like a problem caused by a body clock that’s scheduling sleep too early in the night (and missing out on the window of time you actually have available to sleep). 

Let’s dive into the science a little more. There are two main forces that work together to keep you asleep. One is the homeostatic sleep drive, or “sleep hunger,” which builds while you’re awake and the other is the circadian sleep drive, which rises and falls about every 24 hours. When you’re well-adjusted to sleeping on a day schedule, there’s a hand-off from your homeostatic sleep drive to your circadian sleep drive. 

Think of this as a baton relay race, where the baton is your sleep, and the track is the length of time you’re hoping to be asleep for. That makes your homeostatic sleep drive the first racer, and your circadian sleep drive the second racer. When your homeostatic sleep drive nears the end of its turn, there’s a hand-off to your circadian sleep drive in order to keep you asleep until the finish line. However, if your internal circadian clock is out of whack—or, analogy time, like the second racer isn’t where they need to be for the hand-off—the passing of the baton doesn’t go so smoothly. And even though you were hoping to stay asleep for the whole race, the fumbled hand-off wakes your body up hours earlier than you wanted.

There are many negative effects that happen when your circadian clock is off track with your schedule, and waking up in the middle of the night is just one of them. Luckily, this does not have to be permanent. The fact that you have the power to throw your clock a little off track, also means that you have the power to get it back on track. That’s what we’re here to help with.

Sleep Meme Review

We Rate Sleep Memes, Pt.3

We’re back! If you’re just now tuning in (check out part one here), the title pretty much says it all. We take sleep-related memes we find online, we use them as an excuse to talk about sleep and circadian science, and we rate ’em.

Meme #7

Good news: If this is you, it might not be you forever. A study of more than 40,000 people across a wide range of ages found that the number of people saying they don’t feel rested when they wake up goes down as people get older—from almost 30% of teens, to less than 10% of folks over 60.  

This could be because people’s internal rhythms tend to shift to be earlier as they age. So older people might be waking up at a time when their body is more ready to be awake, while younger people—especially teens with early school start times—are getting woken up while their body’s still sending the signal for night. 

One way to test and see if this is you: Go camping. If you feel a lot better when you wake up in the woods, it might be a sign that your grogginess is coming from the light in your home at night tricking your body’s clock into slowing down and making it run late the next morning. That could be a sign you need to dim the lights at home a lot as you get ready for bed. 

You might also just feel this way because of sleep inertia, the general grogginess you get after waking up that can last for a few minutes to a couple hours. You’ll probably feel sleep inertia to some extent even if you go camping, but at least you’ll be camping. 

Originality: 1.5/5. This meme topic has been around since the dawn of time.  

Overall quality: 5/5 Love this potato. 

Meme #8

Alright, so, here’s what could be going on:

  • There’s a thing called the “wake maintenance zone.” 
  • It’s a period of a few hours during the day where you feel more alert. 
  • For somebody whose body clock is really well adjusted to their home time zone, the wake maintenance zone happens in the evening—like, a few hours before bed.
  • You can think of it as a surge of energy to get stuff done before the sun goes down. 
  • For somebody whose body clock is adjusted to the wrong time zone, or just generally out-of-whack, this surge of energy can happen any time, regardless of what the sun is up to. 
  • Your body clock gets shifted by the light exposure you get, as well as when you sleep, workout, and take melatonin
  • So if you’ve had a really irregular sleep pattern, or you’ve gotten light and dark at weird times, it’s totally possible that you could have moved this surge of energy to 3am

One thing to try: Stop thinking about only sleep duration, and start thinking about sleep regularity. Pick a bedtime that works for your schedule and stick to it as much as you possibly can. If you can’t keep a regular bedtime, try your best to keep a regular light/dark pattern. You might be awake at 3am, Walter White, but you might not need to have the overhead lights on. 

Originality: 1.5/5. Ye olde meme topic.  

Overall quality: ⅘. I can just hear him saying this.

Meme #9

If your brain does weird things when you’re up late at night, you’re not alone. There’s been a lot of research and a lot of interesting results on how the brain changes as you stay up. Generally speaking, people tend to be more impulsive and less able to keep their thoughts and actions in check. 

Losing sleep is part of it, for sure. Staying up can affect the chemicals in your brain, as well as the ways different parts of your brain talk to each other. 

But your body’s clock also has a lot to do with it as well. A number of neurotransmitters, including dopamine, follow circadian rhythms, meaning that they’re going to go up or down at night regardless of whether or not you go to sleep. 

In this way, being awake at night while your brain is experiencing a circadian rhythms-driven change in chemicals is a bit like being on an ice rink when a Zamboni is cleaning it. You’re not supposed to be there, and normal rules don’t apply. It’s slippery. You can fall on your face (ice rink version) or fall into a long rumination on an embarrassing thing from 2012 (staying up late version). 

If you’re interested in reading more on this, check out the Mind After Midnight Hypothesis published earlier this year. 

Originality: 2.5/5. I saw memes like this before 2017 even existed.

Overall quality: ⅘ Now I’m thinking about my own argument in 2017.

Circadian science Sleeping troubles

Sleep Regularity + Students = An A+ Idea

College, as any student can attest to, is a hectic life.

Look no further than my past spring semester for a prime example of this. Taking multiple difficult classes while managing club activities and a social life was a whirlwind that was both exhausting and invigorating at the same time. The thorn in my side, however, was Advanced Calculus, a class for proving the underlying mechanics that we used in Calculus 1 and 2.

In my defense, Advanced Calculus is a difficult class even for math majors. They say if you’re able to pass it, you can get a math degree! I’m relieved to say I managed to scrape by and am on my way to finishing up my undergraduate degree in math (and computer science) next year.

I passed—isn’t that all that matters? Yet, with all the things I want to do in my college years, I found myself wondering: is there room for more optimization? I couldn’t help but think of the story of the British Cycling Team and their transformation from being the worst cycling team in the sport to utterly dominating it in a few years. What did they do, exactly? They accumulated little optimizations that eventually compounded into huge advantages. Some of these tiny changes include wearing more aerodynamic racing suits, testing different massage gels for faster recovery, and (drumroll, please) using better  pillows and mattresses for sleep.

I’m convinced now more than ever that sleep is a severely underrated optimization in anyone’s life (exponentially more so for shift workers). Yet for students, the reigning sentiment is that we must fuel ourselves with Monster in order to work late into the night, whether that’s studying for finals, cranking away on projects, or catching up on assignments. Sacrificing sleep to stuff our heads with lecture material is tradition, but does this really work?

Well, maybe not. In “Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing”, Phillips et al. were able to find a compelling correlation between sleep regularity and average GPA by using a metric called the Sleep Regularity Index. This index calculates the probability of an individual being in the exact same state (aka sleep or awake) 24 hours later at any point in time. They found that an increased SRI correlated with a higher GPA. In fact, during a 30-day period, there was a considerable gap in GPA between the regular and irregular sleepers: 3.72 (Regular) versus 3.42 (Irregular). Importantly, they found no such relation for GPA and sleep duration. In other words, you might be throwing your grades off track simply by staying up later than usual, even if your overall sleep duration averages out to a decent amount.

Now, association doesn’t necessarily mean causality. There’s a lot that goes into a grade. Sleeping regularly by itself won’t be the reason why you ace a final, but it can certainly tilt the odds in your favor. One fact the study highlighted was that an irregular sleep schedule had the same effect as traveling westward by two to three time zones. I imagine that being jet-lagged isn’t the most optimal state to study in. And that feeling of jet lag could negatively compound upon itself over multiple days, adding up to a pretty big effect.

A nice thing about the sleep regularity index is that you don’t need Advanced Calculus to calculate it—there are multiple versions of code to calculate it online. And if sleep regularity is key, as it sure seems like it is, then optimizing everyday life around a consistent bedtime is probably for the best. That’s something for college kids everywhere to keep in mind when life gets hectic again this fall!

This blog post was written by Jessica So, one of Arcascope’s interns. Thanks, Jessica, for your hard work!

Circadian science Lighting

What matters besides light?

A Guide to Non-Photic Zeitgebers

We can all agree that the difference between night and day is, well, night and day when it comes to light. The progressive change in light present in our environment is subconsciously tracked by our bodies and that information is used to help time our sleep-wake cycles. Of course, not everyone has the physical ability to perceive the changes in light which occur over the course of the day. Yet some blind individuals are still able to entrain accurately to their environment without these crucial photic cues. How is that so?

Light is the strongest “zeitgeber”— or, environmental cue that provides input to the circadian clock. Our bodies use the signals from zeitgebers to try to synchronize our internal clocks with our environments. For example, the decrease of light over time that you experience while watching a sunset can communicate to your body that nighttime is approaching. If you keep the lights on instead, your body’s clock can be delayed and production of the hormone for night, melatonin, can be suppressed. Because of this, it’s important to think about what signal your light exposure is sending to your internal clock (cough, screens at night, cough). But light is not the only player in town. There are other zeitgebers besides light that influence your circadian time.

Before getting into the weeds, it will help to have a mental map for how your body’s clocks are organized. Our circadian clocks are composed of a central clock and peripheral clocks. The central clock acts as the command center located in the suprachiasmatic nucleus (SCN), sending signals to the various tissue-specific peripheral clocks spread throughout the body. The phase of each peripheral clock is influenced by both the central clock and factors specific to that system, allowing different biological functions to be coordinated through the central clock while being autonomous enough to respond to stimuli specific to that system. For example, as we’ll discuss below, the metabolic clock is driven by both the central clock but is also affected directly by meal timing. Some signals may primarily affect peripheral rhythms, while others can affect both peripheral and central rhythms.

Zeitgebers, such as light, communicate with SCN
Zeitgebers, such as light (a), communicate with the SCN which houses the central circadian clock. Other signals, like meal timing (b) can relay their own signals to the body’s peripheral clocks in organs and tissues (c and d).

Before we talk about these non-light inputs to your body’s time, let’s talk about phase-response curves. The standard way to track how a zeitgeber advances or delays your central circadian pacemaker is through phase-response curves (PRCs). These graphs represent the timing of a zeitgeber stimulus (x-axis) and its quantitative effect on the timing of a circadian biomarker (y-axis), like shifts in melatonin timing or core body temperature minimum. A phase-response curve can tell us when a zeitgeber will advance you, when it will delay you, and when it will have essentially no effect. 

Phase-response curve
Phase-response curve showing circadian time of exercise vs. phase shift, determined by presence of 6-sulphatoxymelatonin (aMT6s) measurements. Participants performed 1 hour of moderate treadmill exercise at the same clock time for 3 consecutive days.

Exercise has been shown to induce central clock phase changes dependent upon the timing of activity. One study in particular, which produced the PRC above, recruited 101 physically active adults to investigate the effects of exercise on circadian phase. Participants were put on a 90 minute ultradian light schedule (60 minutes light/wake followed by 30 minutes dark/sleep) for approximately 6 days. Baseline aMT6s (urinary melatonin) measurements were made for individuals and averaged across the whole sample of participants. The difference between the individual and sample phase was determined and then subtracted from the external clock time of exercise to calculate a “circadian time” adjusted for interindividual differences. 

Each participant performed 1 hour of moderate treadmill exercise at the same clock time for 3 consecutives days following baseline, isolating the effects of exercise on phase. Moderate exercise was quantified as 65-75% of the heart rate reserve calculated for each participant based on their individual maximal heart rate. This study concluded that exercise at 7am and between 1pm and 4pm causes phase advances to aMT6s timing, whereas exercise between 7pm and 10pm provoked phase delays. 

These results can be read from the PRC above by identifying the selected time along the x-axis and reading the corresponding point’s phase shift, quantified by the y-axis. For example, exercising at 7pm (19 h) results in approximately -0.75 h phase shift. The negative value indicates a delay, whereas a positive would indicate an advance. Thus, exercise at 7pm causes a little less than an hour phase delay based on the above PRC. 

A similar pattern of phase advance and delay regions can be observed in the human response to light, especially in studies with parallel protocols or similar duration of stimulus. Intuitively, the analogous behavior of morning advances and evening delays produced by light and physical activity makes sense—light and activity are often correlated, so if they told really different circadian stories, it would be pretty strange. The authors of the exercise PRC research note that the phase shifting strength of exercise is comparable to that of light exposure, making exercise another great tool for your circadian management tool belt.

Phase-response curve showing Dim Light Melatonin Onset
Phase-response curve showing Dim-Light Melatonin Onset (DLMO) determined circadian time of melatonin supplement vs. phase shift. Participants were held on an 3.5 hour ultradian light-dark cycle (1.5 hours dark/sleep period followed by 2 hours light without sleeping) with administration of 3.0 mg of melatonin following the dark/sleep period. 

Oral melatonin supplements have also been shown to shift central clock outputs like dim light melatonin onset. In general, melatonin dosing tends to do the opposite of what light exposure would do at the same time—delaying you when you’d be advanced by light, or advancing you when you’d be delayed by light. While most people don’t think of melatonin as something that can be mistimed, the phase-response curve tells us that melatonin at the wrong time might have no phase shift whatsoever, or could delay you when you’d really prefer to be advanced (e.g. if you want to fall asleep faster at night). 

Meal Timing Study, factors controlled by light.
A visual depiction of results from a meal timing study showing which factors were controlled by light (and the SCN, purple, top), and which were controlled by meal timing (green, bottom). Larger arrows mean more significant control by that input.

Eating patterns are interesting. When you keep light exposure patterns fixed and change the timing of meals, the vast majority of relevant outputs—melatonin, cortisol,  hunger, triglycerides, and genes like PER3 and BMAL1—stick with the patterns set by light (in other words, they follow the SCN). A few of the players track with meal timing, however: glucose, and, to a lesser extent, PER2 and insulin patterns, showed significant phase shifts in response to the food time changing.

This means that misaligning your meal timing with your light timing could result in a kind of desynchrony, in which your light and your food are sending two different time-keeping signals, and in turn throwing your metabolic processes out of whack. This desynchrony—or, specifically, avoiding this desynchrony—could be the reason why time-restricted eating (TRE) has been found to improve cardiometabolic health. 

So light’s not the whole story. On the one hand, that means there are more circadian-relevant factors to have to worry about; on the other, that means we have more knobs to turn as we try to help people achieve optimal circadian health. Can’t get bright light? Why not try exercise instead? Need more than just a light dose? Here’s the right time for melatonin, for you. At Arcascope, we want to use all the tools available to us to help you optimize your external and internal cues, in search of synchronous bliss.

This blog post was written by Carrie Fulton, one of Arcascope’s interns. Thanks, Carrie, for your hard work!


  • St Hilaire MA, Klerman EB, Khalsa SB, Wright KP Jr, Czeisler CA, Kronauer RE. Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker. J Theor Biol. 2007 Aug 21;247(4):583-99. doi: 10.1016/j.jtbi.2007.04.001. Epub 2007 Apr 4. PMID: 17531270; PMCID: PMC3123888.
  • Celine Vetter, Frank A.J.L. Scheer, Circadian Biology: Uncoupling Human Body Clocks by Food Timing, Current Biology, Volume 27, Issue 13, 2017, Pages R656-R658, ISSN 0960-9822, https://doi.org/10.1016/j.cub.2017.05.057. (https://www.sciencedirect.com/science/article/pii/S0960982217306231)
  • Youngstedt SD, Elliott JA, Kripke DF. Human circadian phase-response curves for exercise. J Physiol. 2019 Apr;597(8):2253-2268. doi: 10.1113/JP276943. Epub 2019 Mar 18. PMID: 30784068; PMCID: PMC6462487.
  • Burgess HJ, Revell VL, Molina TA, Eastman CI. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab. 2010 Jul;95(7):3325-31. doi: 10.1210/jc.2009-2590. Epub 2010 Apr 21. PMID: 20410229; PMCID: PMC2928909.
  • Burgess HJ, Revell VL, Eastman CI. A three pulse phase response curve to three milligrams of melatonin in humans. J Physiol. 2008 Jan 15;586(2):639-47. doi: 10.1113/jphysiol.2007.143180. Epub 2007 Nov 15. Erratum in: J Physiol. 2008 Mar 15;586(6):1777. PMID: 18006583; PMCID: PMC2375577.
  • Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annual review of neuroscience. 2012;35:445. doi:10.1146/annurev-neuro-060909-153128.
  • Wehrens SM, Christou S, Isherwood C, Middleton B, Gibbs MA, Archer SN, Skene DJ, Johnston JD. Meal timing regulates the human circadian system. Current Biology. 2017 Jun 19;27(12):1768-75.
  • St Hilaire, M.A., Gooley, J.J., Khalsa, S.B.S., Kronauer, R.E., Czeisler, C.A. and Lockley, S.W. (2012), Human phase response curve to a 1 h pulse of bright white light. The Journal of Physiology, 590: 3035-3045. https://doi.org/10.1113/jphysiol.2012.227892
  • Kripke, D.F., Elliott, J.A., Youngstedt, S.D. et al. Circadian phase response curves to light in older and young women and men. J Circad Rhythms 5, 4 (2007). https://doi.org/10.1186/1740-3391-5-4