Why Do You Feel Sleepy After Eating? Podcast with Keith Murphy

Everyone knows what it’s like to feel sleepy after a big meal. How do you feel after Thanksgiving dinner or after getting a huge lunch at an Indian buffet? If you’re like me, you’re ready to crash. But why do you feel sleepy after eating?

Is it the tryptophan in the turkey?

Is it from too many carbs?

What you eat, how much you eat, and when you eat all play a role. (For more on how meal timing affects health, check out this blog!) Consequently, there has been some doubt as to whether the “food coma” is even a real thing. Rcently, however, some clever researchers identified a good way to study this phenomenon. Surprisingly, it involves studying fruit flies (Drosophila). And by studying the behavior of these flies, we now better understand why we feel sleepy after eating.

In the latest episode of humanOS Radio, I interview Keith Murphy, a graduate student working in the Ja Lab at the Scripps Research Institute in Florida. To explore why we feel sleepy after eating, he and his colleagues have developed novel systems to track sleep and food consumption patterns in fruit flies.

In a recent study, Keith and his colleagues noticed that fruit flies also get sleepy after eating – they sleep more after after big feeds. The research team was interested in whether different components of the meal influenced the sleep-inducing effect. To test this, they gave the flies food with varying amounts of salt, protein, and sugar to gauge the effects of different nutrients. Perhaps surprisingly, only protein and salt were found to make the flies sleepy after eating. Interestingly, sugar had no discernible impact.

So, what’s going on?

The researchers used genetic tools to switch neurons on and off in the brains of the flies (one reason why fruit flies are such a useful way to study this stuff – you can’t do that in humans!). They found that the flies get sleepy after eating because of activity in specific circuits in their brains, as we discuss in greater detail in the interview. It’s worth pointing out that the systems that play roles in post-meal sleepiness are conserved across a wide range of different species, meaning that this is likely relevant to other animals, including humans.

Sleep is obviously a vulnerable state for animals in natural environments, leaving them at the mercy of lurking predators and the elements (this is one reason sleep is so fascinating!). The fact that brain circuits make flies sleepy after eating suggests that it post-meal sleepiness has a purpose. Professor Ja, Keith, and the researchers in the lab have some hypotheses, and are striving now to figure out why this is so.

Listen below to learn more about Keith’s intriguing study and what it might mean for our own sleeping and eating patterns!

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Keith Murphy - 00:06: What people have slowly been finding is the genetics of flies some to be heavily conserved. There are a number of studies showing that serotonin and dopamine and all the basic molecules that you think of with human sleep have a major role in fly sleep.

Kendall Kendrick - 00:24: Human OS. Learn. Master. Achieve.

Dan Pardi - 00:35: Keith Murphy. Welcome to my podcast, Human OS Radio. Tell our audience where you work and the type of research you do.

Keith Murphy - 00:42: I work at the Scripps Research Institute in Florida. I'm a graduate student. As part of a integrative program in neurobiology at Florida Atlantic University. I work in the laboratory of William Jaffe. In terms of what we do, our lab among all the labs here is really diverse. So we not only study sleep, you know, we can talk about today, but we also do feeding behavior and mating behavior and generally how behaviors some to affect health in livestock.

Dan Pardi - 01:11: Tell us how you got into sleep research.

Keith Murphy - 01:13: Yeah, so it's actually ten years ago that it was discovered that the fruit fly which is extremely simple organism seemed to conserve the basic features of sleep on like how deeply they sleep, that is was important for memory, that they would regain it when they lost it. Bill primarily before recently had just worked on feeding behavior, so when I joined his lab, he was developing a device that could tell us exactly when fruit flies were eating and how much they were eating by using these small little capillaries where we basically just machine vision tracked how much fluid was drawing into the fly.

01:48: Originally, we were just looking at feeding behavior but because flies have been developed as a really good model for figuring out sleep worked, he said, "Well, what if we could pair this eating behavior or this feeding measurement with exactly when flies were sleeping and would we find something interesting there?" So I was sort of the first segue of the lab into sleep behavior but it's gone pretty well since.

Dan Pardi - 02:10) A friend of mine, Paul Shaw, you're probably familiar with him, he does work at Washington St. Louis, he was a early person to the fruit fly sleep paradigm and made some great contributions there. I think a lot of people are surprised that fruit flies have any sort of relevance to us, but just like you described, they seem to consolidate sleep. Is it that they have a certain set of genes that make their behavior and physiology somewhat relevant to us?

Keith Murphy - 02:34: Yeah, so absolutely. In fact, I just talked to Paul pretty recently and he was one of, if not the major proponent of studying fly sleep with the Tononi lab. Really, of course, because they're fruit flies, there's going to be basic differences in sort of the architecture of sleep, but what people have slowly been finding is that the genetics of flies seem to be heavily conserved.

Dan Pardi - 02:56: Yeah.

Keith Murphy - 02:57: There are a number of studies showing that serotonin and dopamine and all these basic molecules that you think of with human sleep have a major role in fly sleep. The balance of this or whether or not serotonin drives sleep positively or inhibits it, seem to be pretty conserved. So I guess since the flies come up, we've learned not only that they conserved some of these features, but on top of that, we're starting to learn new things. For instance, a work of Paul's that was really interesting, I forget. It was like 2005 or something it was published is that [inaudible 00:03:28] proteins which is something that is critical for stress response in mammals seemed to be really important in actually regulating whether or not we accumulate sleep loss. I thought that was a really nice example of a human gene that was now shown to affect sleep because fruit flies are so easy to study genetically speaking.

Dan Pardi - 03:47: When you use the word "conserve," for those who aren't familiar with it, can you explain what that means?

Keith Murphy - 03:52: Conserve just basically means does the gene encode a protein, which is sort of the fundamental functional unit of the cell which makes up our body. Does the animal have a very similar looking gene that makes that protein and does the protein work in a similar way.

Dan Pardi - 04:08: In humans, yeah.

Keith Murphy - 04:09: Yeah, in humans. Can we find something useful from using it in flies?

Dan Pardi - 04:13: Is this the first study that you had done looking at sleep in Bill's lab?

Keith Murphy - 04:18: Yeah, so this is the first of hopefully what will be many. You know, we've been working on a number of studies that show how sleep and feeding integrate. This just happened to be one of the first things that came up and maybe one of the more interesting things. We'll definitely be having other studies that show the importance of metabolic function and sleep regulation coming out pretty soon. This was definitely the first.

Dan Pardi - 04:44: Tell us about the study a little bit. Give us a little more detail so we can understand what you did.

Keith Murphy - 04:49: Yeah, sure. So in humans, and this is something that was surprising. Actually, maybe I'll just talk about what we found first. So by pairing together high-resolution measurement of feeding in the fly and also measuring the sleep of the flies and again, this is on a individual level, so flies are basically just walking around in an environment and machine vision tracking is telling us, "Okay did the fly eat a meal and what did the sleep look like before and after in a short window?"

05:15: What we found consistently over and over again was that the fly seemed to exit from probability of sleep when it goes to eat and right after eating it experienced much more sleep and that this lasted for about 40 minutes. You know, it was something we sort of almost expected because anecdotally everybody kind of talks about this food coma type behavior. You know, "I ate a ton of food today and I'm really tired." So we sort of just thought, "Okay well, this is just saying that the fruit fly's relevant to this behavior. When we went and looked at the human literature, we really only found about four or five studies that had really been attempted to see it in humans. And something that you've probably faced and a lot of people face is that it's really difficult to resolve subtle behaviors in humans.

Dan Pardi - 06:01: Right.

Keith Murphy - 06:01: So it's something it's not a hundred percent concrete. You not only have that but every human in the study is slightly different so it just creates this big variability that makes it hard to measure. So through no fault of their own, studies really didn't show a hundred percent that the behavior was actually occurring and the fact that they were very unable to see it with high resolution made it really difficult to study the behavior.

Dan Pardi - 06:24: Yeah.

Keith Murphy - 06:25: So once we saw that, we decided, "Okay, well, let's use the flies to investigate how this behavior works, food coma type of effect."

Dan Pardi - 06:33: How do you measure sleep in the fruit fly?

Keith Murphy - 06:35: There's actually a number of methods you can go for. The first and best method is just to track how they're moving and you can track their posture at the same time. From the original papers, it was shown that with some probability, as a fly's immobiled, you know, the likelihood that it asleep becomes increasing to the point where it's about 100% at five minutes. So really the rough measure is just to say, you know, "Is the fly moving or not?"

07:02: The second measure which we go into in the paper is to actually deliver vibrations to the chamber and to ask, "Well, how much does it take to wake the fly up?" So this is sort of analogous to, you know, if you're sleeping at your desk and your friend pokes you very gently, you might not wake up, but if they punch you in the arm, yes, now you'll wake up. What we can do in the fly is we actually take these little motors from cell phones and we attach them to the back of the chamber and we ramp up the vibration and we asked, "At what point does the fly begin to respond to this vibration?" A fly that's asleep will usually respond to very high vibrations where a fly that's awake will respond almost immediately with a gentle vibration.

Dan Pardi - 07:42: Oh, okay. How creative.

Keith Murphy - 07:44: Yeah, it's pretty fun some of the [inaudible 00:07:46] we get to go at.

Dan Pardi - 07:47: Yeah, that's really neat.

Keith Murphy - 07:49: There's one more just to really convince people who are listening. You can actually record from the fly brain while they run around on like a ping pong ball. It's kind of like a treadmill for people. That's when you can really see their brain activity downshift as they sleep, but that's something you can't do on any high [inaudible 00:08:06] screens. If there's a lot of animals you need to look at, it would be impossible to do. But that would be sort of the last, just so you guys know.

Dan Pardi - 08:13: So it's like the equivalence to actigraphy in humans which is looking at movement, right?

Keith Murphy - 08:18: Yeah.

Dan Pardi - 08:18: An activity for anybody that is listening that's not familiar with that term, it's how FitBit and other quantified self devices will measure if you're sleeping or not. It's just assessing movement and then predicting whether or not you're in sleep or not or what stage of sleep that you're in. That's been well-validated and used in clinical research for quite a long time. It has its limitations, but it also has its real value as well. Sounds like the other work you're doing is equivalent what's considered polysomnography in human which is when you have multiple electrodes studying brain wave activities directly. Do you like that comparison?

Keith Murphy - 08:52: Yeah, actually the FitBit comparison is one of my absolute favorites and I've even kind of thought about trying to collect that data and somehow pair it with fluid consumption data, but you know, they don't have that on the FitBit yet. But yeah, absolutely excellent comparison.

Dan Pardi - 09:08: Okay, we have different ways to measure whether or not they're asleep. Then you wanted to look at what they were eating. Were you feeding them different quantities of food and different compositions of nutrients within the food they were given?

Keith Murphy - 09:21: Right, so the original finding which was just that they slept more after eating was just on a regular diet with sort of a normal amount of sugar and protein. When you want to see some of the subtleties what you'll do is change things in a more dramatic way. What we did was when we first began to ask, "What nutrients drive this effect?" We started with sugar which we really felt would have an effect because it seems to regulate long-term sleep. So an animal that's starved of sugar will wake up but sugar didn't seem to have any fast effect. When we started to ramp up protein, we saw actually a really nice effect as well as salt and sort of the final one that we really expected and actually had a big effect was volume. At the end of the day, it seemed like those components of food made the animals more tired after eating and sugar sort of didn't some to do anything.

Dan Pardi - 10:07: So that's something that I can relate with. I know when I have a big meal, that can make me sleepy. Were you able to then explore what was happening internally in response to the big meal or the different compositions of the meal?

Keith Murphy - 10:20: So I guess another reason we used fruit flies or model organisms in general is because whereas in humans we can go into the fly and sort of turn off all the neurons in their brain and all of the molecular pathways and we can begin to ask, "Which one of these is responsible for driving this behavior?" So we originally just went in and started turning off neurons one by one looking for a defect. What we found is that the homologue of human tachykinin neurons seemed to be regulating the behavior. Basically when you shut these neurons off, the flies no longer become tired after eating.

Dan Pardi - 10:55: When you mean homologue, you mean the equivalent in the fruit fly to the gene that humans have?

Keith Murphy - 11:00: Right, right.

Dan Pardi - 11:01: Okay.

Keith Murphy - 11:01: So when we went back and looked, what are these neurons responding to? Is it just fluid intake in general, or is it a particular feature? It seemed the protein was actually affecting these neurons and turning them on. What this really told us is that not only is there a neuron that responds to this specific component, but there are probably others responding to all of the other components of food and they all somehow integrate. So this is kind of interesting because in people you sort of think becoming tired after eating is this generalized response. Probably happens because blood is flowing out of our brains and through our stomach, but this told us that there are dedicated neurons or little electrical units that seem to trigger the sleep response.

Dan Pardi - 11:42: Yeah.

Keith Murphy - 11:42: You know, maybe they might exist in humans as well.

Dan Pardi - 11:45: That is super interesting. So I was a little surprised that the glucose didn't cause sleepiness because some of the work from Denis Burdakov shows that neurons that are fundamental to generating wake hypocretin/orexin system, are some neurons that are glucose-inhibited. So in the presence of glucose, that'll decrease their activity. And the way that I describe hypocretin neurons is that they're almost like a symphony conductor telling other parts of the wake network when to be active so people that have narcolepsy are missing hypocretin neurons and therefore they're sleepy all the time. So inhibiting those neurons would then cause drowsiness and sleepiness.

12:18: So that makes sense to me, have a big carbohydrate meal at lunch, and then in the afternoon, you might feel more sleepy than if you had let's say a salad and protein. Then again, you might've just had a lot more calories with the big carbohydrate lunch. Are you familiar with Dennis's work and were you surprised by that finding that sugars didn't cause sleepiness?

Keith Murphy - 12:35: Yeah, absolutely. So Dennis among others have definitely shown really great evidence that orexin neurons sense sugar intake and the glucose in the blood. What's interesting and I'll just make note of this is that some collaborators of ours found that the neurons that we were looking at also seemed to mediate wakefulness driven by a lack of sugar intake. So this sort of suggests that these function just like orexin neurons to wake us up when our blood glucose is low. But on the same note, just because these neurons don't show an affect in terms of sugar in the short term, they may also show it in the long term and what that means to me is that orexin neurons probably function over a long period of time but can also function very quickly in response to non-glucose mediated input.

13:21: Something interesting to note and you sort of mentioned it is that if you take out orexin neurons, animals become narcoleptic. That means that in any state, whether the animal is fed or starved, these neurons have to be firing a little bit. Because, you know, if don't eat for awhile and our blood glucose is low or if we've eaten a ton of food and our glucose is high, we don't just start passing out and becoming narcoleptic, right?

Dan Pardi - 13:43: Right, rt.

Keith Murphy - 13:45: I tend to think of orexin neurons now as a long term steady state switch which modulates sort of a very slow gradient of wakefulness, but that they might also integrate these quick signals, something like protein or salt. I can also mention some other things we started thinking about if you're interested.

Dan Pardi - 14:02: Please.

Keith Murphy - 14:02: As soon as we saw that sugar had no effect, didn't mean there wasn't like orexin neurons that ... It still could be, but it also could mean maybe it was analogous to something else. And there was recently this work by Steven Liberles up at Harvard that showed that basically vagus or vagal neurons which are really long fibers that connect our brain through our stomach. He found that these responded to volume and salts. Seeing that and knowing a little bit about the vagus nerve and how it indirectly connects with the sleep center of the brain, we thought, "Well, you know, maybe our neurons are more like this vagus nerve where the reach all the way to the stomach and they communicate this fast information. This is not to say these don't interact with orexin neurons and have some sort of a complex system function, but it sort of says that feeding can regulate sleep in a number of ways, not just blood glucose levels, right?

Dan Pardi - 14:56: And that makes so much sense to me. So many things in our body are ... There's redundancy, there's multiple mechanisms that are working together or concert or in opposition to each other. It's highly complex. I have been interested myself to see the work looking at ion balance around neurons and how that influences their polarization or how active they are. There was some interesting work by Maiken Nedergaard at University of Copenhagen that was published in the Journal of Science I think earlier this year. But he was showing that just simply by altering the ion status, you could create a wake state or a sleep state and make an animal go to sleep usually when they wouldn't want to and if you could alter the extra-cellular levels of potassium and calcium, magnesium, and hydrogen ions, then you could either make an animal go to sleep or make them wake up right away.

Keith Murphy - 15:39: Yeah, yeah, absolutely. Neurons as like a fundamental unit are just really sensitive to how much debris is just sitting outside the cells can change whether or not they fire, especially if it's something that's sort of meant to stimulate some. In that same vein, I was originally thinking, "Well, salt content is just going to change how much any set of neurons are firing." So if you put it in the stomach and the stomach is projecting the [inaudible 00:16:02] like for sure salts could definitely make us tired. Not any different from that study showing it could happen locally in the brain.

Dan Pardi - 16:08: Was there something else too that you thought might be contributing to this effect of high-salt diet? You think it's a component of the protein or is it a particular amino acid that is causing the effect or is it just overall protein intake?

Keith Murphy - 16:21: Great question. So we get asked that all the time and we did start looking into it. Of course, probably people would love for me to say that tryptophan is like especially potent in doing this, but that's not the case. In fact, it seems like it's peptides actually. What a peptide is is the medium complexity protein. So amino acids are the basic unit which didn't some to drive the effect, but for whatever reason, these medium chain ... And not even whole proteins, but these medium chain seems to drive the effect.

16:48: I think from what I can tell from someone else's data in my lab is that peptides for whatever reason are very easily transported across the gut membrane and they might be better able to signal our brain through whatever neurons that we should go to sleep whereas whole protein, they'll stay in the stomach until they're shredded down into these peptides. For whatever reasons, amino acids didn't seem to have an effect. Even though, you brought up Dennis earlier, and he had a study that showed that amino acids actually sort of inhibited the drive of orexin neurons. So again we sort of thought, "Well, maybe it's analogous to orexin neurons, but again that seems not to be the case.

Dan Pardi - 17:24: Tell us a little bit more about the leucokinin system. So this is something that the fruit flies produce that is relevant to is it tachykinin system in humans?

Keith Murphy - 17:33: So I'll tell you a little bit more about what we found with the leucokinin system.

Dan Pardi - 17:37: Great.

Keith Murphy - 17:38: Sort of a funny thing is, all these studies leucokinin and sleep came out in a very short period, all here in 2016. But at the same time we were working on our stuff, Justin Blau's lab up at New York University actually showed that leucokinin neurons, or at least the upstream cells might be regulated by our internal circadian rhythm. So he showed that the sleep output was essentially an output of these cells. We saw that and said, "Oh, well that's pretty interesting. Since we found the same thing, maybe ours is a circadian-gated behavior."

18:09: So when we actually went back and looked, we found that the inhibitory effects on sleep that these upstream leucokinin neurons seem to have really occurred majorly when lights went off or like I guess you could say at dusk. If you look at any other time of the day, they didn't seem to have an effect. Even more interesting and sort of broad to that idea is that I've tried to think about the food coma, being tired after eating a lot of food. It really could be a circadian thing because I know at some points in the day, like when I eat at lunch, that hits me really hard. But if I'll eat a lot for dinner, I don't seem to feel it quite so much. I really do believe that the circadian component that we showed in our paper and that Justin showed in his was a very real thing.

Dan Pardi - 18:51: We have a natural dip in our circadian rhythm alertness drive in the afternoon somewhere between two to four, so where the same meal that has the sleep-inducing effect eaten at noon wouldn't have a similar effect in what's called the wake-maintenance zone that happens after that period. So your alertness drivers are most active in the evening and so whatever sort of external signals that are coming in to the body, their influence is going to be measured against the backdrop of whatever sort of alertness drive you have, what sort of sleep deprivation you've been experiencing, right? So it's again, pretty complex, but something that could promote "sleepiness," we'd put that in quotes, might be you more calm at some time of the day and it might actually make you want to really conk out in the middle of the afternoon, so that circadian component is really key.

Keith Murphy - 19:38: Yeah, right.

Dan Pardi - 19:38: Other people had identified some interesting work related to the circadian component of leucokinins. Tell us about how the leucokinin system was regulating the sleep state of the flies.

Keith Murphy - 19:48: So you mean like in an overarching sense of all the things that are integrated or did you just mean in our study?

Dan Pardi - 19:54: Just in your study. What did you notice about its activity and then you can give us your take about the overarching influence of how does that fit into the-

Keith Murphy - 20:01: Right, right. So it was essentially that there are downstream, so neurons that receive signals from leucokinin we just really refer to them as leucokinin receptor neurons. These seems to reach right into the main sleep center of the fly brain. When you shut these off, the flies actually woke up from needing protein. So normally we would see that as we increase protein, the flies got more tired. But when you remove the single set of cells there really weren't many this response entirely flipped, which kind of suggested that protein actually has some sort of waking effect that was sort of masked by these neurons. Which again really demonstrates the complexity of the system and how nothing's exactly clear as all things balancing each other out.

20:45: Then we layered on top of that, so now we looked at one set of neurons that were upstream. These seem to be turned on just during a particular time of day and they seem to shut down the response of LKR neurons in general. We could really see that because when we stimulated these neurons in flies, we can actually use temperature to turn neurons on and off. We could actually completely suppress the animal's sleep after eating, no matter how much food we gave them or protein, the animals were perfectly awake after eating. So again, there's just layers to this network and this study only really begins to identify a few parts and lays them out as something for everybody to take a look at and create a comprehensive model of. I'm sure in human, hopefully the network starts to be more thoroughly looked at. It's probably going to be even more complex because of the fly brain depends on the order of hundreds of thousands of neurons whereas the human is billions, right?

Dan Pardi - 21:36: When reading your paper, I did find that interesting that there was a thermogenic component to the sleep induction which we all know that a drop in core body temperature is part of the sleep initiation process and we see our core body temperature continue to decline to [inaudible 00:21:49] at some point during the night, somewhere around two to four in the morning and how that can be really important for getting the depth of sleep and again initiating it.

21:58: In fact, harkening back to my conversation with Jerry Siegel, we talked about hunter-gatherers' sleep and how their natural sleeping environment is probably colder than most westernized people and how is that once you acclimate to being comfortable with let's say 55 to 65 degree temperatures in your room, quote unquote, might that actually enable deeper sleep and then speculatively, did that enable these hunter-gatherer populations to get less sleep than was expected and even on the lower end of what's considered normal for humans. But I thought that that was interesting that some of these systems that we're talking about were stimulated by temperature. How did you measure that, by the way?

Keith Murphy - 22:35: So I will say that our studies don't exactly show what you would fit. Originally we used just something called the trip channel which is the temperature sensitive channel which basically turns neurons on and off. We were able to go in and turn on whatever neurons we wanted for whatever period we wanted. By turning them on, we could see "Well, what kind of behavioral effects did they have?" At the same time, we could see what effect does temperature have on this behavior? What we found, and this was interesting because again, a lot of our findings seem to be contradictory to long term sleep, but it seemed that the higher the temperature, the more pronounced this increase in sleep after eating became. Again, like you said, core body temperature drops as we sleep. Even Leslie Griffith's lab I'll mention recently had a paper that showed that lower temperature has allowed flies to basically sleep better at night and less during the day, more as they should or how they would want to sleep given prey/predator interaction and how things might've evolved.

23:33: But for our study, things just kept coming out different than we had expected which really to me just means post-granular sleep or the food coma is different from long term in that maybe it's important only for a short window of time. So whatever rules we had about sleep, for now, we can throw them out the window. What makes sense in a short period of time like right after eating unless it disregards total rules for the minute. Sort of the way we've been thinking about it, anyway.

Dan Pardi - 23:59: Really fascinating. I'm really glad to hear in the beginning you said that you are interested in doing a lot more work on the subject. What are your next steps?

Keith Murphy - 24:07: The first thing we're going after ... So we identified a bunch of neurons in this paper and there are a bunch that we don't even talk about, some that are volume selected and so on. But one of the neurons we found which we really don't know anything about were another set of circadian selective neurons and we're going to go in some elaboration to figure out why are they time selective, what kind of inputs to the sleep region do they have and just elucidate the circuit a little bit more.

24:34: On another branch, which I think is a little bit more interesting to most people is why are we tired after we eat food and why are we tired after we eat even more, why does this effect scale up? We have two theories at the moment and maybe you can comment and let me know your thoughts.

Dan Pardi - 24:48: Sure.

Keith Murphy - 24:48: One which we definitely ... Or at least, I definitely am a huge proponent of is memory. So we know in mammals and flies that there's a short period of time after we learn something that if we go to sleep, we're much more likely to remember it. This makes evolutionary sense because if an animal has to go way out of it's way to find food and it's been starving for awhile, it eats a ton of food, it passes out, it remembers sort of the experience of getting there. "What did I smell, what did I see?" Things like that.

25:18: The other avenue that we're thinking and this has been postulated in theoretical papers is what about nutrient absorption? There's something about being asleep that aids in our gut absorbing nutrients. Whether or not it's energy moving towards the gut to allow us to absorb protein or whether or not it's just simply if your intestines are shaking around and moving, maybe you're going to be excreting more or just basic physics don't allow for absorption or [inaudible 00:25:46] quite as well. Those are the two functional avenues we've begun testing. I think they should make for some really interesting paper.

Dan Pardi - 25:53: One thing that's become increasingly clear to me over the last couple years is the real elegance of energy coordination depending on the time of day and energy needs and usage and so it makes a lot of sense where if you have a big meal, your body's going to want to focus its resources on processing it. So that does make sense to me.

26:11: This might be apocryphal, but my mentor Jed Black who is the director of the Stanford Sleep Clinic for almost 15 years, he does some work in the pharmaceutical industry trying to develop medications for narcolepsy and he worked in Switzerland. So living over there was a different cultural experience and he talked about how looking in some of the older historical texts from his children's reading, they noticed that supper was actually more in the middle of the day and it was the biggest meal of the day. Obviously we have a siesta, which in so many cultures, that is a common behavior and we have virtually eliminated it now, although some of the more forward thinking companies are working in back into the mix.

26:49: Maybe there's just a certain amount of hippocampal recording that take place of trying to take in your environment and all the things that's it's learning before it's optimal to sleep, just like you said, for the consolidation of memory. So I think both are plausible ideas to explore.

Keith Murphy - 27:04: Yeah, you've raised an interesting point which I hadn't thought about. I've heard from my friends who have visited Europe and Spain and so on and they've said, "Oh, yeah, over there, like everybody sleeps right after lunch." It's a common practice. Nobody questions it. Here, that's blasphemy if I do that. So this would've been an old practice, right? And we still experience it. It's still part of our physiology, right? If an old practice that was more based on our general physiology would be to eat a ton more in the middle of the day, then this whole food coma thing, it sounds like it was something intended by nature that we have actively fought as hard as we can to get away from. For good reasons, like you really don't want your employees sleeping during the day.

Dan Pardi - 27:45: Yeah.

Keith Murphy - 27:45: But it definitely happens so it's interesting that you brought that up.

Dan Pardi - 27:48: The peak light exposure for the hunter/gatherer populations that he studied was about nine AM. Then they would seek shade at around noon because it was the hottest time of day. So that also aligns with being a more quiescent, not as active, being in shade, making a big meal then relaxing while it's hottest. It coordinates with the environmental exposures and trying to optimize foraging activities and limiting exposure to the hottest time of day. So, yeah, I think we're coming up with an interesting model here.

Keith Murphy - 28:18: Yeah. I'll say one more thing that's interesting that you brought up is middle of the day, humans are looking for shelter to avoid the sun and the heat. Interestingly enough, fruit flies do the very same thing. Maybe they're higher ranked than they should be, but there's some papers that went very high just by showing flies seem to prefer being under a bridge environment in the middle of the day. So again, if you're not convinced fruit flies are a good model for sleep, there are all these weird intricacies that really make them feel kind of human.

Dan Pardi - 28:45: I can't wait to see what results you come up with next to help us better understand these interesting aspects of human physiology through the lens of a fruit fly. Thanks for all the great work you do and maybe I can bring you back on in the future to talk about what you've discovered next.

Keith Murphy - 28:58: Yeah, absolutely. Thanks so much for having me, Dan. I really appreciate it.

Dan Pardi - 29:01: Appreciate it, Keith, have a great one.

Keith Murphy - 29:02: You, too.

Kendall Kendrick - 29:03: Thanks for listening and come visit us soon at HumanOS.me