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Relatore 1 

Welcome to the Hubermann Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today my guest is Doctor Sachin Panda. Doctor Sachin Panda is a professor and director of the regulatory biology. Laboratory at the Salk Institute of Biological. Studies his laboratory has made numerous important contributions that impact mental health, physical health, and human performance. For instance, his laboratory discovered the neurons in. The eye and. Neurons within the brain that regulate our so-called circadian rhythms, circadian rhythms, are 24 hour rhythms, and everything from gene expression to the overall functioning of tissues. Our levels of mood and alertness, our ability to sleep, appetite, and much, much more. In addition, over the last decade, Dr. Pandas laboratory has made critical discoveries in terms of how our patterns of eating overtime impact our biology and. Health, in particular his laboratory, pioneered discoveries related to so-called intermittent fasting, also sometimes referred to as time restricted feeding. Today, Doctor Panda and I discussed how our circadian behaviors, everything from one we wake up to when we view light to when we avoid viewing light to when we eat and what we eat and when we socialize. And how we socialize impacts our biology and our psychology. Energy and how all of that has a strong impact on our health. During today's discussion, you will learn how restricting your feeding to specific periods within each 24 hour cycle or perhaps even exploring longer patterns of fasting and eating cycles can impact everything from the health of your liver to your gut to your brain. And how all of that impacts things like mood and your ability to perform cognitive work. Indeed, today's discussion goes deep into all aspects of intermittent fasting, AKA time restricted feeding. We talk about the basic science. As well as the recent clinical trials that have explored time restricted feeding in a diverse range of people, including men, women, children, people with diabetes, people who are otherwise healthy and much, much more. I'm quite aware that intermittent fasting is a topic of much debate these days. We go deep into that debate, and by the end of today's discussion. You can be certain. That you will have learned all the latest and all the details all made very clear to you thanks to the incredible expertise discovery and clear communication of Doctor Panda. As some of you may already know, Doctor Panda has authored several important books on the topic of intermittent fasting and how it can benefit various aspects of health. Those books include the circadian code. And a more recent book, The Circadian Diabetes Code, both of which we've provided links to in the show note. Options. In addition, if any of you are interested in learning more about doctor Pandas work, including seeing his publications and reading those publications or supporting his laboratory, you can do that by going to his laboratory website, which we have also LinkedIn. The show note captions. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort. To bring 0 cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is HVMN Ketone, IQ HVMN ketone. IQ is a supplement that increases blood ketone. I want to be clear that I am not following a ketogenic diet. Most people fall into this category. They are not following a ketogenic diet. They are omnivores and they do eat carbohydrates, so their standard fuel source for the brain and body is not ketones. However, I found that by taking ketone IQ, which we know increases blood, ketones. I can achieve much better focus for longer periods of time for any kind of cognitive work and much greater energy levels for exercise, especially if I'm going into that exercise fasted and find myself a little bit hungry when I start that exercise. And this is no surprise. We know that ketones are the brains and bodies, preferred fuel source, even if you're not following a ketogenic diet. So in other words, I and many other people are now starting to leverage endogenous ketones as a fuel source for the brain and body. And yet we are not following a ketogenic diet. And of course, if you are following a ketogenic diet. Ketone IQ will further allow you to increase your blood ketones as a source of. Brain and body. Fuel. If you'd like to try ketone IQ, you can go to hvmn.com/hubermann to save 20% off your order. Again, that's hvmn.com/huberman. Today's episode is also brought to us by. 8 sleep 8 Sleep makes smart mattress covers with cooling, heating and sleep tracking capacity. As I've talked about before on the Human Lab podcast, there is a critical relationship between sleep and body temperature that is, in order to fall asleep and stay deeply asleep, your body temperature needs to drop by about 1 to 3 degrees, and in order to wake up in the morning and feel alert, your body temperature needs to increase by about one to three. The problem with most people's sleeping environment is that even if you make the room cool, the actual environment that you sleep on, that is your mattress and underneath your covers is hard to regulate in terms of temperature. With aid, sleep regulating the temperature of that sleeping environment becomes incredibly easy. In fact, you can change the temperature of that environment across the night, making it a little bit. At the beginning of the night, even cooler, still a few hours into your sleep, which really helps getting into very deep sleep and then warming it as you approach morning so that you wake up feeling most alert. I've been sleeping on an 8 sleep mattress cover for over a year. For now, and it is completely transformed by sleep. If you'd like to try 8 sleep, you can go to eightsleep.com/huberman to save up to $150.00 off their pod. Three, cover 8 sleep currently ships in the USA, Canada, UK, Select countries in the EU and Australia. Again, that's eightsleep.com/huberman. Today's episode is also brought to us by thesis. Thesis makes custom nootropics. Now I am not a fan of the word nootropics because it translates to smart drugs. And as a neuroscientist, what I can tell you is that you. Have circuits in. Your brain that allow you to focus. 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Again, that's take thesis.com/huberman and if you use the code Huberman at checkout, you'll get 10% off your order. The Huberman Lab podcast is now partnered with momentous supplements. To find the supplements we discussed on the Huberman Lab podcast, you can go to live momentis, spelled OUS live momentous.com slash. Uberman and I should just mention that the library of those supplements is constantly expanding. Again, that's live momentous.com/huberman. And now for my discussion with Doctor Sachin Panda. Sachin, Doctor, Panda so good. To see you again. 

Relatore 2 

Yeah. Great to see you. 

Relatore 1 

We are colleagues still, but we used to be right across the street from 1. Another in San Diego. 

Relatore 2 

Yeah, I remember those days. 

Relatore 1 

So I'm delighted that you're here. I think we're going to talk about a. Number of things mainly. Intermittent fasting time, restricted feeding and health, but also the many other things that you're doing. Just before we started recording, we were discussing your recent paper in nature. That involve recordings from post mortem, human retina. So maybe if there's time at the end we can get back to your lab. Has shown that they can essentially maintain or resurrect neurons from. Dead people in order to potentially and eventually provide transplants to rescue vision in the blind, so that's extremely exciting. But of course not the main focus of today's discussion. So we'll have to split it up. The first question I have is how am I supposed to define fasting and time restricted feeding? In meaning, when I go to sleep every night, I'm not eating. So in some sense, everybody. Is doing time restricted feeding to some degree or another? Yeah, at what point can we start thinking about a pattern of eating as time restricted, feeding so-called intermittent fasting? Does it have to do with how regular one is about the start and stop times? How do you think about defining intermittent fasting time, restricted feeding and maybe? Just to simplify the conversation is one term more correct than the other in terms of describing this incredible pattern of feed? 

Relatore 2 

Well, you know about intermittent fasting covers many types of fasting. Actually, it started long time ago and it's embedded into the history of caloric restriction almost 100 years ago, people showed that if you reduce calorie intake in a rat, then that rat can leave for long time. And in those experiments, the calories were reduced every single day. And that led to the idea that if we cut down our calories by. 20% say then we can potentially live longer by doing two things. One is preventing age-related disease or even if we fall as fall sick, maybe we can accelerate cure and keep the repair mechanism going so that we can live longer. But it was very difficult to count calories every day and reduce maintain that. I must say that it's not that caloric restriction is impossible or we are not doing it in fact. Lot of us, we do count calories in our subconscious mind and every time you took out a, you took out. We take out a soda bottle or something. I'm looking at OK, 160K calorie, 30K calorie, 0K calorie we're doing. So the point is it's it's we are doing subconsciously some kind of calorie counting but reducing calorie by 2030% every single day is not possible for many people. So then the idea came in mouse and rat experiment whether they can eat every other day. 

Relatore 

UM. 

Relatore 2 

And in fact, this every other day feeding also led to very similar, almost equivalent health improvement as. Continuous calorie restriction. So then the idea was well, every other day is a little bit hard for humans, but just imagine I would just get to eat only one day and then another day. Then the idea can model for humans. Can they eat less for one or two days in the week, so that led to this 5/2 diet where people who can eat for five days and then two days that will reduce calories. So that's also intermittently people are fasting. Then as you know well to longer also. With this idea that periodic fasting maybe four or five days in every month or two months, three months, you can fast or reduce calorie. And he also found many benefits of calorie restriction was there. 

Relatore 1 

Were those studies on humans? 

Relatore 2 

Many of these studies started in mice, but alternate day fasting 5 to Walters period fasting. All of them have now been done in humans, not for longevity of course. You cannot do this for a long time, but for weight maintenance for reducing some signs of aging or reversing those things. So all of them have been done in humans, mostly healthy humans, and in some cases people with pre diabetes or some aspects of metabolic disease. So that led to the. Idea that that all these forms of fasting in which. The total caloric intake on any given day is reduced for one or more days in a week. A month that became that umbrella term became intermittent fasting. So if you. Look up the scientific literature. Most intermittent fasting involves intentionally reducing calories. For at least one or two days in a week or. Few days in a month, so when we published time restricted feeding the initial mouse experiments and even now most of the mouse experiments we want to test what is the impact of time restriction versus calorie restriction. So in these experiments we don't reduce calorie. On any day of mouse life, so the mice ate the same number of calories as they are libitum fed mice. But still they see health benefit. So that's why we call it time restricted fitting. But since it involves. Living without food for several hours for some people, which is it can be very difficult. The initial experiments was done. They were done. For 8 hours of feeding and 16 hours of fasting, that kind of became popular, and so that that's why people use the same term as intermittent fasting. And now if you. Say intermittent fasting in popular literature or popular media than people usually refer to time restricted eating. So now coming back to. How do you define time restricted fitting? So the way we have been trying to define experimentally and also in literature is trying to. Confine all your energy intake from solid and liquid food combined within a consistent window of eight to 12 hours, because that's something that doable. Of course, people have done time restricted treating with four hours, six hours and some people even try to eat everything within two hours one meal a day. The point is, those are not feasible to maintain for a very long time for a lot of people. 

Relatore 1 

One question about the six hour versus 8 hour versus 12 hour feeding window. Is it important that the feeding window begin and end at the same time more or less, and if so, how much flexibility is there? 

Relatore 2 

Yeah, more or less. 

Relatore 1 

So for instance, I'm somebody that I am not terribly hungry in the morning I like to. Drink water, usually some caffeine and electrolytes. Yeah, in the period before my first meal. And my first meal always lands sometime between 11:00 and 11:00 AM and 12 noon. Yeah, there are exceptions. Occasionally I'll have a breakfast, a proper breakfast, as it's called. I guess it would be improper if you're in a minute. For me, but typically 11:00 AM or noon is when I first eat and my last bite of food is typically around 8:39 PM. That's what works for me. Is that consistency affording me any benefit? And let's just leave aside total caloric number, macro nutrients, plant based meat, etcetera. But is there any benefit to shortening that feeding window that we? Are aware of. Or extending that feeding window or being even more rigid about the start. And the end of that feeding window. 

Relatore 2 

So the start of the feeding window, that's interesting because it the concept of time restricted feeding. When I describe animal studies, it's feeding for humans. It's eating. So the concept actually came from the science of security and rhythm. So that means. Our body has an internal timetable that's present in every cell, in every organ that pre programs many. Molecular aspects of the cells that leads to Physiology and all that stuff. So that essentially there is a predetermined timetable for every cell, every organ to do certain things at certain time. And the circadian clocks as. You and I know are more sensitive to light. Light is the most dominant time giver. So for example, when daylight saving time changes or when we travel from one time zone to another time zone, we feel kind of crappy because our daily activities are out of sync. From our internal clock, so that was known for a very long time. But then around the year 2000, 2002, there was a famous experiment by Uli Siebler from Switzerland. What he did he just. Fed the mice at the wrong time, mice are knocked on all their night feeders, and when he fed the mice during daytime and the liver clock instead of. Following its own routine liver clock actually started following food. So that means by changing our feeding time we can change, we can tune our liver clock. And subsequently the same experiment has been repeated many times, and then we repeated that in 2009 and we figured out, yes, actually outside this. Brain center called suprachiasmatic, nucleus, or SCN, which? Is considered the master circadian clock. Rest of the brain even. Follows when we eat and that came out from Pierre Chambon's lab in Europe, where they systematically looked at even places that are very close to the ocean. For those who are who know dorsomedial hypothalamus or paraventricular nucleus. All of this within a couple of. Four or five millimeters of the CNN, but they were. Following food cue. So then and now, if we think about it. So for example, when the daylight saving time changes just one hour change or one hour change in alignment between our internal time and external time leads to kind of feeling groggy and filling. Not out of peak performance for one or two days, so the rule of thumb is when the time giver. Changes by one hour, then our internal clock takes at least a day to catch up. So that means if you're flying from LA to New York, you're moving through three time zones. Then on an average it will take 3 three days to catch up with the New York Times. For some people, it can be. Even slower, and for some people it can be 2 days, but the bottom line is yes, there is a desynchrony so then. What does it mean for the body so they one of the function of clock is to anticipate when you're going to wake up, for example. So the blood pressure slightly goes up or heart rate goes up or breathing goes up. Similarly for food. Almost every organ that is involved in feeding or eating digestion, all of them, have clocks. So even from saliva production, there's the first phase of digestion to secretion of all the digestive juices and the stomach and then absorption of nutrient and liver metabolism. Everything, the whole village expects when you're supposed to eat and they're getting ready for you to eat the 1st. Meal after fasting for a long time, so that's why it's breaking the faster breakfast and when that time changes, when you change it by two or three hours from one day to another, then sometimes they're like, oh, food didn't come maybe. We will come at a wrong time. We were at the wrong time and then they will track the new eating time. So suppose that one day you have been eating every day at 8:00 AM ice I ate at. 8:00 AM is that? 

Relatore 1 

When you start your reading window, when do you? When does your feeding window shut? 

Relatore 2 

6:00 PM so I eat for around 10 hours. 

Relatore 1 

OK. 

Relatore 2 

And then one day, if I switch to 10 and then what happens is. The clock is thinking well. The food didn't arrive at 8, but it arrived at 10. Maybe tomorrow the food will arrive somewhere between 8:00 and 10:00, so we'll be ready around 9:00. 

Relatore 1 

I see. 

Relatore 2 

So then the. Next day I come back and eat at 8:00 o'clock. Then I may eat, but my clock is not ready to digest that food. So that's why this idea is you have to be consistent to take advantage of this anticipatory activity. Of our cloth. And differ. Systems to get the best. 

Relatore 1 

Out of it. Is there evidence that those anticipatory systems in as they relate to digestion, help us better assimilate our food? I would imagine so. I mean, if you have the gastric juices that are going to help digest the proteins, fats and carbohydrates and already deployed at the time when you eat, I could imagine that food will be better utilized than if you don't. So in other words, what is the advantage of having these anticipatory signals in terms of potential health benefits? 

Relatore 2 

The anticipatory signal is really important from even even from working up. The reason why many people feel not really completely when they wake up to an alarm clock because the alarm clock wakes you up but your body is not prepared so that sleepiness after waking up to an alarm clock is due to a body is not prepared for that. And then the best example is when the. You know when. The daylight saving time changes particularly when we have to wake up one hour early. What happens? People who have underlying heart condition when they are waking up, when the body is not ready or heart is not ready and all of it from the heart has to start pumping a little bit harder than there is. Chance of heart attack and info. That people have looked at hospital records and they find that on those days there's a sharp rise in heart attacks and car accidents too, because your brain is not coordinated, so you cannot make those fine decisions. 

Relatore 1 

In car accidents, right? 

Relatore 2 

So that's a great example of anticipatory activity. But coming back to digestion, one thing is and this is something that many people might have experience. There are many rhythms in our digestive system and one of the rhythms is our. Our intestine has this peristaltic function so it kind of contracts and expands and that moves forward. Food doesn't move due to gravity, so it goes back and forth, and that peristaltic action actually slows down at night. Few hours after our last meal. And so that's why when people eat late at night, for example, then that food doesn't get digested because there is not enough digestive juice first thing and 2nd, even if it gets digested in the stomach, it doesn't move properly. So then the next morning people get up and think. Of course, people consume some alcohol very often, and then they think that this is hangover, but those who don't consume alcohol, then they have the food hangover because it doesn't digest. So that's one extreme example where food. At the wrong time. Can so healthy food at the wrong time can be crap? Or junk, yeah. 

Relatore 1 

I've experienced that where if I've worked late or I couldn't eat dinner or something and then I get home. I always debate whether or not to try and sleep, but if I'm too hungry, oftentimes it's challenging. And so for me, sometimes consuming something that at least seems. Easily digestible like yogurt or something in a liquid form is better for me than if I eat a meal. I've made the mistake of going to the refrigerator, being super hungry and eating a bunch of food at 10:00 or 11:00 PM and then falling asleep. And indeed the SLA. If I'm tired enough, can be quite deep, but the next morning I feel just completely physically and and cognitively weighed down. So I think what you just described makes a lot of sense. So yeah, is it so if someone were to select a a feeding window regardless of whether or. Not it falls into classic intermittent fasting time. 

Relatore 

Yeah, yeah, yeah. 

Relatore 1 

Restricted feeding sounds like. Just eating your first bite of food and eating your last bite of food at more or less the same time each day has benefits. I have this question you mentioned feeding versus eating and I think it's actually not just a grammatical semantic issue. And here's why. We tend to think about when you take your first bite of food and then when you take your last bite of food. But of course, foods digested different rates, more fat in there is going to digest, make carbohydrates digest slower, et cetera. I mean, there's all these adjustments to the glycemic index and so forth with foods and combination. Is it better to think about not eating? But you're fed state and blood sugar. So for instance, I often get out. Just on social media, does blank break a fast? So and so I like to think about it scientifically, like, OK is does plain water break a fast? Does air break a fast? Does 1 grain of sugar. Of sucrose break a fast? Well, probably not, but does one teaspoon of sugar break a fast? Well, you could say yes, but transiently like so. I mean, when we're talking about breaking a fast, are we talking about a rise in blood glucose or are there molecular signals downstream of of a rise in blood glucose? That cannot be reversed. In other words, if I'm going to eat my first meal every day at noon, and I'm gonna eat my last bite of food at 8:00 PM and at 9:00 AM for whatever reason, I have coffee with one teaspoon of sugar in it. I suppose in the strictest sense I've broken my fast, but maybe by if I went for a hard run that morning, maybe by 9:30 AM, I'm back in a, quote UN quote fasted state. So what is the fasted state really? Because when I'm eating at 8:00 PM, just to give another. Example I'm start fasting at 8:01 perhaps. Yeah, but I have my blood glucose is elevated, so I'm not really fasted. 

Relatore 2 

No, no, no. Yeah. 

Relatore 1 

I I'm fed. It's just that I'm not eating the verb right. OK, so, so I again, I I don't want to get overly detailed just for sake of getting detail, but I think a lot of the confusion out. There about what breaks a fast. Is related specifically to this. Issue. Yeah, which is if I eat a whole pizza after sitting around all day, it's very different than if I eat a whole pizza after having run out 26 mile. Marathon that. Very different. Yeah, metabolically speaking. So how should people think about fasted versus fed? Can we be mildly fasted versus severe fasted? Can we be fed ish versus very fed? Anyway, I'll. I'll stop asking questions now because they all relate to the. 

Relatore 2 

Same thing, yeah. Now there's a very interesting question. And then unfortunately, as you can, as you have, you might have seen in. Life the most obvious questions are often unanswered because it's so hard to do this damn experiments, because if you really want to address this in humans, you have to bring humans, put them in isolation, just like you said. I can now imagine planning five or six different experiments. Each experiment should involve. 8 or 10 volunteers. It's gender, sex. And then do it so it's difficult. So now let's go back to see. How do we let's dissect it in terms of, say, indirect calorimetry? So for example, indirect calorimetry is based on this principle that whatever oxygen we breathe in and carbon dioxide, we breathe out. If we can measure these two, then we can figure out whether our body. In total, we we are not saying whether it's the liver, gut or fat or muscle in total, whether it's consuming glucose or fat as energy source. The idea is when we when we are without food for several hours then. Ideally, our body will tap onto glycogen first and then do a little bit of fat, and then when the body is mostly running on fat then that ratio of CO2 to oxygen will come to 0.7. But what is interesting is we can do these experiments in mice, so we can go to mice and ask, OK, So what happens in mice so? And mice, mice are a little bit very different because mice are not simply little people, they're the metabolism is different. They store relatively less glycogen than humans do in terms of total metabolism. So they. Overnight, within 12 to 14 hours the RER respiratory exchange ratio or this ratio will go from one when they are consuming mostly glucose or carbohydrate as energy source, it will slow down slowly. Go to point 7.75. It's after 12 to 14 hours. They're kind of mostly running on fat. So now as we give them food. Within 10 or 15 minutes, they're not actually consuming couple of grams of food. They might have consumed, say 100 or 200 milligram of that chow. So which is less than say 5% of the food. And then the area will immediately begin to rise, as if. That small amount of food stopped that fat burning process and cranked up the UM. Carbohydrate burning process. 

Relatore 1 

When you say fat burning process, you mean body fat stores being burned, right? Not dietary fat, correct? 

Relatore 2 

So it's all body fat means that that's why I said we don't know where that fat is being burned, because we're just measuring how how much mice is bidding in and out. So for example, it can be from the skin. Subcutaneous fat. Belly fat, but yeah. 

Relatore 1 

Not dietary fat. 

Relatore 2 

Now, by that time, the dietary fat is already observed and digested, and hopefully it's sitting in the liver or adipose tissue somewhere. But it's the fat less body fat. Yes, thank you. 

Relatore 1 

For yeah, yeah. The reason I ask is that nowadays I think more than half of the battles about nutrition that I see online relate to this issue where I won't name names, but someone will come along and say. Low carbohydrate diet allows you to burn more. Fat and the more nuanced people out there will say, well, that's true. But you're also talking about dietary fat. You know the word fat can confuse people. 

Relatore 2 

Yeah, yeah, yeah, yeah. 

Relatore 1 

I realize you're not doing that. You're you are certainly not one of the people guilty of doing this. But indeed you eat more fat, you'll burn more fat, but that doesn't mean. You'll burn more body fat, in fact. I think the data say. Under conditions of caloric restriction, you'll actually burn less. I hope I don't. 

Relatore 2 

Yeah. Yeah, because they. 

Relatore 1 

I'll probably get. I'll probably get pitchforks sent through the mail toward me on on that one. But but I think that's true, whereas you know people who consume carbohydrate can still burn body fat, even though the majority of the fuel they're burning is from carbohydrates. 

Relatore 2 

Yeah, so here in this case, for example from mice, we know that as soon as they start eating, the RER goes up. Coming back to your question, what would be ideal for us to do? The experiment would be OK. So we'll go back to that and then give the mouse maybe 100. Milligram of food. And mouse runs around in the case, and then we'll continue to measure to see how long it takes for the mouse to come back. And then so that's one aspect. So now let's see. Let's stay on this and then I'll come back and talk about non caloric food and how whether that is considered. 

Relatore 1 

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Relatore 2 

So there is a famous experiment that was published last year by Jota Khasis lab and it came out in science. And that relates to caloric restriction and. We kind of started with this idea. We started discussing that the rat experiments were done with caloric restriction, and researchers gave reduced calorie consumption by 20% or 30% and gave that food the rats, and then subsequently mice and they all lived longer. What is interesting is. In all those experiments, the researchers came and gave this bolus of food at one time, whereas they had libitum fed mice or rats they had access to food all the time. So they're eating all the time. And then these rats were given 20% less. And what happens is these mice or rats? Then I'm going to take that less food, which is rest on now and just eat a little bit of lunch and then snack after three hours or snack after three hours, they gobble up all that food within two to three hours maximum 4 hours food is gone. 

Relatore 1 

So they're sort of on the omad diet, the one meal a day. 

Relatore 2 

Yeah, they're almost like in one meal a day, three to four hours. Food is gone. Or you can sit there on. 4 hours eating or feeding and 20 hours fasting. So then the question became well, the benefit of calorie restriction as we know is it due to reduced calorie. Time restricted feeling or timing. There is a timing component to it that they are eating all of that within three to four hours and then there is a long fasting and this is a difficult question to answer because now. You have to ask these poor grad students or technicians to come and split that food into 8 or 10 or 15 different small portions and then give them to mice in every two hours. So Joe Takahasi, who actually published the 1st paper in 2017, showing that most characteristics and I mean he used the protocol that was used by calorie restriction field. It actually creates a condition of time restriction. So he showed that and then he went back and worked with engineers to come up with a smart case where he could actually tell he could program how much food is given to mice at what time of the day or night completely. So then he took this for example. Suppose say the ad libitum fed mice. It's say 5 grams of chow in a day. And if you want to reduce calories by 20%, then the CR mouse should get 4 grams of food. And it divided this into 9 or 10 meals and then gave them in every 90 minutes. So and this gets they're eating small. Meals throughout day and night, so there is no fasting. So you can say that, well, this mouse actually is not getting into fasting because in every few hours is getting some food. And then he measured how long the mouse is going to live. And he used account means this is a very standard protocol. People count how many mice are dying on which day and then examine them to see whether they died because they there was an accident or they actually there was a natural cause. And then they calculate at the end what is the half life. So 50% survival, because that's on an average. That's a good indicator because if there is an outlier that will live for a long time, then that can skew. So what was interesting was the Addleton fed mice. Of course, they lived certain number of days and then this. Calorie restricted mice. That never got into super fasting, but kind of eating snacking throughout day and night that also lived 10% extra, 10% longer. So that means caloric restriction extended lifespan by 10%. 

Relatore 1 

I've wondered about this because recently. You know, there's been. There were a bunch of news headlines about intermittent fasting, and I, and frankly, I was frustrated if you looked at one major news outlet, they would say time restricted feeding affords no additional benefit beyond caloric restriction for weight loss, then another. Popular press venue, let's call it that same study described as time restricted feeding. Doesn't work. Yeah, right. And then another one, maybe someplace even more extreme, you know, time restricted feeding only beneficial because of caloric restriction or something like that. 

Relatore 2 

Yeah, yeah. 

Relatore 

Yeah, yeah. 

Relatore 1 

So what you've essentially got are three different interpretations of the same data, all of which are, well, two of which are true, one of which is false in my opinion. But what I think people take away from that is ohh time restricted feeding isn't valuable, which is not the case. I think for many people it's a convenient way to eat because at least for people like me, it's simpler to designate between. And portions of my day when I'm eating and portions of day my day when I'm not eating as opposed to eat portion control for other people. Portion control can work. But all of that is related to either maintenance or loss of weight. None of it deals with the potential health benefits independent of weight loss, yeah. 

Relatore 2 

Right. So. 

Relatore 1 

And so I I think that if we can segment those out, obviously in humans, it's hard to know if a given. Treatment or experiment is extending life because you don't really know how long people would live anyway. Yeah, right. Whereas with mice, you have some sense of when the mortality is likely to occur. So what? What can we say about time restricted feeding and longevity in terms of biomarkers or in terms of any other indication that people who start and stop their feeding window at a consistent? Time somewhere between 8:00 and 12 hours per 24 hour cycle. Are tilting the scales towards living longer as opposed to living. 

Relatore 2 

Shorter this example of this news article that you mentioned is really interesting because that relates to Joe's Geotech has his study because I described that if you split calories and eat throughout the day throughout day and night, then the mice lived 10% extra. But if you now give mouse the same. Calorie restricted diet. And fit them during daytime. Whether within 12 hours or two hours, then the mice live 10% extra. 

Relatore 1 

Beyond that, yeah, so 20% longer. 

Relatore 2 

20%. 

Relatore 1 

So OK, so let me make sure I understand that. So that so that I make sure I understand, if you take a certain number of calories and you distribute them throughout the 24 hour cycle. It's caloric restriction the mice will live 10% longer, yeah. If you, however restrict that to the active cycle of the. So for humans, the daytime then. 20% then they live 20% longer, so it's not just total caloric intake. Yeah, and meaning, it's not just important to be sub maintenance and calories for sake of longevity. 

Relatore 2 

20%. 

Relatore 1 

It also is important as to when in the 24 hour cycle, yeah, you eat those calories. Do I have? 

Relatore 2 

That right, so now that's still this story is not over. Because this mice were fed during daytime and they're not. Supposed to it. 

Relatore 1 

That's right. So for us, it would be the equivalent of being on the night shift and only eating at night. 

Relatore 2 

Only on the nation. 

Relatore 1 

But a subtler sub maintenance calorie diet, I guess is the right way to say it. 

Relatore 2 

But when he fed mice during night time, when they're supposed to eat, and they're seeing this getting the same number of calories within 12 hours or two hours. And the mice left 35. Percent longer than the. 

Relatore 1 

35% longer, so scale to human lifespan which. You know we. Don't know, but but a 35. Percent longer would mean that. And again, no one knows, but humans now what is the average mortality in the United States? Somewhere around 80. 

Relatore 2 

US life. So it's around 80. It used to be 80 now. Slow reduced little bit because of COVID. But let's take 80. 

Relatore 1 

OK so. 

Relatore 2 

People are then now living. 

Relatore 1 

Somewhere between 25 and 35 years longer put I'm putting some error bars on there. 

Relatore 2 

Yes. Yeah, yeah, yeah, yeah. So that was really profound, but. Now you pointed out biomarker and other stuff. So now. If you look at any given time within that experiment, and actually Joe went back and had a separate cohort of mice very similar. And so that he could take tissue samples. And of course, in this case, you have to sacrifice the mouse. And he looked for. He did lot of molecular analysis. With known markers, for example hemoglobin A1C equivalent or glucose control cholesterol, all this stuff. He could not find anything. That predicted the benefit of caloric restriction. So that means in this experiment, whatever we know so far, the predictor of longevity, none of them could predict whether this C are only mouse, which at throughout day and night. That mouse is going to live less than the night Fed mouse that was going to live 3525% extra. 

Relatore 1 

Does that mean that there are biomarkers related to longevity that we just haven't discovered yet? 

Relatore 2 

So that's exactly so. That means whatever we know so far about biomarkers, those. He could not use to predict. Maybe there was a lot of noise. Maybe he wanted. He had to use more number of mice to get there because, you know biomarkers. I'm not going. To predict in every instance there is some error. What is also very interesting is if you look at the body weight and body composition of all these mice, there is no difference in body weight and body composition. 

Relatore 1 

Across all these different groups. 

Relatore 2 

Across all these groups. 

Relatore 1 

So it doesn't matter when they ate, provided they were sub sub maintenance calorie intake so less. Fewer calories than is required to maintain their weight didn't matter what pattern of eat. They were the same way. So that in many ways seems to mimic the human studies where they say, look, it doesn't really matter whether or not you use clerk restriction or or you start your feeding window in the morning or start your feeding window in the evening or you or you portion control, forsake of weight, weight loss. 

Relatore 2 

Because you're taking a snapshot of that and then another thing with the human study that we are referring to here, that in that human study. People are actually already eating within 10 hours window. Habitually when they selected these people to have them enroll in the study. So they were already eating for 10 hours and fasting for 14 hours. All participants had to reduce their caloric intake, and they reduced by almost 25%. The CR Group continued with 10 hour sitting window and the CR plus time restricted group had to hit the same number of calories within. 

Relatore 1 

8 hours, so it's just a 2. Hour difference. 

Relatore 2 

It's just a 2 hours difference, so now. 

Relatore 1 

OK, so that people, I just want to make sure people can understand. So in this human study, which is the one that I felt. At the popular press venues, all except one venue got either semi wrong or badly wrong in terms of their conclusion. That was my interpretation anyway. Was that either people came into the study eating basically in a 10 hour feeding window which goes back to my first question, which is that most people are not eating in the middle of the night, or if they're on shift work and they are. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

Then they're sleeping during the day anyway, so they're eating in a 10 to 12 hour feeding window anyway. So you're saying they either did caloric restriction portion control within the 10 hour window, or another group within. The study. Sub maintenance calories or caloric restriction CR as we're calling it the acronym CR but restricted that to an 8 hour feeding window and they didn't see any difference in. Terms of weight loss. 

Relatore 2 

Weight loss and also. 

Relatore 1 

Yeah, but it's not all that surprising, right? I mean, if it's just a. Two hour difference. 

Relatore 2 

Yeah, exactly. So we have done that experiment in mice and we don't see difference in not only weight loss. Many other markers. And I was telling you about this jota Kazis paper, where I told you that he allowed his mice to eat within two hours or 12 hours. Sub caloric diet. 

Relatore 1 

2 or 12. 

Relatore 2 

2 or 12. 

Relatore 1 

Yeah, that's dramatic. 

Relatore 2 

But still he did not see change in longevity. Even within those two. So that means when you do calorie restriction and then. At least per month and you are within 12 hours window. That's that is giving the mice the best benefit, the optimum benefit and 2-3 or five or 12 per mouse doesn't matter, at least for longevity. 

Relatore 1 

Can we conclude for humans that whether or not a feeding window? 4 hours 6 hours, 8 hours or 12 doesn't matter provided the calories are are similar or. 

Relatore 2 

Well, I won't go to that extent because we don't know many of these particularly we don't know how this sort of eating window will affect both sexes because you know we always think many of these. House experiments, even that I told you about. Those are done only in male. 

Relatore 1 

Mice that should be changing, right? Because the NIH, I know this cause I'm on study section, which is just a. Bunch of people who. Require who review grants is that every grant now has to include sex as a biological variable. It's hard to get away with. Well, rather I should say it the way it should be stated, which is people are required. And should want to look at these phenomenon in male and female mice. Yes, especially if there are differences. So in this case. 

Relatore 2 

There are many. I mean, there was also another paper in time restricted feeding that also came out a big paper showing that they thermogenesis was accounting for loss in fat, mass in time restricted fed mice. That was also done only in male mice. So this is we are paying attention to it. So we are now doing all of our studies in male and female and we do see big differences between male and female coming back to humans. What typically happens is when you're trying to do 4 hours or six hours or time restricted eating, people will inadvertently reduce. Their caloric intake. 

Relatore 1 

Just because of gut volume, I tried one meal per day and and I felt like I was eating so much at that one sitting. Yeah, that it led to a lot of gastric distress and I get tired after the meal and part of the reason I like to do time restricted feeding is I have. More energy. And certainly in the fasted state, I feel more energized, especially if I'm ingesting a little caffeine or something. Like that. 

Relatore 2 

So people will reduce energy intake and then? Some people who are more active, they can actually unconsciously, they may be spending more energy in their physical activity and basal metabolic rate. All of this combined than how much they. Thing and that can have a very adverse effect in long term because we know that this energy deficit and in fact there is a scientific term for that, it's called Red S relative energy deficit in sports. 

Relatore 1 

Relative energy deficit in sports, OK. 

Relatore 2 

Yeah, that's because nearly 40% of athletes. Not the NFL guys, but you know, a lot of people who do track and. So and nearly 40% of athletes actually experience these Reds Reds without knowing. 

Relatore 1 

Can male and female athletes both experience Reds? So it's Reds, Reds, relative ex relative energy deficit in sports. Interesting is the first I've heard this acronym. 

Relatore 2 

Male and female. Re energy. 

Relatore 1 

We have a new acronym, folks, this is. Good to add to it a list of other acronyms, but I so males and females can experience it so. In females I've heard that. Meds can lead to amenorrhea, so loss of of of the menstrual cycle. 

Relatore 2 

So that's so common that so prevalent that in fact many women, many female athletes, they take it for granted that yes, if they are more active then they will lose their menstrual cycle, which is which may be common. But it's not normal or optimum for health. 

Relatore 1 

And even if they don't want to get. Pregnant. Yeah, yeah, yeah, yeah. We had an expert on female hormones come on and say the very same thing that regular cycling is a of of of ovulatory menstrual cycle is is important to try and. 

Relatore 2 

It's very important. 

Relatore 1 

Maintain. Yeah, yeah. 

Relatore 2 

And so that's one. But then what is really concerning is it does affect bone health. And in this state, people actually over long period of time the lose bone mass and the bone also becomes more prone to injury microfracture and fractures. So again, it's a risk means if some people are trying to eat within very short time and they're physically active, that happens. And it also has impact on means the reason why. These women are losing menstrual cycle as their HPG axis is disrupted. Hypothalamus pituitary gonadal axis. And it starts in May start again offstream at hypothalamus pituitary. So that means the HPA axis, hypothalamus, pituitary and adrenal axis may also get disrupted. One of the symptoms of rats is also depression, anxiety, bipolar like symptoms. And we know that many. Many athletes experience that we think that, well, this this might be just peer pressure that always trying to compete and we know them. Unfortunately, there are few athletes who just can't cope it, and there are many attempted suicide or suicide, so this is a serious issue and there's also another new topic. And the lab. To come up with a mouse model of Reds and then study it, but this is one risk why we should not reduce our heating interval to two such. To one meal or very short time because it can have adverse side effects that we don't know now and maybe in future we'll figure out when we systematically study them. There are studies that are published showing 4 hours and six hours time. Restricted eating has benefits on weight loss, but those are on healthy individuals and they were. And the studies. So they the study team took were already monitoring. They made sure that there was no sudden weight loss or weight loss. Below some safety. So those are very different from regular people who may be even normal weight, even with within the healthy range. If they do, then they can potentially. So that's why what we think is 8 to 10 hours, maybe the ideal spot to begin with and. Once you are physically active and you are also spending a lot of energy in physical activity or sports, you can even go up to 12 hours because in mice we have done that experiment up to 12 hours, they do get a lot of benefits, not all. 

Relatore 1 

But so this is 12 hours of feeding, yeah. 

Relatore 2 

12 hours of 12 hours of. Yeah, in humans again, nobody has done systematically 12 hours, but there was one study in Europe from Tianhai collect lab and tihai and I we collaborate. So they used our mysekf and clock app. This is a research app we developed just to this is mostly used in time. Eating studies. And he had nearly, I think he started with 200 Swiss participants, but then at the end, he selected and took very small number of group people who are very meticulous about recording all their food and divided them into usual feeding, whatever they wanted to eat, whenever they wanted to eat. And they were given the advice of Swiss nutrition advice that's given to improved health and reduced blood glucose, almost like diabetes prevention program in the US. And then the other group was given advice to eat within 12 hours. This is very early on in timeless rating and we thought that the mice were getting some benefit. Let's try with the 12 hours has any benefit. The bottom line is. At the end of three months and six months, what he reported is both groups lost same amount of body weight. And then there was not too much significant difference between groups, but both groups actually improved their health. So the bottom line is the Swiss nutritional advice that he was giving, which is the standard of. There it achieved the same amount of weight loss as just giving people this advice that it within 12 hours. So one way to look at it, look at the. Results like this. And then he went to more extent and actually looked at every single meal these people consumed. So the close to, I think close to 60 or 70,000 mill. Records and pictures he went through and then classified them to say whether these are good quality food S they call it the Nova classification. 12341 is the food that you can almost eat raw fruits, vegetables, yogurt and dairy products that you can almost without any preparation. And then second, Nova, two is kind of home home cooked food that most people will prepare in few minutes and then three and then fourth one is the food that you can never prepare at home. So for example biscuit or cookies that we usually. Purchase and a few other. And usually the Nova four are unhealthy ultra processed foods. So which we should not retain. So the advice is to. Reduce #4. And what he found was people who got all this advice to improve their nutrition quality. They actually improved their nutrition quality. They reduced their Nova for food. And people who were in time restricting the eight within 12 hours, they did not change the nutrition quality. But what is interesting is they both got the same modest weight loss. So that begs the question that in the maybe 10 high will do this experiment again to combine nutrition advice with time restriction and maybe reduce the time to 10 hours and that might help. 12 hours is something that I say. Anyone from 5 year old to 100 year old can do and if you are trying to maintain weight that might be a good way and combine that with exercise it will be great. 

Relatore 1 

And you and people can more easily avoid Reds. In that way women and for non athletes or recreational exercises, it sounds like women. If they distribute their calories across 12 hours or less likely to lose their menstrual cycle. 

Relatore 2 

So again, this is something that we have to look carefully. They have to be. Because we do have the my security and clock app that many people download and self monitor and they share the data for researchers and once. 

Relatore 1 

We will provide a link to that, by the way, it's. A great it's. 

Relatore 2 

A great tool, yeah, but but once in a while we do get this input from some women saying, oh, I started doing your time rating. And I I'm seeing all these problems. And then I asked them, OK, So what? Else are you doing? They typically improve their nutrition quality so. That eating only salad and. So they're trying to increase the fiber intake and it's really hard to eat so much of uncooked food because cooking helps to absorb more nutrient and then at the same time, they're running 5 miles every day. And of course, all of this combined, like, can lead to Reds like symptom. So that's why. 12 I think is a good point if you're combining physical exercise and better nutrition quality, because in mice also we have seen that if mice are eating healthy food and they're eating within 10 to 12 hours. Then they also live longer than mice that are eating healthy food. But distributing that calorie over a long period of time. And this is rough Hardy cavers finding from NIH. He has systematically done this study with two different types of diet and in mice, and he finds the same thing that. Even mice that are eating within 12 hours, they do live longer than mice. That eat randomly, even healthy. 

Relatore 1 

Food I I recall a recent study. I think it was either published in cell reports or cell reports. Forgive me for not remembering which both of course cell press journals, excellent journals, which explored time restricted feeding in the context of low carbohydrate or non low carbohydrate diet. So is low carbohydrate. Versus low carbohydrate and time restricted. Yeah, so these all caloric matched. Yeah, right. Between groups and then non low carbohydrate diets. So, so more standard. I think it was somewhere in the neighborhood of 60% of calories from complex carbohydrates and and as I recall, the the greatest weight. Remember same calories across groups. Folks was achieved with low carbohydrate plus caloric restriction. Yeah, and I wondered why all the popular news venues didn't cover that study, but that's why I'm bringing it up now. I thought this is really interesting and and I'm somebody who's cycled low carbohydrate diet. And before I find it hard to sleep after about three or four days of being on a low starch. Yeah, diet. Just personally I so I like to eat some starches. Yeah, especially if exercising intensely or working intensely. That's just. Yeah, a little editorial there that but. Look, I know many people who do just feel better on a low carbohydrate diet, but yeah, well, what do you think of those data? Because it speaks to the idea that, OK, it's not just the total number of calories. It's not just the quality of those calories. It's the timing of those calories and maybe carbohydrate restriction in conjunction with. Time restricted feeding might be the best path for people who are looking to lose weight. 

Relatore 2 

No, I I totally agree that when it comes to nutrition, quality, quantity and timing, all these three matter, nearly 40% of people who maintain healthy body weight because 60% are overweight and obese. 40% are maintaining healthy body weight and out of those 40% I would say nearly majority of them. Are very aware about how much they're eating and what quality of food dieting. 

Relatore 1 

So you're really an optimist. You're looking at the 40% of the glass that's or should we say not full. Yeah, that was a pun intended, but the no, it's a very interesting way of looking at rather than saying, you know why or 60% of Americans. Obese, saying why are 40% not obese? That's a very interesting way to look at. 

Relatore 2 

It I mean subconsciously, we're always making that decision means I know means I'm sure that you're not going and eating cheeseburger every day because you want to improve. 

Relatore 1 

You know. Yeah, right. 

Relatore 2 

You want? 

Relatore 1 

Yeah, exactly. I wouldn't feel good. I enjoy a cheeseburger now and again, but I. No, not certainly not at this stage or any stage of my life. I think that. I think people actually think the pandemic had a lot to do with this. I think that people started to take a look at what they were doing to support or not support their health generally. I know people gained a lot of weight during the pandemic. Other people got really into fitness. I've seen some colleagues, you've always maintained you've always been in good shape. Which is the first time I've seen you in a while and you seem to have aged backwards, so you are a poster for your own ideas and hypothesis about time. And but but I. I noticed that during the pandemic, a number of people emerged from the pandemic in better shape. Other people in much worse shape. It seemed like there was a it was like a bimodal. Distribution there, yeah. So yeah, I get the sense that starting and stopping eating at more or less the same time each day, even if caloric restriction is not the main focus. Yeah, has additional benefits. Can we talk about some of those benefits as they relate to the other things that impact health? So for instance, if you're starting and stopping eating at more or less the same times each day, are you sleeping better? Are you getting more predictable shifts in alertness and sleepiness? Like can you predict when you'll feel good enough to exercise? Maybe we could talk about that because you of course. Are well known for time restricted feeding and the science around that, but also other things as well. Not the least of which is circadian biology generally. So I always think of the main time keepers for our system being feeding light. And social connection. Did I miss? And maybe and temperature. So how do these combine with one another and using timing that we begin and stop feeding as kind of an anchor point we. 

Relatore 2 

Explore that a little bit. So, you know, we got into this beginning and end and then we you asked for the. Calorie how much calorie will break the 1st? One thing that I want the listeners and viewers. Bring back to this timing of one way when you're breaking the first because we equate health with weight body weight and that's when we are talking about nutrition quality and quantity, because both of them have impact. So now let's think about mental health. Because a lot of people do struggle with mental health, they have anxiety or depression. And also so gut health, because there are a lot of people who also have acid reflux or heartburn. And we know that acid reflux or heartburn can be exacerbated by caffeine intake in empty stomach. Those who have acid reflux or heartburn, they're prone to that then having black coffee in the morning. Before any food can upset their stomach. So that's why in those cases, it's very clearly that caffeine for them becomes the trigger that something the food is supposed to come and then the stomach is not seeing the food. So it's overreacting, producing excess acid, and that comes up to the esophagus. And that's what they're experiencing. So if people have that kind of condition, then maybe they should consider when they drink their first coffee is breaking their. Overall fast or kind of putting them, putting their health at risk for acid reflux. The other thing is people who have anxiety, panic attack. We know that caffeine can. Judge you off so. 

Relatore 1 

Especially on an empty stomach. 

Relatore 2 

Especially on an empty stomach. So for them again. Caffeine can be a trigger, so that's why I want to kind of differentiate that there is this mental health and other aspects of health. And these are two clear examples where anxiety panic attack related to brain health or acid reflux related to our gut health in those cases. When we consume that caffeine in the morning can affect so. 

Relatore 1 

Do you avoid caffeine in the morning? No, actually. 

Relatore 2 

Here is the interesting history about caffeine and this is something I did not know and I was once invited to this history of night time activity. And maybe we can take a little bit of detour and talk about night time activity because that fascinates me. As a circadian biologist. Because over the last 200,000 years means we assume that humans Homosassa Piens evolved 200,000 years ago. So we have been as a species, we have been living on this planet for 200,000 years. And only in the last. You can say couple of 1000 or 5000 years when we came to control fire or maybe you can even go back to 100,000 years. There is some debate. So then the question is well. When you control fire and will light it up, the fire and we could light up whenever we wanted, we can add fuel and we can stop the fire when we don't want it. That's the key. Ability in humans that differentiates them from all the other species. No other species. We can always say yes, there are signs of this intelligent decision making. For example, we know many codes can make decision many, many animals. They kind of figure out, strategize how to get food, but controlled use of fire is something very specific. Human and when we started controlling fire, fire did not essentially extend the day. Because fire created a evening that was very different from what people did during the day. And what people used to do during day, they walked a lot means gathering food was almost everything that we did. And so in the evening after the after the after we brought food, mostly tubers or maybe lentils to cook, or once in a while animals, so that we can. Would BBQ all of those things happened around fire and fire was so expensive that it was mostly communal fire? So if you go back to, for example, Masai? And all these sorry populations that have no access to electricity and are still living, kind of that historical life. Fire is a communal event and they sat around. They cooked food and then what happened? They did not talk about work. They talked about culture, they talked, they sang, they danced, they strategized. That's how politics started. Philosophy started. Science started all of these things that are very unique to human civilization started around Fireside Chat. So in that way, if you think about it, we are still doing Fireside chat. The only thing is we have the microwave and the television, our social media. 

Relatore 1 

And now we chat with our thumbs. 

Relatore 2 

Right. So it's still so we are hooked to that evening activity because that's when we are completely free from the pressure of the work and we want to express ourselves. That's our independent time. So that. Most people find it very difficult to do time retreating and stop eating at 6:00 o'clock because it's ingrained in our in our even DNA that we want to eat and socialize in the evening. So now let's Fast forward and see what is the role of coffee in this. If you look at coffee concepts and particularly cafe where people can come and have a little bit of coffee and socialize, it also started as an evening activity and this is in. Now we can go back to Istanbul because that's one place where coffee cafes started in mid 16th century. So we are talking about 1540 to 1570 and that's when. I'm sorry I'm forgetting the name of historians who actually invited me and. OK, his name is Jamal Kafadar, and I must be butchering the name, but I will. 

Relatore 1 

We will provide the spelling and the wonderful thing about social media is somebody will tell us on YouTube the proper pronunciation. So it is a great opportunity if you know the proper pronunciation, please put it in the comments on YouTube. 

Relatore 2 

I'm actually I'm even checking right now in my Endnote library. It's not picking up that, so I must be. 

Relatore 1 

That's right. We'll provide a link, provide a link. 

Relatore 2 

So what happened was so coffee was introduced and people came and drank coffee and talked about politics. 

Relatore 1 

At night at night. 

Relatore 2 

That evening and it actually started with Sufi branch of Islam because they are the ones who conjunct coffee in the evening. And this is the branch of Islam where they actually sing and dance and all that happened in the evening. So singing and dancing by the Sufi. And then here in Istanbul, people started congregating and having talk about politics. But then around the same time. Some you know. In Turkey, there was a good, sizeable number of Muslims who have to do 5 prayers a day. Number of prayers at set time. The first prayer is very early in the morning. And then they figured out that if they wake up and immediately have coffee, then they can stay awake for the first prayer. And in that way, they felt pretty good and they woke up. So that's how it started as a morning drink to stay awake. And kind of get get on with the day. But what happened was I don't know whether you have ever tried Turkish coffee. It's very thick. 

Relatore 1 

Yeah, a few years ago, right before the pandemic. 2019 I traveled to Turkey is first of all, the food is amazing. The coffee is indeed very, very thick and. I have a pretty high caffeine tolerance. Yeah, from drinking so much coffee and yerba mate over the years and still do I really enjoy it? But yeah, it's it's very intense. And So what you're saying is that. Coffee intake started as a way to extend into the night the ability to extend into the night at all was because of the ability to harness fire and then coffee stimulatory properties were. Leveraged toward mourning, which is essentially like the way I think about it. We didn't episode on caffeine and some someone else. Michael Pollan, not I described it this way that you sort of taking a loan out on your energy bank account with coffee, you're suppressing the adenosine system. Adenosine makes you sleepy, but that adenosine system will kick in later. So you're you're it's a credit card. Source with an interest. Yeah, right, right. And the interest being an energetic. Lag that you're. And to experience in the afternoon, yeah. 

Relatore 2 

But what happened was, with the strong coffee that gave heartburn and acid reflux to a lot of people. So then. They started eating something with coffee, and that's how the culture of breakfast started in Turkey. 

Relatore 1 

So coffee actually led to the development of breakfast, not the other way around. 

Relatore 2 

And that? Yeah, so it definitely. 

Relatore 1 

That's very heartening. No again, no pun intended for the the caffeine lovers among us, which I count myself. One of those. 

Relatore 2 

So essentially the food before coffee became breakfast. So you kind. Give something to your to your stomach or it's busy digesting that. And then when the coffee comes in, it's not reacting to coffee and creating acid reflux. 

Relatore 1 

So it wasn't as fascinating. So it wasn't that breakfast is necessary on its own. It was essentially a buffer against the gastric distress. Caused by caffeine intake. 

Relatore 2 

At least in that culture, means in that context, we cannot say that whether the same thing happened in all over the world where coffee is not consumed, but still people eat something. 

Relatore 1 

You said you start your first meal of the day at around 8:00. What time do you wake up? 

Relatore 2 

I wake up around six. I started to six. 

Relatore 1 

What time do you have your first? 

Relatore 2 

No, actually, I have. So that's why I brought up this story because I have coffee after my breakfast. 

Relatore 1 

I'm a big proponent of delaying caffeine intake for a few hours after waking for other reasons that my listeners have heard me talk about endlessly, so I won't bother with that now, but I think. Allowing the just suffice to say that allowing some of the natural waking up signals to occur and using light to kind of clear away and adenosine to further extend an activity at is better than using a stimulant. But until a few hours later. This is fascinating because I've never thought about the link between extension. Into the night socialization or socializing, rather feeding and caffeine. I'd like to take a brief break and thank our sponsor inside track. Inside Tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long. Term health can. Only be analyzed from a quality blood test. The problem with. A lot of blood and DNA tests out there. However, is that you get data back about metabolic factors, lipids and hormones and so forth. But you don't know what to do with those data inside. Tracker solves that problem and makes it very easy for you to understand what sorts of nutritional. Behavioral, maybe even supplementation based interventions you might want to take on in order to adjust the numbers of those metabolic factors, hormones, lipids and other things that impact your immediate and long term health to bring those numbers into the ranges that are appropriate and indeed optimal for you, if you'd like to try inside tracker, go to insidetracker.com slash. Huberman, they have a special promotion right now through PIE Day, March 14th, where you can get 31% off their ultimate plan. This is their biggest promotion of the year. Again, if you go to insidetracker.com/huberman you can get 31% off their ultimate plan. 

Relatore 2 

Now actually I'm kind of. Speaking what many other researchers have found, and this this particularly. This fireside chat I'm forgetting again the name of the scientist. I think she is from University of Washington, Seattle. She went to Africa and kind of recorded what people are talking. Of course you could not understand what they were talking. 

Relatore 1 

Twitter and whether or not Tesla's stock is going up. Of course, no, just just kidding. Folks, exactly. 

Relatore 2 

And then came back and tried to translate and then figured out that what they were talking during daytime and in the evening were very different. So so so. 

Relatore 1 

What are they talking about at night? Do you? 

Relatore 2 

So exactly so this is like they're talking about matchmaking and talking about politics and strategizing to gather food or or even singing and dancing. So this is, if you think, if we think about it, how we manage. To our bedtime, what we do between sunset and bedtime. Affects most of our health. 

Relatore 1 

I'm going to think about that for a moment. I totally agree. And by the way. I'm a huge. Believer and and I'm in living in great hope for the idea that. Right now I do think that scientists understand a lot more about the different stages of sleep, slow wave, sleep, REM sleep, etcetera than we do active waking states like we talk about being focused or being alert, but that's not those aren't scientific terms as we know, but I do. Believe and I've noticed a distinct difference between the 1st. 8 hours of the day in terms of cognition and we know that the catecholamines are at much higher levels plus cortisol, dopamine, cortisol, epinephrine. All of that is really at much higher levels than in the later evening and so the this evening time it all, it's certainly in the context of mental health. We know that morning and evening, we are basically different creatures. 

Relatore 2 

Yeah, they're different picture. So that's why I I think in the evening, if you think about it. Again, this is again another set of research from my good friend for us here, who Iglesias. Oh, yeah. 

Relatore 1 

Yeah, I'm a big fan of Horacio's another. He's a fellow Argentine, so occasionally we riff about things related to that, but he's a wonderful biologist. Are you guys collaborating? Yeah. OK. 

Relatore 2 

He's he's kind of, I say he's very humble and keeps a low profile, but he did. Amazing, amazing research. 

Relatore 1 

Totally agree. 

Relatore 2 

And he does research that we want to know, but nobody is ready to do it because field research is very difficult to go to the wilderness or go to the places where there is no electricity and then record when these people are eating, sleeping or. In this case, activity exposure to light, that's what Horacio has done and he puts this active watch, which is kind of a modern activity tracker, but it's a little bit more refined because it also collects light information. What he found was most of these Argentinian towers, who have no access to electricity. They consistently go to bed somewhere between 3 to 3 1/2 hours after sunset, so this is very important because we always think that. Our ancestors, when they didn't have electricity as soon as the sun went down, they just went to sleep, no? The fire extended the evening so they were staying awake for three to four hours. Kind of. You know, decompressing themselves that we say and and doing all these activities, cooking, sharing meals and then they would. Go to sleep. And if you look at the sleep onset variability, it was very small, like they're going to bed almost within 15 to 30 minutes standard deviation. 

Relatore 1 

So no night owls versus morning people, this kind of. 

Relatore 2 

Exactly. So we will. Get to that. 

Relatore 1 

None of this this the I get attacked by for many reasons. It just goes with the the business I'm in and being public facing these days. But every time I talk about viewing sunrise or low angle sunlight, you know, getting some sunlight early as someone says. Well, I'm a night owl and they just it's almost like a a protest of trying to protect identity. 

Relatore 

Yeah, yeah. 

Relatore 1 

It's become this ideological I I I identity related thing. I'm a night owl. I'm a morning person and I'm not. But you're telling me that in these cultures where there isn't electricity, but there is fire, people are going to sleep within all of them within about 15 minutes of one another. So there is no such thing as a night owl or a morning. Person in the context of. 

Relatore 2 

So you actually asked him pointedly because and then he said no, he has not seen and he has dragged hundreds of people. And if we ask, there are many. Many sleep researchers, at least the public facing sleep physicians or experts, they will say, yeah, we can say 1/3 of people are night owl 1/3 of morning and then 1/3 in between. But. 

Relatore 1 

Yeah, they call them like bears, wolfs and you know, and I'm not being disparaging that idea. I think people really do feel as if as if they Orient towards one pattern or another. 

Relatore 2 

When I was an undergrad student, I never went to bed before midnight and actually midnight was my. Going to bed time exactly like 11:45. I'll try to get ready to hit bed and then by 12, I'm in bed and I used to get up at 6615 with him, with an alarm, of course. 

Relatore 1 

It's still a that's a pretty short sleep. 

Relatore 2 

And but then daytime. I used to take 45 minutes to one hour nap and there was regular like even if. Whenever I got time, of course in college, you know, you don't have the whole debt. Like in high school, you don't have opportunity to NAP, but in college. You can. I might. 

Relatore 1 

Been one of those kids with his hoodie on, napping on the desk, but they come around and. They wake you up so. 

Relatore 2 

Yeah, but in in this case, just come back to the dorm and after lunch, usually I used to take nap. So then in grad school. I remember I rarely went to bed before 2:00 AM and I could have clearly said that I'm a night owl. And actually, I was at night. Night owl was very comfortable staying up so late. I was very productive doing experiments, writing all these manuscripts, mostly and. But then afterwards, when I look back in post Doc, when I had when we had our daughter, then things started changing because you have to. Put the baby to sleep. And then after the baby sleeps, it's almost when you have a baby, your life revolves around the baby. So then we have to dim down the light. There is no caffeine and alcohol drinking or any other things after the baby sleeps because we cannot do too much noise. So then I realize that no, I'm actually not a night owl, and I became kind of more normal because I could go to sleep between 10:00 and 11:00. And that's how I thought, well, maybe this is very unique to me. But what is interesting is. I have another colleague, good friend, Ken Wright, Junior Colorado at Colorado, and he also had grad students and and postdocs like me who strongly believed that they were night owls just like everybody else. And he took Ken took the whole life for camping, and when they were camping, of course, there is less life. And a lot of physical activity hiking during the day and they all went to bed between 9:00 and 10:30 PM. 

Relatore 1 

So that study. 

Relatore 2 

I love. 

Relatore 1 

Yeah, what Sachin just described was a study. I think there were. Two studies and what's interesting is I recall is that after going camping for a weekend where people. 

Relatore 2 

There are two, yeah. 

Relatore 1 

Wake with the more or less with the sunrise and go to sleep a few hours after sunset, their melatonin rhythms and cortisol rhythms and sleep wake rhythm. Persisted on that schedule for several weeks despite returning to environments where there was a lot of artificial lighting, which I find amazing that yeah, just a weekend of consistent rising and going to bed with the sunrise and sunset. Yeah, more or less. Allowed a a reset that was very long lasting. 

Relatore 2 

So actually even in Horus yesterday he found that almost all the towers they wake up around sunrise time and it's amazing when I look at the standard deviation, it's like so tight. 

Relatore 1 

So take that night owl so-called night owls. I also didn't Graduate School. I would work until 2:00 AM. I loved it. I blast music in the lab. Everyone was at home. Pretty much not everyone. But there were the the night crew. And then I'd get in sometime around. Get up or sometime around 9:30. Ten and then get in around 11. And it was no problem because I was going to stay so very late. And then over time I notice I've become more locked to a standard schedule. So I think what we're saying is that the clock can our internal clocks can shift. Yeah, but this idea that we are genetically. Bias towards one schedule or another may need revisiting. That's what that's the conclusion I'm taking from this. 

Relatore 2 

Yes, I guess there are a couple of aspects. One is, you know some people are genetically so preprogrammed because the other flip side is what is called technically familial advanced sleep phase syndrome. So these people, you can give them caffeine or whatever, but they will fall asleep. Say at 8:00 o'clock they cannot stay awake till 9 or 10. And since it's a very strong phenotype in sleep and circadian rhythm field, they are very well studied. So in fact Louis Ptacek and Ingui Fu, they were the first one to track one family like this, and then they figured out there was a mutation in one of the clock genes, period two, that clock gene and that mutation. Allowed the clock to run in a way that these people went to bed very early. 

Relatore 1 

I guess historically. Given these fireside chats that those people were probably not contributing much to the political discussion, whatever they was decided after they went to sleep is what they woke up into. That reminds me because as you were describing the difference between night time discussions versus morning discussions, is there any theme to what is discussed in the morning versus in the night time where people just sitting there? Eating and sipping their caffeine and just waking up. But is is there. Are there any ideas about what morning discussions really consist of? 

Relatore 2 

Morning discussions or daytime discussions are mostly about work and like hunting, gathering or farming. All that stuff. And even these days, that's what we do. We, you know, you go to, I go to work and it's mostly one meeting after another. And we're talking about how means different different committees and you're solving problems or your students come with questions, you have your TA or the office hours. All these things work related. We're not talking. I mean serious philosophy of unless you're in a philosophy department and you're talking about political science. And also we are not singing and dancing. So that's why the evening activity even these days are very different. And typically the evening activities are where we express ourselves. We express who we are, we feel like we are free and you know you and I. We have this academic intellectual freedom we can talk about our work just like we're talking now. There are a lot of people who work for even in tech industry. They may be working for Google and all these big tech company. They cannot talk about their work to anybody else. 

Relatore 1 

It's all secret. 

Relatore 2 

It's all secret, so just imagine they're staying. So they're spending. More than half of the wake up time at work. Thinking and doing work, but they cannot talk about that work, even sometimes to their own family. So then what happens for them? A lot of people also do the same thing, like the person who is going and baking in a restaurant or cooking, or the person who is taking trusts and driving nurses and doctors. 

Relatore 1 

Or nurses and doctors can't talk about their patients. There's confidentiality. 

Relatore 2 

Yeah, they can't talk about it. And some people just don't want to talk about it. It's so stressful. They don't want to. Bring that stress home. So that's why I always say that from sunset until we go to bed, during that time we try to find time for ourselves. People say this is me time. The me time is essentially we want to truly express who we are or we want to entertain ourselves because. On the fireside chat. It's not that everybody was a performer. There are also some audience. So we always switch our roles. Sometimes we are performing and sometimes we are observing. So that's what happens with me time so. 

Relatore 1 

I love this. So maybe social media time should be restricted to just maybe a small portion of that evening time, because I would hope that people would also interact socially with in, in the real sense, yeah. 

Relatore 2 

Or maybe in a constructive way. Or maybe we use that for come back to your family members whom you love, or you can have some productive discussion or something. So it's it's kind of interesting. 

Relatore 1 

I think it's extremely interesting because I think, again, this this conversation about time restricted feeding is really a conversation about. 

Relatore 2 

Securian rhythms. 

Relatore 1 

And sleep wake activity and human evolution. 

Relatore 

Right. 

Relatore 2 

So that's why let's go back to this night owl because we we kind of made a comment that maybe it's not genetic, but this is where I'm still wrapping my head around because you know these days there's some Java studies where they're trying to look at night owls. To see whether there are some genetic Lincolns. And you know, sometimes we always think, yeah, if you take half a million people, of course you'll find some low side that. But going back to this idea that are some people more sensitive to light. So that it's likely that the same level of light, even in the same household, may make some people stay awake late into the night, whereas other people are more resistant to light so that they can go to bed early. And since light has become so prevalent these days, and this tobus story that we are talking about. People going on camping there is we have. Removed that light. So there is some evidence that peoples light sensitivity, particularly the IP RGC of this intrinsically photosensitive retinal ganglion cell or the simple speakers, the blue light sensors in our eyes. There seems to be even one log unit change in sensitivity as measured by pupil constriction. 

Relatore 1 

So for some people. A small amount of artificial light at night could really shift their circadian clock. Yeah, wake them up essentially. 

Relatore 2 

And then put some and. 

Relatore 1 

Then yeah, I'm very sensitive to light at night. Yeah, exquisitely sensitive to. 

Relatore 2 

It so then you are like a. 

Relatore 1 

In many ways I've been told this. Thank you. Yeah, I think. I have actually switched to using a red night light, but I should be clear, not a fancy high cost red light forsake of any kind of infrared simulation, but a red party light type light and I find that that was based on reading one study that we covered in an episode on Jet Lag and shift work which. Was that it seems to reduce the cortisol releasing properties of light at night to use red shifted light. So I just use a red light bulb. I actually travel with one. If I go to an Airbnb or hotel and I switch the red light and I find that I fall asleep and stay asleep throughout the night much more consistently, especially in when I'm in new environments where which always makes it disruptive. To sleep. It's made an enormous difference in the depth and duration of my sleep, and because oftentimes hotel lights, you know, in the bathroom, you'll turn them on and just you're just getting being and you're right. Some people don't seem. To to be bothered by that I. I I really struggle with that. 

Relatore 2 

And in fact, in Tinas right after puberty. It seems to be. I think that's when the teenagers become more sensitive, sensitive to light and it's very it's well known that the teenage boys and girls, they tend to stay awake late into the night and they can stay up to 12 past midnight. Although they can stay off that lid, that doesn't mean that their sleep schedule is reduced. Their body still needs the same amount of sleep as other teenagers, so that's why they are more likely not to wake up at 6:30 or seven when we expect them to wake up and go. To school, I have a question. 

Relatore 1 

And I ask every circadian related biologist I can come into contact with this and no one has been able to give me an answer one way or the other, but I grew up hearing that every hour of sleep before midnight was of more value or potency than the hours after midnight. And indeed, I find that if I go to sleep at 9. 30 or 10 PM. I can wake up at 3:00 or 4:00 AM feeling pretty fantastic and ready to lean into the day, but if I get the equivalent number of hours of sleep starting at midnight, I feel like complete garbage when I wake up after 5-6 hours. So is there any truth to the idea that going to sleep within? Three hours of sunset is somehow better for our circadian timing mechanisms. 

Relatore 2 

Well, there are few things. One you said that you are very sensitive to light. So I assume that you also have weird bright light in the evening as best as you could can. 

Relatore 1 

As best I can, yeah. 

Relatore 2 

And then what is happening is with absence of that bright light, your melatonin levels begin to rise. So you are prepared for sleep. Of course, this is something that we cannot measure. Just measuring melatonin in every one hour or 30 minutes is very difficult and there is no consumer facing product here. So it's likely that your your body is preparing very well under this dim light to fall asleep, and when you are trying to stay awake and go sleep at midnight, then maybe from midnight for the first three or four hours, you are sleeping well. But then after that, your melatonin level might be beginning to fall. And it's not only melatonin, your core body temperature, and then your heart rate and everything is changing to make you awake. But the sleep debt that you have accumulated is pushing you to be in bed. So there is the. Tension between the circadian aspect and your sleep date, and unfortunately you cannot have good night of restorative sleep for the second-half of the sleep because of the. 

Relatore 1 

Tension that makes good sense. 

Relatore 2 

Yeah. So that's why. You are not the only one, and there are many people who who. Experience that and in fact a lot of people think that, well, this may be the way I sleep. Maybe I'm not. I'm not designed to sleep restoratively until. You know, I sleep one day just like the camping trip, and they realize what you're what you're missing? 

Relatore 1 

And then they realize what what it feels like to be have that. I want to make sure that we talk about the other aspect of fire, which is you had a paper that came out recently, very interesting paper studying firefighters and time restricted feeding and firefighters. Would you share with us the the general contour and maybe even some of the specifics of? Of that study, because I think it's very interesting for for sake of shift workers, but for everybody really to understand that these results. 

Relatore 2 

So let's go back to shift workers, because this also relates to all of us. I always say that each of us is a shift worker or has lived the life of a shift worker and we have experienced how terrible difficult it is. And now let's start with what is the definition of a shift worker shift work like lifestyle? There is no universal definition. Unfortunately, but there are many European countries, and particularly if you go to International Labour Organization, then you will find some references. Different European countries have slightly different definition, which essentially points to. If you stay awake for two or more hours during your habitual sleep time, and when they say habitual sleep time, they assume that we have, just like you said, we are kind of programmed to sleep somewhere between say 10:00 PM and then stay in bed and kind of wake up after 5:00 AM. So the idea is, if you stay, if you're staying awake for two or more hours between 10:00 PM and 5:00 AM. And you are engaged in some activity, whether it's physical activity or intellectual activity. You are not lying in bed and wondering, worrying about something but actually working. So that defines that's defined as shift work and you don't have to do it every single day. Even if you do it once a week. For 50 weeks. Then that itself is enough to disrupt your Physiology and metabolism behavior. Brain function like a shift worker. The reason is, as we discussed. When you change. Our external timing queue. So in this case when you travel, jet lag for or traveling across three days, 3 hours of jet lag will take three days to reset. Similarly, if you're staying awake for two hours extra, or if you're waking up two hours before your habitual wake up time, then we just don't get wake up and then be engaged in some activity in the dark. Most of us and means unless you are wearing a infrared goggles. We turn on light and light resets our clock, so in that way. Every time we stay up for two or more hours, even for one night, then for the next two nights, our clock is kind of trying to catch up. So in that way, for three days. The day of the disruption and then two days following the disruption, a clock is trying to catch up with the outside time. So our clock our body is not on time without. So that means almost for half of the. Week or half of the year, our clock is trying to catch up. So that's the definition of shift work. So now let's come back to. Department of Labor Statistics, U.S. government they have not been tracking what percentage of people are doing shift work accurately because there are many difficulties in tracking too. But it's generally accepted that one in five working adults. Is a card carrying shift worker card carrying shift workers means they are nurses, doctors, firefighters. And bakers truck drivers. And many in the service industry. So that's one in five. So 20% of working adults. Then if we think about. All the college students, just like I was doing, and you must have done. They also expect. 

Relatore 1 

Grant deadlines. 

Relatore 2 

Grant deadlines. Then we are also experiencing experiencing the lifestyle of a shift worker because we are delaying sleep. Even if you're delaying sleep by two hours for most of the cholesterols for five days and then the weekend, you're trying to catch up. That's kind of a circadian disruption going on. Then you take 1.5 or 1.6 million new months. In the US every year, so when the child is born, then that mother is a shift worker and actually that mother is worse than a shift worker because you know, you don't know what time of the night the baby will wake up and how many times. And there is no weekend in motherhood. So they're also living the life. Of a ship worker. We don't count many food delivery and Uber driver Lyft drivers are shift workers, but they many of them, we know that they live so in that way. Within the actual number of people who are experiencing the life of a shift worker is somewhere around 50% of the adults population at any given time. So that's why it's also another point that you might have heard from people they'll say, oh, I cannot do time restating. Because my schedule is messed up, I work in a different way and that. Comes into play. So that's why we thought, OK, so we should try something on shift work. Another point is, although one in five people are shipped workers, they carry disproportionately heavier burden of disease. As almost all age-related disease that we can think of, whether it's high blood pressure, usually high blood pressure starts in 40s or 50s. High cholesterol, gastrointestinal problem, indigestion. Chronic inflammation of the colon and and even colon cancer in many cases. And then, of course, diabetes. All of these disproportionately more prevalent among ship workers. But then when you think about clinical trials, whether it's a drug. Or a lifestyle. Often one of the top 10 exclusion factor criteria is shift work, so people who are doing shift work, we exclude them from many of these trials. One thing is. Most physicians and most scientists, even people who do shift work, they know that they are the body and mind is so messed up. That often time, even medications may not help them. And so that's why we don't try new medication. Why to take the risk when we know it may not help them. And then when it comes to lifestyle intervention, whether it's sleep extension, for example, we cannot do because they are supposed to stay awake and do their job. We cannot ask them to stay asleep at night. And then physical activity and exercise, some people can do, but some people are so tired after all night that they don't have the energy to do physical activity and then nutrition. Again, most nutrition studies involved the participants to come to the clinic and get. One-on-one or one or attend group sessions and they cannot come. And they cannot even sometimes come to the clinic, visit when people have to take draw blood. And in fact, there is another caveat that. If suppose I am healthy. I have perfectly normal blood pressure, blood glucose, cholesterol, everything is normal and I live the life of a ship worker just for five nights. That means I'm sleeping less, maybe four or five hours. And even if I don't eat at night time, of course, many shift workers also feel hungry. And just for to keep their work, they eat. Just after five days, my blood glucose level will read almost like I'm pre diabetic. 

Relatore 1 

I actually saw a study in publishing prostheses at the National Academy that showed that even 100 lux dim light present in the room while people are sleeping with eyes closed can lead to disruptions in morning blood glucose levels and directions that are not good. Yeah. One night, so the the faint clock in the corner, or even a night light that's too bright could be problematic, by the way, folks, these effects are reversible, so I whenever I say these things, I we get a lot of comments about, Oh my goodness, what have I been doing for years? But, you know, kids. With nightlights this. Is an issue, but what I'm hearing is that. One in five people are. Truly shift workers in the classic sense. Their jobs require they work at night or into the night and sleep into the day. But far more people are shift workers by virtue of the fact that they're tweeting or working, or watching movies at night, even though it's not work, and that they're not being paid for that time, they are essentially operating like shift workers. If we add those two groups together, would we say it's what a 1/3 of Americans? 

Relatore 2 

Would say half of America. 

Relatore 1 

Half of America. 

Relatore 2 

Yeah, if you if. You take teenagers because you know high school students and college students because again, going back to HORACIOUS study, because whereas you're also collected. Activity data from high school students and college students, and we have replicated that with high school students and college students in San Diego. So that's Seattle and San Diego and this study now there are many sleep researchers that have been collecting this data. And what we find is typically the high school students, they are going to bid, say, around midnight, and college students, at least the UCSD students. We found maybe one out of 100 who went to bed before midnight. 

Relatore 1 

That that reminds me that Horacio Iglesias just published this really nice paper showing that, counter to what we believe students now, there's the University of Washington in Seattle. I should mention where it's very dark in the winter. Young people, these are people in their 20s are staying up later. In the winter months compared to the summer months, yeah, which is, you know, totally counterintuitive. 

Relatore 2 

Sounds good. 

Relatore 1 

You think everyone stays up late in the summer and goes to bed early in the winter. But because of artificial. Lighting. It's the. 

Relatore 2 

Exact opposite, yeah, so and another means I don't know how your monitored it, but my other suspicion I'm not saying whether it's true in winter. We are more likely to consume. No coffee. Hot chocolate in the evening and that might also be delayed. Sleep onset. That makes sense. So in that way, again, here is another thing which can be related to policy or practice at Educational Institute. So what happened during COVID was everybody went to remote learning. The assignments became digital and assignments. Some mission became digital and there are many systems online systems that came into play. And by default, the assignment submission deadline became midnight. So then now what is happening is I don't know about Stanford. Maybe you are when you are giving assignment, when is the deadline midnight? So then most of us, most students, they will try to cram as much as possible, try to solve as much as possible and some mid at midnight. And it will be really cool to go back to your System Administrator to see is there a so many frequency plot of frequency distribution of what time people are submitting. Assignment because we know means when we submit our grant. 

Relatore 1 

So I mean, you know, you hear about the obesity crisis, the crisis of metabolic disorders, not just in the US, but everywhere in the world. I mean, it's really striking. I remember going to a Keystone meeting, scientific meeting in the early 2000s, and there was a map of the United States and it showed where the obesity rates were over 30% in adults and the entire country basically was lighting up like crazy. Now it would be the entire country, but there were these kind of zones in the middle that were. We're almost devoid of of obesity, Colorado. Namely Idaho at that time. Those are now also falling under the umbrella of of rampant obesity. And you and everyone is speculating, OK, is it, you know, is it seed oils, is it, is it this is it, that is it highly processed foods. I'm guessing it's all of those things, including lack of activity, but one has to wonder, given everything we're talking about in terms of metabolic dysfunction, late shifted eating all these issues with late shifted eating and staying up late with artificial lighting, but they're not. 

Relatore 2 

It's all of those, yeah. 

Relatore 1 

That could be one of the major factors in the so-called obesity crisis. 

Relatore 2 

It's likely you know, we all, let's say, freshman 15. That's right. This this gives gaining 15 pounds in their freshman year in college, and this is where I think, as educator or professors, it would be interesting to go back and see what can we do because another thing that's also becoming more and more common, for example, I I give a. Circadian rhythm class means I just give 2 lectures and I remember when I started 1517 years ago that lecture used to be around 1:30 PM or 2:00 PM in the afternoon and it's a 2 1/2 hour lecture. So it's done by 5. And for the last before the pandemic, I realized that they changed the timing. Now the lecture was starting at 7:00 PM. So it's finishing by nine 9:30 PM and these kids, they had to go and eat. After 9:30 and study, socialize and then Fireside chat, and then to express themselves like to feel free from assignments, one of them going to do that after they submit the assignment, then they're going to do. 

Relatore 1 

Study. Socialize. Fireside chat. 

Relatore 2 

So that's why we have to go back and revisit this issue, say, OK. So for adults, for most of us who are working a day job, our deadline is 5:00 PM in most cases, right means at least in university system, the person who is submitting the grant or who is doing. And taking care of my IRB or icook, they're. All living at 5:00 o'clock. So for me, everything has to end. 

Relatore 1 

By five, I think for most people out there, so this raises a a kind of macroscopic question, which is maybe it's not so much about restricting the feeding window, but maybe it's about feeding mostly and and being active mostly in the early part of the day. I mean, you know, I. Could imagine a time. 3-4 years from now, when it's about when waking up early and going to bed within 3 hours of sunset is the protocol which harnesses all other protocols. Right. You're going to exercise. You're going to do it in that time you're going to. You're going to do it in that time. You're going to socialize, you're going to do it in. In time and in doing so, you're also avoiding a lot of the issues related to disrupted sleep. 

Relatore 2 

So that's why all these things, as you said Timeshifting is just one aspect of the security and health and these are all interconnected and going back to the comment about within 3 hours of sunset, yes. That's good. But then what happens in? Toronto or Vancouver in winter. 

Relatore 1 

I guess they're going to bed very, very early, but also. Waking up very, very early. You know, one of the things that I hear all the time because I'm always beating on the drum of getting the morning sunlight, even if through cloud covers. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

People say there's no sun here this time of year, and I I forgive me, but there is sun. Unless you live in a cave, their sun is just coming through cloud cover. No matter where you live in the world, there's sun. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

Unless you live in a cave, of course. So I want to make sure that we didn't overlook what was the major conclusion of the firefighter study? 

Relatore 2 

OK. So we'll. Go back to the firefighter story. So the reason why we did this study was. As I said, there are a lot of us who are living the lifestyle of firefighters or shipped workers and shipped workers are excluded from studies. So that means whatever we are learning about lifestyle or even medications that may be beneficial for people who actually have. A normal schedule. But not for people who have a disrupted schedule. And if you look up clinicaltrial.gov, there are more than 400,000 studies listed, and if you search how many studies are on shift workers, it's less than 1000. And many of you ask most of them are to see what is wrong with shift workers. Like, that's how we know that shift work increases our risk for metabolic disease, cancer and even some aspects of dementia. But if you ask how many studies have done to improve the health of shift worker alone, that's less than 50 means. I means I have to go back and check the actual number, but it's. Less than 50. So that's why we got super excited. We thought from circadian rhythm perspective, that's something to. So this study. Again, this kind of study is only possible because I'm at Salk and we are affiliated with UCSD, and I can work with UCSD physicians to do this study. So I collaborate with uh doctor Pam Tog, who is the director of Cardiac Rehab Center in UCSD. And Pam has many firefighters as her patients, and we both know that the number one cause for death and disability on work for firefighters is not fighting fire but just getting heart attack and. So they have a very high incidence of heart attack and stroke, and they're also highly prone to different kinds of cancer. And it may be difficult to ascribe cancer to disruption, security and disruption, because they're also exposed to a lot of toxins anytime fire burns, that smell of fire is essentially smell of. Carcinogens and they're breathing, even if they have the hood on and respirator, they still. So the idea was very simple. We know that firefighters nearly. 70% of firefighters in the US full-time firefighters because there are volunteer firefighters and then full-time firefighters. The full time firefighters, 70% of them work 24 hours shift. So for example in San Diego, they come in at their shift is from 8:00 AM to 8:00 AM the next day and they do, at least in San Diego, they do one day on one day off on off 4 cycles and then four days off. And but in some fire departments, they actually do 48 hours shift. So they come for two days, 2 days of two days, two days off and. Then four or five days off. 

Relatore 1 

Thank you, firefighters. Yeah, yeah. 

Relatore 2 

So then the idea was OK, so we'll screen firefighters and then find firefighters who are metabolically unhealthy, and then we'll see whether they can actually follow 10 hours time restricted eating because. The point is, if firefighters can follow it, then. Everybody else will be. Because with all that stress, if they can. And this is again where I should also acknowledge the San Diego Fire and Rescue Department because without their help, we could not have even submitted the grant and at that time, David Picon, who is the health and Wellness Battalion Chief, he is the one who actually approached us because. He's very careful, he knew. That the job that they do. Max them weaker in long term and can kill them in long term. So he was always looking for new solutions so he approached us and man we said this is the idea he said well I love this idea because we are not asking them to sleep more or we are not going to cut down the overtime or shift or. Change the work schedule. The only thing we'll be doing is ask them to eat within 10 hours. And hopefully we can. 

Relatore 1 

Do this consistently between the days that they're working and not working, yes. So that means if they're from 8:00 AM to 8:00 AM working, then the next day, then they go home, then they're gonna eat on the same schedule they did when they were at the fire Firehouse. Yeah, but while at home. So they're not allowing themselves to to deviate from that, that. 

Relatore 2 

So we we thought whether they can do it or not because the number one goal or the primary outcome in this clinical trial was feasibility. 

Relatore 1 

OK. 

Relatore 2 

Can they do it? And then second was, if they do it, then what happens to their blood sugar and weight and all? This other stuff. And then we started the study and we hit the next hurdle and that is. You know, firefighters are very, very tight knit community and they want to make sure that you understand their culture and the best way to understand their culture is to live the life of a firefighter. So Emily Manugian, who is the first author, C and then we had a dinner jourian who is now in Med school. She was a research coordinator at that time. They volunteer, they said OK. We'll go to the. Busiest fire station in San Diego and will live the life of a firefighter and the San Diego Fire and Rescue and the city. They all agreed they reported for duty at 7:30 in the morning. They assigned a bed in the station because all fire stations do have some beds for. Fired firefighters to rest and they have assignment, so they have assigned a. Right. Yeah. So every time a 911 call came, and if that fire station in that fire station, that fire engine was called then just like other firefighters, they had to run, get into the gears and just the shoes and a jacket and a helmet and get in the seat and attend the call. Of course, they won't go to the site. They just get out of the truck. Right there. And come back. So in that 24 hours, Emily got 10 calls at night that she had to run to, but there were more than 10 times the they got the 91 every time the 911 call 10. Then there is a bit that goes out. All firefighters were sleeping or resting. They would get up, or if they're doing something, they'll look up to see which engine is called. 

Relatore 1 

So it's not just the ones that go out, it's everyone gets woken up. 

Relatore 2 

Everyone gets woken up, so that means in a night typical night they're waking. 101520 times. Sometimes, so they're almost like, you know, new moms are like firefighters because they don't have any idea what time the baby will cry and for what reason. Also, they don't know so similarly. So that's what Emily did. And then next morning, once he came back. 

Relatore 1 

But scratch school seem easy. 

Relatore 2 

I'm like. 

Relatore 1 

Yeah, so if? 

Relatore 2 

So then we did the study and we essentially assigned all the firefighters. We recruited, 150 firefighters. We assigned half of them to Mediterranean diet because you cannot do any harm. You have to give them something good. So that's another thing they said. No, we want something that we know works for firefighters and there was a Mediterranean diet study. So. So everybody was supposed to follow Mediterranean diet and then half nearly 75 of them were supposed to eat within. 10 hours. We did not fix the 10 hours because we said you pick your own 10 hours, that you can stick to. 

Relatore 1 

But it has to be consistent from day-to-day. So if you start eating at 9:00 AM, you finish it, not at, you know, at 7:00 PM and every day, OK, more or less. 

Relatore 2 

And then try to be, yeah. Try to try. Try to be consistent because we said yes we understand that there will be some things and you can take maybe half an hour here and there and we'll see how many times you can do it and. What is interesting was although they are all doing. 24 hour shift. More or less just to begin eating somewhere between 8:00 AM and 11:00 AM and they. Did not skip any meal. They had their first meal or what we call breakfast, but it was several hours after waking up because they are waking up at 5:00 or 6 and they're driving to come to work at 7:30 or 8 and the eating the first meal, say, between 8:00 and 11:00. And then they finished meal 10 hours later, and what we found is more or less most of them could stick to doing this at least five days out of seven days. And then at the end of the study, when we looked at the health parameters. One thing that I said. We recruited everybody who can, so that means a lot, nearly. One in three firefighters were completely healthy. They had no sign of any any illness, no high blood pressure, high blood sugar or high cholesterol, depression or anything. So since we have 1/3 of the population who are already healthy, and then everybody has slightly different conditions, some have high blood pressure, but they don't have high blood glucose, somebody has high blood glucose but not high blood pressure. So it is kind of heterogeneous so. We did not see big difference in weight loss or any weight change between these two groups. Another thing is firefighters actually run almost 8 to 9 miles when they're at the job, because that's part of their exercise routine. But then one thing that changed significantly in the time resituating growth was what we call VLDL particle size and particle number, because this is something that we know is very low density lipoprotein, these are atherogenic and if we can manage them much better than we reduce the risk for. So that's one parameter of that changed in the time retrofitting group. Even when you combine all healthy and healthy everybody. Now, if we take firefighters who are beginning with high blood pressure. Then we saw significant reduction in that systolic as well as diastolic blood pressure. And the change in blood pressure, of course, we don't claim that in the manuscript. But when we talk about it, some physician would get up and say, wow, that looks like almost they're on a blood pressure lowering drug. So the extent of blood pressure lowering is equivalent to somebody taking a anti hypertensive drug. And then those who started with high. Blood sugar. Of course. We didn't have too many Type 2 diabetic, but there are few few pre diabetic. And they could better manage their blood glucose. And this is interesting because once shipped workers. Become pre diabetic or diabetic. They have more difficulty in managing their blood sugar than non shift workers because the work schedule itself will mess them up too much, even if they're on many medication they have. 

Relatore 1 

That's fascinating. And I I'm really glad that you explained the study in such detail, because I would have thought, you know, from reading the abstract. And I did look at the data, but if someone were to look at the abstract, they say, oh, firefighters, they're waking up in the middle of the night and they're, you know, throwing on their gear and going out to calls and do it. But I understand correctly, all firefighters are being woken up by the signal. Which makes the firefighter population a bit more similar to the more standard population who's waking up in the middle of the night to use the bathroom. Getting on social media for a couple of minutes or flipping on the lights. I mean it's it's maybe not as severe as what firefighters are doing. But we know there are blood sugar regulation issues related to those multiple middle of the night wakings especially if people are then staring at screens. So I think it's really important that people were able to hear about the the deeper contours of the study. I mean this result of regulating blood sugar better is really powerful. I get asked all the time. You know, I've got a new kid or I'm a shift worker. How can I do this morning. Sunlight viewing. What I'm hearing is that keeping a regular meal schedule every. 

Relatore 2 

At least 5-5 out of seven days. 

Relatore 1 

Yeah, we have five out of seven or as close to every day sort of like sleep. I always say trying to get a really great night's sleep 80% or more of the nights of your life. And on the other 20%, hopefully it's for fun reasons, a great party. 

Relatore 2 

Even. Yeah, yeah, yeah, yeah. Yeah, yeah. 

Relatore 1 

Or something like that, or a celebration of some sort. 

Relatore 2 

Yeah, yeah, yeah. 

Relatore 1 

That seems to me a great anchor point when one can't reliably control their sleep wake cycle, does that mean that if somebody is coming off of shift work and they're very, very tired that they would be better off staying awake and eating than sleep? 

Relatore 2 

Well, it's yeah. So this is where we get into the nuances. So here the firefighters are 24 hour shift work. So that means and they have been working this shift for a very long time. So they have figured out. And one thing is yes, firefighters are different from nurses and healthcare workers who have to work throughout the night. And they're staying awake throughout the night for US firefighters, they get opportunity to sleep. Then even with their. 10 calls. They actually have opportunity to come back and go to sleep. And in fact, when Emily and Adina they were and the fastest and what they observed was firefighters after they, after attending a call, they're not coming back and playing cards or trying to watch the news or get the score, they know they will just. Go back and lie in the bed and switch off the light. Whenever they got. Any opportunity to sleep, they would try to sleep. So in that way. Their sleep date and sleep pressure during daytime is not as strong as a night shift nurse or a truck driver who is driving all night because they have. They're staying awake throughout the night, so when people say yes, you found this and can you extend it to other shift workers? My answer is no. We have to go back and figure out. That's why we went to the station and figured out what to work for. If I have to go and do this for some nurses, maybe even I will go or our staff will go and figure out what is the work schedule, what happens. Do they have opportunity to eat? Do they have opportunity to even take 5 minutes break? What do they do during break and all of these things come into play but here another thing is. I always said that in other time restrict reading paper we see change in nutrition quality and quantity, but here we also saw that somehow both groups inadvertently they improve the nutrition quality because everybody was told to eat Mediterranean diet, they increase their fruits and vegetables and olive oil. Text slip. And when they had to stop eating early, they also reduced the alcohol intake. And this is very significant because many shift workers just to cope with this shift work that tend to depend on alcohol at night and caffeine in the morning. So they begin their day with caffeine and end with alcohol. And now we can relate that many normal people who are not doing shift work. We also more or less begin our day with caffeine. And many of us and with alcohol. And then when they reduced that eating to 10 hours and then we saw a significant reduction in alcohol intake in the time recruiting group, but not in the standard of care or Mediterranean diet group. 

Relatore 1 

I certainly support that we did an episode on alcohol and. I was shocked. When I researched that to learn that. Zero to two drinks per week is essentially the threshold beyond which you start seeing health. Deficits, in particular cancers and metabolic disruption, sleep disruption and increased anxiety when people aren't under the influence of alcohol. I mean, it's pretty incredible how alcohol is kind of escaped as the the opposite of caffeine and therefore not a health hazard. It's and and. Here I'm. I'm somebody I have a drink every once in a while. No big deal. For me, I I can have it or not have it. But it's just striking how alcohol, despite extensive data that it can really disrupt health even at three drinks per week, is is just avidly consumed as if it was kind of like food or caffeine. It's really incredible. I I want to make sure that I circle back to something you mentioned earlier because I know they're going to be a number of people that asked this. If I recall, you said that provided that the feeding window is not shorter than 8 hours that men, women and children can use time restricted feeding. 

Relatore 2 

Well, when I say, yeah, So what I what? 

Relatore 

Is that right? 

Relatore 2 

I say is. 12 hours per hour 1212 hours because we did a study that was published in 2015 and again behind many of our studies. 

Relatore 1 

12 excuse me 12 hours. Thank you for that clarification. 

Relatore 2 

There is a story, so we're publishing all these mouse stories and then I would go to conferences and then of course the some, some. People would give me a look saying, well, you must be doing something wrong. This just breaks the ex law of thermodynamics, because how come they're eating the same number of calories and not getting wet? Of course, by that time we figured out that at least in mouse. Time retrofitting also changes the gut microbiome in a way that the mice may be pooping out a little bit more fat than sugar than absorbing them. So one thing that happens in time repeating, at least in mice, is the liver cholesterol metabolism to bile acid and bile acids. Excretion in the gut changes because the gut microbiome changes, so this is very nice study when Amir Janin power was in the lab. Now he has his own lab in UCSD. And he meticulously did that. And we we even did bomb calorimetry from the poop and metabolomics from the poop. And then we figured out that they excrete some some calories and then that brown fat activity goes up. So they may be burning some of these extra calories. 

Relatore 1 

So they're more thermogenic. 

Relatore 2 

More thermogenic, but anyway so you know. One nice thing awesome thing about salt is. If they see that your science is going well, then they will find ways to help you. And this is yeah. 

Relatore 1 

That's terrific. 

Relatore 2 

And this is when Bill Brody was our president. He was the president of Hopkins for 12 years, and then he was president. And that time he had started this innovation grant program, which was funded by orwen Jacob. Arun is the founder of Qualcomm, and there's also a faculty at UCSD, so he understands there are very few. Tech leaders who actually spent some time in academia so he understood the pain of getting grant money when you have some interesting idea or test some ideas. So that's. 

Relatore 1 

No knock on the NIH, but I'll do it anyway. And because I sit on study section for the NIH, I mean, NIH wants to see proposals for things that are so certain to work that they're mostly done. And so really groundbreaking work can happen and does happen with NIH funding, but more often than not is it is the generosity of philanthropists like Owen Jacobs and other people that allow the really pioneering. The new stuff. The cool stuff. The the groundbreaking stuff. The stuff that really. No, I'm not gonna say really matters. It all matters. All important but. 

Relatore 2 

That matters, but you know it's high risk. And NIH means NIH is not just government is not making money from thin air means it's taxpayers money. So there is a little bit responsibility or conservative that, OK, so we should not waste taxpayers money on paying this guy kind of project too much. 

Relatore 1 

To be clear, we're not talking about politically conservative, we're talking about scientifically conservative. You'll be so careful with language nowadays. Pretty soon, we're just gonna sit and stare at one another at the microphones. To stay safe. So that's interesting. So the. 

Relatore 2 

So then we. Started this and then what we did was we, I had a awesome grad student and we got this funding from Irvin and also there were some. Any philanthropy matters. So actually the way we say is yes, if you give me 50 bucks, then that 50 bucks towards goes towards buying the gloves and eppendorf tubes for one post doc for maybe seven days. 

Relatore 1 

So, so true. I think a lot of people don't realize that 99% of laboratory scientists just they they don't make any money off their discoveries. And even if there is a patentable discovery, typically the the divide between the institution and the company, that will, when she put that to market is so. Them in favor of the the others involved that you know, scientists really do this as a as work of passion, labor, labor, of love. So so we. 

Relatore 2 

We came up with this app, my security and clock at that time, and we took some, you know, lessons from tech leaders, particularly from Amazon, one click checkout. Because without most nutrition, apps actually ask people to. Detail describe what they ate, go to their food library and then Corson size. We said OK, so we'll just sort out all of that. We just ask people to take a picture of the food, open the app one click, take a picture, second click and press save, third click and when they save the picture actually came to our server did not stay on their phone. And we asked 156 people who are not shipped workers just regular worker or homemakers to be part of the study. No student was allowed to be part of the study because we know that there's lifestyle is like shift and we monitor for three weeks and. So here is some nuances and I want people to understand. So suppose say when somebody is starting to eat at say 7:00 AM and. Since the recording, everything we we got every single thing, even if they ate half a cookie, they had to take a picture and they actually took picture because it's not. It became second nature after three or four days that every time they add something, even if there was a glass of water, they actually took a picture because we asked them take picture of everything. We'll figure out what it is. What is surprising was we found the median. So the median number of times people eat within a day 24 hours day is actually 7, so it's not. It's not that we're eating three times a day, we actually snack a little bit and then we. 

Relatore 1 

Seven times per day. 

Relatore 2 

Seven times and there are 10% of people. The top decile was eating. 12 times a day. And it makes sense in retrospect. Maybe I'll fall into that 7 or 8. Before I did this study, because, you know, getting up, having coffee with cream and sugar is 1. And then I ate my breakfast. That's two. Then I came to the lab and I found that cookie. I went to a meeting and there was some cookie and something else. That's another one and lunch. And then afternoon somebody asked me to go out and have a meeting. And so if you think about it, it's very normal that we can go 7 to 8 * 10 times. But then. If we look at what time say I start breakfast and as I said and we see that in many people, they'll start at 7:00 o'clock in one day, then 7:30 another day, then 8:15 another day or they go back to 6:00 AM because they have to get up early and go to work. So we take all these food data from three weeks and then ask. What is the time when your body system is expecting it to eat? Because it's kind of averages out. It's kind of thinking, OK, maybe for. You if you're. Eating breakfast at, say, somewhere between 6:00 and 73745. Eat it. Maybe you are expecting food around 7:00. O'clock. Let's forget about 6:15. That's an outlier. And then similarly, at the end of the day, somebody is eating, finishing the last bite or the nightcap, whatever you call it. Say one day at 9 PM, 930 PM, 10111230 or one. Let's ignore that one and 12:30. But still we got somewhere between 7:00 to 11:30 for that person over three weeks time. So this is how we kind of figure out what is the likelihood that your body will. Encounter food. So when we do that, what we found was nearly 50% of adults in our study, eight for 14 hours, 45 minutes. That window when your body is expecting food. So it's. Easy to say that 50% of adults. Eating within 15 hours or longer. 

Relatore 1 

And and quite frequently throughout that. 

Relatore 2 

Quite frequently too. And then if we asked what fraction of our dogs were actually eating the conventional. Within 12 hours, three meals a day or something like. That's 10%, so this. 

Relatore 1 

The snacking has gone up dramatically, however. You want to define snacking, the frequency of of food intake. The day. 

Relatore 2 

And outside this breakfast, lunch and dinner, there are all these small snacks here and there. And also for a lot of people, the dinner is delayed and we went back and looked at, OK, So what kind of food people are eating late at night and all that stuff? And what came out interesting, which is very counterintuitive, is people who prepare their own dinner, they're more likely to eat later at night. Because they're coming home and then they're taking some time to prepare dinner, and then they're sitting down and eating, or maybe eating next to the computer. Whatever it is, so it's kind of interesting that came out, but coming back to your point, that's why I say that nearly 90% of adults. Are eating for more than 12 hours. So that means a lot of people can. There is scope or there is enough headspace to reduce and eat within. So as I said, all of this are interrelated, so only think about children. Most sleep researchers agree that children and teenagers should sleep somewhere between 9:00 to 10:00 or 11 hours because young children, even 5 to 10 year old, they should sleep 9 to 10 hours. 

Relatore 1 

They're just pumping out growth hormone and. Growing, growing, growing. 

Relatore 2 

And then the teenagers, actually the recommendation is and they should be sleeping 9 hours. If you take teenagers. Take out all the stimulatory inputs to them and then remove homework assignment and everything, and then let them kind of equilibrate to their homeostasis. What they're likely how many hours they're likely to sleep. That turns out to be somewhere between 8 1/2 to 9 1/2 hours. Which also means that going back to sleep. Nearly 90% of. High school students in this country are chronically sleep deprived because most high school students don't get 9 hours of sleep on a regular basis. Maybe in the weekend. 

Relatore 1 

Probably because of devices, they're on iPads and phones. 

Relatore 2 

And also as I said, this new idea that midnight is your assignment, some missing time. I'll come back to that again and again. 

Relatore 1 

Yeah, I I'm hearing that again against the teachers. Take note I it's an, it's a very interesting idea as a way to kind of anchor behavior earlier in the day. Yeah, learning to in I mean. Public health is complicated because people are incentivized by fear, but they, you know, you get more bees with honey, as they say, right? 

Relatore 2 

Yeah. Yeah, yeah, yeah, yeah. 

Relatore 1 

You know, there's the incentivizing people to wake early or not necessarily with the sunrise, but wake earlier and go to sleep earlier and eat within an 8 to 12 hour window. 12 If it's children, it sounds to me like you know that all these health benefits are what I think are going to incentivize people more than, for instance, this idea that, well, if you don't do this, you're gonna get dementia or something. 

Relatore 2 

So that's why I said, yeah. No, no, it sounds like. 

Relatore 1 

Of that sort, right? But. 

Relatore 2 

Like everyday people will feel more healthy and more productive. And so that's why I said that even if children are supposed to sleep for 9 hours, of course they're not eating during those nine hours. And we're not feeding children and putting them down to sleep because, you know, their core body temperature will be high, they cannot fall. Asleep, so at least they should have their last meal one or two hours before going to bed. Because typically. Parents feed them and maybe give them a shower or a bath, and then they read the bedtime stories. So it's. One to two hours before bedtime. They're finishing food similarly, on the other hand, after they wake up, it's not that we're waking them up and then. Feeding them so. Hopefully we're not doing that. So that's a 12 hours seems to be. Optimum and it's not only I'm saying that if we put all the health recommendations together from Pediatrics and then it makes. 

Relatore 1 

Sense fascinating. I have a question about structuring meal intake or food. Take during the eating window. I have a good friend. Actually he's he's the neurosurgeon at Neurolink now. But he came up through Stanford and. And he has a habit of eating, of skipping one meal per day within a feeding window. So it might be breakfast, lunch, skip dinner one day, then it might be breakfast, dinner the next day. Lunch and dinner the next one. So it's not in keeping with the same start time always, but the end time is either going to be earlier or the there's a gate. It's never later. It's never later. What do you think about that? As a strategy? You know, in many ways it feels like that fits with the way that a lot of peoples lives. So sometimes. For instance, if I'm on a podcast, I don't tend to eat much during the middle of the day, cause it makes me a little bit groggy. The postprandial dip in energy, so I'll do breakfast well. But again at 11 and that's the first. That's when I break my fast. Finish and then dinner, maybe a snack in the middle of the day, but other days it's three meals. So does it matter overall, as long as one isn't allowing the start time and the ending time to drift out, is it OK if you go from 12 hours to 7:50 eight 10412? As long as you don't exceed that the the brackets are you OK. 

Relatore 2 

So this is where the security and aspect come in, because if you're going, if you're moving that breakfast time or dinner time, 3-4 hours essentially. Causing maybe a metabolic jet lag. You know, in short term in weeks, months or maybe even few years, you may not see any change, but at the same time we don't know what is the long term consequences. One thing is we. Always think. I'll come back to this point again and again. We think that our body weight. Is a marker of health or body composition. Is a marker of health. It's not always true because, as I said, it should drift. Feeling, you know, having some pang of depression or anxiety or healthy, high healthy. 

Relatore 1 

LDL, like high LDL, is a lot of thin people have or or low body fat people have very. High LDL. 

Relatore 2 

So those are the things that we don't connect with our habit. And since circadian rhythm and meal timing, meal structure now is a very new field I think. Our studies will come out only in a few years because right now people are just going back and retrospectively looking at some diet record one day of diet record and trying to clean too much out of out of it. But I think hopefully things will improve where people will become it. It will become standard to at least look for one week of diet, record meal time and what they're eating all that stuff because now mouse studies also showing where the front loading carbohydrate or front loading fat or. Protein has benefit over, so I think these studies are starting so. I should not comment whether that's good or. 

Relatore 1 

No, I think it's great to hold off until then, we have you. Back on to discuss. I have a question about fasting on the longer term and there it's a near infinite space. We could explore of two days of fasting and one day. I know people that every once in a while they just decide. I'm fasting. They've either been eating too much at parties or they're not feeling well or whatever. They just decide I'm fasting for 24 hours and they'll still consume water and caffeine, but they'll just fast. Is there any health benefit or? Detriment, you mentioned the circadian clock shifting effects, but if somebody wakes up on Sunday and they, you know, they. Ate too much or they feel they ate too much or they don't like the food they. Ate on Saturday. They're not really feeling it, and they're just going to fast into Monday. Is there any known benefit or health detriment to doing that kind? 

Relatore 2 

Of thing. Yeah, there's a actually a rich literature on this complete fast. And in fact in many religion. People practiced complete fast as a. Way to cleanse their. Body and people have seen that there are benefits to that. So in fact the every other day eating in mouse model or even in humans, there are also initially some studies were done. There are many health benefits. And right now there are even fasting clinics in Germany where people check in and they're under strict supervision and then they do complete fast or maybe a small bowl of soup which has 100, two 100K Cal. And that's all they get to eat sometimes. 2-3 days, four days, five days even they have gone up to three. Or four weeks. 

Relatore 1 

Forsake of weight loss is that. 

Relatore 2 

Why from many different things and they come out pretty well? Of course, they're under supervision. Make sure that they are getting macro micronutrient. Sorry, the micronutrients, vitamins and electrolytes. So those studies are pretty solid. People have observed that. And then in fact, there are even idea that fasting this kind of fasting can have huge impact on brain and people may come out of. Treatment resistant depression or something, but you know, so those studies are very difficult to do now. Only case of 1 here and there that we hear once. While, but hopefully in future we'll see whether the depression anxiety, the mental health aspect will benefit from fasting because now as there is more and more evidence that there's this gut brain access and whether the presence of food or the microbiome changes in the gut. If they can affect brain, then maybe long term fasting, periodic fasting, a few days of low calorie diet back-to-back will be interesting to see how it impacts brain health. 

Relatore 1 

Very interesting. What are your thoughts on fat fasting where people trying to limit their blood glucose by only eating mainly fats mainly healthy? Typically, they'll eat healthier fats of avocados, olive oils and nuts, and you know, and some animal fats perhaps, but. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

As a way to keep blood glucose low and also time restrict, this goes back to the kind of low carbohydrate thing. What are your thoughts on that as as a general strategy for health, I mean it combines sort of two general themes that are out there. I think both of which are, you know, data are still incoming that restricting the feeding times. It can be beneficial as well as keeping. Overall blood glucose lower can be beneficial. 

Relatore 2 

Yeah, I think there is too much emphasis now on blood sugar spiking or we don't know this kind of eating pattern, for example, means we're essentially telling pancreas that, OK. These are the eyelet cells that produce insulin. It's OK you can take, take a break. Go on vacation for for a month or two or three months. My question is, it will be interesting to see what happens to those eyelets because. For example, we know that if we. Disuse are unused. Our muscles, those muscle atrophy muscles, will become weaker. We don't know whether long term consequences of this very low carbohydrate diet where you're not essentially engaging the. Islet cells periodically. What is its impact? So if there is no impact, maybe it's OK. Well, maybe because. As you know, many people who actually work on ketogenic diet, the researchers themselves, they find it very difficult to stay in true ketogenic diet because the true ketogenic diet is consuming less than 10% of calories from carbohydrate. 

Relatore 1 

And not very many from protein. A lot of people think ketogenic diet allows them to eat massive amounts of meat and that's not really the case. Just one clarification for people. Sachin was referring to islet cells of the pancreas, which are the ones that manufacture insulin. So the question is whether or not taking in low levels of. Glucose, by way of a low carbohydrate diet that those islet cells are going to shut off their production. Very interesting. I mean, the liver is a very plastic tissue, I mean. It tends to. React very dramatically to to lifestyle changes. 

Relatore 2 

So that's why it will be interesting to see what happens. Means we know that even muscle disease, for example, people who become bedridden. They lose some muscle mass, but when they come back and exercise they gain it back so it will be interesting to see what happens in these people who are going through long term ketogenic diet. And of course once in a. Well, because of social pressure or something else. If they don't have access to food or something happens, they may consume some sugar. Some blood glucose will spike, but it's not that every spike is bad. I mean, the reason why we have insulin is for good reason. 

Relatore 1 

The buffer that spike. 

Relatore 2 

To buffer that spike. And also you know people always say that well if you have insulin produced or insulin like growth factor, those are really bad and you should. A word that and I think that's a little bit extreme and. 

Relatore 1 

I mean, that's the insulin growth factors involved in muscle protein synthesis, tissue repair, maybe even cognition, so. 

Relatore 2 

And it also goes back to. Say empro activation and all that stuff, people get really excited about how to reduce them to activism, rapamycin and all that stuff. So this is where, again, from circadian point of view, I ask people to think so. Two very popular drug like molecules or drugs that people think will increase longevity or metformin, it's. Many people agree not all will come to a consensus that it activates MP KINESE or the sensor in the cells that sense that your cells are fasting. 

Relatore 

OK. 

Relatore 2 

So metformin kind of activates it so that it kind of you can say. Although it may not be scientifically accurate, the you know fasting an appeal. 

Relatore 1 

So it sort of mimics fasting. And I and the and the thing I'd lump in there with metformin is that berberine is kind of the poor man's metformin. It's a yeah tree bark extract that also dramatically lowers blood glucose. 

Relatore 2 

Yeah, yeah. And it mimics kind of that fasting. And then rapamycin also kind of reduces inter activation. And people have shown that. Rapamycin and metformin. Can extend mouse lifespan and improve health. OK, so now let's go back to the calorie restriction study that I mentioned in calorie restriction. People are giving food as a lump sum and they were essentially doing time restriction. The mice were doing time restriction. If we think about it. During daytime, when experimenters are coming to the vivarium, the mice should be sleeping and fasting. And they should naturally have high level of MP kindness if they are truly fasting, and they should also have low level of mtor activity because M2 responds to insulin and that should go off at night. So my suspicion is in many of these experiments where the mice were allowed to eat at libitum, even normal standard chow. 

Relatore 1 

We are. 

Relatore 2 

We know that as mice get older, they actually consume a little bit more food during daytime. 

Relatore 1 

Which is the equivalent of human night time. 

Relatore 2 

Humans. Night time meeting. 

Relatore 1 

There is like night time eating. We know as an issue. I didn't realize that was more of an issue as. People age, but yeah. 

Relatore 2 

So we don't know, but at least in mice, because, you know, we can put the mice in calorimetry, look at every single bite they're eating how much they eat. So I guess it was natural to see that researchers found that there is some. M2 activity during daytime when the mice were not supposed to have M2 activity because they should be fasting and since they ate little bit they were snacking during daytime amp kinase activity was not at its peak. Giving metformin. Kind of. Mimic their fasting state and reducing mtro activity by drug like rapamycin. Also kind of mimics some aspect of the fasting state. So my suspicion is, since these studies were done always in mice who are supposed to be in the fasting state, and both emptor sorry, rapamycin and McCain is activated, or metformin kind of mimicking that fasting state, that's why we have seen those benefits and it will be interesting to see. If that experiment will be done in humans in long term, because many people are very excited about, you know, there is long term metformin study and and a lot of people are actually consuming good amount of rapamycin off level, they can get their own. So that's my curiosity. I'm not saying whether it's good or bad or whether there is science or not. That's something I'll be interesting to control for and see uh, because recently I I saw one of my again uh close friend and colleague at scripts. Katya lamiya. She did a very simple, elegant study. People should have done like forming. They took mice and then measured the blood glucose at different time of the day and in fact, just like human blood glucose, our blood glucose fluctuates a little bit. She saw that rhythm and then in every two hours or three hours. On different days, of course. So you have the same dose of metformin to mice. And what she found was that different time of the day, metformin had very dramatic change in glucose reducing ability. So which means that even if you take metformin and give at different time of the. They for the mouse or even for humans. In very long term, of course, in these mice, these mice were not diabetic or anything or healthy mice to begin with. So in long term, we might see benefits that are very different. So this brings to this idea that, well, maybe metformin, say. At the end of the day, evening metformin may trigger that fasting state much earlier than end of digestion, whereas metformin, in the beginning of the day may not, at least from longevity perspective, I'm not talking about diabetes type 2 diabetes here. So the same thing with amtor is amtor going to have much better impact if taken during evening, morning before meal. These are my thoughts that go along with all this fact story that we talked about. 

Relatore 1 

Do you take Metformin or Burberry? 

Relatore 2 

No, I haven't taken. Although you know I have close friend and colleague Robin Shaw, who is now the Director of Cancer Center at South he. Extensively works on AMP kinase and its mechanisms and so it's always fun to talk to him to say. 

Relatore 1 

He's a he's a fan. Yeah, I've taken berberine before and I have had two different very distinct experiences with them. First of all, berberine when ingested with carbohydrates and particular carbohydrates that have a lot of simple sugars, definitely. I know this because I measured my blood glucose. I did the experiment, allows you to flatten out your blood. Glucose response. So you know, in some sense, if you're, you know, there is this idea, if you're going to eat a particularly big meal or sugary meal and you don't want to get a massive blood glucose rise, you take. Berberine, or metformin, metformin. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

It's prescription that's I went with berberine cause it's as far as. I know it works as well, yeah. 

Relatore 2 

At least for healthy. 

Relatore 1 

For healthy people. 

Relatore 2 

Yeah, yeah. 

Relatore 1 

That's right, yeah. When I took berberine and did not ingest large amounts of simple sugars or carbohydrates along with it, I experienced profound hypoglycemia. I felt like complete garbage for about 8 hours and I had one of the worst. Headaches of my. Life because it which makes sense. You just got a blood sugar crash. So if you lower blood. Your blood sugar when you already have a fairly low blood sugar and you're not ingesting carbohydrates, you can really bottom out your. Your blood glucose. So just say it's. I say that as a for two reasons. One is kind of a cautionary note and the other one that when you think about the biology of these compounds, it makes perfect sense. And I think that and I did not pay. Attention to circadian effects, yeah. 

Relatore 2 

Yeah, I mean. So you know, when I joined Salk on that, we know Ron Evans was the kind of the big leader in in metabolism and he works on nuclear hormone receptors. These are the master regulator of metabolism and normal cells, cancer cells and many other. And what was interesting was in the first few years, Ron did a very simple experiment. He just looked at what time of the day this nuclear hormone receptors are turned on at gene expression level and some at protein level. And they found that almost all of them. Have a circadian pattern, at least in some tissue. So he went to that length to say even that circadian is metabolism and metabolism is circadian. The reason why we have a circadian rhythm. Is to have a deli, rhythms and food seeking behavior and eating. And also go through a period of time when we should be fasting. And then on the other hand? All the metabolic regulators also have to follow that rule and almost all metabolic regulators, everything that we can think of, connected to metabolizing macronutrient protein, carbon fat, they should also have a circadian rhythm or diurnal cycle to align. So for example, fat oxidation should be in opposite phase with feeding and. You know, in retrospect, at that time it was kind of amazing to say Ron could forsee, of course, he's smart enough to forsee and. Predict that this is going to happen to circadian pill because at that time we are thinking about the suprachiasmatic nucleus sleep wake cycle and we are not thinking too much about metabolism so. That's the awesome thing about salt being at SOG because we have 50 Pis really crammed into two awesome buildings and with open lab structure. So you bump into each other and talk to you so. 

Relatore 1 

And with an ocean view, yes, it's an amazing place. I was lucky enough to have an adjunct position there when I was when my lab was at UCSD. And it is an amazing place doing incredible ground breaking work, which of course includes yours. Listen, Sasha and I. I'm clear now that we have to have you back on for another series of discussions. Seriously speaking, if if you would be so, so kind and willing to do that. I want to thank you for several things. First of all, for your taking the time today to sit down and discuss these incredibly interesting ideas in detail, you know much of what we talked about. On the podcast. Is obviously grounded in science and and often, but not always, as actionable, and so much of what we talked about. Today is actionable in the sense that many people are already doing certain dimensions of these things. Some are not. Some are hearing about it and considering it. You've given us dozens, have listed some out dozens of tools and considerations based on whether or not people are engaging in shift work or not. I think a lot of people are going to realize that they are shift workers. Even though they didn't. Think they were because of their nature of their habits. Now it to light and to activity and so forth. I absolutely love the firefighter study because of its relevance to the general population also, and not another nod to fighter fighters and shift workers everywhere. Thank you. And you know, I think. Among the colleagues I've known for several decades now, you really are one of a very small few who've managed to do both animal studies and human studies, but also animal studies with a very clear eye and a pointer toward human health. And that's such a vital and rare thing, especially in this day. Of extremely competitive funding. So I want to thank you for your time today, for the knowledge you shared the actionable aspects of that known. Which the signs that you're doing in your laboratory, we will provide links for people to learn more about you and of course to go to the app so people can engage in some of the signs directly. And of course, you have several wonderful books now that we will also linked to, both of which I've read and are are wonderful, in particular the book the first book, but also a book related to diabetes. And so for diabetics and people interested in metabolic and and blood sugar regulation. On there. So yeah, on behalf of myself and my team here at the Human Lab podcast and all the listeners, I just want to say thank you so much. Your time is valuable and the fact that you share it with us and educate so many people. 

Relatore 2 

Is really a gift. Thank you. And actually, likewise, there are very few scientists who. I have taken this leadership role that you have taken to. Come and communicate science to the public. It's not easy because sometimes you have to distill it down to simple sound bite to the point where the scientists and they'll say, oh, that may not be right, but we always have to keep in mind that we are always living in the dark is of. Science, because the reason why I say that this is not my court, actually this is from one of my scientific hero Paul Simmel from scripts here. This is think about it 10 years ago. What you what you thought was right and the best has already. But one thing is the security in rhythm and aligning it to our internal clock to our habit is very important. And as you mentioned, we have our my security and clock app which is research facing. But we have also distilled all of this down to five or six. Timing component and we have a new app called on time health get on time health. 

Relatore 1 

Can people access that through the standard app stores? 

Relatore 2 

Yeah, so now it's a little and and App Store. Sorry Apple App store. And we want to see how, because people always think about fasting. But as we discussed today. Feeding, fasting or eating, fasting and activity and sleep are kind of interlinked and we have to kind of balance both of these. So that's that was the idea behind this on time health program and thank you, Andy, because what you're doing is immensely necessary. Particularly these days when science is moving at a very fast pace, there are a lot of results coming out. Sometimes something can be very confusing and you spending your time. To communicate science. Is exceptional, so thank you and. 

Relatore 1 

You're you're most welcome. It's. Days like today where I get to sit down and and talk to brilliant colleagues like you who are doing the important work that that really matters so much. And so as you mentioned a moment ago that there's a lot of darkness and confusion out there. But thank you for being. One of those whose shining light thank. You thank you for joining me for today's discussion with Doctor Sachin Panda all about circadian biology and time restricted feeding. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific 0 cost way to support us. In addition, please subscribe to the podcast on both. Apple and Spotify and on both Apple and Spotify. You can also leave us up to a 5 star. For review, if you have questions for us or comments about the podcast or topics you'd like me to cover, or guess that you'd like me to include on the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. In addition, please check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast on various episodes of the Human Lab Podcast, we discussed supplements. While supplements aren't necessary. For everybody, many people derive tremendous benefit from them for things like improving sleep. Supporting hormones, improving focus and so on. The Human Lab Podcast is proud to have partnered with momentous supplements. We've done that for several reasons. First of all, momentous supplements are of the very highest quality and are used with various sports teams and various studies through the Department of Defense and so on, and momentous supplements tend to be in single ingredient formulations. Single ingredient formulations are absolutely essential if you are going to develop the most cost effective and biologically effective supplement regimen for you, because Simply put, they allow you to adjust the dosage of individual ingredients to alternate days that you take different ingredients to cycle them and. The 4th in addition, momentous supplements are available internationally, which many other supplements are not. If you'd like to see the supplements discussed on the Human Lab podcast, you can go to live momentis spelled OUS live momentous.com/huberman if you're not already following me on social media. It's Huberman lab on Instagram, Twitter, Facebook. And LinkedIn, and that all of those places I cover science and science based tools, some of which overlap with the contents of the Huberman Lab podcast, but much of which is distinct from the content covered on the Hubberman Lab podcast. Again, it's Huberman lab on all social media platforms. If you haven't already subscribed to the Human Lab Podcast Neural Network newsletter, it's a monthly newsletter that includes free. Tool kits for things like toolkit for sleep, how to enhance the quality and duration of your sleep toolkit for focus, toolkit for neuroplasticity, toolkit for deliberate cold exposure, heat exposure and summaries of podcast episodes. All of those tool kits can be found by going to hubermannlab.com. Go to the menu, Scroll down to newsletter and simply give us your e-mail. We do not share your e-mail with anybody, and again, the newsletters and toolkits are completely. 0 cost and you will also find some PDF examples of previous toolkits. Again, that's hubermann lab.com. Thank you once again for joining me for today's discussion with Doctor Sachin. And I hope you found the conversation to be as informative and actionable as I did. And last but certainly not least, thank you for your. Interest in science.