Welcome to the huberman live 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 dr. Sachin Panda, dr. 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 rhythm. Circadian rhythms are 24-hour rhythms in everything from gene expression. To the overall functioning of tissues are 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 our
Health, in particular, his laboratory Pioneer, discoveries related to so called intermittent fasting also, sometimes referred to as time, restricted feeding today. Dr. Panda and I discuss how our circadian behaviors everything from. When 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 and how all of that has a strong impact on our health.
During today's discussion, you will learn how restricting, your feeding, two 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 some 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.
Ation of dr. Panda, as some of you may already know dr. 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. No captions. In addition if any of you are interested in learning more about dr. Pandas work including seeing his Publications and reading those Publications or supporting his laboratory. You can do that by going to his laboratory website.
We have also linked in the show, no captions. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research rules at Stanford. It is however, a part of my desire and effort to bring zero 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 H VM. N Ketone IQ H VM, n Ketone. IQ is a supplement that increases blood ketones. I want to be clear that I am not following a ketogenic diet most
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again. Yeah, I got to see you.
We are
Our colleagues still, but we used to be right across the street from one another. Yeah. Remember those days. Yeah, yeah. 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. It involves recording is from post-mortem Human retina. So maybe if there's time at the end, we can get back to your lab has shown that you can.
Essentially maintainer 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,
Buddy is doing time restricted feeding to some degree or another. Yeah. At what point can we start thinking about a pattern of eating? Is 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 feeding
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 a hundred years ago. People showed that if you reduce calorie intake in a rat then that pad can live for a long time and in those experiments, the calories are reduced every single day and that led to the idea that if we cut down.
Our calories by twenty percent, say, then we can potentially live longer by doing two things. One is preventing, is related disease or even if we follow us 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.
My must say that it's not that caloric. Restriction is impossible. 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 detective we take out a soda bottle or something. I'm looking at okay 160 kilo calorie 30 kilocalories 0 KK. We are doing that. So the point is it's we are doing subconsciously, some kind of calorie counting but reducing calorie by 2030.
Percent 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. 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 little bit hard for humans but just imagine or just get to eat only one day and then another day, then the idea came well for humans, can they eat less for one or two days in the week? So that led to this 5:2 diet for people who can eat for five days and then two days after reduce calories. So that's also intermittently people are fasting then as you know,
Valter Longo also came 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
were those studies on
humans? Many of the study, started it in mice, but alternate day fasting 52 and Walters periodic first fasting. All of them have now been done in humans, not for longevity, of course.
Beakers cannot do those for a long time but for weight maintenance for reducing some signs of aging or reversing those things up in done. So all of them have been done in humans, mostly held the 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 calorie can take on any given day.
Day is reduced for one or more days in a week. A month that became that umbrella term become 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 a few days in a month. So when we published, I'm 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 the ad libitum fed mice, but still the see health benefit. So that's why we call it time restricted feeding. 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 eight hours of feeding and 16 hours of fasting that kind of became popular. And so, 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 restraint fitting? So the way we have been trying to Define experimentally and also in literature is trying to confine all your energy and take from solid and liquid food combined with in a consistent window of 8, to 12 hours, because that's something that doable. Of course, people have done time Distributing with four hours.
Six hours. And some people even try to eat everything within two hours. One meal a day we found is those are not feasible to maintain for very long time. For a lot of people.
One question about the six hour versus eight hour versus 12 hour feeding window,
Is it important that the feeding window begin and end the same time? Yeah, more or less. Yeah. And if so, how much flexibility is there? 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 land sometime between 11:00 and 11:00 a.m. and 12:00 noon. Yeah, there are exceptions occasionally
Have a breakfast, a proper breakfast, as its called, I guess it would be improper if you're intermittent fasting for me, but typically 11 a.m. or noon, is when I first eaten. My last bite of food is typically around, how do I? Yeah, 39. Yeah, that's what works for me.
Yeah.
Is that consistency? Affording me any benefit set. Let's just leave aside total. Caloric number macronutrients plan based meet at cetera. 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 end of that feeding window.
Yeah, so they stocked up the fitting window. That's interesting because they concept of time. Just a feeling when I describe animal studies, it's feeding for humans whose 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 time table for every cell, every organ to do certain things at certain time. And this Acadian clocks as
You and I know are more sensitive to light. Light is the most dominant timegiver. 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 out of sync.
From our internal clock.
So that was known for very long time, but then around the year 2000 2002, there was a famous experiment by Julissa blur from Switzerland. What he did, he just fed the mice at the wrong time. My son knocked on all their night, feeders, and when he fed the mice during daytime, 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 if in, we repeated that in 2009 and we figure out. Yes, I actually outside this brain Center called suprachiasmatic nucleus or scn, which
Is considered the master security and cloth almost rest of the brain even follows when we eat. And that came out from Pure sham, one slab in Europe, whether systematically looked at even places that are very close to the occasion. For those who are no dorsomedial hypothalamus paraventricular nucleus, all of this, within a couple of 45.
L of the aesir. And but they were following ft Q missing. So then now if we think about it, so for example, when the daylight saving time changes, just one our chance, one our change in alignment, between our internal time and external time relates 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 gave her
Changes by 1 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 average, it will take 33 days to catch up with the New York time. For some people, it can be even slower and for some people, it can be two days, but the bottom line is, yes, there is a decent crony. So then what does it
Mean for the body. So they one of the function of the 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 a 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, that is the first phase of
Jason to secretion of all the digestive juice in the stomach and absorption of nutrients and liver metabolism, everything, the whole village expects when you are supposed to eat and that getting ready for you to eat the first meal after fasting for long time. So that's why it's breaking the fast of breakfast. And when that time changes, when you change it by two or three hours from one day to another than sometimes I like,
Go food, didn't come, maybe we'll come at a wrong time. We were at the wrong time and then they will track the new eating times. So, suppose I have one day. You have been eating every day at 8. A.m. I say, I
ate at a dance. Is that when you start your eyes time window, when do you, when does your feeling Windows?
Shut? 6:00 p.m. So I for around 10 hours, okay? And then one day if I switch to 10, and then what happens is,
Clark is thinking, well, the food didn't arrive at it, but it arrived at 10. Maybe tomorrow, the fertile arrived somewhere between 8 and 10 so we'll be ready around nine.
So then the next day, if I come back and eat at 8:00, 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 for clock in different systems to get the best 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 the time when you eat, could imagine that food will be better utilized and if you don't. So in other words, what is the advantage of having these anticipatory signals? In terms of potential health benefits,
the anticipatory signal is really important from even even from working up. The reason why many people feel not ready come
Lately when they'll 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 dear to a body is not prepared for that. And then the best example is, when the, 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're waking up when the body is not ready, your heart is not ready. And all of a sudden they had has to start pumping little bit harder. Then there is a chance of heart attack. And in fact, people have looked at hospital records and the find that on those days. And there is a sharp rise in heart, attacks in the car accidents, and car accidents to because your brain is not coordinated. So you cannot make those find decisions. 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 experienced the many rhythms in our digestive system and one of the rhythms is our lower intestine has this peristaltic function, so it kind of contraction expands and that moves for more food, doesn't move due to gravity. So it goes back and forth. And that peristaltic action 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 second, 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
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 cut or junk?
Yeah I've experienced that. Where if I've worked later I couldn't eat dinner or something and then I get home. I always debate whether or not to try and sleep. Yeah. But if I'm too hungry often times 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 a mistake of going to the refrigerator being
Hungry and eating a bunch of food at 10 or 11 p.m., and then falling asleep. And indeed the sleep if I'm tired enough can be quite deep. But the next morning I feel just completely physically and cognitively weighed down. So I think it what? You just described makes a lot of sense so is it? So if someone were to select a feeding window regardless of whether or not it falls into classic intermittent fasting time restrictive eating sounds like eating your first bite of food and eating your last bite of food at more or less.
The same time each day. Yeah, 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 food is digested. Different rates, more fat in there is going to digest make carbohydrates digest, slow or Etc. 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 asked on social media, does blank break a fast. So and so I like to think about it. Scientifically like okay is does plain water break a fast. No, does are break a fast. Know does one grain of sugar? Sucrose, break a fast? Well, probably not. But does one teaspoon of sugar, break? A fast? Will 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. So I'm going to eat my first meal every day at noon. And I'm going to eat my last bite of food at 8 p.m. and at 9 a.m. 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, a.m. I'm back in a quote-unquote, fasted state. So what is the fasted State? Really? Because when I'm eating at 8:00 p.m. just to give another example, I'm start fasting at 8:01 perhaps. Yeah. But I have my blood glucoses Elevate so I'm not really fasted nighttime fed. Yeah. It's just that I'm not eating the verb right. Okay. So so again.
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. Yeah, 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. Yeah very different. Yeah, metabolically speaking. So how should people think about fasted vs. Fed? It can we be mildly fasted versus severe fasted can we be fed
Versus very fed. Anyway, I'll stop asking questions now but because they all relate to the same theme.
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 imagine planning five or six different experiments. Each experiment should involve eight or ten volunteers its 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 an 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 this
To then we can figure out whether our body in total. We are not saying whether it's deliver got fat or muscle in total, whether it's consuming glucose or fat. As energy source the idea is when we file, when we are without food for several hours, then ideally our body will tap on to glycogen first and then to little bit of fat. And then when the body
is mostly running on fat, then that ratio of CO2 to oxygen will come 2.7. But what is interesting is we can do this experiments in mice, so we can go to mice and ask, okay, so what happens in mice, so in mice, a little bit, very different because mice are not simply little people there. 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. This ratio will go from one when the consuming mostly glucose or carbohydrate as energy source, it will slow down slowly. Go to point seven point seven, five sub to 12 to 14 hours, they're kind of mostly running on fat.
Now, as we give them food within 10 or 15 minutes, they're not actually consuming couple of grams of for there. They might have consumed say 100 or 200 mg of that child so which is less than say five portion of the food and then the rer will immediately begin to rise as if that small amount of food, stop that fat burning process and cranked up the carbohydrate bonding
process. When
You say fat burning process, you mean body fat stores being burned, right? Not dietary fat,
correct? Yeah, so it's all body fat means that. That's why I said, we don't know who have that fat is being burned because we're just measuring how much mice is breathing in and out. So for example, it can be from the Skin. So subcutaneous fat belly fat
but not dietary
fan. Know, by that time the dietary fat is already observed and digested and hopefully it's sitting in the liver or adipose tissue somewhere. What?
State factors body fat. Yes, thank you
for. 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 confuse people? I realize you're not doing that. You're you are certainly not when 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 that, under conditions of caloric restriction, you'll actually burn less. I hope I don't know, probably get, I'll probably get pitchforks. Send through the mail toward me on that one, but but I think that's true where as, you know, people who consume carbohydrates can still burn body fat, even though the majority of the fuel they're burning is from carbohydrates. Oh
yeah. So here, in this case, for example, from mice, we know that as soon as they start eating the area,
Goes up coming back to your question. What would be ideal for us to do the experiment would be. Okay, so we'll go back to that and then give the mouse, maybe 100 mg of Ford, 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 say, let's stay on this. And then I'll come back and talk about non-caloric food. And whether that is
considered,
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So there's a famous experiment that was published last year by Joe takahasi slow 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 give that food the rats and then subsequently mice, and they all lived
What is interesting is in all those experiments, the researchers can get this bolus of food at one time, whereas, the ad 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 twenty percent less.
And what happens is this mice or rats? They're not going to take that less food, which is restaurant now and just ate little bit of lunch. And then snack after 3 hours or snack, after 3 hours, they gobble up all that food within 2 to 3 hours, maximum four hours food is gone. So they're sort of on The Nomad
diet, the one meal
there. Yeah, the almost like in one meal a day three to four hours food is gone.
Or you can say they're on.
Four hours eating of 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.
Our time, restricted, feeling or time in, 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 this, poor grad students or technicians to come and split that food, and to 8 or 10, or 15, different small portions, and then give them two mice in every two hours. So, Joe Takahashi, you actually publish
First, the first paper in 2017, showing that most caloric restriction, stood in the, 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 the smart kids where he could actually tell he could program. How much food is given to Mize at what time of the day or night completely.
Ram.
So then he took this, for example, suppose a, the ad libitum fed mice. It's five grams of ciao in a day, and if you want to reduce calories by 20% and the CR Mouse should get four grams of food and it divided this into nine or ten meals, and then give them in every 90 minutes. So, in this case, the I think small
Meals throughout the 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 accountants. This is a very standard protocol. People count how many mice have 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 calculated the end. What is the half-life? So 50% survival, because that's on average, that's a good indicator because if there is an outlier that will live for long time than that can skew. So, what was interesting, was the ad libitum fed mice. Of course, they live certain number of days and then this
Calorie restricted mice that never got into Super fasting but kind of eating's snacking throughout their night and also lift and person extra then person longer. So that means caloric, restriction. Extended lifespan by 10% at wonder about this because recently,
You know, there's been there were a bunch of news headlines about intermittent fasting and 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. Yeah, 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. So what you've essentially got our 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 0 time. Restricted feeding isn't valuable, which is not the case. And I think for many people, it's a convenient way to
To eat because at least for people like me, it's simpler to designate between portions of my day when I'm eating importance of day my day when I'm not eating as opposed to eat portion control. Brother, 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, right. So, and so, 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 was likely to recur. So 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 eight and 12 hours per 24, hour cycle are tilting the scales towards living
Longer as opposed to living shorter.
This example of this news article that you mentioned is really interesting because that relates to Jose, Jacques is study because I described that if you split calories and eat throughout the day, the throughout day and night, then the my slave 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
beyond that. Yeah, so 20% 20%, so. Okay. So let me make sure I understand 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. Yeah, it's caloric restriction. The mice will live ten percent longer? Yeah. If you however, restrict that to the active cycle, you have that. So for humans, the daytime then
20% Then They Live 20% longer so it's not just total caloric intake. Yeah, it meaning it's not just important to be sub maintenance and calories forsake a longevity. It also is important as to when in the 24-hour cycle. Yeah. You eat those calories. Do I have that, right? So
now that's still the story is not over because this might want Fair during daytime on the not supposed to
it. That's right. So, for us, will be the equivalent of being on the night shift and only eating at night, but a subculture or sub.
Antonin, Scalia read ayat, I guess is the right way to say it,
but when he fed mice during night time, when they're supposed to eat and it's seeing this getting the same number of calories within 12 hours or two hours and the mice left, 35 percent longer than the control,
35 percent longer. So scale to human lifespan, which are, you know, we don't know. But a 35% longer would mean that and again, no one knows but humans are now what is the average mortality in the United States?
Where you wish my fix. Yeah. So it's around a, do you do is to be written out, slow to reduce little bit because of covid, but let's take 80.
Okay, so people are then living somewhere between 25 and 35 years longer but I'm putting some error bars on.
Yeah, because that was really profound but now you want it 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 court 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 of glucose control cholesterol, all the stuff he could not find anything that predicted the benefit of calorie restriction. So that means in this experiment, whatever we know so far the predictor of longevity, none of them could predict for the this CR only Mouse, which it throughout the day and night, that Mouse.
Is going to live less than the night fed mouse. That was going to live. 35 25% extra.
Does that mean that there are biomarkers related to longevity that? We just haven't discovered
yet? Yeah, 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 miles to get that because, you know, biomarkers are not going to predict in every instance,
There is some error. What is also very interesting is, if you look at the body where it and body composition of all these mice, there is no difference in body weight, and body composition across all these different groups, all these groups. So it doesn't matter when
they ate. Yeah. Provided, they were submerged sub calorie maintenance calorie intake. So less fewer calories than is required to maintain their weight in matter what pattern of eating. They were the same way. Yeah, 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 caloric, 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 for sake of weight control weight
loss, taking a snapshot of that. And then another thing with the human study, that we are referring to hear 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 there are already eating for 10 hours and fasting for 14 hours. All participants had to reduce their caloric intake and the reduced by almost 25%. The see our group continued with 10 hours it in window, and the CR plus time restricted group had to eat the same number of calories within eight
hours, so it's just a two-hour different
suggested, two hours difference,
okay? So the people
I just want to make sure people can understand. So in this human study, which is the one that I felt that 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. Yeah. Or if they're on shift work and they are 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 eight sub maintenance calories of caloric restriction, CR as we're calling it the acronym CR, but restrictor that to an 8 Hour feeding window and they didn't see any difference in terms of weight loss. Yeah, but that's not all that surprising, right. I mean if it's just a two-hour difference.
Yeah, exactly. So we have done that experiment in mice and we don't see a difference in not only weight loss, many of the markers and I
Telling you about this Joe takahashi's Paper where I told you that he allowed these mice to eat within two hours or 12 hours. Sub calorie diet, 2 or 12 2 or 12. Yeah, that's dramatic. But still, he did not see change and Longevity even within those two. So that means when you do caloric, restriction, and then at least four marks and you are within 12 hours window, that's that is
Giving demise the best benefit, the optimum benefit, and 235, or 12 for a mouse. Doesn't matter. At least for longevity.
Can we conclude for humans that whether or not a feeding window is for our six hours? Eight hours or twelve? Doesn't matter provided the calories are are similar or
same. 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.
Love fact, both success because you know, we always think many of this mouse experiments. Even that I told you about those are done, only in male mice, but
that should be changing, right? Because the NIH, I know this because 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. You it's hard to get away with or rather I should say it. The way it should be stated which is people are required and she want to look at
These phenomenon in male and female mice. Yes, especially if there are differences.
So in this guy is there are many men. There was also another people and Timeless to defeating that also came out. A big people showing that they thermogenesis was accounting for loss and fat mass in time just referred my eyes. There 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 May.
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 four hours or six hours of time retreating people will inadvertently reduce the calorie intake.
You just because of got volume. I tried one and a day and then I felt like I was eating so much at that one sitting. Yeah, that it led to a lot of gastric distress and I'm tired after the meal and part of the reason I like to do time, restricted feeding as I have more energy. Yeah. And certainly in the fasted State. I feel more energized especially if I'm ingesting a little caffeine or
Something like
yeah. 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 the physical activity and basal metabolic rate all of this combined than how much dieting 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.
As relative energy deficit in sports
relative energy. Deficit in sports,
okay? Yeah. It's because nearly 40% of athletes, not the NFL, guys, but, you know, a lot of people who do track and field and nearly 40% of athletes actually experience this Reds reddish without knowing
can male and female athletes both celebrates red. So it's Reds are EDS relative, and the relative energy.
Deficit in sports. Interesting is the first I've heard this acronym we have a new acronym, folks. This is good to add to it a list of other acronyms but so males and females can experience it. So in females, I've heard that Reds can lead to amenorrhea so loss of men's of the menstrual cycle.
Yeah, 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 than they will lose their menstrual cycle, which is, which may be common, but it's not normal or Optimum / health and
even if they don't want to get pregnant, yeah we had an expert on female hormones. Come on and say the very same thing that regular cycling is a variable of ovulatory. Menstrual cycle is important to try and maintain. Yeah.
And so that's one. But then what is really concerning is
It does affect bone health. And in this bed people actually over a long period of time. The lose bone muscle and the bone also becomes more prone to injury micro fracture 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 Miss division. Why?
These women are losing. Menstrual cycle, is there, hpg axis is disrupted hypothalamus, pituitary, gonadal axis,
And it starts in más tarde, even of stream at hypothalamus and pituitary. So that means that HPA axis hypothalamus, pituitary and adrenal axis may also get disrupted. One of the symptoms of rates is also depression, anxiety, bipolar like symptoms. And we know that many many athletes experience that. We think that, well, this, this maybe just PR pressure that always trying to compete. And we know there are unfortunately there are few our class who just can't cope it and
many attempted suicide or suicide. So this is a serious issue and there's also another new topic in 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 eating interval to to such to one meal or very short time because it can have adverse side effect that we don't know. Now, maybe in future, we'll figure out when we systematically study.
There are studies that are published showing four hours and six hours time restricted eating has benefits on weight loss but those are on healthy individuals and they were in the study. So the, you know, the study team to give were already monitoring the made. Sure that there was no sudden weight loss, or weight loss below some safety level. So those are very different from regular people who are who maybe even normal weight.
Even with within the healthy range if they do that and they can potentially. So that's why what we think is eight to ten 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 lot of benefits, not all but so this is 12 hours.
12 hours of trading, 12, hours of Australia in humans. Again, nobody has done systematically 12 hours but there was one study in Europe from 10 high, Colette lab and can high. And I we collaborate so they used on my security and clock app. This is a research app we developed just to this is mostly used in time, restricted, eating studies and he had nearly I think he started with 200.
Which participants but then at the end, he selected and took very small number of groups, people who are very meticulous about recording all their food and divided them into usual feeling whatever they wanted to eat whenever they wanted to eat and they were given the advice of Swiss nutrition advice. That's given to improve health and reduce blood glucose almost like diabetes, prevention program in the US and then the other group was given advice to eat within
All of ours, this is very early on in time retreating. And we thought that the mice were getting some benefit. Let's try whether 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 is not too much significant difference between groups but both groups actually improved the health. So the bottom line is this
Us waste, nutritional advice that he was giving Which is the standard of care there. It achieved the same amount of weight loss as just giving people this advice that eat within 12 hours. So one way to look at it, look at the result is like this and then he went to more extend and actually looked at every single meal. These people consume so they're all close to I think close to 60 or 70,000 Mildred.
And pictures he went through and then classified them to say whether these are good quality food. So they call it the Nova classification. One, two, three, four, one is the food that you can almost eat raw fruits, vegetables, yogurt, dairy products that you can almost without any preparation. And then second Nova to is kind of a home-cooked food that most people will prepare and few minutes and then three. And then fourth one is
The for that, you can never prepare at home. So for example, biscuit or cookies that we usually purchase and few other things and usually the Novak for on health, the ultra-processed foods so which we should not be attained. So the advice is to reduce Novak for. And what I found was people who got all this advice to improve the nutrition quality, they actually improve the nutrition quality, the reduce the Nova for food.
And people who are in time, reciting the edge within 12 hours, the did not change the nutrition quality but what is interesting is the both got the same modest weight loss. So that begs the question that in the maybe ten 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. So 12 hours is something that I say,
Anyone from five-year-old, 200 year old can do. And if you're trying to maintain weight, that might be a good way and combine that with exercise will be
great and un people can more easily avoid Reds. Yeah, no way women and for non athletes or recreational, exercises sounds like women if they distribute their calories across 12 hours or less likely to lose their menstrual cycle.
Yeah. So again, this is something that we have to look carefully. They have to be because we do
You have the mice akkadian clock have that many people download and self Monitor and they share the data for researchers. We
will provide a link to that, by the way, it's a great, it's a great
tool. Yeah. But once in a while, we do get this input from some women saying, oh I started doing your time retreating and I am seeing all these problems and then I ask them, okay, so what else are you doing? They typically improve the nutrition qualities of dieting. Only solid and few. And 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 nutrients and then at the same time, the running five miles every day, and of course, all of this combined Lake 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 the eating, within 10 to 12 hours, then they also live longer.
Longer than mice that are eating healthy food, but Distributing that Cal over a long period of time. And this is rough hard acabas, 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 it randomly even healthy food.
I recall a recent study I think it was either publishing so reports.
So reports medicine, forgive me for not remembering, which will both, of course, L press journals, excellent journals, which explored time restricted feeding in the context of low carbohydrate or non low carbohydrate diet. So it was low carbohydrate versus low carbohydrate and time restricted. Yeah. So these all caloric matched, right? Between groups and then non low carbohydrate diets or more standard. I think it was somewhere in the neighborhood of 60 percent of calories from complex carbohydrates. And, and as I recall the
The greatest weight loss. 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, before I find it, hard to sleep. After about three or four days of being, on a low starch. Yeah, just personally, I so, I
Eat some starches, especially if exercising intensely or working intensely. That's just a little editorial there that but look, I know many people who do just feel better on a low carbohydrate diet, but what do you think of those data because it speaks to the idea that, okay, 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.
Lose weight.
No, 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 or obese, 40% of maintaining healthy, body weight and out of those 40 percent. I would say, nearly majority of them are very aware about how much dieting and what quality of food, they're
eating us, you really an optimist you're looking at the 40% of the glass. That's what should we say, not full.
Yeah. That was a pun intended but the know that's a very interesting way of looking at rather than saying you know why? Or sixty percent of Americans obese saying why are 40% not obese. It's a very interesting way to look at it.
Yeah, I'm in subconsciously, we're always making that decision means. I know when some sure that you are not going and eating a cheeseburger every day because you want
to improve. Yeah, no, yeah, exactly, I wouldn't feel good. Yeah, I enjoy 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. Yeah, I know people gained a lot of weight during the pandemic. Other people got really into fitness. I've seen some colleagues, we've always maintained you've always been in good shape. Actually, 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 hypotheses about time, restrictive feeding. But but I noticed that during the pandemic. A number of people emerge from the pandemic. In better shape other people in much worse shape. It seemed like there was a it was a 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 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? Yeah, 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 timekeepers for our system, being feeding, light
activity and social connection. Did I miss
Ed maybe temp and temperature. Yeah, yeah. So how do these combined with one another and using timing that we begin in stop feeding? His kind of an anchor point? We explore that a little bit. Yeah.
So you know, we got into this beginning and end and then we you asked for the calorie how much calorie will break the fast.
One thing that I want the listeners and viewers to bring back to this timing of when way when you're breaking the fast because we equate Health with wit body wet and that's why 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 who struggle with mental health, they have anxiety or
Depression and also Sagat 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 and take an empty stomach. Those who have acid reflux or heartburn, they're prone to that and having black coffee in the morning before any food can upset the stomach. So,
So, that's why, in those cases is very clearly, that caffeine for them becomes the trigger, that's something the Ford is supposed to come, and then the stomach is not seeing the Fords 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 there.
Overall fast or kind of putting them, putting the health at risk for acid reflux. The other thing is people who have anxiety panic attack. We know that caffeine can judge you off.
Especially on an empty
stomach 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
Xiety panic attack related to brain health acid reflux related to our gut health. In those cases when we consume that caffeine in the morning can affect. So
you avoid caffeine in the morning
and I actually here is the interesting history about caffeine and this is something I did not know and I was once invited to this history of nighttime activity.
And maybe we can take a little bit of detour and talk about nighttime activity because that fascinates me as a circadian. Biologists because over the last two hundred thousand years means, we assume that humans Homo sapiens 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 a couple of thousand or five thousand 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 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. The differentiates them from all the other species, no other species. We can always say yes, there are signs of this intelligent decision making for
A we know many crows 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 to human. And when we started controlling fire fire, did not essentially extend the day because fire created a evening. There is very different from what people did during the day.
And what people used to do during the 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 wild animal, so that we can, we could barbecue all of these things happened around, Fire and Fire was too expensive that it was mostly communal fire. So if
Go back to, for example Maasai and all these and such sorry populations that have no access to electricity and the still-living kind of that historical life fire is a communal event and they sat around the cooked food and then what happened? They did not talk about work. They talked about culture, the talked, they sang, the danced, they strategize. That's how politics started.
Philosophy started science started all of this things that are very unique to human civilization, started around fireside chat. So, in that way, if we think about it, we are still doing fireside chat. The only thing is we have the microwave and the television or social media.
So now we chat with our thumbs,
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 hours of that sour independent time. So that's why most people find it very difficult to do time. Resetting, and stop eating at 6:00 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 con jobs, and particularly Cafe, where people can come and have little bit of coffee and socialize, it also started as a 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.
So if we are talking about 1542 1570 and that's when I'm sorry, I'm forgetting the name of historians who actually invited me. And okay, his name is Jamal, Crawford are and I must be butchering the name. But I will
try will provide the spelling. And the wonderful thing about social media is somebody will tell us on YouTube the proper pronunciation so is a great opportunity. If you know the proper pronunciation, please put it in the
Comments on YouTube
and I should, I'm even checking right now in my endnote library. That's not picking up that. That's right. We will provide a link. So what happened was so coffee was introduced and people came and drank coffee and talked about politics at night at night at evening. And it actually started with with Sookie branch of Islam, because they are the ones who consume coffee in the evening. And this is the branch of Islam. Where the
They actually sing and dance and all that happened in the evening. So singing dancing by the soupy 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 sizable number of Muslims who have to do five 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. They walk 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.
Yeah, a few years ago, right before the pandemic 2019, I traveled to Turkey is force. Well the food is amazing. The coffee is indeed very very thick. Yeah. And I have a pretty high caffeine tolerance. Yeah. From drinking so much coffee in 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
Is that coffee intake started as a way to extend into the night and the ability to extend into the night at all, was because of the ability to harness fire and then coffees stimulatory properties were leveraged toward morning, which is essentially like the way I think about it. We didn't have a soda on caffeine and some someone else. Michael Pollan, not, I described it this way that you're sort of taking a loan out on your energy bank account coffee, you're suppressing the adenosine system identity me.
Are you sleepy but that adenosine system will kick in later. So your it's a credit card of sorts with an interest, right? Right. And the interest being an energetic lag, that you're going to experience in the afternoon.
Yeah. But what happened was, the strong coffee that give heartburn and acid reflux to lot of people. So then,
The started eating something with coffee and that's how the culture of breakfast started in
Turkey. Also coffee actually led to the development of breakfast, not the other way around and that. Yeah. So that's very heartening. No again, no pun intended for the caffeine lovers Among Us which I count myself. Yeah.
Those so I sincerely the food before coffee became breakfast, so you kind of give something to you.
To his stomach. So it's busy digesting that and then when the coffee comes in, it's not reacting to coffee and creating acid
reflux. So it wasn't this fascinating. So, it wasn't that breakfast is necessary on its own. It was essentially a buffer against the gastric distress caused by caffeine and
list. And that culture means in that context, we cannot say that what are the same thing happened and all over the world where coffee is not consumed, but still people eat something in the morning.
You
said you start your first meal of the day at around 8. What
time do you wake up? Wake up around 6:00. I started to see
what time do you have your first caffeine?
No, actually, I have. So that's why I brought up this story because I have coffee after my breakfast.
Fantastic, 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 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 and activity 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 tracker.
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Now actually, I'm kind of speaking. What many other researchers have found and this this particularly this fireside chat and 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,
We are
talking Twitter and whether or not Tesla's stock is going up. Of course, no. Just just getting folks
and then come back and try to translate and then figure out that what are talking during daytime and in the evening were very different. So, so, so what are they talking about it? And I do. Exactly. So this is a 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 Sunset to our bedtime, what we do between Sunset and bedtime effects, most of our health,
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 Etc. Then we do active waking States. Like we talked 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 first
Just
eight hours of the day in terms of cognition, and we know that the catecholamines are at much higher levels, plus cortisol. So dopamine cortisol epinephrine, all of that is really at much higher levels than in the later evening. And so 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. Yeah, completely.
Yeah, so that's why I think in the evening, if you think about it.
Again this is again another set of research from my good friend Horacio
who they glacius. Yeah. Oh yeah I'm a big fan of for us is another he's a fellow Argentine so occasionally we're if about things related to that but he's a wonderful biologist you guys collaborating.
Yeah his kind of I say he's very humble and keeps a low profile but he does amazing, amazing research old angry. He does research that we want to know.
Oh, but nobody is ready to do it. Because field research is very difficult to go to the wild honest, 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 her Asia has done. And he puts this active watch, which is kind of a modern activity tracker but it's little bit more refined because it also
Light information.
What I found was most of this Argentinian tova's who have no access to electricity. They consistently go to bed somewhere, between three to three and a half 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 want to sleep. No the fire extended the evening. So they were staying awake for 3 to 4 hours kind of, you know.
Decompressing themselves that we say and then 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 deviations.
So no night owls versus morning people, this Godly. So we'll get to that. None of this. This I get attacked by for many reasons. That just goes with the business. I'm in of being public facing these days. But
Every time I talk about viewing sunrise or low angle sunlight, you know getting some sunlight earliness someone says well I'm a night owl and they just it's almost like a protest of trying to protect identity. It's become this ideological. I identity related thing. I'm a night owl, I'm a morning person, 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 with in all of them within about 15 minutes of one another. Yeah, so there is no such thing as
A night owl or a morning person in the
context of him pointedly. Because and then he said, no, he has not seen when she has tracked 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 one-third of people are Night Owl, 1/3 of morning and then 1/3 of in between but
they calm like Bears wolves and you know, and I'm not being disparaging of that idea.
People really do feel as it is if they Orient towards one pattern or another.
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 am in bed and I used to get up at 6:00 6:15. It's
hello. That's a pretty short
sleep with an alarm of course. But then they time I used to take 45 minutes to 1 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 day unlike in high school. You don't have opportunity to now. But in college, you can.
I might have been one of those kids with his hoodie, on napping on the desk, but they come around and they wake you
up. Yeah. But in and this guy's just come back to the dorm and after lunch. Usually, I was to pick now. So then in grad school,
I remember I need it really went to bed before to an and I could have clearly said that I'm a night owl and actually I was at Nite Owl is very comfortable, staying up so late. I was very productive going experiments writing all this manuscripts mostly and
But then afterwards, when I look back in postdoc, 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 slaves, it's almost when you have a baby, your life revolves around the clearly. So then we had to dim down the light, there is no caffeine and alcohol drinking.
Or any other things after the baby slaves because we cannot do too much noise others, it's then I realized that, no, I'm actually not a night owl and I became kind of more normal because I could go to sleep between 10 and 11 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 can write Junior Colorado.
At Colorado. And he also had got students and postdocs like me who strongly believe that they were night. Owls just like everybody else and he took Ken took the whole love for camping and when they were camping, of course, there is less light and a lot of physical activity hiking during the day and they all went to bed between 9:00 and 10:30 p.m.
So of that study. Yeah, what such in just described was a
see I think there were two studies there are two. Yeah. And what's interesting is I recall is that after going camping for a weekend where people wake with the more or less with the sunrise. Yeah. And go to sleep a few hours after Sunset. Yeah. They're melatonin rhythms and cortisol rhythms and sleep-wake rhythms persisted on that schedule for several weeks despite returning to environments where there was a lot of artificial lighting which I find amazing that just a week.
End of consistent rising and going to bed with the sunrise and sunset. Yeah. More or less allowed? A reset. That was very
long-lasting. Yeah. So actually even in Horacio study, we found that almost all the tobi's, the wake up around sunrise time and it's amazing. When I look at the standard deviation, it's like so tight.
Take that night. Owl. So called night owls. I also didn't graduate school. I would work until 2 a.m.
Um, I loved it. I blast music in the lab. Everyone was at home, pretty much, not everyone, but they were the, the night crew and then I'd get in some time around, get up work, sometime around, 9:30, 10:00 and then get in around 11:00 and it was no problem because I was going to stay. So very late. And then over time, I noticed 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
That's a conclusion. I'm taking from
this couple of aspects. One is, you know, some people are genetically, so pre-programmed because the other flip side is, what is called, technically familial Urban sleep, phase syndrome. So these people, you can give them caffeine or what about this is what they will fall asleep. So at 8:00, they cannot stay awake, till 9:00 or 10:00. And since it's a very strong phenotype in sleep and circadian.
Um field, they are very well studied. So in fact, Luis Potosi I can in guifu 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 to that clock Gene and that mutation allowed the clock to run in a way that these people went to bed very
early, I guess historically.
Given these Fireside Chats. Those people were probably not contributing much to the political discussion, whatever there was decided after they went to sleep as what they woke up into. That reminds me because as you were describing the difference between nighttime discussions versus morning discussions, is there any theme to what is discussed in the morning verses in the night time? Where people just sipping their eating and sipping their caffeine and just waking up. But is there are there any ideas about what morning discussions really
consistent modding discuss on Sade time discussing?
Are mostly about work and like hunting-gathering a farming, all that stuff. And even these days, that's what we do. We go to, I go to work and it's mostly one meeting after another, and we're talking about how many different different committees and we are 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 immense serious,
Philosophy of unless you are in the philosophy department, at you're talking or 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, 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
Work just like we are 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 companies. They cannot talk about that work to anybody
else. It's all secret,
it's all secret. So just imagine that staying a, 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 members. So then what happens for them, a lot of people also do the same thing like the person who is going and baking and Restaurant of cooking or the person who is taking truss and
driving or nurses and doctors can talk about their patients, there's
confidentiality. Yeah. Yeah 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 role. Sometimes we are performing and sometimes you have deserving. So that's what happens with me time
I love this so maybe social
Via time should be restricted to just, maybe a small portion of that evening time, because I would hope that people would also interact socially within the
religion, a constructive way, or maybe use that for connect with your family members whom we love, or you can have some productive discussion or something. So, it's kind of interesting.
And I think it's extremely interesting because I think again, this, this conversation about time. Restricted feeding is really a conversation about security and Rhythm and sleep-wake activity and human evolution,
right? But that's fine.
Let's go back to this night owl because 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 gwas studies where that trying to look at night owls to see whether there are some genetic Lincoln's and you know sometimes we always think yeah, if you take half a million people, of course you'll find some loci that huh.
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 these Toba story that we are talking about or people going on camping, there is we have removed that light
So there is some evidence that People's Light sensitivity, particularly the IP R GC of this intrinsically, photosensitive retinal ganglion cell or the simple speakers the blue light sensors. In our eyes that seems to be even one log unit change, in sensitivity, as measured by pupil constriction.
So for some people a small amount of artificial light at night, could really
If their circadian clock and wake them up
essentially, and then put some it matter.
Yeah, I'm very sensitive to light at night. Yeah, exquisitely sensitive to it. Oh, so then you are like a teenager. Yes, 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 for sake of any kind of infrared simulation, but a red party light type light and I find
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 redshifted light. So, I just use a red light bulb actually travel with one if I go to an Airbnb or hotel and I switch to 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 she always makes a 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 bean and you're right. Some people don't
seem to be bothered by that.
I really struggle with that.
Yeah. And in fact in Tina's, right after puberty there 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. There tend to stay awake late Into the Night.
the night and they can stay up to 12 minutes, past midnight,
Although they can stay of that led, that doesn't mean that their sleep schedule is reduce their body. Still needs the same amount of sleep as other teenager so that's why they are more likely not to wake up at 6:30 or 7:00 when we expect them to wake up and go to school,
I have a question and I asked every circadian related biologists 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.
Eat 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 10:00 p.m. I can wake up at three or four 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 five six 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.
Well there are two things. One is said that you are very sensitive to light. So I assume that you also avoid bright light in the evening as I Kenya as best as you could can. 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 because measuring melatonin and
An hour or 30 minutes is very difficult and there is no consumer-facing product yet. So it's likely that 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 world, but then after that, you melatonin level might be beginning to fall and it's not only melatonin your
Core body temperature, and then a 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 this tension between the security and aspect and your sleep debt. And unfortunately, you cannot have good night of restorative sleep for the second half of the sleep because of the tension that makes good sense. Yeah, so that's why, you know, you are not the only one in. There are many people who
Who experienced 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, restorative lie. Until, you know, I sleep one day, just like the camping trip. And then
they realize what you, what? It feels like to, what you had, what you're missing. Yeah, absolutely. I want to make sure that we talked about the other aspect of fire, which is a, 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 general contour and maybe even some of the specifics of that study? Because I think it's very interesting for for sake, of shift workers, but for everybody really to understand these results.
Yeah. So let's go back to shift workers because this also relates to all of us. Because I always said that each of us is a shift worker, or has lived the life of a shift worker and we have experienced how terrible
It is. And now let's start with what is the definition of a shift worker shipped 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'll 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 slip time, they assume that we are just like you said, we are kind of program to sleep somewhere between set, 10 p.m. and then stay in bed and kind of wake up after 5 a.m. So the idea is, if you stay, if you're staying awake for two or more hours between 10 p.m. and 5 a.m., and you are engaged in some activity, whether it's physical activity or intellectual activity, you
I'm 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 chance our external timing Q. So, in this case, when you travel jet lag or or traveling across three days, three 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 and guests in some activity in the dark.
But most of us aren't means unless you are wearing a infrared goggles. We turn on light and light research, 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 clock is trying to catch up with the outside time. So clock our body is not on time without clock. So that means almost for half of the week 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 US Government. They have
Not been tracking, what percentage of people are doing shift, work accurately because there are many difficulties in tracking to, 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 Baker's truck drivers and many in the service industry.
Yeah, 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, their work
deadlines, Grant
done, their lines than we are. Also experiencing experiencing the lifestyle of a shift worker, because we're delaying sleep. Even if you're delaying sleep by 2 hours for most of the college students for five days and then the weekend, you're trying to catch up that's kind of a security and disruption going on.
Then you take 1.5 1.6 million, new moms 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, we think the actual number of people who are experiencing the life of a shift worker is somewhere around fifty percent of the adult population at any given time. So that's why it's also another point that you might have heard from people, they will say, oh, I cannot do time retreating
because my schedule is messed up. I work in a different way and that comes into play, so that's why we thought. Okay, so we should try something on shift worker. Another point is all the one in five people are shipped workers. They carry disproportionately heavier burden of disease because almost all is related disease that we can think of whether it's high. Blood pressure. Usually high blood pressure starts in 40,
50s high cholesterol. Gastrointestinal problem in digestion, chronic inflammation of the colon and then even colon cancer in many cases and then of course diabetes, all of these disproportionately more prevalent among shift 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 shipped 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, the know that they are the body and mind is so messed up.
That oftentimes even medications may not help them. And so that's why we don't try a 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 have been sometimes come to the clinic visit when people have to take group draw blood and in fact, there is another caveat that just if suppose I am healthy
I have perfectly normal blood pressure, blood glucose cholesterol, everything is normal. And I live the life of a shift worker. Just for five nights. That means I'm sleeping less maybe for 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 5 days. My blood glucose level will read almost like I'm
pre-diabetic. Wow, I actually saw a study and published in proceedings of the National Academy that showed that even a hundred looks dim Light present in the room. While people are sleeping with eyes closed can lead to disruptions in morning.
Blood glucose levels in directions that are not good. Yeah, one night. So the the faint clock in the corner, or even a nightlight, that's too bright. Yeah. Could be problematic by the way. Folks, these effects are reversible. So I whenever I say these things, I get a lot of comments about. Oh my goodness. What have I been doing for years? But you know kids with Night Lights. This is an issue. Yeah. But what I'm hearing is that 1 in 5 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 in 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 third of Americans I would say half of America half of America. If you're take Tina, just because you know, high school students and college students because again, going back to horacio's study because whereas you
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 Seattle and San Diego, and this study now, there are many sleep researchers, they have been collecting this data and what we find is typically they high school students, they are going to build, say around midnight and college students. At least the UCSD students we found, maybe one out of a hundred who went to bed.
Before
midnight. The that reminds me Horacio glaciers just publishes really nice paper showing that counter to what we believe students and others at the University of Washington, 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, you think, we everyone stays up late in the summer and goes to bed early in the winter, but because of artificial lighting, it's the exact opposite.
Yes, and another man's. I don't know how to tell her a CO monitor did, but my other suspicions, I'm not saying whether it's true in Winter, we are more likely to consume more coffee, hot chocolate in the evening. And that might also be
Laying sleep. Onset 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 assignment submission become 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 in. Maybe your when you are giving assignment, when is the deadline midnight, typically 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 submitted midnight and it will be really cool to go back to your system. Administrator to see is there a freak? Show me? The frequency plot of pickles distribution of what time people are submitting, their
Assignment because we know means when we submit our grant.
Yeah. 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 2000's in. There was a map of the United States and it showed where the Obesity rates were over 30% in adults and the entire country because he was lighting up like crazy. Now, it would be the entire country. But there were these kind of zones in the middle that
Were almost devoid of obesity Colorado. Yeah I'm Lee Idaho at that time those are now also Fallen Under the Umbrella of rampant obesity and you and everyone is speculating. Okay. 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 shift today.
And staying up late with artificial lighting whether or not that could be one of the major factors in the so-called obesity crisis
slightly. You know, we always say Freshman 15, that's right because this gives a gaining 15 pounds in their freshman year in college. And this is where I think, as educator professors, will 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 give a
security under them class means I just give two lectures. And I remember when I started 15, 17 years ago, that lecture used to be around 1:30 p.m. or 2 p.m. in the afternoon and it's a two-and-a-half hour lectures or it's done by 5. And for the last before the pandemic, I realized that they change the timing. Now the lecture was starting at 7 p.m. such finishing by 9:00 9:30 p.m. and this
It's, they had to go and eat after 9:30, study. So, study, socialize fireside chat fireside, chat. And then to express themselves, like to fill free from assignments. One of the going to do that after the submit the assignment, then they're going to do that. So that's what we have to go back and revisit this issue. Say, okay, so for adults for most of us who are working at day job
Our deadline is 5 p.m. in most cases, right? Means at least in University system. The person who is submitting. The grant of, who is doing taking care of my IRB, or I o'clock. They are all leaving at 5:00. So for me, everything has to end by Phi.
I think for most people out there so this raises 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 in and being a
Active mostly in the early part of the day. I mean, you know I could imagine a Time 34 years from now. When it's about when waking up early and going to bed within three hours of sunset is the protocol, which harnesses all other protocols, right? I'm going to exercise, you're going to do it in that time, you're going to eat, you're going to do it in that time, you're going to socialize, you're going to do it in that time and in doing. So you're also avoiding a lot of the issues related to disrupted
sleep. So that's why all these things that you said Timeless repeating is just 1
Aspect of the security and health and these are all interconnected and going back to the comment about within three hours of sunset. Yes, that's good. But then what happens in say, Toronto or Vancouver? In winter time.
I guess they're going to bed very very early but also waking up very, very early. Yeah, you know, one of the things that I hear all the time because I'm always beating on the drum of getting morning sunlight in. If the cloud cover is people say there's no sun here this time of year and I forgive me, but
There is Sun unless you live in a cave. There's sun is just coming through cloud cover you, no matter where you live in the world, their son. Yeah, 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
starting about? Yeah, 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 shift workers, and sipped workers are excluded from studies. So that means whatever we are learning about lifestyle or even medications that
Be beneficial for people who actually have a normal schedule, but not for people who have a disrupted schedule. And if you look up, clinicaltrials.gov, there are more than 400 thousand studies listed. And it is such, how many studies are on shift workers? It's less than 1,000. And then, if 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 are done to improve the health of shift, working alone, that's less than 50 mins. I means I have to go back and check the actual number, but it's less than 50. Wow. So that's why we got super excited, we thought from CKD another perspective, that's something to address. So this study again this kind of study is only possible because I'm it's all canned way affiliated with UCSD and
I can walk with UCS D Physicians to do this study, so I collaborate with dr. Pam table, who is the director of cardiac rehab center in UCSD. And Pam has many firefighters as her presence. 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 stroke. So they have a very high incidence of heart.
Attack and stroke, and they also highly prone to different kinds of cancer. And it may be difficult to ascribe cancer to disruption circadian disruption because they are also exposed to a lot of toxins. Anytime fire bonds that smell of fire is essentially smell of carcinogens and their breathing even if they have the hood on and respirator the still girl. So the idea was very simple. We know that firefighters nearly
70% of firefighters in the u.s. full-time firefighters, because there are volunteer firefighters, and then full-time, firefighters the full time firefighter, 70% of them work 24 hours shift. So, for example, in San Diego, they come in at their shift is from 8 a.m. to 8 a.m. the next day and they do at least in San Diego. They do one day on one day off on off four cycles and then four days of. And, but
In some fire departments, they actually do forty eight-hour shift. So the come for two days, two days off, two days, two days off and then four or five years
of brutal. Thank you firefighters.
Yeah, I'm in. So then the idea was okay, so we'll scan firefighters and then find firefighters who are metabolically unhealthy and then we'll see whether they can actually follow 10 hours time, rest, iterating. Because the point is, if I
Firefighters can follow it. Then everybody else should be 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 health, we could not have even submitted the Grant and at that time, debit picon, who is their health and wellness? Battalion chief. He is the one who actually approached us because he's very careful, he knew,
That the job that the do makes them weaker and long-term and can kill them in long term. So he was always looking for new Solutions so he approached us and then we said, this is the idea. He said well I love this idea because we are not asking them to sleep more. We are not going to cut down their 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 do this
so consistently between the days that they're working and not working. Yes. So that means if they're from 8 a.m. to 8 a.m. working, then the next then they go home. Then they're going to eat on the same schedule. They did when they were at the fire fire house. Yeah but while at home so they're not allowing themselves to deviate from
that. Yeah. So we talked whether they can do it or not because they number one goal or the primary outcome in this clinical trial was his ability. Can they do it? And then second one,
The do it. And what happens to the blood sugar and wait and all this other stuff and then we started the study and we hit the next hurdle and that is
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 Manoogian who is the first author see and then we had Adina jidori on who is now in med school. She was a resource coordinator at that time. They volunteer they said okay 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, there are assigned a bed in the station because all five stations do have some beds for firefighters to rest and they have assigned bed. So they were assigned a bed. Yeah. So every time, a 911 call chem and if that fire station in that fire station, that fire engine was called then just like other firefighters they have to run get into
Gears, just the shoes and jacket, and the helmet and getting receipt, and attend the call, of course, their own go to the side. They just get out of the truck where there and come back. So, in that 24 hours, Emily got ten calls at night that she had to run to, but there are more than 10 times. The they got the 91 every time, the 911 call can then there is a bit that goes out.
Or firefighters were sleeping or resting the get up if they are doing something they look up to see which engine is called
and interesting. So it's not just the ones that go out, its, everyone gets woken
up, everyone gets woken up. So, that means in a night, typical night they're waking up 10 15, 20 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 there are. No. So, similarly,
Is five. So that's what Emily did. And then next morning when she came back just
as radical seem easy. Yeah,
so so then we did this 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. That's a 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 are supposed to eat. Within 10 hours, we do not fix the 10 hours because we said you pick your own 10 hours that you can stick
to breathe.
Has to be consistent from day to day. So, if you start eating at 9 a.m. you finish it, now add, you know at 7
p.m. and then try to be. Yeah. All right. It's time to 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 because although they are all doing 24-hour shift, more, or less chose to begin eating somewhere between 8 a.m. and 11 a.m.
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're waking up at 5 or 6 and the driving to come to work at 7:30, or 8:00 and eating the first meal save between 8:00 and 11:00 and then the finished meal ten 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 this study, when we look at the health parameters, one thing is, as I said, we recruited everybody who cares. So that means a lot, nearly one in three, firefighters for 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 one third 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 do not see big difference in weight loss or anywhere change between these two groups. Another thing is firefighters actually Ron almost eight to nine miles when they're at the job, because that's part of the
Exercise routine.
But then one thing that changed significantly in the Timeless treating Groove was what we call, be LDL 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 and we reduce the risk for atherosclerosis. So that's one parameter that changed in the time, retrofitting group, even when you combine all healthy unhealthy, everybody,
Now if we take firefighters who were beginning with high blood pressure, then we saw a 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 there on a blood pressure lowering drug. So, the extent of blood pressure lowering is equivalent to somebody taking a
Drug amazing. Yeah, and then those who started with high blood sugar, of course we didn't have too many type 2 diabetes, but there are very 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 managing their blood sugar than non shift workers, because the work schedule self will miss them off too much, even if they're on many,
Medication. They have
difficulty, that's fascinating and I'm really glad that you explain 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 are there 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 is 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 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. Yeah. So I think it's really important. That people were able to hear about 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 day.
I missed five out of
seven, seven, seven, or as close to Everyday, sort of like sleep. I always say try and get a really great night sleep 80% or more of the nights of your life and on the other 20%, hopefully, it's for fun reasons. A great party or something like that, or celebration of some sort.
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 then sleeping?
Well, it's yeah. So this is where we get into nuances. So here, the firefighters are 24 hour shift workers so that means and they have been working this shift for very long time so they have figured out. 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 as firefighters. They get opportunity to sleep then 7 with their 10 calls. They actually have opportunity to come back and go to sleep. And in fact, when Emily and Dana they were and the fastest on what they observed was firefighters after they, after attending a call, they're not coming back and playing cards or trying to
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. So, whenever they got any opportunity to sleep, they will try to sleep. So, in that way, they are sleep debt 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 had their 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 figure out what would work for them if I have to go and do this for synopsis. 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, Russia feeding paper we see change in nutrition quality and quantity, but here we also saw that somehow both groups inadvertently, they improve the nutritional quality because everybody was told to eat a Mediterranean diet, the increase, the fruits and vegetables and olive oil, and text slightly. And when they had to stop eating,
Early. They also reduce the alcohol intake and this is very significant because many shift workers just to cope with the shift work that tend to depend on alcohol at night and caffeine in the morning. So they begin their day with caffeine and and 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 reduce that eating to 10 hours and then we saw a significant reduction in alcohol intake in the time of the shooting group, but not in the standard of care or Mediterranean diet
group, I certainly support that we did an episode on alcohol and I was shocked when I research that to learn that zero to two drinks per week is essentially the threshold Beyond which you start seeing Health, deficits in particular cancers.
In 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 an end here I'm somebody I have a drink every once in a while no big deal for me 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. Yeah is it?
It's just avidly consumed as if it was kind of like food or caffeine. It's really incredible. 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 had asked us. 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
well when I say yeah. So what I say is
12 hours, but 12, excuse me, 12 hours, thank you for that. Clear. Because we did a study that was published in 2015 and again, behind many of our studies there is a story. So we are publishing all this Mouse stories and then I would go to conferences, and of course they some, some people would give me a look saying, well, you must be doing something wrong. We this just breaks the X law of thermodynamics because how come they're eating this
Number of calories and not getting wet, of course. By that time, we figured out that at least in Mouse time repeating also changes the gut microbiome in a way that the mice may be pooping out little bit more fat and sugar than absorbing them. So one thing that happens in time retrofitting at least in mice is the liver cholesterol, metabolism to bile acid and bile acids excretion in the
Gut changes because they got microbiome changes. So this is very nice study when a merger in power was in the lab now he has his own live in UCSD and he meticulously did that and we even did bomb calorimeter E from the pope and metabolomics from the pope and we figured out that they excrete, some some calories and then that brown fat activity goes up. So they may be
Some of these extra calories so they're more thermogenic. What thermogenic? But anyway. So you know, one, nice thing. Awesome thing about Salk is
If they see that your science is going well then they will find ways to help you and this is fake. Yeah, 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 or when Jacob, or when is the founder of Qualcomm and was also a faculty at UCSD. So he
Stand. 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
no knock on the NIH. But I'll do it anyway in the because I sit on study section for the NIH. 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
The nod is it is the generosity of philanthropists like Irwin Jacobs and other people that allow the really pioneering the new stuff. The cool stuff. Yeah, that the groundbreaking stuff, the stuff that really, no, I'm not gonna say really matters at all matters. It's all important
matters, but, you know, it's high risk and and I itch men said I was just not, just government is not making money from thin air and saves taxpayers money. So there is a little bit responsibility or conservative that, okay? So we should not waste
A money on Pie in the Sky kind of project too
much where we're not talking about politically conservative. We're talking about scientifically conservative to 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 so that way is dr. Days. And then what we did was we had a awesome grad student and we got this funding from Marwan. And also, there are some any philanthropy matters. So, actually the way
He says, yes, if you give me 50 bucks, then that 50 bucks towards goes towards, buying the gloves and a friend octaves for one postdoc for maybe seven
days. So it's so true. I think a lot of people don't realize that 99% of laboratory. Scientists just they don't make me any money off their discoveries and even if there is a patentable discovery typically The Divide between the institution and the company that will eventually put that to Market is so slim in favor of the the others involved that
You know, scientists really do this as as work of passion, labor, labor of love.
So so we came up with this up my security and clock at that time. And we took some lessons from Tech leaders, particularly from Amazon one-click checkout because we thought most nutrition apps actually ask people to detail, describe or the Ed, go to the Barefoot library and then person sighs, you said, okay, so we'll just sort court, all of that.
I just ask people to take a picture of the food. Open the app one click, take a picture second, click and press set, third click. And when the serve the picture actually came to. Our server did not stay on their phone and we asked a hundred fifty six 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 ship workers and we monitor for three weeks.
Weeks. And so here is some nuances and I want people to understand. So suppose, a one somebody is starting to eat at say, 7:00 a.m. and since the recording everything, we we got every single thing. Even if they add half a cookie, they had to take a picture and they actually took picture because it's not, it becomes second nature after three or four days that every time they had something, even if there was a glass of water, they actually take
Picture because we asked them take pictures of everything, we'll figure out what it is.
What is surprisingly? We found the median. So the median number of times people eat within a day 24 hours a day is actually 7. So it's not it's not that we are eating three times a day. We actually snack little bit and seven times per day, seven times and there are ten percent of people. The top decile was eating 12 times a day and it makes sense in retrospect some
Times, maybe I'll fall into that seven or eight foot before. I did this study because, you know, getting up having coffee with cream and sugar is one. And then I ate my breakfast. That's two, then I came to the love and I found that cookie that's three. I went to a meeting and there was some cookie and something else, that's another one, then launch, 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.
Eight times ten 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 Monday than 7:30 another dead and 8:15 another day they go back to 6 a.m. because they had to get up early and go to work. So we took 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 average, is obviously not thinking, okay, maybe? Four,
You if you're eating breakfast at say somewhere between six and seven 3745 eight, maybe you expecting food around 7:00. Let's forget about 6:15, there's an outlier. And then similarly at the end of the day somebody is eating finishing the last byte or denied cap. Whatever you call it say one day at 9 p.m. 9:30 p.m. ten eleven, twelve Thirty or one Let's ignore that one. And 12:30 but still we got somewhere between seven.
To 1134 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 fifty percent of adults in our study it 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. Wow.
And and quite frequently throughout
frequently to. And then if we ask what fraction of our dogs were actually eating the conventional within 12 hours, three meals a day, or something like that, that's 10%. So,
these snacking is gone up dramatically. However, you want to Define snacking, the
frequency of food intake. Yeah, the day 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, okay, so what kind of food before I 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 I coming home and then that again some time to prepare dinner and then they're sitting down and eating of maybe they're eating next to the computer. Whatever it is. So what is kind of interesting?
That came out but coming back to your point that's why I say that nearly 90% of adults 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 it within. So as I said, all of this are interrelated so know anything about children.
Most sleep researchers agree that children and teenagers should sleep somewhere between 9 to 10 or 11 hours. Because young children, even five to ten year old, they should sleep 9 to 10
hours which is pumping our growth hormone and growing growing
area. And then the teenagers actually the recommendation is they should be sleeping 9 hours because if you take teenagers take out all the stimulatory inputs to them and then remove homework assignment and everything. And
And let them kind of equilibria to their homeostasis. What they're likely, how many hours, they're likely to sleep, that turns out to be somewhere between eight and half to nine and a half hours.
Which also means that going back to sleep. Nearly 90 percent of high school students. In this country are chronically sleep-deprived because most high school students don't get nine hours of sleep on a regular basis. Maybe in the weekend
probably because of devices are on iPad.
Also, as I said this new idea that midnight is your assignment submission time, I'll come back to that again. And
again, I'm hearing that again against a teacher.
Take note, I it's an inch. It's a very interesting idea as a way to kind of anchor Behavior earlier in the day. Yeah, learning to. 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. You know there's 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
yeah so that's why children. Yeah it
sounds to me like you know the 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 going to get Dementia or something. That's
right like ever did people feel more healthy and more productive and so that's why I said that, even if children are supposed to sleep for nine 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 higher, they cannot fall asleep. So at least they should have the 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 story. So it's 1 to 2 hours before bedtime, the finishing food. Similarly on the other end after the wake up, it's not that we 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 am saying that if we put all the health recommendations together from pediatrician and then it makes sense.
Fascinating, I have a question about structuring meal and take your food intake during the eating window, I have a good friend actually, he's he's the neurosurgeon at neural link 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,
Do 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 there's a gate, it's never later. Yeah, 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 people's lives run. So sometimes for instance, if I'm going to podcast, I don't tend to eat much.
During the middle of the day because it makes me a little bit groggy that postprandial dip in energy, so I'll do breakfast. Well, but again at 11 and as a first, that's when I break my fast 11-ish and then dinner, maybe a snack in the middle of the day but other days, it's three meals of it. So does it matter overall as long as one isn't allowing the start time and the ending time to drift out is it okay? If you go from 12 hours, to tend to 8810 for 12 as long?
As you don't exceed that the the brackets are you? Okay,
so this is where the security and aspect come in because if you're going if you have moving that breakfast time or dinner time three, four hours since early causing, maybe a metabolic jet lag, you know, and sought Turman weeks months or maybe even few years, you may not see any change. But the same time we don't know what is the long-term consequences. One thing is we always
I think I'll come back to this point again. And again, we think that a body where it is a marker of health or body, composition is a marker of help. It's not always true. Because, as I said, it should reflux feeling, you know, having some Pang of depression, anxiety, or
LDL like high LDL. I led a lot of people have or low body fat. People are very high
LDL. Yeah. So those are the things that we don't connect with our habit.
And since the key under the mat Mill, timing Mill structure now is a very new field. I think good 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 glean too much out of it but I think hopefully things will improve where people will become it will become standard to at least look for one week of diet record Mill time and what they're eating.
All that stuff. Because our now Mouse studies also showing what a front-loading carbohydrate or front-loading fat or protein has benefited over. So I think this studies are starting. So I should not comment whether that's good or bad.
I think it's great to hold off until when 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. 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 eat too much or they feel they too much, or they don't like the food, they ate on Saturday, they're not really feeling.
And they're just going too fast into Monday. Is there any known benefit or health detriment to doing that kind 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 in humans that are also initially. Some studies were done, there are many health benefits
And right now that I've been 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 100 200 kilo Cal and that's all they get to eat. Sometimes, two three days, four days, five days. Even they have gone up to three or four weeks
for sake of weight loss is that
way for many different things and they come out pretty well healthy.
Because they are under supervision, make sure that they're getting macro micro nutrients are in 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 brand 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 one here on the air that we hear once in a 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 this gut-brain axis and what are the presence of food or the microbiome changes in the gut, if they can affect brain, then maybe long-term fasting period of fasting. A few days of
All calorie diet back-to-back will be interesting to see how it impacts brand Health.
Very interesting, what are your thoughts on fat fasting, where people try and limit their blood glucose, by only eating mainly fats, mainly healthy, typically they'll eat healthier fats, avocados olive oils and nuts, you know, and some animal fats, perhaps. But as a way to keep blood glucose low and also
Time restrict. This is goes back to the kind of low-carbohydrate thing. What are your thoughts on that 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 data are still incoming that restricting. The feeding times, it can be beneficial as well as keeping the overall blood glucose lower can be beneficial.
Yeah, I think there is too much emphasis now on blood sugar spiking or we don't know this kind of eating
For example, Manchuria, essentially telling pancreas that, okay? It's or the islet cells, that produce insulin, it's okay. You can take take a break, go on vacation for a month or two or three months. My question is, it will be interesting to see what happens to those eyelids. Because, for example, we know that if we this shows our own use or
Muscles that is muscle. Atrophy muscles will become weaker. We don't know what the long-term consequences of this. Very low carbohydrate diet, where you are, not essentially engaging the islet cells, periodically, what is its impact? So, if there is no impact, maybe it's okay. Maybe, because as you know, many people who actually work on ketogenic diet, the researchers themselves, they find it very difficult.
Pickle to stay in true ketogenic diet because the true ketogenic diet is consuming less than 10% of calories from carbohydrate,
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, such in, 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 blood glucose, by way of a low carbohydrate diet, the those islet cells are
going to shut off their production, very interesting. I mean, the livers are very plastic tissue, I mean, it tends to react very dramatically to Lifestyle
Changes and so that's why it was interesting to see what happens means. We know that even muscle tissues, for example, people who become better than the lose some muscle mass but when they come back and exercise they get it back. So it'll be interesting to see what happens in these people who are going through long-term, ketogenic diet and of course, once in a while because of
Social pressure or something else. If that don't have access to food or something happens, they may consume some sugar, some blockers will Spike. But it's not that big spike is bad. I mean the reason why we have insulin is for good reason to buffer that Spike the 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 it should avoid that and I think that's a little bit extreme
and I mean that's it
Insulin growth factors involved in muscle protein synthesis tissue repair. Yeah, maybe even cognition. So
yeah and it also goes back to say a activation and all that stuff, people get really excited about how to reduce him to activation rapamycin and all that stuff. So this is where again from CKD and point of view I asked people to think so.
Two, very popular drug like molecules or drugs that people think will increase longevity or metformin, which many people agree. Not all will come to a consensus that it activates a kinase, or the sensor in the cells that sense that your cells are fasting. So metformin kind of activates it so that it kind of, it can say, although may not be scientifically accurate, the
You know, posting an appeal
so sort of mimics fasting and 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 tree bark extract. That also dramatically lowers blood
glucose, yeah, mimics kind of that fasting. And then rapamycin also kind of reduces enter activation and people have shown that rapamycin and Metformin can
Extend Mouse lifespan and improve health. Okay, so now let's go back to the calorie restriction study, that I meant, sir in calorie restriction, people are giving food as a lump sum and there are 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 this should naturally have high level of empathy kindness. If they are truly fasting and they should also have a low level of mtor activity because M corresponds to insulin and that should go off at night.
Some, my suspicion is in many of these experiments where the mice were allowed to eat ad libitum, even normal standard ciao. Now, we are we know that as mice, get older. They actually consume little bit more food during daytime
which is the equivalent of human nature. Humans night time it 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 so we don't know. But at least in mice because
You know, we can put demise in calorie metre. Look at every single by dieting, how much they're eating, so I guess it was natural to see that researchers found that there is some mtor activity. During daytime. When the mice were not supposed to have a activity because they should be fasting. And since they are little bit, there was snacking during daytime, MP kinase activity, was not at its peak.
So, giving metformin kind of mimic their fasting State and reducing mtor activity by drug. Like rapamycin also kind of mimic some aspect of the fasting state. So my suspicion is since this studies, but Don always in mice who are supposed to be in the fasting State, and both hamtor. Sorry rapamycin. In a kinase activator. Metformin kind.
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 and long-term because many people are very excited about. You know, there is M, total long-term metformin study, and then lot of people are actually consuming good amount of rapamycin of 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 that will be interesting to control for and see because recently, I saw one of my again, close friend and colleague at scripts and cut your lamia suited up. Very simple, elegant studies. People should have done it, made from infield, so took mice, and then measure their blood glucose at different time of the day. And in fact just like human blood glucose, our blood glucose fluctuates little bit, she saw that to them and then in a bit
Hours or three hours on different days. Of course, to get the same dose of Metformin to mice and what she found was a 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 a different time of the day for the mouse, or even for humans, in very long-term, of course, in these mice, this much for not diabetic or anything.
For healthy Minds 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, and end up digestion. Whereas metformin the beginning of the day manat at least from longevity perspective. I'm not talking about Diabetes, Type 2 diabetes,
So the same thing with mtor is a going to have much better impact if taken during evening, morning before mail. So these are my thoughts that go along with all this fat story that we talked about.
Do you take Metformin your Burberry?
I know, I haven't taken although you know, I have close friend and colleague, Reuben Shaw, who is now the director of Cancer Center at saw
All key extensively works on MP kinase and it's mechanisms and so it's always fun to talk to
him to see if he's a fan. Yeah, I've taken berberine before and I've 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 Rises, you take berberine or metformin? Metformin. It's yeah prescription that's I went with berberine because it's far as I know it works as well
at least my healthy people.
Yeah, for healthy people. That's right. When I took berberine and did not ingest large amounts of simple sugars or carbohydrates along with it. I experienced
I found hypoglycemia. I felt like complete garbage for about eight hours and I had one of the worst headaches of my life because which makes sense, you just got a blood sugar crash. So if you lower blood, your blood sugar, when you already have fairly low blood sugar and you're not ingesting carbohydrate, you can really bottomed 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 circadian effects.
You know, when I joined Salk on the, we know Ron Evans who is the kind of the big leader in sick 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 and the first few years, Ron did a very simple experiment, he just looked at what time of the day, this nuclear hormone receptors are turn on a gene.
Special level and some at protein level and I found that almost all of them. Have a CKD and pattern at least in some tissue. So he went to that length to say even that security on is metabolism and metabolism is circadian. The reason why we have a security on rhythm is to have a daily rhythms in food, seeking behavior, and eating and also go through a period of
When we should be fasting. And then on the other hand, all the metabolic Regulators also have to follow that Troll and almost all metabolic Regulators, everything that we can think of connected, to metabolizing, macronutrient protein, carb and fat. They should also have a security under the more diurnal cycle to align or misalign. 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 see Ron could foresee, of course, is smart enough to foresee and predict this is going to happen to see katieandphill. Because at that time, we were thinking about the suprachiasmatic nucleus sleep-wake cycle and we are not thinking too much about metabolism. So that's the awesome thing about song being at Salt, because we have 50 P eyes, really crammed into stew.
Awesome buildings and with openlab structure. So you bump into each other and talk to. So and with an ocean view oh it's awesome Bill. Yes
it it's an amazing place. I was lucky enough to have an adjunct position there when I when my lab was at UCSD and it is an amazing Place doing incredible groundbreaking work, which of course includes yours. Listen to such an eye clear. Now that we have to have you back on for another series of discussion, seriously,
Speaking if you'd be 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 often, but not always is 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
Out in considering it you've given dozens of I've 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. Yeah. Even though they didn't think they were because of their nature of their habits now to light and to activity and so forth, I absolutely love the firefighter study because of its relevance to the general population. Also a Not Another Not to fight or 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 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 share the actionable aspects to that knowledge.
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. Yeah. So people can engage in some of the signs directly and of course you have several wonderful books. Now that we will also link to both of which I've read and 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 blood sugar regulation there. So yeah on behalf of myself and my team here at the
A room and a 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 is really a
gift. Yeah. Thank you. And actually likewise, there are very few scientists who 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 a simple, sound bite to the point where the
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 said that this is not my court actually this is from one of my scientific hero Paul Schimmel from scripts. Yellow says, think about it, 10 years ago. What we what you thought was right? And the best has already changed. But one thing is this Acadian Rhythm and aligning it to
To our internal clock to our habit, is very important. And as you mentioned we have a my security and clock app which is research facing. But we have also distill all of this down to five or six timing component and we have a new app called on time health or get on time Health
Access the through the standard app stores.
Yeah. So now it's available in and app store. Google 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, the 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 are doing is immensely necessary. Particularly these days when science is moving at a very fast
Space. 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 you're most welcome. It's days like today where I get to sit down and talk to really in 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 who Shining
Light. Thank you,
thank you for joining me. For today's discussion with dr. Sachin Panda, all about circadian, biology and time restricted feeding. If you're learning from and are enjoying this podcast, please subscribe to our YouTube channel. That's a terrific. Zero 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 five star review if you have questions for us or comments about the podcast or topics you'd like
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