Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health August 5, 2019 100 By William Morgan [Rhonda]: Hello, everyone.Today my guest is Dr. Satchin Panda, who is a professor at the Salk Institute for BiologicalStudies in La Jolla, California, where he studies the body’s internal circadian clock,what regulates their circadian clock, and in turn, how this affects a wide variety ofprocesses including our metabolism, our sleeping patterns, and how active we are, and so muchmore.Satchin, considering that every single living organism on the planet Earth has this internalbiological clock, their circadian clock, can you explain to people who’ve never heard whata circadian clock is, what it is and why it’s so important?[Satchin]: Yes, so all lives on this planet evolve under a rotating Earth.So that means for 12 hours, approximately 12 hours they had access to light and foranother 12 hours they were in darkness.So, that environment, that changing environment put a tremendous pressure for them to comeup with a timing mechanism so that they can anticipate when it’s going to be evening orwhen it’s going to be morning so that they can time their activity and sleep accordingly.So that’s why almost every organism on this planet have this internal clock that helpthem anticipate time.And why this is important is if you think about a diurnal organism, an animal that’sactive during the daytime, the animal has to anticipate when evening is going to comeso that he can rush back to the cave or somewhere, some hiding place.So similarly, just before the dawn, this animal has to wake up before even light hits, andthen go out and get the first grub.So that’s why there is this tremendous pressure to have this biological clock or internaltiming to essentially anticipate what is going to happen.So for most people, we know when we go to bed, maybe after six to eight hours, we wakeup.So our clock actually tells us, “Yes, it’s going to be morning.Get up now.”So similarly, almost every part of our body has clocks that help us to anticipate whenthe food is gonna come or when we are supposed to run, when we are supposed to take rest.So, what we are learning is almost every organ in our body has a clock and it helps thisorgan to be at peak performance, peak activity, at certain time of the day, and then to restand rejuvenate at the other time of the day.[Rhonda]: So, is this internal biological clock, the circadian clock, it’s not somethingthat we’re just immediately born with, right?It’s not something that just…[Satchin]: Yes.So when we are born, we, kind of…when babies are born, they actually don’t have this daily24 hours rhythm in activity or sleep.They don’t to bed for six or seven hours.So what we suspect is although they have a clock, those clocks are not wired together.And at the same time, babies also need a lot of food, because that’s their growth phase.So, during the first maybe four to six months, the babies wake up in every three to fourhours, cry, eat a little bit, and go back to sleep, and then wake up again, and do that.Then after 8 to 12 weeks, they actually begin to have some kind of consolidated sleep.So they go to sleep and wake up at the right time, wake up after a few hours, but it’snot tied to light-dark cycle.So they kind of drift.So that’s the phase many parents may not notice because we now live in a very artificial environment,but that’s the time when there is a clock but it’s not tied to outside light and darkcycle.So around six months of age, that’s when the whole development process and the clock isfunctional, it’s tied to light-dark cycle, it’s wired properly, so the babies go to bed,hopefully, in the evening and then sleep for nine to ten hours, wake up.So when we are born we do have clocks, but they are not connected together until aboutfour to six months of age.[Rhonda]: Oh, interesting.And you mentioned…so there’s, there’s clocks in all of our organs and there’s different…yourwork, you’ve done a lot of research on what regulates these different clocks.[Satchin]: Yeah.[Rhonda]: There’s a master regulator clock, and there’s other clocks in different organs.Maybe you can explain.I read somewhere that something between 10% to 15% of the entire protein-coding humangenome is actually regulated by these circadian clocks, and anywhere between around, like,40% to 50% of those genes are actually involved in metabolism.[Satchin]: Yeah.[Rhonda]: So, there’s, there’s a wide variety of processes that are regulated by these clocks.[Satchin]: Yeah.[Rhonda] Maybe can you explain a little bit about the central master clock and…[Satchin]: Yeah.[Rhonda]: …what regulates that?[Satchin]: [laughs] Yeah.So this is a field of study that is actually not driven by a disease but pure curiosity.So for a long time, people thought that there might be a master clock in the brain becausewe always connect circadian clock to sleep-wake cycle.And fortunately, there was actually a master clock.And in fact, almost 40, 45 years ago, people who are working on different parts of thebrain…because at that time, 40 years ago, people thought that different parts of thebrain regulate different behavior.So they are defined like cubic millimeter area of brain that regulates something.So we’re systemically taking out parts of the brain in mouse, rodents, and differentlarger rodents, and then figure out that when they hit this small part of the brain calledsuprachiasmatic nucleus, so that means we know that our eyes send optic nerves thatcrisscross and there is a part of the brain called optic chiasma, so it’s above the opticchiasma.So that’s why suprachiasmatic nucleus.So that’s…[Rhonda]: Say that 10 times fast.[laughs][Satchin]: Yes [laughs].Suprachiasmatic nucleus or SCN, it’s composed of around, say, 100,000 neurons, I guess,in humans, really small, maybe one millimeter by one millimeter.That’s the size of this brain part.If you remove that brain part in a hamster, then this hamster doesn’t, will not have anysense of time and go to sleep at random time and will wake up after two or three hoursand it continues.But what is most exciting is if we take SCN from another hamster and transplant, it’slike a brain transplant experiment, then this hamster will get all the rhythms back.That’s the earliest example of neural transplant transferring behavior from one animal to anotheranimal.And that essentially established that there is part of the brain that accesses mastercircadian oscillator or circadian clock because it orchestrates this daily rhythm in wakingup and going to sleep.And just imagine, only when we are awake, we eat, or we exercise.So that’s why all other organs related to eating, for example, our gut, our liver, ourfat, all of them are driven by this feeding behavior.Similarly, our muscle is driven by when we run.So that’s how the SCN acts as the master circadian oscillator.So if we damage the SCN then we lose all circadian rhythm.So what happens in some of the neurodegenerative disease, like very advanced stage of Alzheimer’sdisease dementia, if the SCN, this part of the brain is affected, then people lose theirsense of time in terms of when they go to bed or when they stay awake.So this presents slowly, they turn into a state where they don’t have a sense of dayor night.They stay awake throughout the night and may be sleepy throughout the day.So that’s why this master clock is so much important for our health.[Rhonda]: And that might also have a feed-forward loop because then, you know, if your masterclock is thrown off and you’re awake when you’re supposed to be sleeping and sleepingwhen you’re supposed to be awake, that’s also been shown to affect hippocampus and long-termpotentiation.So, you know, you’ve got this, sort of feed-forward loop.But specifically with regards to the, the master clock, light is what regulates thismaster.[Satchin]: Yeah.[Rhonda]: It’s what sets it.[Satchin]: Yeah.[Rhonda]: So can you…and this was some of your early findings.[Satchin]: Yeah.[Rhonda]: Can you talk a little bit about that?[Satchin]: So for a long time people knew that light resets our clock, and in fact,in nature, with change of season, the sunrise and the sunset time do change, and we haveto adapt to that sunrise and sunset time, otherwise animals cannot go to sleep and wakeup at the right time.So what is interesting was for a very long time, people couldn’t figure out what, whereis the light receptor that resets the clock, because there are many blind people out therewho cannot see anything but they can reset their clock.So if they go from east coast to west coast, they fly, then they also have typical jetlag and after three to four days they get used to the new time zone.And similarly, there are laboratory animals that are blind, they can’t see a thing, butif you change their light-dark cycle, then they readjust in six to seven days.They actually readjust the same way as mice with normal vision.So this was kind of an unanswered question in vision science for 75 years.What is this extra light receptor in the eye?And we knew that it was in the eye because many people who go to war and lose both oftheir eyes because of gunshot wounds, and people who have cancer or a tumor growth inboth eyes and the eyes are removed, they can’t reset their clocks.So they, kind of run free.They kind of free run, because our clock is not exactly 24 hours.And our clock is very close to 24 hours, 24 hours, 15 minutes, 24 and a half hours, somethinglike that.So, if we cannot entrain our clock to light-dark cycle, then every day we’ll be working off15 minutes or 30 minutes late.And then after 10 to 15 days, we’ll be completely out of sync with the society.And that’s what happens with this [inaudible 00:10:57].If you combine these two observations, people without their eyes cannot reset their clockand blind people can still reset their clock, then that essentially tells us that theremust some special light receptor.So almost 16 years ago, three different groups figured out that there is a new light-sensingmolecule that must be present in some of the remaining cells of the retina in blind people,and our group was one among them who discovered this new light receptor called melanopsin.It’s actually from frog melanosomes.So this is a clear example of how basic science actually leads to understanding human health.So if you put a frog under light, then the frog’s skin will change its color.And because frog skin has a light sensor that detects light, and then puts kind of a naturalsunscreen.[Rhonda]: Like melanin making…[Satchin]: Yeah, and so it spreads melanosomes.So melanin pigments are spread.And interestingly, the same protein that spreads melanosomes in frog skin is also present inhuman retina and mouse retina, and only in 1000 to…sorry, 2000 to 5000 cells.And these are special light-sensitive ganglion cells, we call them, and these cells senselight in the blue spectrum and send that information straight to this suprachiasmatic nucleus orthe master clock.And that’s how every day, in the morning, with the first sight of light, these melanopsincells sense light and then tell the SCN that this is morning and this is time to sync up.So that’s what it is called.[Rhonda]: Okay.So that first bright light exposure…[Satchin]: Yeah.[Rhonda]: …sets the clock and tells your body, you know, “Okay, this is the start.”So then you start to change gene expression, things are going on in the brain, you’re morementally aware of things that happen.All these little changes happen throughout the day that are on this rhythm.[Satchin]: Yeah.[Rhonda]: What happens, then, if you, let’s say, you don’t have…let’s say you live ina very dark apartment or, you know, a dark apartment in the winter in Sweden or somewhere,you know, where it’s, like, dark, you know, so you don’t get that bright light exposure.How does that affect…[Satchin]: Yeah.[Rhonda]: …someone’s circadian clock?[Satchin]: So you kind of use this interesting term, bright light.And actually, that’s very important for melanopsin because we know we have rhodopsin that’s extremelysensitive to light and that helps us to see the star and enjoy the moonlight, but that’svery low amount of light.And actually, a clock is not sensitive to that amount of light.Just imagine, if our clock was sensitive to dim light, then we’d be completely what becauseeven in nature, the lightning or starlight or moonlight that we can see can reset ourclock.So, one interesting thing with melanopsin, it’s very less sensitive to light.It’s a very lousy photoreceptor.So that means you need a lot of light.For example, you may need almost 1000 lux of light to fully activate melanopsin.And then another interesting part of melanopsin is it integrates light over time.So that means it actually remembers how much light exposure you previously had.So for example, if I switch on a flash, then for 100 milliseconds you see a thing and thenafter the flash is gone, your visual system restart, you don’t see that thing.But melanopsin stays active for several seconds after lights are off.So that characteristic helps you to count how many minutes you had exposure to light.So in that way, not only you need bright light, you also need several minutes of bright lightbefore it’s fully active and can do all of its function, particularly to reset the clockor to do few other functions, and I’ll get to that.So, when we discovered melanopsin, we thought that these cells connect only to the masterclock, but what we’re learning more and more is it has multiple different functions.It also connects to part of the brain that suppresses or that regulates sleep, so thatmeans many of us know that it’s very hard to sleep in a lighted room and that’s becauseof melanopsin because it senses light, and in diurnal organisms like us, it does knowthere is light, so you’re not sleepy, so you stay awake.It also indirectly connects to part of the brain that produces melatonin, and melatoninis the sleep hormone.So, when we have lot of light and also for a very long period of time, then it shutsdown melatonin.It helps us stay awake.But during daytime, in the morning when we wake up, we need that big jolt of light formelanopsin to really activate and suppress the melatonin, make us more alert and resetthe clock, and turn on hundreds of genes in the SCN and start secretion of many neuropeptidesand all that stuff.So that’s why it’s becoming…we are learning a lot about what quality of light and howmuch of light do we need in the first half of the day to keep us awake, and how littlelight or what kind of light we need in the evening or second half of the day so thatwe can go to bed well.So in dim environment, it becomes…means, many people know that dim light or cloudydays make us depressed, but now we have a molecular biology explanation why is that.At the same time, it also tells us maybe if we have blue-shifted light during the firsthalf of the day that may help us to stay awake, to stay alert, and also to reduce depression.But in the evening, we actually should stay away from that light.So it’s a very interesting thing about our environment because so far everything in ourenvironment, whether it’s carbon monoxide, carbon dioxide, oxygen, temperature, everythingcan be set at a set point throughout 24 hours.And this is interesting stuff about light.We need more of that in the first half of the day, and as little as possible in thelast half of the day or in the evening.So it’s a very interesting area.[Rhonda]: And modern day society is also not very conducive to that, those needs becausewe have artificial light, we have televisions, we have computer screens, we have iPhonesand Android phones, and you know, so everything’s emitting this bright light or blue light…[Satchin]: Yeah.` [Rhonda]:… which is what’s activating themelanopsin recep-…[Satchin]: Yeah.[Rhonda]: …or melanopsin and inhibiting melatonin production.I remember reading some study that was published some years ago where humans that were exposedto around, I think it was around 10,000 lux of light, upon, you know, 30 minutes of waking,so, um…[Satchin]: Yeah.[Rhonda]: …you know, early exposure, and they were exposed to it for a number of hours,something like seven hours.I mean, it was, like, bright light, you know, all day, almost like being outside.[Satchin]: Yeah, yeah.[Rhonda]: And then their cortisol levels were measured at various points in the day.And so cortisol is one of those hormones that’s regulated by this, the circadian clock.[Satchin]: Yeah.[Rhonda]: And it peaks about the time we wake up…[Satchin]: Yeah.[Rhonda]: …or something like that, right?[Satchin]: It rises when we wake up.So that promotes alertness, and melatonin is the opposite, it [laughs] promotes sleep.[Rhonda]: Right.And it also…I mean, cortisol regulates… in itself, it’s regulating…[Satchin]: Yeah, huge amount.[Rhonda]: …you know, 20% of protein-coding genes.[Satchin]: Yeah.[Rhonda]: So it’s doing a lot.But these people…the thing with cortisol you want it to peak when it’s supposed topeak.[Satchin]: Yeah.[Rhonda]: And you don’t want it to be active all the time.You know, things like chronic stress…[Satchin]: Yeah.[Rhonda]: …that can activate cortisol and, you know, this can lead to dysregulation of,you know, 20% of the human genome…[Satchin]: Yeah.[Rhonda]: …or something like that.Anyways, these people that were exposed to the bright light had a 20% or 25% decreasein cortisol levels, you know, during parts of the day when it wasn’t supposed to be high.[Satchin]: Yeah.[Rhonda]: It’s very interesting how just the bright light exposure itself…[Satchin]: Yeah.[Rhonda]: …seem to regulate the stress hormone or at least keep it…[Satchin]: Yeah.[Rhonda]: …so it wasn’t going out of control.What about people that, you know, get…so people that are exposed to bright light inthe evening, so, you know, you’re working late or you’re, you know, watching television,and that’s going to trick your brain and think, “Okay, reset.”Is that kind of what’s happening?[Satchin]: Yeah, so what is happening is in the evening when we have that extended periodof light, it’s sending a wrong signal to the brain saying this might be part of the dayand that also doesn’t allow melatonin level to build up so we have trouble going to sleep.And ultimately, we go to sleep and we wake up either sleepy or we wake up very late intothe day.And in the late in the day, then our body is getting a signal, “Oh, this might be themorning.”But at the same time, these days we spend more than 90% of our time indoors and manyof the indoor environments have less than 1000 lux of light and many places have actuallyless than 200 or 100 lux of light.So that means even though we wake up, we don’t get that very bright light that we are designedto get in the morning.So our body gets confused completely when it’s day or when it’s night.Although we kind of can work our way through, our body is not completely compliant or completelyis figuring out when it’s day or night.So that’s why all the circadian rhythm, all these rhythms and gene expression in differentorgans are completely desynchronized.You can imagine a car running with a bad timing belt and the spark plugs sparking at wrongtime, so you can’t run that car too long.So that’s what happens in our body.[Rhonda]: Right.I know for myself I…there’s a few things, there’s a couple of things that I, changesthat I’ve made to my lifestyle within the last year or so that have made a huge difference.And that is one, I now live in a place that is not a dungeon.[Satchin]: Yeah.[Rhonda]: So I used to have, you know, windows that were blocked by other buildings and itwas not facing, you know, the west side.I mean, just no light was coming in.[Satchin]: Yeah.[Rhonda]: And that really did affect my mood.Like, even though I was eating well, exercise, all these things, you know, that helped, butI definitely felt that my mood was affected by that.So I moved and now have bright light exposure first thing in the morning which has reallyhelped my circadian rhythm in addition, so…but also, I don’t get exposed to bright or bluelight in the evening.So I have these lights, I don’t know if you’re familiar with them, they’re Philips Hue.[Satchin]: Yeah.[Rhonda]: And so they’re, you can program these lights to switch off blue light andonly have red light.They do other colors as well than red light.[Satchin]: Yeah, yeah.[Rhonda]: And so I have it now where…well, now that it’s summertime, I used to have itprogrammed with the sunset, but now that the sun’s setting later, it gets too dark in myplace, so about 5:30 the red lights come on.[Satchin]: Yeah.[Rhonda]: And then I have an app on my phone…I’m sorry on my computer called F.lux…[Satchin]: Yeah.[Rhonda]: …which then blocks the, it filters the blue light…[Satchin]: Yeah.[Rhonda]: …and it corresponds to the sunset…[Satchin]: Yeah.[Rhonda]: …or the time zone that I’m in…[Satchin]: Yeah.[Rhonda]: … or that anyone’s in.So those are some of the things that I’ve done, and I now am very much able to go to…youknow, about 10:00 at night, 10 p.m., I’m, I’m sleepy, I, you know, I brush my teeth,it’s time for bed, and I wake up now probably around 7:30, 8:00.That’s it.So I get a nice, a good amount of sleep…[satchin]: Yeah.[Rhonda] …but it’s pretty regular and routine.[Satchin]: Yeah.[Rhonda]: So those are some little lifestyle changes that I’ve made to my life that havemade a big difference.What about people, like I’m getting to travel to Asia at the end of next week, jet lag,you know, so obviously, when you travel to another time zone, your circadian clock canreset.Do you think the most important thing is bright light exposure when it’s light?Is that what’s gonna help reset me?[Satchin]: Yeah, so it’s a very complicated question because [laughs] there’s light, andalso there is food, and we’ll get to that.[Rhonda]: Yes.[Satchin]: But one important point that you’ve brought up is jet lag, and although we relateto jet lag when we travel, there are nearly 15% to 20% of population in this country orin any industrial country that works in dayshift and night shift.So almost in every few days they are going through that jet lag that we dread to go through.So for them, it’s very stressful to go from day shift to swing shift to morning shiftto night shift, and all these shifts.And what is interesting is most employers think that it’s very stressful, so let’s letthem do the swing shift or night shift for maybe four days in a week.And then for three days, they’re again trying to be social, they’re trying to catch up withtheir friends and families.So it’s very stressful for them.And that’s the biggest area where light management or lifestyle management will have a huge impacton figuring out how best to schedule this shift work so that these guys will go fromday to night shift to swing shift without compromised fitness and with a good familylife.So we’re still learning how to shift them.It’s not easy for them to shift in every week for four days in one shift and three daysin another shift.But light is a very important aspect of that.Particularly, individuals who work the night shift, they come home and they try to sleepthroughout the day in a dark room, of course.And then, if it is winter time, they barely get any light, any sunlight or bright light.And at work, you never get…indoor environment, we rarely get more than 1000 lux of light.So these people are continuously staying, kind of, in a dim winter environment duringthat night shift.And so that’s one area where managing light will have a huge impact on productivity, health,social life, etc.But as I said, light does half of the job, and then the other half is done by food.[Rhonda]: Right.[Satchin]: You also pointed out another thing.You brought up the example of stress hormone, cortisol.Cortisol is regulated by circadian clock, but at the same time we know it’s a stresshormone.So if you have stress in the middle of the night when cortisol is not supposed to behigh, it will not just wait for the morning time.Your cortisol will go up, and we know that.So similarly the master clock sends the signal that when it should be day, when we shouldbe eating, and when we should be fasting, and accordingly, the liver clock, the gutclock, all these clocks that time themselves.And when I say time themselves, what happens is, just imagine there is, you are kind ofdriving in a downtown area with a lot of stoplights and green lights, right?And if you imagine if there is no light anywhere, then there will be a lot of accidents, sothere will be lot of traffic congestion.So having the lights turned on and off at the right time help the traffic move.Similarly, in our liver, if you imagine, we are eating a lot of different type of foodthat has to be metabolized, that has to be broken down, sorted out, then a lot of thingsthat we don’t need for our body, for example, the artificial sweetener, the coloring agent,the flavoring agent, all of them go to another conveyor belt.They get excreted out, and the protein gets broken down and they build up other part ofthe cell.So a lot of things are going on at that time.So it’s almost like you are bringing in food, dividing them into different parts, and movingthrough this conveyor belt, the traffic.So not everything will happen at once.So there is time for protein to break down, there is time for glucose to be made, thereis time for nucleotide to be made, there is time for bile acids to be made, the differenthormones to be made.So these clocks actually have timed different things, and when clocks break down, then whathappens is you can imagine there are traffic jam and a big pile-up.So the metabolites, metabolism is not efficient anymore.There is a lot of byproducts just lying around and that stresses the cell and then we getto the disease.So the point is, although we have clocks, these clocks also respond to when food iscoming in.At the same time, when the food is coming in and the kitchen is not ready, the foodis not going to stay in the garage.So our body is not built that way.It will come and then it will light up the fire and for that we prepare, but then thetraffic lights are not on, so there will be a traffic jam.So that’s why the peripheral clocks…actually, they have a clock but they also respond tofood, and the food tells them when to time their activity.So when we travel, our lighting changes and our food time changes.[Rhonda]: Yes, yes.So you kind of are changing gears here and I think it’s very important to point out forpeople that aren’t familiar with this.So we’ve been talking for some time about this master regulator clock and the suprachiasmaticnucleus reaching the brain and how light is what sets that clock, what regulates thatclock, and in turn, those are regulating a wide variety of different physiological processes.[Satchin]: Yeah.[Rhonda]: But then you just mentioned something very important, and that is that in additionto that clock, there are other clocks, for example, in our liver, in our muscle, in ourhearts that also are regulated, but your research, and maybe we can start to talk about this,they seem to be regulated by something different.[Stachin] Yeah.[Rhonda] By when you eat, by when you take in food.And I know for myself I’ve always…I’ve known, you know, about the circadian clocks in theliver and how they regulate metabolism.I know that, you know, we’re most insulin-sensitive, you know, during the early morning hours,and most insulin-insensitive in the evening.And so I’ve always tried to not eat too late because, “Well, I don’t wanna eat this high-carbohydratemeal when I’m the most insulin-insensitive.”It doesn’t make any sense.It’s much easier for me to do that in the winter months when it’s, you know, gets darkearlier.I find it more difficult when spring and summer occur because it’s lighter are out, I’m workinglater, you know, and therefore, you know, I eat later.But so let’s talk a little bit about how food regulates…[Stachin] Yeah.[Rhonda] …these clocks and these different tissues.[Satchin]: Yes.A few years ago, we started looking at which genes are regulated by CLOCK in differentorgans.So if we look at liver, there are somewhere between 3000 to 5000 genes that are turnedon at certain time of the day or night.And so that’s…[Rhonda]: A lot of genes.[Satchin]: A lot of genes.So, that’s almost 30% of expressed genome or whatever.Um, but what is interesting is, we said, “Well…”We did a very simple experiment where these are done in mice.so the night-eating mice…mice usually eat during the night time, that we asked, “Well,there is a master regulator in the brain that’s telling the rest of the body when the timingis, when it’s day or night, and let’s give mice food in the middle of the day, just likethe shift workers work in the night time, they eat.If we do that, then what happens to the liver?That all liver genes, that cycle, that take the cue from light-dark cycle or from thefood?”Because we have these two groups of mice, both groups of mice are in the same light-darkcycle.One group it’s doing day, one group it’s doing night.The liver takes cue from light-dark cycle then all cycling gene should be identicalin two groups.If the liver clocks take cue from eating time, then the day-fed animals will have a differentclock than the night-fed animals.And that’s exactly what we found, that even though the light-dark cycle are the same forboth animals, the liver clock responds to when the mice ate.So the day-fed animals had the same 3000 genes cycling.The night fed animals had the same 3000 genes cycling.But now the genes that are turning on during daytime in the day-fed animals, now they turnon at nighttime in the night-fed animals.So that means the time when we eat tells our liver clock when to turn on the genes andwhen to turn off.The light has very little impact.We cannot say no impact, very little impact on the cycling genes in the liver.So that experiment has been replicated now, and what we are learning is almost every organin our periphery outside the brain kind of follows when we eat.So then what becomes very important in the daily life is the first sight of bright lightand the first bite of food.Those two determine how our body clocks work.So now we are working on how this timing of eating or timing of light affects our healthin general.[Rhonda]: And you have a certain term, I guess.I don’t know who coined the phrase, but it’s called time-restricted feeding.[Satchin] Yeah.[Rhonda] And you’ve done…there’s been experiments that you’ve done in mice where you’ve feedthem various types of food.[Satchin] Yeah.[Rhonda] High-fat diet, high-sugar diet, normal chow diet, and you’ve restricted their timefeeding, you know, during their, the nights, you know, the mouse day hours, which is actuallythe night because they’re nocturnal, and you found, you know, some very interesting things.So, can you talk a little bit about those findings?[Satchin]: Yeah.So what we have seen is when we, in experimental animals, if they don’t have a clock, thentheir metabolism goes really weird.So just like I said, a metabolism works like this traffic signal in downtown, and if they’renot timed properly, then there’ll be disease.Similarly, for very long time we knew in the field that mice that don’t have circadianclock because they lack a gene or have a mutation, they have various metabolic defect.They have obesity, diabetes, cardiovascular diseases, etc.We also know people who do shift work for a very long period of time, they are alsohighly likely to get metabolic disease, cancer, [inaudible 00:35:27].So there was this idea that clocks are important.If we don’t have a good functioning clock, then that’s bad for us.Then we went back and asked, “Okay, normal circumstances, what are the conditions thatcan actually break down our clock?”And what we found was when mice are given high-fat diet or any unhealthy food, thenthe food itself breaks down their clock.So they actually don’t have a good eating-fasting rhythm, so the mice eat throughout day andnight.And we knew that high-fat diet and high-fructose diet, high-sucrose diet, all of these dietsthat are used experimentally in laboratory condition gave rise to all this disease.And people always thought it’s what and how much the mice ate that determined the disease.But what we found is, well, these mice are also not eating at the same time.So maybe when they eat also matters.We did a very simple experiment where we took two groups of mice, completely identical setof mice, no genes were changed, no drugs were given, and one group of mice ate wheneverthey wanted to eat, and we…to begin to with to give them a high-fat diet.So they’re getting somewhere between 45% to 60% of their food from fat or calories fromfat.So that means it will be equivalent to humans eating all of their food from cheese, nachos,ice cream, or Western diet.[Rhonda]: So they’re getting fat and sugar.[Satchin]: So they’re getting fat and sugar all this time.And then other group got the same number of calories and the same type of food, exactlyidentical food, but they had to eat all their food within 8 to 12 hours in nighttime.So in some experiments we have done 8 hours, 9 hours, 10 hours, 12 hours, like that, andthe most surprising thing is…and this is something that everybody, a lot of laboratoriesaround the world do.There are 11,000 papers saying high-fat diet causes obesity.And we said, “Okay, so now we control for time.”So since time was restricted, calorie was not restricted.So that’s why we call it time-restricted feeding.And surprisingly, the mice that ate for 8 to 12 hours, they did not become obese, diabetic,and they had a normal liver function and they had normal cholesterol, etc.And then in the next set of experiments, we exposed these mice to high-fructose diet,high-carb diet, high-sucrose diet, all kinds of diets either ad libitum, whenever theycan eat, or they are to eat within 8 to 12 hours.And in most cases, we see the time-restricted feeding has huge beneficial impact.Even when mice eat standard diet, normal chow, which is supposed to be healthy, and miceactually eat most of their food, nearly 70% of food during night time.They eat a little bit during daytime, but if they completely restrict that to 8 to 12hours, then their muscle mass goes up, their fat mass decreases, and they are more coordinated.So if you put them in a rotating drum, than they coordinate on the rotating drum for along time.So the bottom line is this time, so in these experiments where we kept what and how muchthey ate constant, the only thing that we changed is when they eat, then we see thishuge beneficial impact, and that correlates with very robust clock in the liver, and inother metabolic organs.And why this is important is two things.One is many of us have daily bad lifestyle.I won’t say bad, but we don’t have much control over what and how much food we eat.As soon as we get out of our home, all the food we eat outside we have very little controlover it.So the only control we have, actually, is in our time.So, that’s why we think this can be a good entry point to a better living by controllingtime.And then the second thing is it also doesn’t take away this idea that nutrition doesn’tmatter, that quality doesn’t matter, because even in our high-fat fed mice, we don’t seethey completely become normal just like the normal chow-fed mice.They’re much healthier.So to have better health, you still have to change what and how much you eat, but timingbecomes much easier to manage.[Rhonda]: So you just covered so much.This experiment that you did right here, this publication, even before, you know, you’vegone onto some small human studies, but this convinced me to do a time-restricted feedingschedule because, well, for a couple of reasons, but…so just, like, to reiterate, these micethat were fed a high-fat diet, they were fed the same amount of calories, but those thatate during their waking hours…[Satchin]: Yeah, yeah, yeah.[Rhonda]: …so for mice, which is night within, I think, it was 12 hours…[Satchin]: Yeah.[Rhonda]; …they gained…I’m sorry, they had 70% less fat mass.[Satchin]: Yeah.So they had 28% less body mass total.[Rhonda]: Right.[Satchin]: And that change in body mass is mostly due to fat because they had 70% lessfat.[Rhonda]: That’s amazing.[Satchin]: Yeah, that’s really…[Rhonda]: Right there and they’re eating the same crappy food, but they’re eating it whentheir liver can process it the best, you know, when they’re, you know, able to regulate theirblood sugar, when they’re able to oxidize fats, things like that.So, that was really cool.And then the second thing was, you know, I eat very, very, very health-conscientious.I try to get a wide variety of vegetables and fruits, and good fats, and, you know…[Satchin]: Yeah.[Rhonda]: So all that stuff, omega-3s but I’m always trying to find more…the low hangingfruit to sort of delay the aging process in a way, or become, you know, as optimal asI possibly can.So, the mice that were fed a normal chow diet, you know, high in fiber and all these things,vitamins, you said they actually had more lean muscle mass.[Satchin]: Yeah.[Rhonda]: That is very interesting because for me, it’s much easier to lose fat thanit is to gain muscle.It’s difficult to gain muscle and as you age, it becomes even more so.[Satchin] Yeah, yeah.[Rhonda]: And muscle mass is very important.It protects you from frailty, things like that.So, any ideas as to how just restricting your…we should probably talk about what starts thatclock.[Satchin]: Yeah.[Rhonda]: What food is it?You know, it doesn’t necessarily have to be a calorie, right?It can be black coffee or something like that.But anyways, any ideas as to what, you know, is allowing you to keep on more muscle mass?[Satchin]: Yes, so that actually is a big mystery, because in the first series of experiments,we are essentially reporting observations.What happens.The reason why we looked into muscle mass is initially we thought that these mice, whenthey’re going through such a prolonged period of fasting, in some experiments they are goingfor 12 to 16 hours of fasting every day.And many would think that when you go through this prolonged fasting you would lose yourmuscle, because muscle, the protein gets used to make glucose.That’s why you measure lean mass.And surprisingly, we found that the lean mass actually increased, whereas their fat massdecreased.That was a big surprise.That’s what we reported, but we haven’t looked at exactly why the muscle mass increases.But what we are seeing recently is there is some correlation.Other people have published recently that nicotinamide riboside, this is a precursorfor NAD, if that is given to mice, they also gain muscle mass or they maintain their musclemass, and this nicotinamide riboside is converted to energy, and increased amount of energyis always better for any cell because that is the precursor to the energy currency ofthe cell, that’s ATP.And what we are seeing is in many of our mouse experiment, we see the energy level actuallygoes up slightly.So this is a natural way to boost up energy level, not only in muscle, in almost everyorgan.So I think that might be one of the many different reasons why we’re gaining muscle mass, butwe can’t explain with the current data why they gain muscle mass.[Rhonda]: Okay.Can I ask you another question?[Satchin]: Yeah.[Rhonda]: So I do know that there are some genes, by the way, that are involved in nitrogenbalance that are regulated by circadian rhythm, but that’s…So I also remember in your paper, I don’t know if it was the same paper or differentone, I think it was the same paper, but you also found something very interesting, andit’s kind of along the same lines here and I’ll tell you where I’m getting at.But you also found that animals that were fed during a nine-hour period had improvedendurance.[Satchin]: Yeah.[Rhonda]: Not improved muscle strength, but improved endurance, and to me, when I readthis, I thought, “Oh, well, if you think about endurance, endurance is aerobic.It requires aerobic respiration, which means it requires oxygen, which means it requiresmitochondria because mitochondria are what make energy in the presence of oxygen.”So have you thought about looking…and this kind of goes along with your NAD hypothesis,but had you looked at mitochondrial biogenesis, mitochondrial function?` [Satchin]: Yeah, so the endurance is a veryinteresting aspect because we see that only when mice eat for eight to nine hours.We don’t see that improved endurance when they eat for 12 hours, although their bodyweight is maintained as nine hours.So this was interesting.So that’s why, as you pointed out, clearly mitochondria might be playing a role, andin fact, in liver we do see increase mitochondria volume, and increase endoplasmic reticulumvolume, so ER and mitochondria kind of work together.That’s what we are learning these days.So the mitochondria volume increases.Another thing is we do see less damaged mitochondria in liver when they eat only from eight tonine hours.Second thing is this mitochondrial effect is not restricted only to liver.We do see increased mitochondrial volume in brown adipose tissue, so in brown fat.As you know, these mitochondria have kind of dissipate until they are literally burningthe fat.So, at least in two different organs, we have seen increased mitochondrial volume.That correlates with increased level of PGC-1alpha that’s involved in mitochondria biogenesis.So, there is all these links that we are seeing and that are also giving us clue where tolook for the mechanism.For example, why PGC-1 level goes up and what triggers that to go up.[Rhonda]: Well, this actually leads me into another area that I wanted to cover.So before we go into the flies and humans, and that is I think people may be confusedby this time-restricted feeding, which is essentially, you know, feeding within ouractive hours.[Sachin] Yeah.[Rhonda]: The daylight hours, and intermittent fasting.So there’s obviously some overlap between the two because if you’re, let’s say, you’refeeding within a 12-hour period.So you wake up, you have your first sip of coffee, that starts your clock.All right.That’s it.So, 8:00, then you better stop eating by 8 p.m.Right?That’s for 12 hours.[Satchin]: Yeah, yeah.[Rhonda]: Then from 8 p.m. all the way till 8 a.m. the next morning, you’re fasting, right?[Satchin]: Yeah, yeah.[Rhonda]: You’re not getting any energy.[Satchin]: Yeah.[Rhonda]: So, so in some ways you’re getting a lot of…there are some overlap betweenthis time-restricted feeding and intermittent fasting, for example, which has been shownto increase ketone bodies like beta-hydroxybutarate, which I know you’ve also shown restrictedfeeding does increase that as well.It takes around, I think, 10 to 12 hours…[Satchin]: Yeah.[Rhonda]: …for your liver glycogen to deplete and fatty acids get immobilized, they go tothe liver, you start to make beta-hydroxybutyrate and other ketone bodies which then get transportedto other tissues and are used for energy in the brain, or they act as signaling molecules.[Satchin]: Yeah.[Rhonda]: Which Eric Verdin at UCSF published.There’s lots of…oh, have…can you, first of all, differentiate for people, like, thedifference between intermittent fasting and time-restricted feeding?Like, what are the main differences, and maybe what some of the similarities are?[Satchin]: Well, both of these depend on this idea, as the commonality is this prolongedperiod of fasting.When I say prolonged, that’s usually longer than six to eight hours because that’s howlong it takes for glycogen to deplete or maybe the fatty oxidation to begin so that we beginto use some of the fat.And you also pointed out ketone bodies and beta-hydroxybutyrate, those are also producedmaybe after 8 to 10 hours.So the bottom line is this, that is when we eat we have a type of physiology where we’reusing glucose and we’re driving some bodily function.And at the same time, we may be also damaging some cellular components because of all thereactive oxygen species that we generate during eating, during metabolizing all of this.So all of these have to be repaired, and for some reason, we do not know why, the repairmechanism happens only during the period of fasting.And during this period of fasting, we switch to a different kind of metabolism.Just like you said, our primary energy source is not the readily available glucose fromfood anymore.It has to come from different sources.In some cases it can come from a little bit of protein, that’s gluconeogenesis or fromfat oxidation or, just like you said, ketone bodies.So these things, this physiology, the fasting physiology, we actually know…we are justseeing the tip of the iceberg of fasting physiology.We’re just learning about a very few molecules.We don’t know what happens to lot of signaling molecules, how the mitochondria actually repairduring fasting.Is it actually necessary, to why some repairs happen only during fasting.Why can’t they happen when we’re eating?So all of these questions are out there but what is common between this intermittent fastingand time-restricted feeding is this fasting physiology that we’re beginning to understand.The reason why we coined and use the word time-restricted feeding is we are not restrictingcalories, at least in experimental animals.So in that way the intermittent fasting came from calorie restriction, and every otherday feeding that had a serious component of caloric restriction that many people thoughtis difficult to achieve.So that’s why we stayed away from the word caloric restriction or fasting, and we usedthe word feeding because people thought, people may have a positive attitude towards it.Other than that, I think the idea of fasting is ingrained in evolution.Just like in circadian rhythm, the animals have access to food only during their awaketime which can be less than 12 hours, and also for diurnal animals, which are hunter-gatherers,the only time, actually, they have to hunt is twilight time because if you ever go toSavannah, or any of the African countries where there is still wild animals, or if yougo to even a zoo, then you know that animals are not active in the middle of the day.They’re mostly active during morning and evening.So in nature, animals actually have only two chances to eat, and the rest of the time they’refasting.So this fasting physiology is a very natural response to repair and rejuvenate, and intime-restricted feeding, we’re kind of exploiting, or we’re kind of bringing back that primordialphysiology that’s ingrained in our genome, that our genome has to respond to that fastingon a daily basis.At the same time it syncs with another aspect of the genome; that is it helps us stay awakefor 10 to 12 hours and to reduce our energy level and go into a sleep or less active statefor the rest of the day.So in that way, it brings back the primordial rhythms in our physiology, metabolism, repairand rejuvenation, whereas intermittent fasting actually helped us to learn various basisfor this fasting physiology.[Rhonda]: That makes sense.I guess, also, what I was wondering is if you think about it, like, so the minute youstart your metabolism clocks in your liver, for example…[Satchin]: Yeah.[Rhonda]: …the minute you start those metabolism clocks by your first sip of coffee and breakfast,the clock’s ticking and you’re insulin-sensitive.You’re gonna be able to, you know, take glucose up into various cells after you eat.And then once you get past that time, so you’re now 12 hours out, you’re not gonna be as insulin-sensitive.So, let’s take someone that is doing intermittent fasting, and they wake up at 6:00 or 7 a.m.They have coffee and breakfast, a big breakfast, and they’re done.So then they fast for 12 hours, so now it’s 7 p.m., maybe 13 hours, 7:30, 8 p.m.They’ve been fasting all day, so they’re getting a lot of the activation of some of these…[Satchin]: Yeah.[Rhonda]: …you know, stress-response pathways like AMP kinase and, you know, they’re makingsome ketone bodies, Kreb, all these similar pathways are being activated.[Satchin]: Yeah.[Rhonda]: …that, you know, time-restricting feeding also activates.But then, they take a big meal at 7:30 or 8 p.m., so 12 or 13 hours after they’ve alreadyset their clock.[Satchin]: Yeah.[Rhonda]: So now in theory, then, they’re…well, I don’t know if this is true or not, maybethe intermittent fasting changes some of this, but, you know, their liver wouldn’t be, youknow, it wouldn’t be working as well at that point.Or do you think that just because they were fasting all day that may change some of thatand allow them to then eat this meal and it wouldn’t have such a negative effect?[Satchin]: Yes, so that’s a very interesting question that we get many times and we arethinking of addressing that.It’s very hard to do that in experimental animal models because if you fast them, ifyou give them two meals, they reduce their caloric intake, but it’s possible to do.But here is something that came out only in last three to four weeks.You mentioned early in our conversation that insulin sensitivity is not the same at theend of the day, and the question is, if you fast enough during the day, is your insulinsensitivity as good enough as in the morning?[Rhonda]: Right.[Stachin]: Then everything you can equalize is at least insulin, which is a big thingin metabolism [inaudible 00:55:42].So recently, what we are finding is actually the smoking gun came almost 10 years ago whenpeople who are doing GWAS studies to find whether there are mutations in given genesthat make us more diabetic or obese, surprisingly, people thought that, “Okay, so we’ll findsome genes that regulate metabolism.”Right?So that is the common sense.But then the big surprise was they found melatonin receptor as one of their top hits.[Rhonda]: Wow.[Satchin]: And some of the clock genes, like cryptochromes, in the top five or ten genes.That is not only in one study.In multiple studies, they found it.So there are the smoking gun.What is melatonin doing with this obesity and diabetes?And recently, what is interesting is people are finding that melatonin receptor is presentin pancreatic islet cells, beta cells, and melatonin receptors, when it’s engaged withmelatonin, it signals and it inhibits insulin secretion.[Rhonda]: What?Really?[Satchin]: Yeah.So it just came out, like, four, five weeks…[Rhonda]: Wait, so you know that I’ve always wondered, because, like, most of the melatoninin the body is actually made in the gut, right?So tryptophan from dietary protein gets converted into serotonin…[Satchin]: Serotonin.[Rhonda]: …and that’s converted in melatonin.This is happening in the gut and…[Satchin]: No, serotonin goes to pineal and then gets into…[Rhonda]: So there’s, so this, so the, it happens in the gut and it also happens inthe brain?[Satchin]: Yeah.[Rhonda]: There’s two separate genes that do this.[Satchin]: Yeah.[Rhonda]: And what’s really interesting is I don’t know what melatonin…why are we makingit in our gut?So I’m wondering if it’s somehow signaling to the pancreas.[Satchin]: Yeah, so this is completely new.So that’s why now it brings up…now, it helps us to connect this dot that people have.I mean, for the last 35 years clinicians know that the insulin sensitivity is very differentbetween day and night.And then the GWAS, the human genetics people came and said, “Yes, there is some smokinggun with melatonin.”And now, finally we are finally saying, “Yes, melatonin receptor can actually inhibit insulinsecretion.”So in that way, having an evening meal, maybe with candle light dinner, is not a good ideabecause you have less light, so you have more melatonin, and that can inhibit… [laughs][Rhonda]: That’s fascinating.I have to get that study.It’s very, very interesting.[Satchin]: So that’s one case where we might think that late night, even if you controlfood calorie, the same calorie taken in late in the night versus early in the evening mighthave different effect.In fact, there was one study that came out from Spain, two or three years ago now, showingthat in a weight loss trial they actually found…although everybody got the same diet,they were controlled for activity, clearly there were two groups of people.One group lost weight significantly, a lot of weight loss, and the other group lost moderateamount of weight.And when they did post-hoc analysis to see what is the difference, the only differencethey found was the group that lost weight, they actually had their lunch…in Spain,people eat lunch at 3:00.So they ate lunch earlier whereas the group that did not lose weight, two months, theyate their lunch later.So that is another piece in the puzzle saying that late-night eating might actually preventweight loss.[Rhonda]: Right.And you’ve now translated some of these findings into some human trials using this smartphoneapp that you’ve developed.So that’s kind of neat as well.[Satchin]: Yeah.So one thing was we wanted to see is when people actually eat.And in typical nutrition studies, people are asked, “When do you eat lunch, breakfast,and dinner?”But that doesn’t capture, really, all snacking and everything.So that’s why we thought how to capture when people eat in a very evidence-based manner.And we thought if we asked people to take a picture of their food, then the picturewill speak a volume.It will have every single component.They would not have time to describe everything on their plate, but we’ll capture that.It will also have the timestamp.So the whole idea was to see when do actually people eat.Are there a lot of people who eat like mice do that nibble throughout the day and night?And if they actually eat until, say for more than 12 hours or 13 hours, then they are theones who may benefit from time-restricted feeding.So when we did this experiment, when we started this project, we thought that…everybodywe asked, they would say, “Yeah, I wake up, I have my first sip of coffee and usuallyI eat all of my food within 12 hours.”So we were very discouraged to hear that.But then we carefully selected people who don’t do a shift work so they will not haveto work in the nighttime, that’s when they’re changing their eating time, and they’re alsonot on any medication that will change their hunger or satiety.So we took really healthy people from San Diego area because we live here, and theyjust had to take a picture of their food.And that way, it was also less stressful for them to enter what they ate, and portion size,etc.[Rhonda]: Way better compliance, I’m sure.[Satchin]: Yeah.There’s only three clicks, because if you think about it, open the app, take a picture,and then press the save button.And the optional was they could actually describe what they ate.But we found very few people actually describe what they eat.So that means just typing that on your left hand when you’re eating is not a very pleasantexperience.What we found is out of these 156 people, nearly 50% people eat during 15 hours.So that means between their first bite, non-water bite, to the last non-water bite or sip ina given day is around 15 hours, which some people think, “Oh, that’s normal because ifthey start their first sip of coffee at 6:00 in the morning, and then after dinner they’rewatching their favorite show, and then had another glass of wine or chips, that can goup to 9 p.m.”But then we asked…well, in mice, we can actually take away food and enforce time-restrictedfeeding.We can’t do that with humans.They have to be self-motivated.So we asked whether it’s feasible for some people to at least restrict the time.So we asked eight of them to see…they were eating for 14 hours or longer and they werea little bit overweight, so we asked if they can eat within 10 to 11 hours.And we said, “We are not going to ask you to change what and how much you eat.The only thing you have to do is select your own time, depending on what time you go towork or what time you come back, select your own time until we’ll have 10 to 11 hours andtry to stick to it every day, even on the weekend.”And surprisingly, all of these eight people, they self-selected their 10 hours, 10 to 11hours, and they stuck to it for 16 weeks, and at the end of 16 weeks they came back.We saw that they had lost around 4%, 3.8% body weight within the 16 weeks.They didn’t have to do too many, they didn’t have to read labels, they didn’t have to typeportion size.But then when we asked them, “Why did you do it,” what is surprising is they said theyslept better and they felt more energetic in the morning, and that’s why they did it.And since they didn’t have to count calories, it was also good.But what is surprising is in mice, if you do the same experiment, mice will chow down.They will eat the same number of calories as when they have free access to food.But in humans, these people in our study, they actually ate 20% less calories.Even though we asked them to reduce their time, they ultimately reduced their calorie.But if you think about it, this is a much better way to control, manage their diet thanto count calories.So in some way this study is inconclusive to say whether time restriction alone wasbeneficial for weight loss.But what it showed is the feasibility that some people can time-restrict and that canbe an indirect way to reduce your calorie.And since we’re collecting picture of every single food, we can also ask another verysimple question.“What is the time of the day when people are more likely to eat certain type of food?”As you can imagine, we found people drink most of their coffees, 70% of their coffee,within four to five hour’s interval in the morning.And people ate 70% of their alcohol in the evening, four to five hours.So now imagine if somebody’s time restricting to the daytime, then he or she is more likelyto lose on alcohol.So in that way, that also improves the quality of diet.So since we humans eat different type of food at different time of the day, depending onwhich interval we choose may indirectly result in change in nutrition quality, and to someextent, quantity.[Rhonda]: And what about the cutting out, like, the ice cream and desserts?[Satchin]: Yeah, so most of the reduction in calorie was due to reduction in late nightsnacks.[Rhonda]: Yeah.[Satchin]: And after dinner, ice cream, dessert, and alcohol.[Rhonda]: So this is a really cool idea, Satchin.I went to your website last night, mycircadianclock.org.Very, I really like the website in general.There’s a blog section, the section explaining, you know, a lot of the science behind circadianclocks and everything that we’ve talked about today.There’s some presentations of you there.I mean, it’s just a really great website.But I also signed up for the app.[Satchin]: Yeah.[Rhonda]: Because I am now on a time-restricted, you know, feeding schedule.And, you know, right now I’m doing 12 hours.I would like to try the nine hours to see if I can get any endurance benefits, whichmay possibly be mediated by beta-hydroxybutyrate …[Satchin]: Yeah, yeah, yeah.[Rhonda]: …because that’s been shown to affect endurance.But anyways, so I went up and I signed up.It’s really simple.You go to the website, you click…maybe you want to explain.Like, I clicked Sign Up or something and then…[Satchin]: Yeah, and then it asks you very simple questions.So the whole idea was if you think about it, this branch of science, circadian rhythm orcircadian research, came out of curiosity.So we actually don’t have a traditional medical school department which will take our resultsand translate to public.Or it’s not even in the public health curriculum because circadian rhythm is such a new field.That’s not there.So, it’s hard to…[Rhonda]: This is so important, and it’s, like, disrupted by modern day society.I mean, it’s, like, I’m gonna be talking about this now.So I’m very excited.This is definitely important.[Satchin]: No, what I was saying is that if you…you brought up this modern day society.In modern day society, light is an enabler.[Rhonda]: You work?[Satchin]: Light enables us to stay awake throughout the night, and then we have 15%of work force who does night shift work, and they are the ones who actually enable therest of us to stay awake.They are the ones who are actually driving the truck, who work in the emergency department,they are food prepping, they are doing all these other service jobs, and they enablethe rest of us to stay awake.And then in their way, within the last 100 years we have gone tremendously from a verynatural day and night cycle to 24 hours light cycle, and that’s the biggest disruption wesee.And that biggest disruption leads to all types of chronic diseases that we see in moderndays.For example, now, out of the top 10 causes of death, if you look at the top 10 causesof death in industrialized country, the five or six, top five or six are chronic diseases,and we know circadian disruption can lead to those chronic diseases.So now the question is if we can do very simple adjustment to our lifestyle, can we preventthis chronic disease by X number of years?So to get to that we need two different information.One is what are the extent of circadian disruption?When do people go to sleep?When do they get up?When are they eating their food?And when are they exercising?So if we can capture what, when, and how much people eat, sleep, and move around, then wehave a very complete, nearly complete picture of somebody’s lifestyle that will be highlyuseful for circadian rhythm research, for your primary care physicians, and also forpublic health and epidemiology.So that’s the first part of the goal, to collect what, when, and how much people eat, sleep,and move around on a daily basis, for at least a week or two weeks so we’ll know how is theirlifestyle during weekday and weekend.And then in the second phase, we can give some health information, because many of thehealth clubs are more geared towards losing weight, doing one thing, and it’s very difficultto really guide people to do this three different things; eat, sleep, and move around on a timelybasis.And it’s a challenge.We are experimenting.So we are actually hoping that some people who are signing up, they will give us feedbackhow to improve our science and also our education and our app so that we’ll see the benefit.In the second phase, they can self-select, just like you said.You’re going to self-select 12 hours, maybe 9 hours.And when you self-select an interval and enter all of your food, and sometimes even if youforget once in a while, that’s okay, because we account for that.We knew we have some algorithm.And then we want to correlate whether this 9 hours is beneficial to you or not, or whethersome people actually get the same benefit with 12 hours.Some people might go to 8 hours or 9 hours.So those information will come in the second phase that goes from second week ’til 16 weeks.Then if you want to continue, we have many users who want to continue for a year or twoand they want to see how seasonally their eating pattern, sleeping pattern changes,that they can have the data and also we gain from that data, research gains by taking thatdata and seeing what is the pattern in the general public.[Rhonda]: Yeah.Also, it’s nice to feel like you’re contributing to research, you know.[Satchin]: Yeah.[Rhonda]: So in addition to this, this myCircadianClock app which is on the AppStore.[Satchin]: And also in Android.[Rhonda]: Android.[Satchin]: Yeah.[Rhonda]: And in addition to that app, you can sync with other fitness data like MyFitnessPal,because you’re gonna be measuring at all these other health parameters.[Satchin]: Yeah.[Rhonda]: I heard you mention something also about a light sensor thing or some…[Satchin]: Yeah, so I wear a light sensor.[Rhonda]: Yeah.[Satchin]: It senses light.But let’s go back to the HealthKit and Google Fit.So most phones now have…if it is a iPhone it has something called HealthKit that comeswith your operating systems, so it’s already in your phone.[Rhonda]: Mm, that’s good.[Satchin]: And that phone, that HealthKit app is sensing every time your phone moves.So it’s almost like it’s measuring your movement just like the Fitbit does and it stores thatdata.It also stores many other kind of data, if you want to store.For example, your own information about your body, your height, weight, age, etc.And it can record up to, I think, 70 plus different parameters depending on if you areusing a special app or even the same app, if you say what do you [01:12:13] for othercompanies and it can store that.But what is interesting is that information is not on the Cloud, so it always stays onyour phone.If you lose your phone, you lose that data.But what you can do is if you want to share what is in your HealthKit or Google Fit…GoogleFit is very similar to HealthKit, but it runs on Android…what you can do is you can syncthat data with an app like myCircadianClock.So anything, any information that you store in HealthKit gets shared with myCircadianClock,and myCircadianClock can also send some data back to HealthKit.So it kind of acts as a hub.So similarly, various apps like MyFitnessPal, and then Nom, and many diet apps, many exerciseapps, they also deposit their data to myHealthKit, sorry, HealthKit or Google Fit.So it’s kind of a data exchange hub.So if anybody has any app where they are measuring what, when, and how much they eat, sleep,and move, or any blood parameter, any other health parameter they are interested in sharingwith researchers, they can sync that to HealthKit and then HealthKit gets synced with myCircadianClockand we can capture all that data and we’ll analyze.[Rhonda]: Very cool idea.I am looking forward to contributing…[Satchin]: Yeah.[Rhonda]: …to that.But I kinda, wanted to…[Satchin]: Talk about the light?[Rhonda]: I wanna talk a little bit about your…so you’ve got so many awesome…somuch awesome research coming out of your lab.There’s also the heart rate…[Satchin]: Yeah.[Rhonda]: Heart rhythm….[Satchin]: Yes.[Rhonda]: …studies.So you mentioned earlier the chronic diseases.If you look at in the United States or industrialized societies in general, the number one killer,people died in most of heart disease.[Satchin]: Yeah.[Rhonda]: Some sort of heart disease, you know, and obviously, lots of different thingsregulate our susceptibility to heart disease.Metabolism, obesity.But you found some very interesting findings doing time-restricted feeding in fruit flies.[Satchin]: Yeah.[Rhonda]: So can you talk a little bit about that?I’m very interested in that.[Satchin]: Yeah.So fruit flies are used in science for many, many years.And they’re, they have a short lifespan.They stay alive maybe 9 to 10 weeks max.So it helps us to figure out whether any intervention, like time-restricted feeding, will have anypositive or negative impact on health span or healthy lifespan or longevity, etc.So what we did was, again, a very simple experiment.We took fruit flies and we gave them food only for 12 hours during daytime, becausefruit flies are diurnal animals, they fly around during daytime, eat, and then at nighttimethey sleep, or they had access to food for 24 hours, and we measured that they were eatingthe same amount of calories, and they were also moving around the same distance.So, inside these bottles they could fly back and forth.And at three weeks of age, their heart is very healthy.It beats rhythmically.And although the fly heart is not like human heart, they also have…[Rhonda]: Most people are probably shocked.Flies have a heart.[Satchin]: Yeah.So their heart is very similar genetic program.In fact, many of the genes that are now known to be necessary for heart development in humanwere discovered in flies and vice-versa.There are many diseases in humans.Those are now put into flies to see what do they do in the heart.So it was a very interesting model.Just like humans, the fly heart also becomes weaker with age.So, by five weeks, the hearts don’t beat rhythmically.They have a little bit of arrhythmia, and then they have the same dialysis.And so then the heart gets dilated with age.The beat-to-beat distance also becomes very irregular.So what we found was when these flies eat only for 12 hours, they don’t develop thatarrhythmia as quickly as the normal flies do, so they are protected from this heartdisease.Then we said, “Okay, so if we introduce time-restricted feeding later in the lifespan, then what happens?”Because one thing we could not do in mouse study, because mice live for three to fouryears, we could not introduce time-restricted feeding later in life.But in flies, when we introduce later in life, they were also protected.The arrhythmia reduced in flies.And when we gave high-fat diet to flies, they also produced arrhythmia and many heart conditionsthat we see in humans and those were also protected in flies.And what is interesting in flies, we also saw the flies sleep better when they eat onlyfor 12 hours.So by five weeks, flies actually are just like very old people.They have fragmented sleep at nighttime, and they are sleepy during daytime, and that iscompletely prevented by time-restricted feeding.They have a good night sleep, they are very active during daytime, the heart pumps nicely.[Rhonda]: Wow.Did you measure heart rate variability?[Satchin]: Yeah, so we did heart rate variability.So there are seven different parameters we measured.[Rhonda]: And that improved?[Satchin]: Yeah, so all those seven parameters improved to some extent.And when we introduced later in life, they also improved.That was the surprise.[Rhonda]: Do know what or why?What’s…[Satchin]: Yeah, so what we found is, again, one connection was back to mitochondria.What we found was the mitochondria were healthy, or in the sense, they did not…they may not,maybe they were not producing as much of the reactive oxygen species.[Rhonda]: The mitochondria in the cardiomyocyte, in the heart cells?[Satchin]: Yeah, in the heart cells.[Rhonda]: Okay.[Satchin]: So we took the heart cells and did gene expression for flies.We looked at all the genes, what we found is a big cluster of genes whose expressionactually reduced.And those are from the electron transport chain.So that implied that maybe they have less reactive oxygen species, or maybe reducedactivity of ETC, electron transport chain, is beneficial.So then to prove that, we actually knocked down few components of ETC and those fliesalso have better heart.So that was one thing.[Rhonda]: Interesting.[Satchin]: Second thing that we found is proteostasis of protein folding is necessary and in manyother organisms people have shown that in different components of protein folding machinery.But here, what we found is there is a new protein folding, a very newly-identified foldingmachinery called ATP-dependent.It’s a chaperonin complex.Eight different components form this barrel-like structure to fold proteins.And this requires energy, and that CCT component has been shown to be important for variousmuscle, sorry, various cytoskeletal protein folding, and it make sense for heart.And in fact, in humans there is a point mutation in one of these ATP, sorry, CCT componentthat has been shown to predispose to some heart disease.So it’s a beautiful story where found both mitochondria and this protein folding machineryare necessary for this time-restricted feeding beneficial, if beneficial effect.[Rhonda]: And this time-restricted feeding was 12 hours?[Satchin]: No, it’s 12 hours because flies are different from us.They don’t have thermoregulations, so when they fast for a longer time, they cannot,they kind of can’t tolerate that.[Rhonda]: Oh yeah, they’ll, they’ll get cold.Okay, so, you know, some of these phones also measure heart rate variability.[Satchin]: Yeah, so it will be interesting.[Rhonda]: That would be interesting, very interesting because that’s like, you know,that’s something that supposed to be very important for having a healthy heart.But if you don’t mind…again, this is just, it’s another reason why this time-restrictedfeeding, it just seems like everyone should be doing it.It’s an easy lifestyle adjustment.I mean, easy enough.You have to be disciplined to some degree, but, you know, it’s not…it’s easy enoughthat you can do.It’s like, you know, by the time it’s 12 hours later, all right, that’s it, you got to makesure you get all your food, your whatever it is that you consume within that 12-hourspan.But something…I wanna shift gears, if you don’t mind.[Satchin]: Yeah, sure.[Rhonda]: Another organ, the gut, because it’s another area of interest of mine, andyou recently published that the gut microbiome, so we’ll quickly go through this.The gut microbiome is also…well, bacteria are living organisms and they are also ona circadian rhythm.And what I found very interesting from some of your recent work is that you showed thatdifferent bacterial species within the gut, at least in a mouse also seemed to, you seemedto have more of these species during certain times of the day and less during certain timesof the day.And this was different in obese animals versus, you know, non-obese animals or…That is very fascinating.Can you explain that just…[Satchin]: Yeah, so bacteria, they’re just like us.They need their own niche, they need their own pH, temperature, nutrition, and all thesefactors.And now we can imagine that when we eat, we kind of change the gut environment, the contentof the gut slightly so that some bacteria may find it easier to grow and then some otherbacteria may find it very difficult to grow in that condition.So what happens is when we eat in a time-restricted fashion, we have a very fixed eating and fastinginterval.Then during eating, that environment will promote a certain set of bacteria to bloomand then the other bacteria kind of become quiescent, quiet.And then after few hours of fasting, then the second set of bacteria will bloom.So in that way, what it helps is, it helps to nurture different, a wide variety of speciesto cohabit in our gut.And they also function at different time of the day.During the daytime so, for example, when we are eating we need lot of bacteria to breakdown starch and fibers, complex carbohydrates, and also conjugate some bile acids and etc.So we need different players to do different things throughout day and night.And by time-restrict feeding, this alternating two different types of environment, one wherethere is lot of food and the pH is very different, versus one when there is fasting, there isscarcity of food, and the pH is very different, by alternating between these two differentenvironment, we promote this diversity inside the gut.And why this is important is we actually don’t understand why, but research from a very differentfield, from gut microbiome field, they are now finding it’s much better to have a morediverse microbiome in your gut than to have only one or two very simple species.So in some way, by having the time-restricted feeding, it promotes the diversityThere are few interesting thing that we found, which we are still working on to figure outwhy it happens, for example, mice that are time-restricted feeding, although the bacteriacould break down the complex carbohydrate to simple carbohydrate, for some reason thatsimple carbohydrate could not be taken up by the gut.It actually went out in the poop.And that was a surprise because usually simple carbohydrates are the ones that get absorbed.So we think that this compositional change somehow protects the complex carbohydratein the upper intestine.So it comes back to the lower intestine where it gets degraded, but we know that the lowerintestine doesn’t absorb sugar.It’s all in the upper intestine.So in that way, by this compositional change, we can completely shift how nutrition is evenabsorbed into the gut.The other thing that we also found is bile acids, which are very…emerging as very importantplayers in health, those bile acids are also better managed with time-restricted feeding,both in the liver and also in the gut.Bile acids are made in liver and then they cycle back and forth between gut and liver.And bile acids are made from cholesterol.So there is an enzyme in liver that gets upregulated in time-restricted feeding.And that enzyme breaks down cholesterol to bile.So you get dual benefit.You reduce cholesterol, increase bile acid.And that bile acid comes to the gut and it helps absorb some fat back into the gut andthere it gets conjugated by this bacteria.And for some reason we don’t understand, in time-restricted feeding they get modifiedin a different way than in normal feeding.So these are some of the new research directions we are taking or trying to understand, howthis gut microbiome interacts with timing of food and then changes the compositionalaspect of the gut.[Rhonda]: That’s very interesting.Have you looked at also the short-chain fatty acids that they produce and whether thoseget taken up by the gut [inaudible 01:26:01]?[Satchin]: So those we are now…so short-chain fatty acids are little bit difficult to lookat because they are volatile.They degrade much faster, so those are the next set of experiments we are doing.[Rhonda]: Okay, okay.So does this also suggest we should time our probiotic intake?Is there…[Satchin]: We haven’t looked into that to see whether the probiotic…[Rhonda]: Is there any data out there that has measured…so for example, I’ve measuredmy own microbiome using a company called nuBiome which allows you to send a little fecal sample,and I’ve done that a few times.Obviously, now it seems like the time of day is very important.I usually do it in the morning…[Satchin]: Yeah, yeah.That’s when…[Rhonda]: …because that’s when…But it seems like the time of day is very important.[Satchin]: Yeah, you can capture the compositional change by time of day.[Rhonda]: Is there any data out there that has looked at how the microbiome species changefrom morning to evening, like,…Oh so there is?[Satchin]: Yes, actually, in humans there are at least one or two papers showing howthe compositional change also changes throughout day and night.And when you have jet lag that messes up the compositional change.[Rhonda]: Right.Yeah, so, you know, very, the…I think there was study showing that microbiome gets thrown off and that leads to obesity.[Satchin]: Obesity, yeah, yeah.[Rhonda]: Or something.This is so much, and then of course the shift workers as well, I mean they’re completely…theirwhole system is off whack.It will be interesting to see whether or not time-restricted feeding can help negate someof the negative effects of…[Satchin]: Of shift work.[Rhonda]: …of shift work.Right.That’ll be very interesting.[Satchin]: Yeah, so that’s what we are doing now, to see whether we can put mice in shiftwork and give them food within shift or out of shift.[Rhonda]: Do you have an option in your app for shift workers so that you could also getsome human data?[Satchin]: Yeah.So, people can say what they…So in the first sign of a routine, and there is a question whether you are a shift workeror a regular worker, and if they say they are shift worker, then we look at that datamore carefully to see how they are changing their diet during day shift and night shift.And also, all shift works are not the same.Some employers actually put people, change shifts every week, every two weeks, everythree weeks, and in some cases, every four months.[Rhonda: Yeah.[Satchin]: So we’ll see on the data.But we are going to introduce another aspect where they can say when they’re going to workand when they’re coming back, because there are now different variations of shift work.Many of the gig works or flexible shift work is not even fixed.So flex hours is a new trend where people can be called up any time and we want to trackto them more carefully.So that’s why we’ll have another feature soon.[Rhonda]: Okay.And what about…So I know when I filled out the questionnaire last night, I, you know,put the city that I lived in.Is it…so let’s say I’m traveling and I take a picture of my food, there’s a time stamp,are you gonna get the time zone, like…[Satchin]: Yeah, so in the new…it always tracks the new time zone because what happensis we thought about it.It’s a little bit complicated to show two different time zones and your home time zone,and the new time zone, but we’ll get to that to see whether we can introduce that featurewhere you can see your data as if you are in the same time zone.How your body is adjusting, you can see that data.We are working on it.It’s, time is a very…what we figured out is time is a very difficult parameter in appsbecause as we are moving, as there is daylight saving time, and all these other time changes…[Rhonda]: Yeah.[Satchin]: It completely…displaying data becomes a challenge.So that’s another half of the challenge.[Rhonda]: Yeah, I know.What you’re doing, but you’re off to a really good start and I’m really excited about everythingthat you’re doing.I have so many more things that I wish I could talk to you about but unfortunately, we’rerunning out of time.I know you have another meeting.You are on Twitter.I follow you on Twitter.What’s your Twitter handle?[Satchin]: Satchin.panda.[Rhonda]: Satchin.panda is your Twitter handle?[Satchin]: Yeah.[Rhonda]: It’s S-A…[Satchin]: A-T-C-H-I-N dot Panda, as in panda bear.[Rhonda]: Right, okay.And your website?Um, mycircadian…[Satchin]: …clock.org.Yeah.[Rhonda]: And that’s where people can find all things circadian clock, all fascinatingresearch, you giving presentations, and also they can sign up…[Satchin]: Yeah, they can sign up, and also almost every week now we’ll have a blog, eitherfrom a…actually, we are getting our first blog from a user.Just like you, this person started before even our human work was done, and he juststarted voluntarily and religiously did nine hours or eight hours time-restricted feedingfor seven months and documented everything, so…[Rhonda]: Oh, wow.[Satchin]: So that’s going up this Friday.So we are very excited.[Rhonda]: Yeah.I really like your blog.I was looking over it last night.It’s very informative.So it’s a nice, nice job.Well, thank you so much, Satchin.I’ve been a huge fan of your work for several years and pretty much all things that I’velearned about circadian rhythm, you know, I’d say 80% has come out of your lab.So I’m very excited to have had the opportunity to speak with you.[Satchin]: That’s very nice of you.Thank you so much.[Rhonda]: I look forward to more research coming out of your lab.You seem to be doing some really interesting things.[Satchin]: Thank you.Thank you. CategoryArticlesTagsand blue light circadian clock circadian rhythm cortisol Dr. Satchidananda Panda Dr. Satchin Panda intermittent fasting jet lag ketone bodies melanopsin melatonin microbiome mitochondrial biogenesis night shift workers pineal gland suprachiasmatic nucleus that the time restricted feeding 100 Comments FoundMyFitness says: June 30, 2016 at 9:17 pm If this video convinces you to try out time-restricted feeding, don't let your data go to waste! You can apply to participate in Dr. Panda's distributed clinical trial and then keep up with your data and submit it to his trial via a simple mobile app. Learn more here: http://mycircadianclock.org/participant Reply Richard Sintery says: June 16, 2018 at 9:14 pm ive been trying this type of eating or diet if you will and am very disappointed. 'if your a body builder of any sorts think twice about trying this. fat % went up 1.5% in one month (16.1% – 17.7%), and muscle mass stayed the same over the same time span 81.8 to 81.8. i wasnt counting calories every single day as i eat similar foods. I was aiming for enough calories to do a slow muscle gain. 3100-3200. maybe 3-4 times i went over the 12 hr cycle by 10-30 mins. all in all i know by body and i'm done with this theory. Reply Lila Chanel says: June 19, 2018 at 7:50 pm Lau Andromeda brought me here…she such a bae <3 Reply JOEJOE says: June 22, 2018 at 1:31 pm So i should just eat my reg. Diet, and start the timer, when sunset comes, until the timer stops, and continue Reply Guillermo Roldan says: June 23, 2018 at 3:56 am So going with an OMAD plan and eating only water is the best way to go? im currently doing 1 meal a day but i wake up and drink matcha tea, and drink 6 to 8 cups of green tea during the day, i might switch to this and eat from 8 to 10 pm only, these studies are amazing Reply Jorge Barreto says: June 26, 2018 at 8:59 pm ok, so i was fasting (still am) eating from 9 am to 5 pm and lost 20 lbs (180 lbs morning weight). Then, I began exercising and kept the same fasting schedule but would workout or do the insanity workouts around 7 pm then take a protein shake and my weight hasn't gone down, I think now my morning weight is 183-84. Since I am more or less taking the shake around 8 pm, am I messing up my 16 hr fasting? Should I work out in the middle of my eating hours and take a shake? Reply Theo Ravelo says: June 30, 2018 at 5:32 pm Does caffeine-free, calorie-free tea break a fast? Reply Jeff Hadley says: July 3, 2018 at 5:06 pm Thank you both so much for this! I learned way more than I expected too. I’m new to finding you both and will be signing up on your site Dr Panda. Dr Patrick I love your podcasts with Joe, you guys are great lol Reply Ankur Dhankar says: July 4, 2018 at 4:10 pm Good job by Rhonda in keeping up with the thick accent 😂I'm also indian and probably have it 😅 Reply Leo Tong says: July 6, 2018 at 11:50 pm What are those random numbers that pop up ? Reply Lance A. says: July 9, 2018 at 3:45 am I notice Panda & Patrick did not agree on melatonin production location.I agree with Dr. Panda. He agrees tryptophan is acquired from diet, serotonin is produced in brain & gut, but that melatonin is synthesized & released at the pineal gland.Dr Patrick proceeded as though they agreed, but they did not. Reply Keep Moving says: July 11, 2018 at 5:39 pm A week of daylight anchoring while camping will reset most folks back to normal. Happy summer everyone! Reply Stuart Tea says: July 12, 2018 at 9:57 pm Brushing your teeth must activate your saliva glands and being part of your digestive system would this start the circadian clock going, most people brush when they wake up and before bed so, the clock would be running from like 6am until 11pm for me I know there are no calories in toothpaste and you don't actually consume it, but it just makes sense In my head that your taste buds and saliva glands taking a major stimulation first thing in the morning would make your clock start Reply Dr Truth says: July 13, 2018 at 7:31 pm The beneficial effects to the mice eating a western diet is surprising in itself, but it's astounding that the effects were simply due to time controlled eating! Thank you so much for sharing this video, Dr. Patrick! Your time and efforts are making a difference in the overall health for humans as a whole, and you should take pride in influencing this important topic. 🙂 Have a great life! Reply John says: July 15, 2018 at 2:09 am Can't noise set your clock? It seems to me that I always wake up before light because the world wakes up around me, the freeway starts to get noisy so I always wake up at 4:30 for some reason even if I never get up till 6:30 Reply Will Simmons says: July 19, 2018 at 1:53 pm Not a very accurate description. The first chunk of this video is about circadian rhythm which left me guessing and having to click around to find the actual content about Time Restricted Feeding, which is what the entire description for this video is about……… Reply John James says: July 24, 2018 at 4:04 am In theory, what time would be best to eat. I wake up at 4 am every morning. So, I eat from 5am to 1pm. Is this the best window period to eat ? Or should I eat later ? I ask because I know sunlight has a lot to do with this. Reply John James says: July 24, 2018 at 4:08 am So is there a perfect time for the window eating period. Is it 7 or 8 am ? Or 9? I wake up at 4 am. Reply Allan Stokes says: July 28, 2018 at 1:03 am I'm pretty sure in Panda's most recent book, he states that black coffee and tea do not start the clock, but the addition of cream or sugar does. Reply Cedric Dalton says: August 9, 2018 at 7:00 pm jesus lady -let the dr.speak. not here to see how smart you are. Reply Sicilian Bull says: August 17, 2018 at 11:50 am Dr. PATRICK you are amazing. Such a wealth of knowledge. Im a jre transplant also. Down 70lbs from time restricted eating and ketogenic diet. Just watched a show called affliction or afflicted i think on Netflix and all i could think about is how these people need to speak to you ! Its worth watching although some really make u feel like its mental. Reply Shannon Kringen says: August 18, 2018 at 5:53 pm thanks for this Reply Mark Sconce says: August 19, 2018 at 10:41 pm This is about mice. Reply CatchCanista says: August 20, 2018 at 3:41 am Dr. Panda, roll your shoulders back, quit slouching, terrible posture! Thank you for the info! Reply Talii K says: August 22, 2018 at 5:17 pm Does oil pulling break the fast? Reply Vince Vengeance says: August 23, 2018 at 8:16 pm to be honest, i never turned off my light when i go to sleep. i've been sleeping with the light ON for almost 20years+ i can't sleep with light turned off. i really don't know what happen. Reply Jooply X Harrington says: August 26, 2018 at 10:55 am She's so hot I would time-restrict my fapping and save it all for her Reply ABCDE says: September 2, 2018 at 12:54 am The circadian clock is not the primary trigger of human sleep, the entropy is. The circadian rhythm controls animals, not humans because animals have less entropy and will than humans. Reply Andrew Fox says: September 5, 2018 at 12:13 am Half an hour in and NO mention or fasting, diet, or even anything about food. Literally only been talking about light for 30 minutes. Interesting stuff (maybe?) but I wish there was a time stamp for the actual content that is advertised… Reply tomislav horvat says: September 6, 2018 at 9:43 am Does water with lemon counts like the beginning of the TRE cycle? If i drink it first thing in the morning… Reply Conan Lee says: September 11, 2018 at 12:30 pm Its not just fat that causes obesity, read about how the sugar industry paid for scientists to say that:https://www.npr.org/sections/thetwo-way/2016/09/13/493739074/50-years-ago-sugar-industry-quietly-paid-scientists-to-point-blame-at-fat Reply Conan Lee says: September 13, 2018 at 1:58 pm Count in as one of the people surprised that fruit flies have hearts. Reply Ga Wa says: September 14, 2018 at 2:57 pm Grub Reply Over Comer says: September 21, 2018 at 1:07 am Lag between audio and visual and the "catch up" made it very difficult to follow on some parts. Did anyone else have this? I have been doing time restricted feeding on and off since the spring. Some days my feeding window is as short as 4 hours it is never over 12 and most of the time is between 8 and 9. I have unfortunately gained quite a bit of weight from doing this. Anybody have a reason why am I being too strict is my body in Starvation mode are my hormones tank I thought a lot of things would get a lot better that I would lose weight and my hormones would be great and on my sleep would be normal but I have gained weight and I have been hypervigilance it is been rough for me to sleep and I feel like my circadian sleep rhythm is off too I have a ton of energy in the evening and it's very difficult for me to wake up in the morning. I almost feel that a 10 hour feeding window for me and a 14-hour fasting window would work better I think the super short feeding window didn't do me any favors Reply cyrusdavirus007 says: October 1, 2018 at 11:09 pm Where do you fit in your supplements like multivitamins, niagen, magnesium? I’m having problems fitting it into my 9 hour feeding window. Reply pangeaforever says: October 2, 2018 at 12:43 am You're awesome Rhonda! I've learned alot from watching your videos and such. I've been doing time restricted eating and intermittent fasting (among other things) and it has helped me lose weight the past year. Keep up the awesome work! Reply Stones Jones says: October 7, 2018 at 2:44 am The most difficult is that I love the night, I love the feeling of the majority being asleep, the silence and feeling of 'peace' it can give. Nowadays it has a lot to with my mental trauma issues, my noisy neighbour finally being asleep etc. Because now many times my sleep suffers and I have to wait for her..why? because my brain is on a lot of stress and many times when I try or even feel super sleepy, cortisol due to stressful thoughts blasts away that sleep I then felt a moment ago. But I have always loved the night, inside home or outside. It has previously and even now (less though) always given me freedom to be creative and to think and ponder about many things of life. I can't see myself finding that in the daytime. I would love to combine it or try but I can't really see how.Nightime being awake has given me a lot of good things, but for a long while, I didnt mind my body and focussed more on brainpower, also drinking energy drinks , etc etc. And I was able to function really well cogntive wise. But things have happened and changed and my cognition functioning has deterioted a lot, but not due to nighttime living but due to extreme stress. Excytotoxicity. But then again, could i have been more resistant to the stress (burning brain feeling even, glutamate, kynurenic acid)if I was awake at daytime instead of nighttime. It's hard to figure out since a lot of factors in and of my situation come to play. Since I – like i mentioned- also stayed up the night many times due to escaping my noisy neighbor, that caused me a lot of stress (in a brain already suffering), i was very sensitive to his noise and still am, now more than ever. Anyway im trying to puzzle this out, what also makes this difficult is that its very hard for me to go outside during the day, since my mental issues, cognitive deficit/damage/trauma can't function at all with too many humans being around. (which is a nightmare ..i have not been like this my whole life, in fact my whole life I loved being around a lot of people, and being out and about in daytime).I would just love to have(have had) a doctor like this woman, someone with knowledge that could give time and listen and a lot of this hell i live could have been prevented, but nowadays every healthcare isntitute is all about numbers, fastfood counseling and bam out the door. People are getting really f*cked by this, especially the already marginalized. This is one of the things that – in my opinion- ruins so many lives and shows how our societies are built for the lucky and healthy, and close the eys on the marginalized over and over again, until they are not there anymore. This is sickening , but the masses here in Europe (and US) are focused on the stupidest things, instead of demonstrating against shit like I mentioned. It's not the muslim guy, or the refugees or whatever, that is destroying your life and society, its the lack of care, the focus on numbers by healthcare (influenced or forced by insurance companies) and just the overall focus on profit instead of humanism.Anyway,.ha..back to thinking how I can change my functioning by changing my rhythm, and how much I can do to lower that cortisol so I can sleep when feeling sleepy. Reply Notshife says: October 16, 2018 at 3:48 am Anyone know what % the actual increase in muscle mass was? I see this type of report often, usually with testosterone, only to find out the difference is 0.1% or some tiny value which could almost equate to measurement error Reply Pilar Diaz says: October 22, 2018 at 9:47 pm Dr. Rhonda, excellent topics. It is important that doctors broaden their horizons by integrating new and innovative methods, nutrition and exercise for the welfare of their patients. We no longer want robotic doctors focused only on the protocols of the pharmaceutical industry. Thank you very much for addressing such current and innovative topics in a professional manner. You and your guests are wonderful. Reply Mike Cola says: November 14, 2018 at 12:53 am This Time Restricted Eating Study Showed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/ 1- A significant decrease in fat mass was observed in the Time Restricted Feeding (TRF) group (−16.4 % vs −2.8 %)2- Fat-free mass and maximal strength were maintained in both groups3- Lower triglycerides in the TRF group4- Blood glucose and insulin levels decreased significantly in the TRF group Reply Deidra Dunn says: November 19, 2018 at 9:00 am Wish y’all would study my circadian clock. I don’t sleep at night but the minute the sun comes up I can go right to sleep!!! Reply Surely Not Srijan says: November 29, 2018 at 10:28 am It's refreshing to see a fellow terrible Indian accent that has something to add. Reply Lemme Get uhhh says: December 1, 2018 at 3:07 pm Thank you so much for having subtitles! Unfortunately I have a hard time understanding his accent but the subtitles made it much easier to retain the information. Many thanks to both of you. Reply Bert Morales says: December 2, 2018 at 5:11 pm Really amazing research, thank you! Does a cup of black coffee or tea in the morning start our circadian clock? The sun is up in the morning, starting the clock anyways, so what is the difference as long as you are not consuming calories? Reply Saptarshi Gupta says: December 4, 2018 at 12:53 pm @Dr Rhonda patrick…can we do TRF & Intermittent fasting at one time ? Reply Paul Miller says: December 7, 2018 at 7:14 pm Such a brilliant, articulate, sharp guy. And such an informed, bright interviewer. Great thanks to both for this enlightening 90 minutes. Wow. Reply Christopher Fisher says: December 12, 2018 at 12:58 am Forgive me if I missed this, but what was your findings of time restricted eating verse intermittent fasting? Reply andthereisntone says: December 14, 2018 at 5:59 pm Time for an update interview, please! Reply 707947 says: December 15, 2018 at 2:27 am Mitochondial volume increase in liver and brown fat https://youtu.be/-R-eqJDQ2nU?t=2782 Reply 707947 says: December 15, 2018 at 2:29 am TRF and IF production of Ketones with around 10 hours fasting https://youtu.be/-R-eqJDQ2nU?t=2836 Reply David James says: December 15, 2018 at 4:35 pm I love her energy. It's so pure unlike almost everything you see here in the USA> Reply David James says: December 15, 2018 at 4:43 pm I started doing 18 hours off, 6 hours on 6 months ago. I also upped my exercise to being active 5 or so days a week. I quit drinking beer as well and just smoked cannabis instead. In 6 months my weight went from 250 to now 190. My body is tight as fuck for being 47 years old. It wasn't hard at all. Homecooked meals, vitamix veggie drink I make, popcorn, granola I make, fresh fruit and a homecooked dinner I make for myself. Never going to be fat again. Reply jakob tbc says: December 30, 2018 at 1:58 am What I'm wondering, if you have one cheat day per week, on which you maybe eat for 12 hours and eat sugar and unhealthy, does it still make sense to have the other 6 days of the week a normal 16/8 IF diet? That's how I am doing it at the moment. Reply David O'Neill says: January 3, 2019 at 12:12 pm In my second year of nutritional therapy from listening to and wanting to be like you . Your changing lives and you've done the same in mine. Thank you Reply Ken Powers says: January 6, 2019 at 5:45 am With regards to insulin sensitivity though, shouldn't you be eating your big carbs meal at the end of the day rather than the beginning? Most research upon a quick search shows that too. Reply zerothehero123 says: January 8, 2019 at 2:11 pm A high fat diet isn't unhealthy. A high fat diet AND high sugar diet is unhealthy. Reply Jables says: January 10, 2019 at 10:16 pm With regards to what does/n't break a fast, I'd just like us to stop throwing a cup of black coffee in the same category as a 6000 calorie pancakes with maple syrup and candy break-fast. I fast from 7pm – 2pm or so daily and I totes doubt that 12oz. of black coffee at 6:30am has a modicum of an affect. JUST SAYIN'. #alsoangryaboutthecoffeething Reply Alejandro Perez says: January 21, 2019 at 2:20 pm In Spain we don't have lunch earlier. We have lunch very late (3pm) and Dinner even later (10 – 11 pm) 🙂 Reply Kain Eaux says: January 21, 2019 at 7:51 pm Dude farted at 115.32 Reply PureNrGG says: January 22, 2019 at 3:27 pm I have a question regarding medication, and breaking of a fast. Since google is failing me with this question, I figure ask here where many knowledgeable people are! While taking prescribed medications, will that break a fast? I read some places it wont, some say only if the meds need to be taken with food… Anyone out there have any insight for me? Much Appreciated! Also, I love everything you do and stand for Dr. Rhonda Patrick! It's straight up motivational! Reply Truth Street says: January 27, 2019 at 4:07 pm Are mice and humans the same? Why don’t they test humans? Am i crazy? Reply Jason Guthrie says: January 29, 2019 at 4:33 pm One question. So water does not count as breaking the fast but vitamins do? What about the minerals in water do those need to be broken down or are they too small to count? Reply Diana Leigh says: January 29, 2019 at 5:49 pm Interesting that he said our clock is not quite 24 hours, but 24 hours and 15 minutes. I have trouble with sleep, and have commented to others that my sleep time slowly moves later and later until my days and nights are reversed. Eventually, I just force myself to stay up all day and go to sleep earlier in the evening, only to begin the process again. Reply Ciro MacCord says: January 30, 2019 at 3:30 pm This interview is absolutely fascinating and compeling! Thank you so much for sharing. Reply jaco joubert says: January 31, 2019 at 5:57 am Good day Dr PatrickMy wife suffers from alopecia-areata, and we know it's autoimmune issue, which starts In the gut. She had het entire thyroid removed due to cancer. Now some studies have shown that, in woman, fasting triggers sympathetic nervous system, which can't be great for rest and repair. So in her case, to heal the leaky gut from all the radioactive treatment pills, can she do intermitting fasting or even prolonged fasting to heal the gut and other systems, without setting of the alert sympathetic system and trigger even more hair loss. What would you suggest we combine Reply lauchzwiebel says: February 1, 2019 at 6:06 am Very insightful Therefore helpful Thank you Reply highview seeker says: February 3, 2019 at 1:37 am Dr Rhonda is one fit nerd goddamn Reply denis says: February 7, 2019 at 4:16 pm god she’s so amazing!! 😭🙏🏼 Reply denis says: February 7, 2019 at 4:31 pm what happens if you fast all day and your first meal isn’t until around 8-9pm. i do OMAD so i fast from around 10pm the night prior to around 830-9pm the next day, eat 1.5k calories then back to fasting. how is this effecting everything? anyone 🧐 Reply Andy Williams says: February 13, 2019 at 6:45 pm This is very interesting but what does he have against mice? Reply Howard Korsu says: February 14, 2019 at 5:32 pm Tried to sign up for the study. I ran into bugs and couldn’t complete the enrollment process Reply Lam rof says: February 21, 2019 at 8:55 pm Sooooo Dark skin is not stupid anymore? What says the KKK and all the historical racists or Europe and America? Reply Lam rof says: February 22, 2019 at 12:23 am Why is it called fasting because you don't eat at night. What? we want to eat 24 hours now? Not eating at night is not fasting it is just living. Reply Spacemonkeymojo says: February 22, 2019 at 5:33 am 6:54 wtf LOL Reply Nigel Legall says: March 6, 2019 at 11:30 pm 1:05 People eat alcohol, priceless Reply Debby Page says: March 8, 2019 at 7:17 pm I IF everyday and usually eat around 2pm or not till evening. However I take nature-thyroid and take it first thing in the morning. I guess that would break my fast? I still am losing weight, feel great and can even get away with “cheating” on occasion by IF. Reply fumblerooskie says: March 8, 2019 at 8:57 pm I have started an eight hour-only feeding window during which I eat whatever I want. I'm currently at the end of week two. I'm taking a daily vitamin, and I try to eat as balanced a diet as possible. I'm finding it MUCH easier than I thought it would be. I do get the occasional hunger pang a couple of hours before I go to bed, but drinking water seems to reduce those relatively minor cravings. Moreover, I feel VERY good. I'm quite surprised by the amount of energy I have. I have no plan to weigh myself until I have been doing this for at least one month. My long term goal is to maintain this regimen for the rest of my life. Reply Jonathan Donnellan says: March 16, 2019 at 11:33 am I work 12 hour shifts. Three days, three nights and three off. I need to change jobs. Reply Chris Williams says: March 17, 2019 at 3:59 pm I thought she was going to say "panda" with a straight face Reply Bruno Gomes says: March 18, 2019 at 4:57 pm i would totally fuck that bitch Reply Greg D says: March 19, 2019 at 6:42 pm Dr. Rhonda Patrick….love your videos and thanks for all of the info. I've been doing intermittent fasting for approximately 8 months…no noticeable change to body composition. I have also done 3-day fasts as few times. But I am wondering if consuming PowerAde Zero or a similar Gatorade product, is acceptable for an extended fast or does something in those drink cause a biological effect that interferes with the extended fast? Reply HawkwardSolo says: March 20, 2019 at 1:43 pm How much of a parallel can we assume between mice and human?I really like your videos and interventions Dr Patrick but you seem very confident that on the metabolism subject, once proven in mice that you should apply it. You probably have very good reasons to do so but I'd like to know more about it. Thanks! Reply Ken Drex says: April 1, 2019 at 12:56 pm Is there any way to download these talks so I can replay them in my car when I have no internet connection? Reply Nobody . says: April 15, 2019 at 2:26 am Thank God I became Muslim . Truly . Reply Pretty Prudent says: April 20, 2019 at 7:10 pm 34:00 Reply Fraudulent Earth says: April 29, 2019 at 7:57 pm And all these amazing, complex biological processes have come about through evolution – REALLY!!! Sounds like intelligent design, to me. Reply Sotiris Venetis says: May 6, 2019 at 6:51 am SO WHEN I WAKE UP I SHOULD GET HIT BY LIGHT…BUT WHEN SHOULD I FIRST EAT…?lets say i have ONE MEAL PER DAY…should it be imedeatly after i wake up…?2 afters…?maybe first exercise…?can i make the meal at afternoon after exersice but 3 lets say 3 hourw before sunset and sleep time…? Reply ebttt says: May 16, 2019 at 3:24 pm To the point 30 minute video would be nice Reply pianowhorethesecond says: May 21, 2019 at 5:04 pm I've been intermittent fasting and found it an easy way to lose weight, but I'm a little concerned that I might not be getting enough nutrition since I'm also vegan. Anyone other vegans doing IF and wondering about this? Not interested in health arguments against veganism here, BTW, I do it for ethical reasons. Reply Christoffer Enfors says: May 24, 2019 at 9:27 pm Ppl reacting to no coffee like their not allowed Porn😂 Reply Mallory says: May 29, 2019 at 8:54 am The captions have a small error at 43:44–43:46, where Dr Panda is saying "converted to NAD" but is captioned as "converted to energy" and this is repeated a couple of times. Reply GD says: May 29, 2019 at 3:53 pm Very informative. I will try this diet now. Reply profitfever says: June 11, 2019 at 11:48 pm Doctor Rhonda Im sorry to be crude but damn you fine. Your skin is perfect. Reply JestemKwita says: June 28, 2019 at 8:34 pm Niesamowita wiedza. Słuchając gościa już jestem na 100% zdecydowany na intermitted fasting. Albo to że mamy komórki od żab czułe na światło i poziom melatoniny wpływa na insulinę. Wspaniała wiedza. Dziękuję Rhonda za Twój kanał. Mam zamiar obejrzeć wszystkie filmy. Jesteś wspaniałym naukowcem. 👏👏👏 Reply Infospeed NYC says: June 30, 2019 at 4:53 pm FYI Rhonda F.Lux is pronounced by it's developers as F Lux https://justgetflux.com/ Reply William Benson says: July 10, 2019 at 9:45 pm Holy smoke, girl. Each of your videos is like an entire trimester in college! Reply mixingrecords says: July 15, 2019 at 4:19 pm GREAT LOGIC and THEORY. Reply Örlogskapten MrPixmoable says: July 18, 2019 at 1:17 pm May I chew sugar free chewing gums during my 3 day fast. Reply Rod Berry says: July 31, 2019 at 8:24 am Do yeast or virus have a circadian clock? Reply lester palocsay says: August 3, 2019 at 12:16 am wealthy people seem to eat supper later are they doing wrong or is lifestyle allowing them to thrive, or lline of thinking causing harm, ? Reply Leave a Reply Cancel reply Your email address will not be published. Required fields are marked *Comment Name * Email * Save my name, email, and website in this browser for the next time I comment.