Dr. Satchin Panda on Practical Implementation of Time-Restricted Eating & Shift Work Strategies August 1, 2019 100 By William Morgan Hello, everyone. Super excited to be here again with Dr.Satchin Panda, who is a professor at the Salk Institute for Biological Science.And this is actually a round two podcast. Previously Satchin and I had a really longand interesting discussion on his research and how…we talked a lot about how thebody’s internal clock, which is known as the circadian rhythm,how that is regulated by the external cues, such as light, and how theinteraction between light in a certain part of the brain called thesuprachiasmatic nucleus.Which is like the master oscillator, as it’s called, or masterregulator, of circadian rhythm and how circadian rhythm regulates,you know, when we’re active, when we sleep, when we’re awake, when we eat,things like that. But also we talked a lot about this other external cue which alsoregulates circadian rhythm in what’s known as peripheral oscillators.Which are other tissues outside of the nervous system, such as the liver and thegut, and how that’s actually regulated by the timing of the food that we take in.And that’s where Dr. Panda’s work comes in, has shed a lot of light on whatthis…what’s called the timing of the food intake and how restricting thattiming of your food intake to a certain period of time, for example 9 to 12 hoursduring the day, can possibly affect a variety of different metabolic outcomesand health factors. So his research in animals has shown that animals that arerestricted to eating within a 9 to 12-hour window have improved glucose metabolism,improved lipid profiles, improved cholesterol, you know, increased leanmuscle mass, decreased fat mass, decreased fatty liver, you know,favorable gene expression patterns, all sorts of, you know, really favorableoutcomes. In addition he’s also shown that when these mice are fed a…what would besort of analogous to, I think, the standard American diet, which is,like, high in sugar, high in saturated fat, just not a really good diet.If they are restricted to this narrow timing, you know, feeding window,which is 9 to 12 hours, they still have improved markers of metabolism andmetabolic function. Which is really hopefully in a way because I think it alsoindicates that there may be some possibility that for people that have areally hard time eating healthy or just don’t eat healthy, maybe even just doingthis one thing where they… I mean obviously we want them to eat healthy.But if they don’t, eat within a certain time window that’s more restrictedpossibly that would have favorable outcomes. So I’m super excited,Dr. Panda, or Satchin. So just sort of since we’re talking about this,do we have any human evidence that the people that have, for example,like metabolic syndrome, if they eat within a time-restricted eating window,there’s any benefits to that without changing their food composition?Well, historically most of these research studies haven’t looked attiming per se, but there was a very nice, comprehensive review published by AmericanHeart Association that went back to many studies where timing,or at least how many times people ate during the day, was recorded.And after compiling all the studies, it was close to 70 or 80 different studiesrelated to fasting of decent quality, how many times people ate,that found that, yes, limiting food to a certain number of hours during the day ormaintaining overnight fasting was beneficial for cardiovascular health.So that’s a very well done meta-review of existing literature.What we need to do now is to look for new studies where this is specifically lookedat where everything else is kept constant and timing is changed so that we’ll seewhether the benefit is seen among individuals who already have metabolicsyndrome. So that’s what is lacking in the field. And, as you know,this is a very new area of research and NIH funding cycle is five years,so any of the studies will take at least five to seven years before we see anyresult and peer-reviewed journals.Particular for, I guess, a clinical trial of actually looking atsomeone with metabolic syndrome. Probably obesity… I mean if a person is obese,it may take a little more than just time-restricted eating to lose weight.Although they may, they may lose some. They may require more of a,like, prolonged sort of fasting, but the time-restricted eating certainly wouldaffect their… I would predict would affect their metabolism.Yeah. So what we see in our study, a small study that was published,and also some of the other studies that may be in the pipeline,when people adopt a time-restricted feeding in their regular life,in real life, not in the laboratory condition or in clinical trial,then they naturally reduce their caloric intake without even counting calories.So, for example, when they stop, suppose their target to stop around 6:00,7:00, or 8:00 in the evening, then the late night snacks and then the late nightglass of wine or beer that used to be their usual habit, they stop that.So in that way they’re doing two things, one is reducing calories and alsoimproving nutrition quality because that extra energy-dense diet is not gettinginto their system. So in that way I’m hopeful that we’ll see some weight loss,and then some improvement in real health, blood biomarkers. And in rodent studieswhat we have seen when we take already fat mice, who have been eating a reallyunhealthy diet for a long period in their life, and then put them on atime-restricted feeding paradigm, they don’t become, like, lean mice in terms ofbody weight. They become overweight, not normal. But surprisingly they’rebiochemically…or physiologically they’re more healthy because their bloodbiomarkers for glucose, cholesterol, triglycerides, they come to almost normalrange. So we have to make the distinction that some people may not lose a hugeamount of weight, but they might actually see benefits in their metabolism andphysiology. So that’s one thing you have to look out for.But this is, the mouse study you were just referring to,they were still fed a poor diet? Isocaloric.Yeah, okay.Yeah, they were still fed a poor diet, isocaloric diet.So imagine if they were fed a better diet and…the obese mice were feda better diet and they were doing time-restricted eating.Yeah, so they would be much better.Much better.They would lose more fat mass and become much more healthier.Can you explain for people who just aren’t very familiar withtime-restricted eating or time-restricted feeding, as we call it with animalresearch, like, just what is that and how does that actually affect your metabolismof glucose and fatty acids and amino acids?Yeah, so let’s kind of step back and ask how does it relate tocircadian rhythm, or the daily rhythms. So if we think of our daily health,our health, our personal sense of how we feel healthy changes from time to timethroughout the day. So, for example, in the morning when we wake up,being healthy means you’re feeling much rested and you’re full of energy to startthe new day. You’re feeling actually much lighter, you should not feel that fullstomach or grogginess, and have a good bowel movement. And then throughout theday being healthy means not feeling too hungry, so having some food in yoursystem, and then being productive throughout the day. And then towards theend of the day being healthy actually means having taken a walk or something soyou are not feeling really…you haven’t moved all day and you’re not feeling thatsense of being constrained in a place. And at night time before going to bed beinghealthy means feeling really sleepy, so that as soon as we switch off the lightand get into the bed we fall asleep. So in this way you can see that being healthy,this definition is very different at different times of the day.And a lot of it actually has to do with physiology or metabolism.So in the morning feeling lighter and not groggy and not having a food hangovermeans you have already gone through…hopefully somebody has gonethrough 10 to 12 or even 14 hours of fasting, not having food in the system,so that your body has metabolized all the food and has processed it and your gut hasalso gone through rest. And then towards the end of the day when you’re going tohit the bed, if we have food in our system, what happens is blood flow isdirected towards our stomach to digest the food and absorb it,so core body temperature remains high. So not having food for two to three hoursbefore going to bed actually helps us to go have that deep sleep,sound sleep throughout the night. So in this way now if we back up and think,“Okay, so when should we eat?,” then it makes sense that, well,after waking up maybe give one or two hours before we start eating,and then before going to bed at least three to four. Depending on what yourmetabolism, two to four hours before going to bed we should stop eating.So that brings up an eating window of, say, up to 10 to 12 hours max when weshould be eating so that we have that personal sense of being healthy throughoutthe 24 hours. So in animal studies what we have done is we ask a very simplequestion. If we take animals and give them food just like most labs do,they have food in the hopper they can eat whenever they want, and we calculate howmany calories they eat. And then we take another group of mice and then give themthe same number of calories and from the same source of food, whether it’s highcarb, high fat, high fructose. It doesn’t matter, we have to give the same source offood, same number of calories to the second group. And they have to eat allthat food within 8, 9, 10, or even 12 hours. Then we consistently find that themice that eat all their food within this 8 to 12 hours window are healthier than adlibitum fed mice. So that led to the term, what we call time-restricted feeding,where the timing of food when we eat is restricted or you define it and stickwithin it. Not caloric restriction, where you have to count calories and restrictit. So in this way it becomes very easier because you just have to…we all know howto manage our time, on a daily basis we are always dealing with time.So it becomes easier because if we start eating around, say, 8:00 in the morningand, based on our lifestyle, we can do 10 hours eating, then I’ll have my dinner,say, around 6:00. So that’s the concept of time-restricted eating or time-restrictedfeeding.And, yeah, I think that having the time where you just sort of say,“Well, I should stop eating by, you know, 6:00,” or, you know,kind of having it so you don’t have to constantly each day think about it,like, “When did I eat my first meal?,” or,” When did I take my first bite?” Ifyou kind of just have this general schedule where it’s, at least during theworkweek, you know, it’s easier.And then another thing I must point out, that in our animal experiments,when we do these experiments, suppose we say eight hours, we’ve fed the animals foreight hours. And then every week we measure their food intake and some weeksthey might eat less. And then we immediately change that schedule to,say, eight and a half hours or nine hours the next week to make sure that theyactually eat the same number of calories. So moving this needle by one hour actuallyis not that detrimental. It still gives them the benefit. And we have also askedanother question, so in animal experiments. In weekend we let them free,they can eat whenever they want. And they definitely go outside of a 12-hour window,they eat almost throughout the night. But still that two days of binge eating can becounteracted by if they stick to 8 to 9 or 10 hours during the weekdays.So that also gives us hope that perhaps in humans occasional eating maybe once ormaybe maximum twice a week can still be tolerated.That’s good to know, I guess a lot of people would be happy to hear that.Yeah.What do you do? So for your typical workweek and then weekendschedule, like, what’s your time eating window?Yeah, so it’s… You know, I travel a lot, too,but I…what I’ve found is if I stick to maximum 12 hours window,then I actually feel much better and more energetically, I sleep well,and I feel lighter, and I’m still productive throughout the day.So I start, say, somewhere around 7:00 or 8:00 in the morning,and then I stop around 5:00 or 6:00 in the evening. And I also try with differenttypes of diet once in a while. One thing with many people who are new totime-restricted eating, or eating or feeding, is when they start it they feelhungry. And what we have found is while having a fiber-rich diet or a protein-richdiet or a slightly higher fat-rich diet actually helps to go through that longertime without food. And slowly you also get used to it. And all of these actuallyincrease your nutrition quality because you’re staying away from simple sugar andhigh glycemic food and you’re leaning more towards food that takes a longer time todigest or longer time to absorb. So that helps. And that way my diet,both diet quality and also the duration have changed. And I usually stick to 12hours, and in many cases I kind of try to stick to 10 hours.Oh, me, too. I try to stick to 10. You’re talking about the peoplefeeling hungry when they first try this out. Has anyone ever looked at howtime-restricted eating affects satiety hormones, like leptin or ghrelin,which would be the one that makes you hungry?Yeah, so we haven’t looked at that in humans, but in mice what we seeis all of these hormone levels that come back to more homeostatic range,that means they don’t go too high and also don’t go to low. So that was kind ofsurprising because we thought that the hunger level will go up and the hungerhormones might go through the roof. But somehow after a few days the body adjuststo it, and then it gets them in a homeostatic range. And also humans who doit, we do see that after two to three weeks the hunger at bedtime is pretty low.They don’t feel hungry. They might feel actually lighter and ready to sleep.So then they realize how it feels like to go to bed with a lighter stomach than witha heavier stomach.Yeah. And then once you actually, if you break thattime-restricted, you know, eating or feeding window, I’ve noticed at least inmyself you actually start to feel worse. Yeah, yeah.Like right now I’m 37 weeks pregnant and through my pregnancy I’vepretty much thrown, you know, my TRE and my time-restricted eating out the window.Well, I do do 12 hours, but usually I do 10, I try to do 10, sometimes 9.Particular if I’m going to go for, like, a run in the morning or something that’sendurance-related, I like to eat within a shorter time window.Yeah.But there are times that I can’t even do…like there have been timethroughout my pregnancy that I can’t even do 12 hours and I eat a little bit afterthat. And I do notice it affects how I feel.Yeah.Like I feel more lethargic the next morning.Yeah. So there’s this food hangover that stays with you.It’s almost like, yeah, as if the food stayed there in the stomach,it didn’t get digested, or the stomach was sleeping when the food came.Right.And we get that response from many of our users,app users, that do say… From myCircadianClock.myCircadianClock app. There are many times when people…Usually what happens is for the first two to three weeks people are very diligent,they try to do it and they get into that rhythm. And then we get this occasionalfeedback. Around week five or six when occasionally they felt like they could goout late at night and eat, and then the next morning they felt horrible becausethey were feeling so lethargic, so groggy. And then they e-mail us saying,“Wow, really it felt like our stomach was really sleeping and I’m not going to dothat again.” That’s interesting.So it’s kind of interesting that that hits around week five,six, seven when people think that they have adapted to a lifestyle and they aredoing okay and maybe they can occasionally east outside the window.And they do that late into the night, and then the body reacts.Yeah.And they recognize that reaction.So for people that aren’t familiar, the myCircadianClock app can befound on the website myCircadianClock. And it’s basically you’re crowdsourcing data.You know, people that want to try this time-restricted eating out can try it outand also send their data to you and take pictures of their food so that you cangather data for your study, yeah. So that’s kind of a neat thing,that people can participate. While they’re trying this out, why not contribute toscience?Yeah. I mean what we realized is even if we get the best fundedclinical trial grant from NIH or DoD or any funding source, most of the clinicalstudies are done with people who live within 20 to 30 miles radius of a clinicalcenter. And so in that way, even if we foresee there will be five or six clinicaltrials in this country, there will be only five or six of those centers.And people who are living within that 20 to 30 miles and have time and energy totravel to a clinical center, spend almost half a day and every two to three monthsor two to three weeks will participate in this study and will see the benefitfirsthand. Then we realized that in that way most clinical trials which are lowrisk like this one actually will benefit…or will sample a very smallfraction of people. So that’s why I came up with this idea that if we have a studythat’s approved by our ethics committee and we make sure that we maintain theprivacy of people, we don’t sell this data, we don’t share this data withanybody else, and we give that assurance up front, then we may be able to recruitor enlist participants who are not living within 40 miles who don’t have time tocome to a clinical center, but are willing to share their data for science.And they can live anywhere in the world, they can share their data.And in this way this has been extremely useful because, again,in any clinical trial if you look at the exclusion criteria, there is such a longexclusion criteria that only 1 in 50 or 1 in 100 who even shows interest inparticipating, they can participate. But if we take that result and then try todisseminate to the rest of the people, those 49 or 99 people who could notqualify, then how are we expecting that this would be applicable to all of them?So it’s kind of a conundrum. So that’s why we thought let’s try this way where theonly exclusion criteria is if you are below 21 because that’s NIH’s mandatoryexclusion criteria. And in this way not only we can see whom it will benefit,we may also see whom it will not benefit. So we can actually a priori figure outwhat are the limitations of TRE. And people who don’t qualify,for example shift workers, they’re mostly excluded from many clinical studiesbecause of the nature of their work, they cannot come to the clinic at the righttime, and this is more relevant to them. So now we have thousands of people who areshift workers and they’re trying this. And from them we are also learning what theycan adapt and how they can adapt this TRE into their lifestyle and whether it helpsthem with alertness being on the job and whether it helps them to sleep on theweekend and all that stuff. So that way this has been extremely useful to havethis kind of study and sometimes we even get responses from our users that we hadnever thought about. So we take that response and see, “Hey, can we do thisanimal study and see what is going on? What is the biochemical basis for this?What is the physiological response in animals?” Maybe that’s how we canaddress… For example, there are many cases there are many immune-relateddiseases and people report that this immune-related disease has improved on thetime-restricted eating. And that is surprising for us. But then we went backto our animal data and we realized that, yes, we actually see systemic inflammationgoes down with time-restricted eating. And that makes sense. If the systemicinflammation goes down, then many immune-related or inflammation-relateddiseases would also go down with time-restricted eating. So there are someexamples like this where our human participants tell us their story.And if it is one or two person, we may not take it seriously. But then it’s 4 or 5 or10 or 15 people telling us the same kind of story. For example,many IBS patients who have irritable bowel syndrome who have been going to the toiletfor five, six, seven, eight times every day. They do TRE, and then theyimmediately see that the number of times they go to the bathroom has gone down.It’s a huge improvement for them. And then we might hear this story once or twice,we may not take it seriously. But then if we hear it 5, 6, 7 times,then we start thinking, “Okay, let’s go back to our animal data.” Because from allthese animals we have collected every tissue that’s imaginable and we have afreezer full of tissues. And then we go back and test what might have changed,what might be changing in the gut, what might be changing in the intestine,did the microbiome change, did the interaction between the microbiome and thehorse change. And that helps us to come up with newer hypotheses and do more focusedstudies. So this has been extremely useful for people to go sign up on themyCircadianClock website, and then download the app and share their data andalso share their experience.Wow. I just love hearing…there’s so many things that youbrought up that I have marked in my head to talk about. But first of all,to speak to your point, this is really… I think it is extremely important thatyou’re gathering all this data from people without all these limitations,aside from the age limitation. Like you said, you’re getting the shift workers.I mean this is hugely relevant for shift work and, you know, people that have IBS,people that have, you know, multiple sclerosis. Obviously people that havecertain conditions are probably consulting with their physician.Yeah, they do.But, still, you’re getting this data, and then seeing these trendswhen people start to say these things over and over. Like, “Oh,my IBS is improving.” And you hear it five, six times, then you start to go tothe mouse data and start to do experiments and tease our mechanisms.Yeah.I mean it’s just fantastic, it’s absolutely fantastic.So the first thing with inflammation you mentioned, do you think that part of thereduced systemic inflammation has to do with the fact that, you know,if you’re eating within the time-restricted window… And this issomething, you know, your metabolism is optimal during this certain time window.So the first time you take in food sort of starts these peripheral clocks on theliver, for example, which regulate glucose metabolism.Yeah.And if you, you know, don’t eat within a window where you’re mostinsulin-sensitive and you start eating later, then you’re going to have moreinflammation because your blood glucose levels are going to rise and it’s going tocause all sorts of problems. Same thing goes with, you know, fatty acidmetabolism, right? Yeah.And the intake of fat itself actually can inhibit the beta oxidationprocess. Yeah, yeah.Right? So, you know, if you’re eating within this certain window,you’re affecting your metabolism. And that, in turn, would then affectinflammation. Yeah.Possibly.Yeah. So there’s also this idea that there is some amount of gutleakiness. And so some of the bacterial proteins or bacterial membrane component,for example LPS and a few other things, can leak through our gut lining intocirculation. And that can illicit immune response. But we know that withtime-restricted eating, since our gut repairs itself at night for us,then during fasting time the gut has enough time to repair so that the gutleakiness goes down. So in that way our immune system is actually less exposed tothese antizymes that might leak through the gut.Right.That’s another way that inflammation can go down.I remember a colleague of mine who his name is Mark Shigenaga.He was a former colleague of mine when I was doing a postdoc with Bruce Ames,he’s a brilliant guy, gut expert. And he was telling me all about…I remember him telling me about how the gut can handle a high fat meal the best inearly in the morning. Yeah.Because of all these repair mechanisms and things that are happening.Like, the first thing in the morning, like, it’s better to eat…he was sayingyour high fat meal was more…your gut could handle it better than it could,like, later on in the evening. So it’s kind of interesting. But the LPS leakageand all this, very relevant for inflammation.Yeah.And the gut is one of the major sources of inflammation.Yeah.So the gut, the gut is also, you know, on a circadian rhythm.And not just the microbiome, but, like, the, you know, the goblet cells in the gutand the ones that are making the gut barrier. And all these, you know,all these cells are on a circadian rhythm. Yeah.So it really does make sense that you want to eat within a certain timewindow for the health of your gut.Yeah. Right?One’s health starts from the gut. It’s our interaction,when we say health is a product of our nature versus nurture, our environment,one of the biggest interactions with our environment happens in the gut through ourfood and how the food is digested, how the microbiome handles that food,our digestion then sends it to our system. So that’s actually the interface betweennature and nurture, so what happens there has huge impact. And we’re actuallyfinding that the entire gut lining from esophagus all the way to cecum is stronglycircadian. There are many transporters, there are many bumps. And even thechannels that absorb drugs and get into our liver, many of them are stronglycircadian. And over the last two years there are also many papers that are comingout showing gut microbiome composition itself is circadian. So that means the bugin our system when we go to bed are very different from…we wake up with adifferent set of bugs in the morning. Right.And this diversity is much more important because a different set ofbugs have their own specialization. So they break down or process different kindsof food, or they also offer different kinds of benefits. So in mouse experimentswhat we have seen is when mice eat a standard diet, a healthy diet,and they eat on a regular rhythm, so they eat mostly during nighttime becausethey’re nocturnal, and eat less during daytime, the their gut…the microbiomecomposition changes nicely in a rhythmic fashion throughout the day.But when they eat this high carb diet continuously, then that diversity goesdown, their gut is mostly populated by a few meso microbes. And then when they eaton a TRF fashion, when they eat only for 9 to10 hours, then some of the minor speciesthat are almost obliterated on that constant eating, they slowly come back andthey start to work. So we see that diversity component slowly coming back.Without even changing the composition.Without changing the composition, sothe diversity comes up. Wow. Amazing.Yeah.That’s amazing. Do you know if shift workers have a higher incidence of,like, IBS or gut issues? I mean there’s certainly a higher incidence of obesityand metabolic syndrome.Yeah, so the shift workers always complain about gut disease.So gastrointestinal problem is the first thing they always report/complain about.So it makes sense from our mouse study and also from what we know from shift workers,that circadian rhythm or circadian eating pattern will have a huge impact there.Yeah, so it makes sense. And what we know from how the gut microbiomealso affects the way we’re absorbing nutrients, it would affect obesity,as well, right? Yeah.So that’s been shown. So maybe there’s also a link to that.So I think on a daily basis, like for example on a daily basiswhat would healthy, another definition of healthiness while going to be bed at nightis not to have this acid reflux or heartburn. Which is essentially a gutsodium…sorry, the proton pump working differently. And what we find in mousestudies is this expression of the level of this proton pump goes down on thetime-restricted eating. So this is one example where many of our myCircadianClockusers reported saying, “Oh, well, you know, the first benefit we found is ouracid reflux has gone down, we don’t get that much heartburn.” And then we gotcurious, we went back to what are the targets of all the acid reflux drugs,and we found this proton pump. And interestingly this proton pump expressiongoes down in mouse gut.That’s awesome. That is so awesome.So this is another example where we would never ask about…we don’thave even the means to ask what is acid reflux and heartburn in a mouse,but we have a means to actually get this response from users and go back and askthe mechanism in a mouse.Yeah, it’s great. I’ve never…the first time I experienced acidreflux was during my pregnancy, late pregnancy, when my husband and I went outand had some, like, fancy meal. And I usually don’t ever, like,eat sugar or dessert, but I had, like, a little thing of, like,ice cream with some, like, chocolate or something. And we were in a hotel,and then, like, we went to bed not long after. And I could believe howunbelievably painful and uncomfortable it was because I’ve never had it in my life.Apparently when you’re pregnant, it’s a problem because, you know,your stomach is getting… Yeah, squished.…squished. But, anyways, I decided at that moment I’m like,“I’m not eating out like that again,” because I don’t want to experience it.But just I’ve heard about so many people talking about acid reflux before and Inever really knew. I was like, “Oh,” you know, “So what? What is it?,” like,“Your stomach is upset.” Yeah.No, you can’t sleep. Yeah.It’s, like, burning. Yeah.It’s like something is coming out burning. It was awful,I had to, like… I could sleep, I had to sit up for, like, a couple of hours.So that, you know…the fact that TRE seems to be affecting, you know,acid reflux, you know, through this specific proton pump inhibitor in somepeople using your app is, like, super cool.Yeah.The shift work is…so back to, like, the shift work and stuff.Because a lot of people have reached out and asked that are…I mean I think it’s something like 20% of the U. S.are shift workers,is that right?So in the U.S. 20% of the workforce is shift workers,but at the same time there are many who are…who may be shift workers,but they are not counted in the Department of Labor Statistics.Like who?So, for example… And nowadays you can include the taxi driversor Uber drivers or Lyft drivers because they don’t classify themselves as shiftworkers. They might have a one regular job that they list, but then in the eveningand weekends or early morning they are kind of doing the second gig and theydon’t list themselves. Then another thing that we came up with is what we callsecondhand shift workers. So these are the family members of shift workers who have alifestyle that are very similar to shift work. And this is something that we foundin a study, in the same myCircadianClock study, in India where we found some peoplewho self-describe them as not shift worker, but then their eating pattern waslike shift workers. So when we asked them again, then we realized that their spouseswere shift workers. And to maintain that strong family bond they wanted to sharemeals with their shift work spouse, shift worker spouse. So in that way we call themthe secondhand shift worker who are not working in shifts, but they are actuallysleeping and eating like shift workers and they may be experiencing the same adversemetabolic consequences of shift work. Right.So in that way the actual number of people, fraction of population,who are experiencing shift work-like phenomena for a few months or years intheir lives may be upward of 30% or 40%.Wow. That’s a lot of people.That’s a lot of people. Because in India and China, thecard-carrying shift workers in the workforce can be around 27% to 30%.And then a fraction of them have family members who are like shift workers becausethey’re secondhand shift workers. So it can be upward of 30%.And some of the negative consequences that are pretty,I would say, scientific consequences that’s associated with shift work,what would be, like, the top few that you would say?Yeah. So cardiovascular disease is right on the top.And then obesity, diabetes. And actually the very early study on shift work andmetabolic disease was linking shift work with diabetes and obesity.And then slowly we started to see that in many of the longitudinal studies withnurses or with health professionals, just random eating patterns and shift workincreases cardiovascular disease risk. And then recently I came across this veryinteresting piece of data that I was not aware of that the number one cause ofdeath and disability among firefighters in the U.S. is not actually related to fire,it’s cardiovascular disease and stroke. So that’s the number one cause,not even firefighting fire. So that tells us that all these chronic diseases arelinked to shift work. And then there also is mounting evidence all over the worldthat shift work is tightly linked or increases the risk of certain kinds ofcancers, including breast cancer. So that’s why World Health Organization hascategorized shift work as a potential carcinogen. So that’s a very seriousclassification because if we know that we have to stay away from carcinogens,even in buildings, if there is a carcinogen, there’s a potential carcinogenused as a paint or there is a reason, then we have to put a sticker.And to think about shift workers, they are actually doing something that’s apotential carcinogen. They do it almost on a daily basis for many,many years. So that’s why I think now there is increasing awareness how tomanage shift work so that they will stay healthy and will reduce the risk ofdisease.And they’re doing something beneficial. I mean firefighters,nurses, you know, police. I mean they’re helping society, so it’s not like you canjust eliminate shift work, right? I mean you need shift work.No, actually our modern society is actually based on those heroes.So we actually call them the guardians of our society because they are the ones inthe middle of the night, they are making the economy running, they are the ones whoare hauling trucks, long distance trucks, and they are the ones who are actuallytransporting cargoes of a plane or ships. They are the ones in the middle of thenight that are taking care of our health and to any emergency.So we have to kind of make sure that these heroes are healthy.So we have to kind of start thinking how to come up with a healthy heroes programwhere we can clearly say these are the lifestyles that they can adopt in relationto their being productive at work so that they stay healthy. And one complexity withshift work is shift work is just not one type of shift, it’s a mixture of manydifferent types of shifts. And, for example, firefighters may be on shift for24 hours straight, whereas a nurse is on shift for only 12 hours.Some of the fast responders may be on shift only for eight hours.And then for them, for some of them, the shift might change two or three timeswithin a month, so they may be on a day shift versus night shift,even within the same week. Whereas in some departments and in some professions theycan be on the same shift for three to four months, which helps them to adapt to thatshift. So in that way I think it will be interesting to bring up this heterogeneityin shift work and figure out which kind of shift work is more manageable than othersand perhaps figure out how we can help, firefighter kind of shift work versusnurse kind of shift work and first responders.Yeah. Do we know from any animal evidence… For example if you takean animal that is, you know, for example, nocturnal, like a rodent,a mouse, which usually eats at night, you force it to now not eat at night but to beawake during the day and eat at day and not eat at night. So if you can shift themto not eat all day, all night, but eat just within a time-restricted eatingwindow, do we know if they eventually adjust, how long it takes for them toadjust? Does their metabolism adjust? Does their circadian rhythm adjust?Yeah, so those studies have been done and there are many differentways to look at it. One is if we just give the same unhealthy high fat,high sucrose diet, instead of giving them at nighttime for 10 hours,for example, give them during daytime when they’re not supposed to eat,when they’re supposed to sleep. So the bottom line is if mice eat randomly,then any kind of time-restricted eating is better than that random eating.So even if they eat during daytime for 10 hours, that still gives them somebenefits. So it’s still beneficial. So there are some concerns with animalexperiments. One is if we feed animals during daytime, definitely they lose somesleep and they just eat. Unlike shift workers, they’re actually not workingthroughout the daytime, unless we force them to really work. So then it becomes atwo-factor intervention. And then at nighttime when they actually go back totheir normal activity, they run around in the cage. So in that way they get a sleepdeprivation pattern factor into it. So they are not as healthy as night-fed mice,but at the same time they have a strong sleep deprivation factor.So that’s why I think among shift workers, coming back to shift workers,if we can control for how much they sleep during their off time and they can sleepenough, if they come up with some sleep hygiene and adopt some sleep rituals thathelp them, and then they adopt the eating pattern that best suits their shift,then it might help.But eating still within a small, more narrow window.Yeah, still eating within a narrow window. Then there is another pieceof [Inaudible] evidence that daytime eating of healthy food is stillbeneficial. And that comes from the area of caloric-restriction studies in rodents.So historically many caloric… CR studies in rodents are actually done in a waywhere the CR mice got their food during daytime. And in most [Inaudible]the animal technicians come around in the morning, and then they see our mice gettheir food around 7:00 or 8:00 in the morning, and sometimes even after 9:00 or10:00 in the morning. And the caloric-restricted mice actually eat allof their food within two to three hours. So they eat. The CR miceSo they wake and just eat because they’re hungry?Because that’s when they have food, access to food,because the animal techs actually give them food. And so they don’t sleepthroughout the day and in the evening they eat, they actually eat right away.So we know from CR studies that all CR animals, most of the CR studies in rodentsshow tremendous health benefits, even though they eat the food during daytime.Wow, I didn’t realize that was done that way.Yeah.So maybe another layer of complication could be not only justtime-restricted eating, but eating less, as well?Well, so one caveat is in the CR study the ad libitum fed mice werefed ad libitum, so that means they were eating at nighttime.Oh.So they were never controlled to eat during the daytime.Oh.So I think those are the new type of studies that need to be done.But at least we know that if the animals, we reduce calories and fed them duringdaytime when they’re supposed to sleep, it doesn’t have any adverse impact,it actually gives them a lot of benefit. Now the question is if we give them thesame number of calories as ad libitum fed mice during daytime,what happens? And we have done that experiment not with a standard diet,with a high fat diet. And with a high fat diet they are better than ad libitum fed.Right, right. So, okay.So I think for shift workers, if they can constrain to acertain number of hours, that’s better. They can improve nutrition,that’s still better. They can reduce calories, then that will be,again, better.And if they couldn’t sleep, maybe do things to help them sleep betterduring the day.Yeah, during their off time.You know, dark, quiet, cool, all the things that help you sleep.Yeah.So there is sort of some hope possibly, possibly for shift workers.And maybe, you know, as more data comes out through your study withmyCircadianClock and also as you get data from myCircadianClock app and then go toanimals and look more mechanistically, things may come out even more.Another sort of question that sort of relates to this is, and people ask thisall the time, is what about people that are…start eating later in the day?For example they wake up 8:00 in the morning, but they don’t eat until noon.So let’s say they eat their first bite of food at noon, and they stop eating at8:00 p.m. So that’s an 8:00 TRE eating window. And they go to bed by 11:00 or so.Do they still have the same benefits or are they losing because it’s like thetime-restricted eating window has kind of shifted to later and obviously there is alight/darkness component to all this to some degree?Yeah, yeah. So those questions we haven’t even teased them inanimal models, but I’m sure some people will start teasing them apart.So what happens is in the morning we know insulin sensitivity is at its best.So people who have a bigger meal earlier in the day, they have less insulin spike,less glucose spike, etc. Having said that, we don’t know for people who are startingtheir food every day at noon whether they’re best insulin sensitivity is atnoon or it actually happens at 8:00 in the morning. So that information we don’tknow. So this is where some studies need human volunteers who are doing this.And maybe some people who are doing…who are starting to eat at noon,one day maybe they can drink a glass of juice at 8:00 and prick themselves and geta glucose reading and monitor themselves. And then another day,a week later at noon, they will eat the same glass of juice and prick themselvesand see how is their glucose response. So that’s a simple self-experimentation withsome healthy people. If they’re out there, then they can do that.And if they post it, that will be really nice. Second thing is what happens towardthe end of the day at night. So this is where it becomes a little bit complicatedbecause, as you said, there is day and night transition. And we know that in theevening as our body prepares to sleep, our melatonin level begins to rise.And that melatonin usually rises two to three hours before our habitual sleeptime. So if somebody is going to bed around 11:00, then that melatonin isbeginning to rise around 9:00. On an average, but some people it might risearound four hours early and some people it will rise exactly at bedtime.And when melatonin rises, there is new data showing that melatonin can bind toits receptor in the pancreas. And this engagement of melatonin with the pancreasreceptor essentially tells the pancreas, “Okay, it’s time to sleep,you don’t have to bother releasing insulin.” So in that way what happens ifsomebody is having a big meal when there’s high melatonin, then there may not beenough insulin to release from the pancreas and glucose may stay high in theblood circulation for a long time. And this study…these kind of studies came topublication because almost 10 years ago large genome-wide association studiesfound that people with obesity or diabetes might have a mutation in melatoninreceptor. And that was confusing because what has melatonin to do with obesity anddiabetes? And you fast-forward 10 years, people went back to the drawing board andlooked at where the receptor is expressed and what it does when melatonin isengaged, and then they found out that there is this effect of melatonin oninsulin. So that’s why people who are eating late into the night,they may not get the best benefit in terms of glucose control because their glucosemight remain slightly higher than if they had the same dinner two hours earlier.If they’re making more melatonin.If they’re making melatonin. So it’s very…so that’s why Isaid it’s complicated. Yeah.But at the same time I would say eating randomly over 12 hours,15 hours, versus eating to this 8 hours, even though it starts at noon,I will prefer the 8 hours starting at noon.Right. So it seems like there’s, in addition to, you know,the timing of your food intake, so we know the first time you’re eating sort ofstarts a lot of these liver enzymes and metabolism…glucose metabolism and allthese things. In addition to that, that circadian rhythm being regulated by justthe food intake, there’s also this whole melatonin issue and the night-daylightcycle and, you know, when you’re starting to make more melatonin.And all that complicates things, as well. Yeah.It seems. Yeah, I remember a study that was done where I think men weregiven the same caloric meal in the morning and the evening.Yeah.And glucose was measured and the blood glucose levels were much higherin the evening versus morning. But, of course, they could have been.Who knows how long… You know, was the morning, like, 8:00 a.m., and then they were doing, you know, 9:00 p.m.or 8:00? So who knows what theirtiming window was, right?The habitual meal, what is their habitual meal?Right.That’s a very widely observed phenomenon. In fact,there was a term for that that was called evening diabetes. So a person might behealthy in the morning based on blood glucose. In the evening if you do the samepostprandial glucose tolerance test and then look at the glucose level,then maybe diagnosed diabetic.Right, right, yeah. Yeah.Well, I think the other component to this would be the fastingcomponent, right? So people think, “Well, I’m only eating within an eight-hourwindow, so I have a much longer fasting period.” And I think that’s maybeuncoupling some of these differences between time-restricted eating,being on a circadian rhythm, and fasting, intermittent fasting,prolonged fasting. You know, there’s so many different terms out there.Yeah.And I think sometimes a lot of it just all gets mushed together in onegroup and it’s, like, all the same. Yeah.But it’s not actually all the same.No, it’s not the same. So, for example, even not having food in yoursystem for 12 to 16 hours, whether it’s fasting or not, that’s debatable.Because some people say, “Well, it’s not fasting, it’s not having food for 12hours.” And I think that’s where I would say not having food for 12 to 16 hours isnot fasting, but maybe giving rest to your system, rest and repair and rejuvenationof your system. So when we think about fasting, or when you think about fasting,two things come to mind. Feeling hungry. And feeling hungry has many differentconnotations, many different intensity. So one sense of feeling hungry is,well, you might feel light. And then second, your stomach may begin to frump alittle bit. And then I always say that is your stomach is telling you,“Well, I’m repairing myself.” You’re not actually really hungry,you’re not getting low energy that you cannot get up from the chair or run orsomething like that. And then after several, maybe one or two,days of fasting, or maybe after 24 hours of fasting, some people will get a headache. So that’s a good sign that, well, your brain is not getting enough energy inits habitual usual form and may be trying to signal the rest of the body that thebody has to send some other form of energy, for example ketone bodies orsomething. So in that way fasting, if you’re measuring fasting or you’redefining fasting in terms of ketone body formation above a certain level,then that may kick in after 24 hours. Or if you have that threshold even muchhigher than fasting, maybe 20, 48, or 72, or even 96 hours before you see that levelof ketone bodies that can be your definition of fasting. So in that way Ithink the way you define fasting will determine whether 24 hours,48 hours, 96 hours, or even 12 hours or 16 hours is fasting. But the way we think,we kind of define how many hours your system should not have food is based onour daily circadian rhythm. Because if you think about what are the key elements tobeing healthy, it boils down to three important things. One is sleep,and the second one is nutritional food, and the third one is physical activity.And these three are interlinked with each other. So, for example,if somebody is sleep deprived or didn’t have sleep, then it’s very hard for thatperson to do physical activity the next day or go on a marathon.So these two are interlinked. Similarly, if somebody is eating for 15,16 hours and has a very heavy meal at the end of the day, then it affects sleep.It also affects physical activity. One cannot run with a full stomach.So these three are interrelated. So on a daily basis what we feel ishaving…limiting food to 8 to 10, or maximum 12, hours helps to coordinatethese three foundations of health to work on a daily basis and give us healthybenefit. So on a very simple sense if I want to relate time-restricted eating andthen maybe long-term fasting, one day of fasting, two days of fasting,or four days of fasting, which definitely have much more benefit,then it’s almost like taking care of your teeth. So brushing every day is liketime-restricted eating. There’s the minimum one can do and that’s somethingnecessary to take care of your teeth. But, again, once in a while,maybe twice a year or three times a year or once a year, depending on how much youwant to take care of your teeth, you want to go see a dentist.So that’s almost like a prolonged fast one has to do once a year.So similarly I do four to five days of water fasting only once a year and thatabsolves all the other sins with my feeding that I might have committedthroughout the year. So in that way I think the difference betweentime-restricted eating and other forms of fasting is one can adopt time-restrictedeating as a true lifestyle, starting even from teenage or even toddler years,all the way through when you are 80s, 90s, or even 100 years old.Whereas this long-term fasting, two days or four days of fasting,forget about even teenagers doing it. And some older people who are very fragile,they might not be able to do it. And you need medical intervention or some kind ofsupervision to do it. Many people who are slightly unhealthy, even some diabeticswho might go hypoglycemic after 10, 12 hours, type II diabetic I mean,they may not be able to do it without medical supervision. So although thoselong-term fasting definitely have much benefit, and that has been shown inmultiple studies, the need is that they can be practiced only by a certain type ofpeople at certain days and need more mental resolve. And it may not be aneveryday lifestyle, whereas time-restricted eating can be an everydaylifestyle.That’s a great way of putting it. It sounds like also you’re saying,depending on what you’re looking at, what biomarker you’re looking at downstream,that also can sort of define something differently. For example,if you’re looking at autophagy or apoptosis that’s happening, you may notsee or be able to even measure it. Maybe it’s happening, but you can’t reallymeasure it well until you’re getting a more prolonged fast, like when you don’teat for four days. Yeah.Whereas, you know, obviously when you’re not eating for 16 hours,if you’re doing a time-restricted eating schedule of eating within eight hours andyou’re fasting every night for 16 hours, you’re in a fasted state in a way.I mean maybe it’s not fasting, but, you know, you’re liver glycogen starts todeplete at, like, 10 hours of not eating and, you know, something like this.And your, you know, adipose tissue is releasing fatty acids and,you know, you do start making some ketone bodies. You wouldn’t necessarily be in ahigh level of ketosis or anything, but, you know, protein deacetylation starts togo down and, you know, these NAD levels rise.Yeah.So it’s like depending on what you’re looking at, I mean these things dostart to happen, like in between meals even.Yeah.So to some degree you can be in a fasted state, maybe,and not be necessarily fasting.I mean it depends on where you set the threshold and whether peoplecan reliably measure that, say, ketone body or even autophagy level when beyondthat threshold. So what used to happen was most labs, the vast majority of labs,they’re not circadian labs. And many of the postdocs and grad students and kind ofreally the ground soldiers who are driving science, they might have differentschedules. So what happens, they come to the lab at different times,and then they might be doing the assay at different times without any control ofwhen the animals were fed or how long they were fed or what type of food they hadaccess to. And then even if the mice had 12 hours of fasting or 16 hours offasting, one might get a result which is slightly higher than what it was withoutfasting with food. But it’s no reproducible because, as we know incircadian rhythm, the same parameter can change over time. Even if we measure justfasting insulin level in mice, for example, or fasting glucose level,that has a very slow, very small change. So in many cases people might discount itas noise in their system because somebody did the experiment in the morning,someone did it in the evening, their bellies are different, so they’ll say,“This is noise.” So that’s why people have come up with the longer fasting to see thethreshold to set a higher threshold that they can reproducibly say,“This is signal,” irrespective of what time of the day the postdoc or gradstudent did the experiment. Right.But then in the circadian lab what we do, we systematically…we arevery careful about timing. So we will sample every one hour, to hours,three hours the same animal over multiple days, one day, two days,or even sometimes three days. And then we ask a very simple question,“Does it rise reproducibly every day around the same time?” Suppose,say, the ketone bodies do rise. And they may not go from 0 to 100,but they go from 0 to 10, every day they go from 0 to 10. Then the second questionis, “What is the benefit of ketone bodies going to 10 from 0 on brain function ormuscle function or heart function?” It’s possible that maybe your brain may not getmuch benefit, but muscle and heart are getting some benefit. And in that way youcan see that if we carefully monitor and then ask specifically what are thebenefits, you can come up with ways where we can say even this 12 hours of fasting,or not having the food in your system, will create some amount of benefit forheart on a daily basis or some amount of benefit for muscle on a daily basis.So that’s why it becomes very difficult, what is fasting, what is autophagy,can we trigger autophagy only by 12 hours fasting or 16 hours fasting,versus 4 days of fasting. Because autophagy may go from 0 to 10,it might benefit only one or two organ systems, it might benefit 10 organsystems.Does it go from 0 to 10? Like, for example, when…Yeah, so autophagy, we have actually published papers showing thatautophagy flux and autophagy gene expression does cycle on a daily basis.And it’s directly regulated by some of the clock components. So mice,genetically and mutant mice, that don’t have these clock components,autophagy level is set high, or the autophagy level is set low,depending on which component will turn up.Does it go up during the fasted and/rested period?Yes. It does go up during a fasting phase in liver.In liver? Yeah.That’s really cool. So the… I kind of got sidetracked here with thisautophagy because I’m very interested in it. Because it’s a part of the repairprocess. Yeah.And the thing that’s so interesting is this repair process being,you know, in the fasting state and, you know, happening during the fasting state.And, like you said, maybe there’s a threshold where, you know,it’s like obviously if you’re fasting for 14 or 16 hours every single day becauseyou’re eating within a time-restricted eating window, that’s also going to havebenefits. And now the threshold may be…you know, you may have less of thosebenefits, but you’re not cleaning up. You know, you don’t have widespread apoptosishappening where you’re killing off all the damaged cells, but you may be clearing upsome protein aggregates or something, you know, every day sort of on this steadystate sort of level, which also is extremely important.Yeah, it’s almost like, you know, if you have a carpet,if you vacuum it every day or every other day, then that remains clean.But at the same time maybe once a year you need a deep clean, a wet vacuum.Right.But if you don’t do that daily vacuum, or at least once in two daysor three days, then that gunk will accumulate.It’s going to accumulate and it’s going to cause damage.Yeah. So that’s why this daily cleaning, even though it’s a lowlevel, very low level cleaning of the system, that has a huge impact,that goes a long way.Have you guys ever looked at, like, DNA damage or repairing any sort ofchallenge? Like if you irradiate… Like animals that are eaten,you know, on a time-restricted, you know, feeding sort of schedule where they’reeating their food, being fed their food, you know, within 10 hours or so,and then challenge them.With radiation or something?Can they, like, repair the damage better because they’re fastinglonger?Yeah. So the circadian clock itself has a huge impact on DNAdamage repair and radiation damage repair. So a few years ago we had done a simpleexperiment that got highlighted in National Cancer Institute website.There’s a very simple, straightforward experiment. We always asked…we asked avery simple question, that is, “How come humans’ skin is always exposed to sunlightor UV radiation and many people get skin cancer but they never get hair cancer?”Because a hair follicle has the most rapidly dividing cells. And so one wouldexpect that they must be most sensitive to radiation damage. And if there is anyradiation damage, that’s where the tumors will start. And we rarely see that.So we went back and checked and we realized that the hair follicles at thebase of the hair actually have a very strong circadian rhythm.And every evening that circadian clock repairs all the damaged DNA and makes surethat the hair can grow back the next day, next morning. And then we asked,“So what is the real significance in real life?” So we took these mice and then dida simple experiment. That is, you know, for many bone marrow transplantexperiments, mice are irradiated, and then their bone marrow is depleted and one canput the new bone marrow in. And they get irradiated to the same extent as humansdo. They don’t die, they actually survive pretty well. And if we irradiate mice inthe morning, 8:00, then those mice lose 85% of their hair. And if we irradiate thesame mice with the same dose at 8:00 in the evening they retain 85% of their hair.So it’s a big, like really, black and white difference because these morningirradiated mice essentially become bald very quickly. And the evening irradiatedmice, they keep their hair perfectly fine. Now if we take circadian clock mutant micewhere the circadian clock is absent, irrespective of what time we irradiate themice, they always lost hair. Of course the story was much more about what…which DNArepair enzymes are regulated by clock and how this clock works,but this is a very simple, straightforward experiment. And similarly people have alsoshown many patients do go through partial hepatectomy. Or people who have livercancer, part of the liver is resected, and then the liver grows back.And, in mouse experiments at least, if partial hepatectomy is done in theevening, then those mice recover much faster than those where the hepatectomywas done in the daytime. So that has inspired some people to think about thissurgery time, what time surgery should be done and/or radiation should be done.So these are some just new ideas that have just come up in animal models in the lastfive to 10 years, so it will take some time to really get some traction in humanstudies.Yeah. It will be interesting to figure out whether it’s,you know, the combination of is it because they’re, you know, getting more restduring that time, during the evening, and then they’re resting,fasted and resting, and so, you know, the combination of them all.Yeah. So we know that the tumors grow slower in mice that eat onlywithin certain times. So time-restricted fed mice, if we just implant a tumor,then the tumor will not grow as much as the mice that eat randomly the same numberof calories. Wow.And that also jives with another piece of data that came from RuthPatterson’s group that women who fast for 13 hours overnight are protected frombreast cancer.They have, like, a 36% lower breast cancer occurrence.Yeah, yeah.Yeah. So that’s really cool. I wonder if with at least the animalexperiments where you’re implanting the tumor and they’re fed at a time-restrictedfeeding schedule, then if they’re having more apoptosis, more autophagy,more DNA repair, all these things are all sort of simultaneously happening becausethey’re in a fasted state for longer? Yeah.Possibly? So it’s possible.Yeah. Yeah.Very cool and interesting. The other thing that is sort of on this wholefasting versus TRE topic that gets asked a lot that I have to ask you has to do withcoffee. Actually, specifically caffeine, like black coffee. So without any cream orany calories or anything like that. So caffeine can start things,like the clocks in your liver?Yeah, it resets the clock. Because the clock is always running,it just resets.It resets it, okay. So a lot of people in the intermittent fastingcommunity, they do a lot of fasting, whether, you know, they’re fasting for 16,24 hours, 48 hours, but they drink caffeine and they notice that they loseweight. And so they say, “Well, I’m still getting results.”Yeah.You know, “So it’s fine, I can drink my black coffee.”Yeah.You know, obviously someone that’s fasting for 48 hours,it’s very different than doing the TRE schedule where you’re eating for 10 hoursa day or 11 hours a day, and then fasting for, you know, 13 or 14 hours every night,right? Yeah.So if a person, for example, that wakes up in the morning drinks blackcoffee at 7:00 a.m. They wake up, have some black coffee at 7:00 a.m.But they don’t eat anything, they don’t eat their first bite of food until…10:00 or 11:00.Yeah. Yeah, something. Then when do they have to stop eating by?Like, is it when the coffee started or is it when they ate the food?Yeah, so this is a question we also get through the app a lot.And we actually posted a blog on our website. So here is a very differentthing. So since we look at circadian rhythm as a whole, it has a sleepcomponent, food component, exercise or activity component. And we know thatcaffeine resets the body clock. So, for example, drinking a cup of coffee issimilar to having exposure to bright light for an hour or hour and a half.So that’s just on the circadian clock itself. Now the question is,“Well, will it reset that clock the same way if the coffee comes in the morningversus evening or night?” And we know that there is a term called phase responsecurve. So that means the same light, it relates to light. The same light willreset the clock differently at different times of the day. During daytime when yoursystem is expecting light, if you’re in a dark room and we see light it doesn’treset our clock. But in nighttime it will reset our clock. So we don’t know what isthe phase response curve for coffee, whether it resets much more at certaintimes and less at other times. The direct impact of coffee on clock is unknown.Then the second thing that relates to coffee is sleep because coffee definitelysuppresses sleep in a lot of people, some people may be resistant.And the reason why we drink coffee is we wake up, we get up from the bed,but we maybe are still feeling sleepy. We want to get that extra energy,that’s why we drink coffee. And along that line, of course, drinking coffee at nightis a straight no-no because it will have impact on sleep. But in the morning we askthe other question, “Are you drinking coffee because you did not rest well,you did not rest enough?” So maybe that’s why you need coffee to reset your mentalclock, or brain clock, to start it. And sometimes it can be just a pure habit oraddiction. For example, I used to like coffee in the morning, and then Irealized, “Well, let’s get rid of coffee. What happens?” Maybe forthe first two or three days I got a headache, and then now I’m used todrinking just hot water. It’s just the feeling of sipping something from a sippycup. It’s almost like a baby sipping something from a sippy cup.And I realized that that’s what I was addicted to. I can actually substitutecoffee with hot water and nothing changed. I still felt energetic after my hot waterand I realized that that was my addiction. After you got over the…After I got over the first two days of headache.…withdraw.Yeah, withdraw symptoms. And then it’s always [Inaudible]the question of metabolism. When we drink coffee, is it going to trigger metabolismor certain things in our gut so that the gut will think, “Well,now I have to start working, the rest is over”? And we think that’s where themetabolism or the function of the gut to absorb, or digest this coffee,send that caffeine to liver, and then to brain does kick start right after we drinkcoffee. Because that’s how we are feeling the effect of coffee in the rest our body,because the stomach started working, it absorbed coffee, it sent it to liver,liver might have metabolized it slightly and started to send it to the rest of thebrain and body. And then it gets back to kidney, it gets metabolized and excreted.So then the question is, forget about circadian clock, now if we think aboutjust metabolism and, say, mitochondria function, or even, say,go back to autophagy, and then ask, “Is caffeine breaking the fasting so that itstops autophagy, or it stops something else? Or is there a crosstalk between,say, caffeine receptor and glucagon receptor so that it does?” No,fasting is kind of slightly over. You may not be in 100% fast,but in 40% or 50% fast. So that’s where things become murky, so that’s why we say,“Well, if you can, drink your coffee within this 8-hour, 10-hour,it’s better.” But at the same time we know, going back to the study that wediscussed, Ruth Patterson study, they did not consider coffee as food.So when they considered 13 hours overnight fasting, that 13 hours actually includedcoffee and tea. So in that we know for cancer, reducing breast cancer risk,this 13 hours of fasting can include coffee, black coffee, and tea.So this is where things are really murky. And we tend to error on the safe side,so we tell, well, if you can have that coffee within your eating window,that’s much better. If you can’t, then just have black coffee.At least that will not trigger your insulin response or glucose response.So that’s what we do, we recommend.Just sort of as a side note because you mentioned it,I recently spoke with Dr. Guido Kroemer, who is an expert on autophagy,and he was telling me about a study he had published a few years ago where thespecific polyphenols in coffee, decaf or caffeinated… So irrespective ofcaffeine, it’s just it’s the polyphenols. Yeah.They triggered protein deacetylation, which is one of thetriggers for autophagy. So it actually increased autophagy.Increased autophagy, yeah. So that’s why we never know,because coffee, or any natural compound, has so many different ingredients that wedon’t know the activity. Yeah.And many of them can have very different effects.When we think of food, we have mostly…the nutrition science,or most of the scientists, are latched onto the effect of protein,carbohydrates, and fat. We discount a lot of xenobiotic. And actually our food is,the majority of it is xenobiotic. Right.And we have no idea what do they do, either alone or in combination.Right. And that actually…that’s another question.I printed out some, but that is a question that’s frequently asked by people in theaudience. Is, like, things that are xenobiotic, like herbal tea,even, I guess, to some degree people are asking about flavored water.So water that would contain, for example, like or stevia or something,you know, does that start the clock? And I think you’ve kind of answered that alittle bit.Yeah. So in that way it may not stop the clock and,also, for your insulin response it’s not actually triggering the pancreas tosecrete extra insulin. You know, insulin is an anabolic hormone,so it’s not actually putting our body into a strong anabolic drive.So in that way, in many ways, it’s okay to have this non-calorie-containing food.But then it gets murkier once we go to, say, Diet Coke or something else wherethere is artificial sweetener, and then we know that the artificial sweeteners havean impact on gut microbiome. And that’s where things become murky.Right.And these are very practical questions, but at the same timewe don’t foresee that even there will be any controlled clinical trial to assessthe effect of these nutraceuticals or even things that we take for granted on a dailybasis. So this is where, again, the N of one experiment, self-experimentation ofyourself, trying different kinds of behavior intervention where you switchfrom water to flavored water and does it make you feel different.I mean it’s not only weight gain. One has to assess sleep, activity,feeling alert, feeling productive.Maybe measuring your fasting blood glucose levels.Blood glucose level if you have a continuous glucose monitoringsystem. Right, even better.And so this is where strongly this self-experimentation byinformed citizens who are very careful, they’re not really…they don’t have anyadverse metabolic disease. And, again, I’m not promoting that everyone should startdoing self-experimentation. People are doing it.But as least whatever they’re seeing they should share.Yeah, they could share it with myCircadianClock.Yeah. So even if they put some notes in the feedback section,then we’ll compile all of those, and then that will help us to take informeddecision about animal experiments. At least we can go back to animals and say,“At least in animals we have tested this, this is how it works.”Right.And in the future maybe that will trigger some…Or maybe you’ll get 10 people to come back and say,“Oh, I started drinking my,” you know, “Diet Coke in my fasting window and all ofa sudden my blood glucose level started to get worse.”Yeah.So you’ll have multiple people telling you this. Well,maybe there’s something to that. Yeah, yeah.But, you know, people are asking about things, like evensupplements. And I think, like, you know, again, you’ve answered that we don’t,you know… You know, are you taking fish oil? Is it a fatty acid?I mean maybe… There’s lots of things here because that is, you know…So if you’re taking a fish oil supplement, then what do you think?That’s different than taking, for example, vitamin D?Well, it’s a question of… I like to compare this to,say, physical activity. Somebody is completely sedentary. For that persongoing for a walk, whether it’s in the morning or evening or midnight doesn’tmatter because this person is getting some benefit of physical activity.Similarly, if somebody is very low on vitamin D or needs that fish oilsupplement, then what time the person takes doesn’t matter because thatdeficiency is getting corrected. Yeah, that’s true.So that’s true. But then if someone now dials it slightly higher andsays, “Well, you know, I want to have this protein drinks that’s 25 grams of proteinafter my exercise late at night. Is it okay?” Then that’s where I’ll say,“Well, then that’s going to affect your gluconeogenesis and muscle recovery.And maybe if you have done a very strenuous exercise, if you’re trainingfor, like, Ironman or something like that, yes, you have to have that to recovery.Yeah. So that was actually a question I think people were…Someone was asking about weight training at night, if that would counter.If they, you know, eat late at night after weight training, if that would counter.And I think that’s kind of pushing it a little bit.Yeah, that’s pushing a little bit.Which is kind of what you’re saying.And, again, it depends on your training schedule and other stuff,what do you want to get the most out of it. Like, for example,if you’re used to training late at night and having that protein and carb drinkright after that, what if you do a little self-experimentation and move that to,say, 5:00 or 6:00 and see whether it actually helps you do one extra pushup orto go for another five minutes, or is it actually compromising your performance.So, again, it’s very personal. And then some of these very kind of athletes whoare pushing themselves to the limit, they want to squeeze the last drop ofperformance out of it. And for them I think self-experimentation is the best waybecause there is no way we as scientists, we can do that kind of study in our labswith a number of subjects who are as competent as them, and then controllingfor everything. So it would be very difficult.But you did show in one of your animal studies that a shorter feedingwindow for these animals, like, for example, nine hours…or it was eight ornine hours.Eight to nine, both of them.Endurance… Endurance went up.…performance went up. So you do have some evidence of being able tosqueeze the last drop of performance maybe.Yeah. So that way you clearly see endurance went up.And the reason why we did that experiment was we thought, “Well,if the mice are feeling fasted for a long time, will their athletic performance ormuscle performance go down?” Because our worry was their performance,athletic performance, might go down. And in that way it might be harmful for somepeople for whom physical activity is needed. And, for example,many shift workers, they need that physical performance.Right. That’s why we did it.And we realized that their grip strength, which is similar to howmuch weight a person can lift, that did not change, that stayed the same.But the endurance, being on the treadmill for a long time, that actuallysignificantly increased, and in some cases it doubles.Doubles? Yeah.I’ve noticed this in myself. I’ve done, like, an eight or nine-houreating, you know, schedule and the next day… So if I’m fasting for a longerperiod, the next day I go for a run in the morning and my endurance is…And this is, I mean, we’re talking like five or six times, maybe seven times I’venoticed it. Yeah, yeah.I mean it’s a clear pattern. Yeah.My endurance is dramatically improved. I mean it’s incredible,like, I just can keep running. Like, whereas usually I’m tired and I reach themark where I’m like, “Okay, this is it, finally I’m getting”…You know, you kind of sprint to the end and now I just keep going.Yeah. No, we see that. There are many people who have given usthis feedback that their endurance does go up. And then what is interesting is,again, their endurance improves, and then once in a while they say,“Well, I can go back to 12 hours,” and then immediately they see the reversal ofthat endurance.Right. It does, exactly. It totally reverses, yeah.Yeah.You know, I know there’s been some recent studies coming out in the lastyear or so where exogenous ketone bodies have been given to endurance athletes andit improved their endurance capacity. Which makes sense because enduranceheavily relies on mitochondria. Right? So, I mean, it completely…I mean if that’s actually part of the mechanism with the time-restricted eatingin terms of a longer faster period one would presume would have higher levels ofketone bodies.Yeah, we do see they have a slightly higher level of ketone bodies.So it makes sense. Yeah.Whereas… Well, I don’t know what exactly you’re doing with the gripstrength, but, you know, it depends on whether or not if you’re pushing them to ahigh enough intensity where they’re becoming glycolytic or not.I don’t know.Yeah. So, again, we don’t know where the dynamic range of thatparticular assay and we can’t ask questions to mice. So this is where peoplewho are actually lifting weights are doing something, a very different kind ofexercise. Endurance exercise versus intense exercise, those are verydifferent. Maybe they can give us feedback to see what happens.Now in your study wasn’t there improved lean muscle mass?Yes, we did see lean muscle mass improvement only on mice that weregiven standard diet, not on high fat diet.Okay.The high fat diet fed mice…Yeah, I wouldn’t expect for them. So they were given…so the micethat were given the normal, sort of healthier diet.Yeah.What was their eating schedule?They were eight to nine hours.So it was a shorter time window they were eating?Yeah, yeah yeah.They had increased lean muscle mass. Now is that something,like, do you know why that is? Has that been looked at?We actually don’t understand that, that’s another thing.But we do see there is an increase in PGC-1 expression in muscle,so there might be an increase in mitochondria function. But surprisingly inthe same mice we saw there is less glycogen in muscle. And that’s kind ofcounterintuitive. You might think that, “Well, the muscles may be loaded withglycogen, so that’s why their lean mass went up.” But at the same time what wethink is maybe, because they have less glycogen, we know that if the muscle hasless glycogen than after normal activity, then glycogen may be completely depleted.And when they eat, they have a much better feeding response. So that means a muchbetter glycogen synthesis response. So they may be making and breaking glycogen,making and breaking triglyceride on a daily basis, or protein on a daily basis.So in that way I think they may be maintaining much better muscle health.Because they’re also going through some gluconeogenesis, they’re breaking downsome protein. So maybe some of the structural proteins that get modified andmaybe they get damaged, they’re kind of getting cleansed, they’re getting cleanedout of the system by this eating and fasting rhythm. So, again,it’s all speculation, so we have to go back to the muscle samples.Yeah. You have the data, you just don’t know the mechanism.We don’t know the mechanism.But people are very interested. I mean increasing lean musclemass is hard to do and there’s a lot of huge interest in it.Yeah. Huge interest.No, actually we have been seeing this reproducibly now in multiplestrains of mice. And it happens with a balanced diet. So this is where thenutrition quality does… Play a role.…play a role. Which makes sense.Yeah. Yeah.So we can’t expect people to eat the same fatty food and expect leanmuscle mass.Right, yeah. So there’s a nutritional component to it in addition toeating within a restricted time window. Yeah.Which completely makes sense. Yeah.Some of these other questions that are just frequently asked.You know, a lot of people just really…they want to do time-restrictedeating and they want to do it right.Yeah.And so, you know, some of these questions can be a little silly,but it just shows how people are thinking. Like, for example, does toothpaste startthe clock? If they’re not swallowing.So if you’re not swallowing it, probably not starting the clock.Yeah. Yeah. It’s not starting, it’s actually resetting theclock. Resetting.So I think we have to also think of time-restricted feeding,although we came from a circadian clock lab. So that’s why we always get connectedwith circadian with circadian clock. But time-restricted eating has also feeding,fasting, that whole physiology type to it. So the other way to ask the question is,“Does brushing your teeth or mouthwash break the traditional definition offasting?” And definitely it’s not breaking that, it’s not putting food in yourstomach so that the stomach will start processing it and insulin starts going upslightly and blood glucose going up. So in that way we ought to keep in mind thatwe’re bringing that definition back once in a while. No, it does not break thatfast.I think that’s a good way to explain it. Some other people are…We talked about the night shift work, and so that was good. And you also mentionedanother thing people asking about is when can you start a TRE schedule in a person’slife, like developmentally. Yeah.Can you start as a toddler? Is that too earlier?I think, yeah, so we know that in newborn the suprachiasmaticnucleus is not even fully developed and it may not be even fully connected to therest of the body. And that makes sense because the babies are going through avery rapid growth phase. And what they need at that time is a lot of nutritionand growth. So TRE may not be desirable at that time, not at all.In fact, since it can trigger adverse effects, so I won’t recommend.I think a rule of thumb is when babies or toddlers begin to sleep eight to ninehours continuously through a night anyway, now their physiology or their sleeppattern is already getting used to being without food for seven to eight and maybenine hours. And that maybe a time when at least one can begin the first term phaseof time-restricted eating. That is to start with a schedule, a well-definedmorning breakfast time and the last meal, or even bedtime. So recently there was astudy done in England saying that babies were having a very regular scheduledbedtime and also last meal, protected from childhood obesity even five,six, seven years down the road. So although they did not measure when thesebabies were eating and all that stuff, what I think is having a regular bedtimeitself is a very strong timing cue that these babies are going to bed at a certaintime and most babies will sleep for 8, 9, even 10 hours. So they’re already into 10hours of fasting just through their sleep. And then it takes an hour for them to getup and then get ready and then start eating. Or for some babies they may finisheating, and then they’re reading a book or something and somebody is reading them astorybook. So you’d add that one hour between the last food and going to bed.So in that way I think the rule of thumb would be when babies start to sleep foreight to nine hours continuously, then that would be a good time to start puttingthem to bed at a fixed time. And then the next thing would be giving them breakfastat the same time every day, or having the last meal or the dinner time fixed.So then their body gets used to it. And then by the time they’re in Elementaryschool it will be easy for them to adopt a 12 hours eating time,and then if they want maybe they can go down to 10 or 12. So that itself is a verygood limit on them. So in that way, I think, it’s a very clear example that TREis something that you can start very early on and it can be a lifelong habit.Excellent. Excellent. Let’s see what are the other really common ones.Some people are kind of curious whether or not there’s…if anyone has looked at oreven if you have any thoughts about within your eating window,like, does it matter if you’re having lots of frequent meals or maybe two meals?Yeah, so that’s a question that comes up very frequently.And, actually, this is where, again, I kind of go back and forth between what weknow about metabolism and response to eating. And we know every time we eat agood amount of food, even a good size snack, there is enough sugar in most ofthe snack that it will trigger an insulin response. Our blood glucose will go up,it will stay up for maybe 90 minutes to a couple of hours, and then it will comedown. So every time we eat we essentially trigger our insulin to go up slightly,so there is this anabolic hormone going up and staying up for maybe one or two hours.So in that way our body is getting into that fat storing mode every time we eat.So with that in mind I would say the smaller number of meals within that eightor nine hours is better than eating every one hour within that eight to nine hours.But, again, this is where we don’t have hard data. It’s just going by myprediction based on what we know from physiology. And this is,again, this might hold true for normal healthy people who do not becomehypoglycemic after six, seven hours of fasting.Right.But we know that there are a lot of people who actually prefer to eattwice. And this is something that we find with many people who adopt TRE,that what happens is after 14 to 16 hours of fasting their hungry to have a goodbreakfast. And if they have a good breakfast with enough, say,protein, fat, and some complex carb, then naturally they’ll not feel hungry forseven to eight hours easily. Right.And then they have another dinner or maybe one snack in between.And essentially that has even happened to me. I eat mostly two meals,my big breakfast, and then I go to dinner, and it actually helps me stay productivethroughout the day. I don’t have to waste that one hour for looking for food,having lunch, and then the postprandial dip. So the short answer is the lessnumber of meals may be better.The same thing for me. It depends on what I eat for breakfast,and I’ve noticed change. Like, if I eat, like, a breakfast that’s got higherprotein, higher fat, I’ll be satiated for much longer.Yeah.As opposed to… Or even have higher fiber.Yeah.As opposed to, for example, if I eat yogurt and some berries.Yeah. Not good.No, not good at all.I will be hungry a couple of hours later.The same thing with me.Yeah. So that’s definitely not my go-to breakfast.But I also wanted to mention, because you were mentioning the,you know, what we do know about metabolism and how even, you know,a small amount of food can trigger an insulin response and, you know,elevate blood glucose levels. Some people might be thinking, “Well,what if I just do, you know, like a ketogenic, just fat only, just eatingfat?” And the reverse of that would be also, I guess, you know,if you think about metabolism, we know that a high fat meal, you know,if you’re going to use that fat as energy, you have to…you know,it has to be imported into the mitochondria and it undergoes this processcalled beta-oxidation, there’s transporters, carnitinepalmitoyltransferases, CPT transporters. Those also are regulated by,guess what, fat. Fat.Malonyl-CoA inhibits it. Yeah.So you could eat that fat meal, and then eat a smaller fat meallater, and that second meal will probably not be used as energy,but stored as fat.Yeah. So that’s what happened.Right.And also another thing is what we find, a lot of people it’s verynatural that some people think that a particular diet is rich in protein,that doesn’t mean that it’s only pure protein. So one simple example is manypeople think that lentils are high in protein, so lentils…they can just eatlentils and they’ll get a protein source. But lentils are only up to 25% protein andalmost 70% carb. So when they eat lentils, they’re actually eating a very nicecarb-rich and protein-rich diet and that carb will trigger a good insulin response.Right, yeah. Great. Let’s see what other ones that are really frequentlyasked. We talked about xenobiotics, obviously pharmaceuticals.If your doctors tells you to take a pharmaceuticals at night, then…Yeah, then you have to take it at night.Yeah.And your doctor overrides any other thing that you areself-experimenting.And as we were talking about a little bit earlier off camera,xenobiotics themselves are on a circadian clock.Yeah, xenobiotic metabolism is strongly circadian.And there are three or four meso xenobiotic degrading enzymes.So actually these are the transcription factors that control many of thecytochrome P450s that break down xenobiotics. And these are stronglycircadian. And, in fact, a lot of the circadian rhythm research we use one ofthe xenobiotic regulators as a reporter, as a marker. Because even the circadianclock components are not as robust as the xenobiotic metabolizing transcriptionfactors and enzymes, so that’s why. In terms of xenobiotics, almost every type ofxenobiotic absorption, metabolism, excretion is strongly circadian regulated.And that’s an amazing area, a new area of circadian rhythm research.So that is what time of the day a medication may be better absorbed andbetter…most effective. Because any medication that we take is actually goingand interacting with a protein, in most cases. It’s going and inhibiting orstopping a protein or activating that protein. What if that protein is actuallynot there? Then we are essentially taking a drug with no benefit when the proteinturns off. So, for example, we take the medication in the morning,but the protein actually comes to play in the evening. So then this medication hasno impact, and then the doctor will keep on increasing the dosage so that it comesto a point where there is some medication that’s remaining at the end of the daythat will start to have its intended effect.Wow.But then the side effects, the adverse side effects will go up withthe increased dosing. So that’s why there is now interesting…there is a lot ofinterest on what time of the day a given drug target reaches its peak,and can we match drug timing with its target so that we can have the same effectwith less of the drug so that we can reduce adverse side effects and we canincrease efficacy. So that’s a whole new area of research that’s going on.And the small or the most impactful statement about that is recently peoplehave found that nearly 70% of FDA-approved drugs have their targets cycling in thebody. So that means for 70% of FDA-drugs just timing can make it a drug or make ita poison. Wow.So that will be an amazing area of research in circadian rhythm.Yeah. I mean personally I’m very interested in this field not…I mean I think it’s very important for that reason, really because so many peopleare taking pharmaceuticals. But I don’t personally take pharmaceuticals,but I do take things like turmeric. Yeah.Curcumin. Yeah.You know, these polyphenols, which are xenobiotics.And I’m interested in can I take my curcumin at a certain time of day and it’smore effective, I get more bang for my buck. You know, because it’s metabolizedquickly, so I would like to find, you know, that time window. That would be kindof cool. So, okay. I think we covered the questions that are pretty frequentlyasked. Yeah, great. So, again, this…getting back to themyCircadianClock I think is sort of key because you’re aggregating data from allover the world, right? Yeah.You have people now from…So we have people from almost every continent, except Antarctica.That would be cool.If somebody is going to Antarctica and really if you are…You need to get some of the researchers that are on the station overthere, the research station.And we haven’t hit the International Space Station yet.Okay. That would be cool too.That would be cool because, you know, in ISS they are going through a90-minute day-night cycle because the space station makes one revolution aroundthe Earth every 90 minutes. So they see a sunrise and sunset every 90 minutes.Wow.And actually they’re the ultimate shift workers.Right.And we know that they struggle with it a lot and recently theISS is fitted with circadian lighting, so they will go through a simulation oflight-dark cycle. Not a light-dark cycle, but blue light increased and red lightincreased, that kind of cycle. So we’ll see how it improves their life.Yeah. That’s really cool. For the data that you’re aggregating…I guess aside from people putting comments, which are probably extremelyuseful. You’re learning, obviously, things like the IBS and all these things you’relearning from people putting their comments. Is there any mode of tracking,like, cognitive function of mental function, or is it just the comments thatyou’re [Inaudible]?Yeah, so we haven’t done anything… Actually, we are going torelease a newer version of the app based on many comments that we received so itwill be a little bit more user-friendly, hopefully. And, yeah,so if we add more functionality to the app, then it becomes more complicated fora lot of people. Yeah.So that’s why we have to find that balance where we have to kind ofstop and then see the right balance. Or maybe bring up some cognitive functions,or link them, link our app to other apps that do cognitive function.I’m just… I’m personally curious in whether or not time-restrictedeating affects cognitive function, mental performance, and also just brain aging ingeneral. You know, because we do know that shift workers, for example shift workersthat have worked like 10 years or more, have, like, their brain’s age at,like, an accelerated rate. Their brains look, like, six and half years older thanage match controls or something. Yeah.And I think there’s some animal studies showing if you make miceeat when they’re not supposed to eat, so when they’re usually sleeping,so for them during the day, I think they’re, like, hippocampal function was,like, messed up or long-term potentiation was messed up in learning memories.Yeah, so there are many studies done. For example,in high fat diet fed mice a lot of cognitive functions and social functionshave been assessed. And we know a high fat diet disrupts our circadian clock,they eat randomly. So in that way we know that there is already a deficit that isalready a problem with brain function. And now they will…those kind of experimentswill guide us to see if we give the same high fat diet within eight hours or ninehours to mice and we do the same assays, what will happen, whether we’ll seeimprovement and benefit. So that’s one set of experiments. The other set ofexperiments that will be very useful… And I’m sure somebody else must be doingit because if I can think of an experiment, somebody else is already doingit. That’s to take all these animal models of Parkinson’s disease or Alzheimer’sdisease, and then put them on time-restricted feeding.Yeah, it seems obvious.And then see whether the performance improves.Yeah.You know, I’ll not be surprised if we see these kind of studiescoming out in the next six months or a year.Well, surely, I mean, if you’re clearing away, at the very leastclearing away some of these protein aggregates because you’re having aconstant fasting period, then if, indeed, those protein aggregates are affectingcognitive function, you would imagine that that would be improvement.And also what we know from sleep research over the last three,four years, one of the big things that came out from sleep studies in the lastfew years is we knew sleep improves learning and memory, synaptic plasticity,etc. But now we are learning that sleep actually improves cleansing the brain.So, for example, the xenobiotics and other stuff, the gunk in the brain gets brokendown and is cleaned during this sleep time. And I would say that there might besome aspect of fasting because, of course, in all these studies the animals wereeating less when they sleep. And so then the question is, “How much of fastingcontributed to cleansing the brain?”You’re talking about the glymphatic system being activated.The glymphatic system.That would be super interesting.Yeah.That would be very interesting.So that’s also another reason why we think that,well, maybe fasting is actually improving sleep by affecting maybe the xenobioticmetabolism or something else. So it’s kind of interesting that we did a very simpleexperiment a few years ago and now we have more questions than answers.And this is exciting.Yes. Do you have any neurobiologists in your lab that would beinterested?Yeah. So we are collaborating with experts in this fieldwho work on neurodegenerative disease to see what is the impact of time-restrictedfeeding on these mouse models. And, of course, we cannot just take one mousemodel, we have to use a multiple number of mouse models to make sure that thisis…at least in mice, we can assess where there are benefits or adverse effects onmultiple strains. And then we can come to human studies.Yeah. I know the glymphatic system is, like, one of the major ways thebrain clears amyloid beta plaques. Like you said, among other gunk and things.Yeah. That’s part of the gunk.Yeah.So that would be extremely interesting to see if your eating schedulealso affected that, as well. Definitely no shortage of interesting things to ask.No, no. So you’ve got a website?Yes. I have a website called mycircadianclock.org.And that website has a lot of information as blogs. And also in the first phase inthe informed consent what we do, we ask people to go through the informed consentto see what they are asked to do or what they may volunteer to do as part of thestudy. They may give us some information about themselves. And in that way we canrelate. As we increase the number of fans, we have more participants.We’ll always have some participants who belong to a certain age group,gender, or socioeconomic condition, so demographic. So in that way we can alwaysfigure out what is their existing lifestyle and what they tend to change,what they can change. And then after the sign-up they get the copy of the informedconsent in their e-mail. So it’s very important that you give an e-mail addressthat actually works, we are not going to use the e-mail for anything else.And we are actually overseen by a committee of ethics, ethics committee,who reviews everything that we do. Any data that we, even in the future,if we want to share, it has to go through that ethics committee,it cannot be given to any entity for profit. And so in that way we maintainprivacy very strongly. And then once they download the app and start collecting,one interesting thing is what we find. People hear about our study throughpodcasts or other things and they start doing time-restricted eating from theget-go. So in that way you don’t get a picture or snapshot of what is theirlifestyle before they adopted time-restricted eating. So one request isfor the first one or two weeks it’s better if they just continue their currentlifestyle. Even if they were eating in the middle of the night once in a while,it’s better to have that in the record so then we can say, “This was”…then peoplecan themselves compare, “This was my lifestyle before.” And then after twoweeks when they set their new goal, or if they say, “Well, I can’t do only 10 hoursof eating,” that’s fine. But 12 hours, or even 8 hours. Then we can compare how waslife before TRE and how is life after TRE, and we can compare those two.And what happens is, yes, we ask to log a lot of different things.Some people do it and some people may not like to do it, but that’s okay.If people can log at least one thing, whether it’s sleep, whether it’s food,then that’s much better than not logging at all. And then another thing that wenotice is some people will get into the habit of time-restricted eating for fourto six weeks, and then they stop recording. And we know that theyactually…they say, “Okay, I don’t need this guidance,” or, “I don’t need to logthis data, I can do it by myself.” And that’s fine. But for us it will be reallynice if they can log at least the first and last meal for up to 12 weeks.Because all of these will help us to figure out whether you’re actually fallingoff the wagon or you got it so that you don’t have to do it for 12 weeks.So in the next version of the app, when we go to our ethics committee and askpermission, we’ll say, “Well, you know, we are finding that people get used to it insix weeks. We don’t have to ask them to monitor everything for 12 weeks.” So allthese things matter. And then once in a while giving us some feedback.If you see some improvement, please it share with us. If you see any adverseimpact, that’s much more important, please share it with us. Because then we’ll knowwhat are the adverse impacts and we can report that to our committee and also wecan go back to mice and then see why this happened. And that at the end of 12 weeks,if people can record, say, their body weight or any other measures that they canrecord, then that will also help us. That will help us to go back to mice or eveninclude in our final publications. Because what we are foreseeing is we might beginto start publishing from the app from the end of this year onwards.And there are many different ways one can dissect the data, so there are manydifferent ways we can publish it. So the more information we have,what happened in response to TRE, the better it is. And maybe we’ll go back andthen have re-contact with some of the participants and ask them after one yearor after two years or after three years, with permission from our ethics committee,“Can you tell us are you sticking with this habit? Or what actually made you notto stick with the habit?” Because those things are also important.What are the other lifestyle factors that are preventing us to stick to an eatingschedule? So we want to learn from people. And we have to kind of learn it the otherway around. Instead of doing controlled clinical trials and taking it to people,we want to get from people’s experience, and then see what sticks,what doesn’t stick, and then go back to basic science.Right. What you’re doing is fantastic.Basic to bedside, and then back to basic.Yeah. You’re getting ideas. I mean you’re thinking about things youwouldn’t have even known to think about.Yeah.Because, you know, getting new data and it’s fantastic.So I definitely encourage people to try this out.Yeah. One of the already published results that came from people’sfeedback is when we did the small time-restricted eating study,there were only eight participants. But all eight of them said they slept better,and we had never asked the mice whether they slept better.Right.So we went back to our Drosophila flies and we saw that they weresleeping better. And then we went back and looked at their brain transcriptome to seewhy they’re sleeping better. So this is one example where we went from a feedbackto doing a basic science research in flies and actually publishing that data inscience, and then moving on to do more molecular studies.Yeah. So maybe that will affect the glymphatic system if the eatingdoes make you sleep better. Yeah.Right? [Inaudible].And so you’re also on Twitter. Yeah.And your Twitter handle is…SatchinPanda. @SatchinPanda.@SatchinPanda.And anywhere else? Got your website and Twitter.Yeah, website and Twitter, and then I’ll start maybe Instagram orsomething. All right. Well, let me know.Yeah. Thank you so much, Satchin.Thank you.Always a pleasure to talk with you.Thank you so much. Because you are doing the right thing for science.It’s communicating science to the masses, this is what we scientists cannot do andwe need people like you. Thank you.[Inaudible], Satchin. Thank you. CategoryArticlesTagsacid reflux and autophagy black coffee fasting cancer prevention cardiovascular disease circadian rhythm diabetes Dr. Satchidananda Panda Dr. Satchin Panda fasting gluconeogenesis intermittent fasting irritable bowel syndrome ketones metabolic disease microbiome myCircadianClock PGC-1a shift work suprachiasmatic nucleus that the time restricted eating time restricted feeding 100 Comments FoundMyFitness says: October 30, 2017 at 10:34 pm Hi, guys! Totally had the baby already (for those of you wondering). A few quick things…1.) If you're thinking of trying out time-restricted eating after this podcast, do not let your data go to waste! Dr. Panda's group has a clever way of taking volunteer data from a broad international cohort and using it for scientific research right through your mobile phone. Please think of participating! Learn more here at myCircadianClock.org. Also make sure to follow Satchin on Twitter at twitter.com/satchinpanda. 2.) This episode has a dedicated page on the FoundMyFitness website with super extensive resources, including an in-depth timeline with links to studies discussed, a glossary and other show notes. Make sure to check that out at foundmyfitness.com/episodes/satchin-round-2. Getting this page out was a big milestone for us and reflects the standard we hope to strive for with all new episodes going forward. If you love this… hug a crowdsupporter today. Or become one at foundmyfitness.com/crowdsponsor. 3.) TONS of podcasts already on the calendar. Stay tuned. 🙂 Reply The Nutrition Resource says: December 14, 2017 at 3:47 am I was curious to know if there are studies looking at salt intake and how it affects fasting. For instance, doing a one day or two day fast you excrete a lot of salt, I would think replenishing it via a bouillon cube (or just drinking saltwater if you're insane like me ;-)) would be fine. Wondering if it affects autophogy etc… If anyone has researched this thoroughly let me know! Thanks! Reply Sean Wardman says: December 18, 2017 at 10:47 am Great video. Hope you had a time restricted labor! Reply Rich Daigle says: December 22, 2017 at 10:36 pm Heard you on Rogan, then watched the original Dr Patrick/Panda in sept. ,was part of Dr. Pandas study…increased vitamins D, E also magnesium, omega3s and sulforaphane …results have been astounding, weight loss approaching 50lbs, but even more amazing is mental sharpness, depression gone, even EYESIGHT improvement …you are changing lives Dr Momma Patrick! Congrats! Reply Grant B says: December 24, 2017 at 1:09 am Hi Mum, You Stopped Time Stamping these Videos??? 🙁 Reply JohnnyC Major says: December 27, 2017 at 1:44 am I don't know man I was going to try this time restricted thing but it don't look like work so well for that girl. Reply 16386r says: December 31, 2017 at 10:09 pm Glad I listened to this. I'm starting a IF diet tomorrow and have been worried about what to do when I rotate to night shift. I rotate every month days/nights. Thanks for the informative video. Reply Knight Rider says: January 3, 2018 at 12:43 am Great interview! I've went back and forth with drinking coffee. I also did the bulletproof coffee for awhile too. I've decided against bulletproof coffee. 2 cups of black organic coffee is perfect for me, then lemon water and tea for the rest of the day makes for a great medium. My mood, energy and productivity is very consistent all day. Reply Robbie Rai says: January 11, 2018 at 3:51 pm Would skipping breakfast have any negative effects? I have been doing 12 pm – 9 pm, but read time article saying missing breakfast causes inflammation Reply Broseph Huntington says: January 11, 2018 at 7:45 pm We gotta call you Big Rhonda now! Reply yogiyoda says: January 14, 2018 at 2:41 pm After watching the two Dr Panda interviews, YouTube is recommending panda bear videos to me. Reply Dr.Raju Rathod says: January 15, 2018 at 2:19 pm love from India…as per ayurveda it all about already mentioned 5000yr ago….please read charaka samhita.. Reply Dr.Raju Rathod says: January 15, 2018 at 2:20 pm good job.dr.panda Reply Jihane Mriouah says: January 16, 2018 at 11:26 pm Hi Rhonda, congrats on the baby and thanks for the content that you create, very stimulating!I listened to this interview again and thought about the cognitive functions data you discuss around 1:45:52 and was wondering if the neuroprotective effects on memory observed under TRE could ultimately be linked to acetylation processes (Increased NAD, increased Sirtuins activity, decreased Acetyl-CoA)? I'm referring to the article published by Peleg S. et al. in 2010 (DOI: 10.1126/science.1186088). I'd love to hear your opinion on this. Thanks! Reply Sam tron says: January 19, 2018 at 11:42 am I do intermittent fasting…2 years, 52kg down, reversed type 2 diabetes…in relation to coffee…it is a natural appetite suppressant…that's why so many people fasting use it. It also boosts the energy…sure…but it's the appetite suppression that makes it so appealing. Dr Rhonda…LOVE YOUR WORK SO MUCH!! THANK YOU!!! Reply Sanna Mati says: January 21, 2018 at 7:39 pm Dr panda xD Reply PalomaNegra85 says: January 22, 2018 at 4:32 pm day 4 on TRE schedule 16:8 and I haven't weighed myself but the bloat is gone, I am surprisingly not as sluggish or hungry in the mornings. I have had insomnia since having my son 4 years ago- its gone! I sleep like a baby each night. I eat pretty healthy mostly, so that has never been the issue. Going to keep up with TRE and see my results in a month. Thanks! Reply EyeInTheSky says: January 29, 2018 at 2:29 pm Does anyone know if going to the gym and doing weights would accelerate ketogenesis since you would have used up a lot of sugar/glycogen from your energy stores via the muscles? Reply Jane Darling says: February 5, 2018 at 2:36 am Hi love these catch ups so informative! Just wondering if a squeeze of lemon in water in the am before u break your fast – is that technically breaking the fast or should i do it closer to when i comsume food? Reply Robert Emerson says: February 8, 2018 at 3:36 am Is the nicotine in chewing tobacco that isn’t ingested a xenobiotic? Reply Marcus AI says: February 8, 2018 at 4:16 pm Just started on Monday. I'm pretty excited to see what happens. Reply maremacd says: February 10, 2018 at 4:12 pm I have such a problem with Indian accents for some reason! Is there a transcript? Reply Over Comer says: February 13, 2018 at 3:11 am I find his voice so incredibly soothing. I could listen to him read product labels or instruction booklets and be in heaven. Not to mention his amazing knowledge and expertise on TFE. Fabulous! Reply Aak 313 says: February 13, 2018 at 6:18 pm I usually don't eat until 1 and stop eating at 9 in the evening. I'll start to take my blood and record the results with as much detail as possible. Reply viola says: February 15, 2018 at 9:53 pm i tried, this app is full of bugs, constant errors, for several minutes trying to submit each picture, food is getting cold, after two weeks of suffering i gave up, don't need this additional stress. Reply Chris Mcclary says: February 17, 2018 at 2:47 am Here’s what I’ve been doing. Time restricted during the necessary 14 hours(no eating, only water), then I allow myself coffee during the the last 2 hours of intermittent fasting. I think I get all the benefits of both. Thoughts? Reply Kathy Maxwell says: February 21, 2018 at 8:57 pm I take thyroid meds in the morning an hour before eating anything. Does this start my metabolic time clock? Reply Gri Court says: February 25, 2018 at 6:55 pm HI! IS TAKING ANY TYPE OF SUPPLEMENTS BEFORE BEDTIME LIKE FOR EXAMPLE MELATONIN 30 MINUTES BEFORE BED STARTS THE BODILY SYSTEM? I DO THE 12HOURS TIME RESTRICTED. Reply Adil Khud says: February 28, 2018 at 10:50 pm Dr Rhonda Patrick, can you please clarify about the experiment when mice were radiated in the evening and they retained 85% of their hair, were they nocturnal and when you translate that to human, does that mean that radiation is better done in the morning since human are not nocturnal? Thank you in advance Reply Totale Transformation says: March 5, 2018 at 3:29 pm I had to cringe all the time how they called 12 to 14 hours of not eating as "fasting"… I battled obesity for 30 years. 4 years ago, I finally won the battle. Different methods, the struggle was huge to get rid of 50 kg bodyweight while packing on muscle. My point is, switching from 16/8 to 20/4 and meanwhile 21/3 made a HUGE difference. So, 14/10 is no way near an effective time restricted eating approach. Either less so is 12/12. If you use a Glucometer and observe your blood glucose during a fast, you will see when your body starts being really empty on glucose energy. During my intraday fast, my BG decreases slowly all the way down to 72 to 76. It starts in the morning with 100 or so. People need to start eating according to their energy needs. A Glucometer might help. I always workout fasted and stay fasted after my workouts for at least 8 hours. This is what mimics evolutionary behavior. This is how I get the most anabolic systemic response and the strongest signaling. I have built a lot of muscle on that protocol and have the best body composition of my life. A certain exercise form is also important to mimic optimal anabolic systemic response. No Amino Acids or supplements or peri workout nutrition. The pure primal protocol. I workout only 10 minutes per day and eat 4500 caloric during my 3 hour window. I can eat 400 grams of carbs and will have the same ketone count like a zerocarber at the 20th hour of my fast. The fasting magic starts happening usually around the 14th to 16th hour. if you start eating then, you basically shut the process off. 20/4 for the win. Please stop calling 12/12 or 14/10 time restricted eating… 🙂 I also always eat at the same time in the evening. Starting at 7 PM until 10 PM. Finally the first time that I heard someone admitting that all this fixed Circadian interpretation might not be correct. Feeding and Fasting sets the major clock. it overwrites all other clocks. According to my post prandial blood glucose I am extremely insulin sensitive. I can stuff 2500 calories with starchy foods, protein and tons of olive oil as my first meal in my 3 hour window and my BG wont go above 120 mg/dl. After 60 minutes I am down to 95. So, studies of people who have not set their own clocks yet by (feeding/fasting) and get tested how they react at certain times might not be the best basis to say, that insulin and BG response in the morning is better than in the evening. Dr. Panda admits this himself at minute 46. Think outside the box. Reply Rational Israel says: March 5, 2018 at 10:53 pm Can you make an edited version of these with highlights and just the practical advice? It would be much appreciated. Reply Ed Collins says: March 11, 2018 at 10:41 am In regards to SCN and TRF ..is there a best time to take thyroid hormone? I don't have a thyroid . Best at night before bed or an hour before breakfast in the morning ? Reply Over Comer says: March 16, 2018 at 11:07 am Have been Time restricting for several weeks. Begin eating at 8 am stop around 3pm. So 7 hour feeding window. Excellent diet. Not losing weight at all. Think I am gaining actually. But I CANNOT SLEEP!!!!! Help!!!! ANY SUGGESTIONS?? Im a Zombie. I am starting an exercise program hoping to wear myself out enough to sleep at night. Think I'm not losing cuz im not sleeping. Headache-y. Fatiqued. Help!! Reply keranjang belanjaan says: March 20, 2018 at 8:20 pm OK so for people that does this, I have a question, how can I implement this with my life schedule. say day 1 im eating at 6 am, so I dont eat until 3 PM, that means my next meal is at 12 am at night? if you guys already had success, please shed some light. question 2: so they talked about this ZERO app and the circadian cycle(13 HOURS, at least according to the app). yet she emphasized multiple times that the optimal is 9-10 hours; not to mentioned she also emphasize that it should be LESS THAN 12 HOURS. So which one is it? Reply aquapurity says: March 26, 2018 at 10:23 pm would something simple like salt start the metabolic clock? Or would it kind of just "sink in" the way water does? Reply 142314 says: April 10, 2018 at 7:21 pm How are the percentages not higher for shift work? Reply ines sanderson says: April 14, 2018 at 3:08 pm Hi, Dr. Patrick, I first heard about the restricted time window eating when you were a guest @joerogan podcast. I was fascinated with all the science supporting it. I have a question for you concerning my schedule: I am a trainer and have early morning clients. My energy is at its highest in the e hours, I workout before training the 1st client, so that means I ‘ m up by 4. To stick to a12 hour window, I would have to eat my last meal very early. I go to bed early, at around 9pm. Any adviceon how to manage my schedule? Thank you. Reply Bob Sundquist says: April 30, 2018 at 6:05 pm The question for self testing with the juice at morning and lunch is what about dawn phenomenon? If you are a person with IR or just have a big liver dump early in AM, it will be artificially high at the start compared to testing at lunch. Reply Mike Cola says: May 17, 2018 at 12:46 am Time restricted feeding works great for me…. I stay in a fasted state for about 14 to 16 hours a day and take in all my calories in an 8 to 10 hour eating window. I like to skip breakfast and break the fast in the afternoon. I wake up ever morning in mild ketosis. My Macronutrient Ratio is;50% – 60% healthy fat (olive oil, avocado oil, avocados, nuts, whole eggs, lean meats, oily fish)20% protein (lean meats, fish, nuts and eggs)20% – 30% carbs (plants) This diet plan is working great for me right now…it keeps by body fat around 10% and I have a lot of energy to workout. I might change the Macronutrient Ratio down the road but it's working for me now. Reply Better Life Broadcasting says: May 17, 2018 at 7:59 pm Is it possible that there's a natural variation in WHEN a human's insulin sensitivity is "best"? I ask because I was raised in the culture of breakfast-is-the-most-important- meal of the day, but I have NEVER, not once in my life, had any desire whatsoever to eat anything, not even something I really like, before noon-ish. And it isn't a conscious decision or a lack of time, my body just doesn't want any food then. And if, for whatever reason, I do eat in the morning I feel kind of nasty for hours, if not all day. Reply Mikka says: May 18, 2018 at 2:29 am So when should we eat? it frustrates me that an answer to this question is so hard to get… when should we eat then? when is night when is day? Reply littlesigh says: May 18, 2018 at 6:18 am Any comments on trading Moringa tea for coffee? Guessing it will start some clock somewhere. This is great stuff Doc! Thanks Reply Better Life Broadcasting says: May 21, 2018 at 7:01 pm So, would there possibly be an optimal timing component to taking vitamins and supplements, just as there's an optimal timing for pharmaceuticals? Reply Dan P says: May 27, 2018 at 3:28 am Hi guys, great video Question: What's the opinion on further time restricted eating in a further compressed window below 8 hours? Or even more aggressive bellow 4 hours? Interested in your thoughts Reply Darius Emrich says: June 1, 2018 at 9:49 am I'd love to hear about bullerproof Coffee and intermittend fasting. I like my coffee with Coconut Oil in the morning at 8.00. After this i eat lunch at 13.00 and Dinner at 22.00.So without my coffee i would be fasting 15 hours. But if you count the coffee it would be only 10 hours. Reply Daniel Milton says: June 5, 2018 at 3:29 pm Does consistency of fasting matter, e.g. one day my eating window is between 12pm to 8pm, but on another day it's 5pm to 1am, and on another it's 2pm to 10pm. Reply Dale Anderson says: June 10, 2018 at 11:09 am mouthwash makes me hungry earlier without fail Reply ifoundthistoday says: June 16, 2018 at 10:19 am this is just my opinion but Dr. Panda says he has a 10hr/12 hr window from 7am/8am to 5pm/6pm this isn't really time-restricted eating … this is just normal eating, isn't it? for years I intuitively eat an early dinner 6pm/7pm and the next meal would be 10am/2pm depending on how I feel or what day it is… weekends are usually closer to 12pm/2pm Reply pfunk26 says: June 18, 2018 at 2:58 pm Skip to 1:10:03 for caffeine Reply Kube Dog says: June 21, 2018 at 2:21 am I wonder if she's met Jordan Peterson through Joe Rogan. JP and his daughter have serious problems they have largely solved through diet. I wonder if she'd have some insights or recommend time-restricted eating for their inflammation issues. Reply silkhead44 says: June 27, 2018 at 2:01 am 16:8 works best for me Reply silkhead44 says: June 27, 2018 at 3:12 pm fantastic talk Reply Chris Nichols says: June 28, 2018 at 7:09 am Unintentional ASMR from Dr Panda Reply KUNAL DUTTA says: July 6, 2018 at 12:35 pm Thanks. Very informative Reply universalsheep says: July 16, 2018 at 4:36 pm i drink decaf because i like coffee and sipping in the morning, but i dont want caffeine. is the little bit of caffeine in decaf going to effect my liver? Reply Foo Ling says: July 20, 2018 at 2:13 am it says the app is only for iPhone. I have an excel spreadsheet of my fasting for the last 85 days. If you want it you can email me and I'll send it to you along with any additional information you'd like. I had a gallbladder attack I charted, weight lose and basic diet. Reply Kris Grant says: July 20, 2018 at 2:45 am I was wondering, if drinking BCAAs or EAAs with my water in the morning will break my fast the same as black coffee? Since the gut will have to digest them as opposed to plain water. Reply gar keiner says: July 31, 2018 at 3:13 pm Hi, thank you very much for the interesting and insightful conversation!I have one question though: What if one has to take medication first thing in the morning (in my case they include e.g. Quensyl, Pantoprazole, Ferro-Sanol, sometimes Prednisolone)? Does that break the fast (activate digestive enzymes?) right away (if otherwise only water is consumed)?Thank you! Reply meyoke - says: August 12, 2018 at 4:51 pm is smoking weed breaking the fast ? Reply Allan Stokes says: August 12, 2018 at 11:25 pm My one complaint with this pair of interviews is that the pre-diabetic frame is taken for granted. Modern society in a nutshell: we're all prediabetic, all the time. But imagine a future TRE world, where the majority of the population had two full decades of adult TRE under their belts: would anybody still be prediabetic? In the red trucks: reactive TRE, in the blue trunks: sustained TRE. Red trunks getting too much homer love in this dialogue. The tiniest sustained increase in blood-glucose level instantly convinces us that blue trunks is weak at the knees. Really? I don't think Mother Nature is quite so quick to send blue trunks packing, who hadn't first left his intestinal tract unflossed (this was their metaphor) for twenty adult years. Reply Allan Stokes says: August 12, 2018 at 11:27 pm 59:28 Now I want Google Glass! (For the first time ever.) Reply robert hingston says: August 18, 2018 at 7:42 am Well if you last meal is at 6pm and you go to bed at 10pm it’s only a few waking hours without food I find it easy been doing it for a long time .. however socially when friends asked to meet up in the evening for meal or beer etc it’s a tricky one Reply K Kelly says: August 26, 2018 at 4:30 am Rhonda has just such a glow when she is pregnant! I've only seen her on Joe Rogan. Reply T says: September 3, 2018 at 10:05 pm I like a 10/11a-5/6p window. Works well for me and every meal is amazing. Lol Reply Oskar Helling says: September 15, 2018 at 4:43 pm I am curious as to what kind of wrist-watch is Dr Panda wearing? What is it with the white layer next to the skin? Is that some kind of measuring device? Reply Muldoonite says: September 16, 2018 at 6:13 pm Does non-flavored sparkling water reset the feeding clock, or can I just treat it like plain water? Great video! Reply bhajanist1 says: October 4, 2018 at 2:31 pm Talks about himself at 13:10 Reply Adrian Andreev says: October 6, 2018 at 4:24 am Very interesting content! Thanks! 🙂 Reply ILOVE2FeelGOOD says: October 9, 2018 at 8:10 am Thankful for this wonderful practical advice!! 💜💛💚 Reply Randall says: October 10, 2018 at 3:43 am 24 hour water fasting omad keto I'm good to go! im sure if I did carbs I would devour more calories and gain weight. Reply Frank From Upstate NY says: October 21, 2018 at 1:20 pm Rhonda…what will you do…the first 2-3 years for your infant/child…that would be classified as "new science or feeding or anything" different for this baby, based on your knowledge, etc.? Reply Atif Khan says: October 24, 2018 at 1:13 pm i started 10 hours window then 9 and then 8, after few months now I am doing 1 to 4 hours max. trust me even 4 hours window now i feel bloated Reply Atif Khan says: October 24, 2018 at 1:16 pm nothing feels better than waking up and sleeping with empty stomach if you are eating at afternoon one meal a day Reply Vũ Đặng Tuấn Sơn says: November 14, 2018 at 5:01 am I myself practice the diet routine Dr Rhonda and Dr Satchin discussed at 47:34. I wake up at 8am everyday but my first bite of food is often at 12pm and have dinner at 7pm. If any research needs human volunteers, I can be one. Reply Hossam Albashrawi says: November 15, 2018 at 10:19 am I am impressed that you, 37-weeks-pregnant lady, was able to sit for this podcast for 2 straight hours without needing to go pee! Reply BushidoKi says: November 19, 2018 at 3:38 am “Dr. Panda and Dr.Cow talk about time restricted feeding” Reply Mario De Leon says: November 30, 2018 at 12:34 am Dose sparkling water break your fast like Lacroix ,pelligrino? Reply U Are The Gym says: December 2, 2018 at 2:35 am so lemon juice and apple cider vinegar in my water would be not good in the morning as well it will break the fast? Reply LinkDead56k says: December 4, 2018 at 1:52 pm What about taking medication??? Will medicine break your fast? Reply Michel Bisson says: December 12, 2018 at 12:50 am Excellent Reply Janoy Cresva says: December 16, 2018 at 5:04 am How is a 12 hour eating window time restricted in any sense? Time restricted eating should be less than 8 hours minimum, and closer to 4 hours. Reply Lavinia Florist says: December 23, 2018 at 9:58 am Yeeee . You are a mama !!!! Reply Lavinia Florist says: December 23, 2018 at 10:00 am Pls some baby and children nutrition!! Reply Christine Ritchie says: December 28, 2018 at 5:19 pm I just downloaded the app but I’m on a prolonged fast right now. I’m planning to start the app when I eat again however, is it ok that I’ll be fasting most days? Reply Fiets says: January 2, 2019 at 5:34 pm Does toothpaste interrupt the fast? Reply Gary Christopher says: January 14, 2019 at 8:11 pm Fantastic and very interesting again Dr Patrick thanks for all the information. Reply melgaudart says: January 18, 2019 at 9:28 pm Shift work info 33:40 Reply David David says: January 26, 2019 at 3:47 am when does he talk about coffee? 1:15:00 ? and does he have a viewpoint other than not taking it out of caution? Reply jaco joubert says: January 31, 2019 at 6:01 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 Adiudicium 1776 says: February 3, 2019 at 2:32 am on the issue of eating late, and melatonin influencing pancreas (~min 48), it would be helpful to look at different cultures – south European countries on average eat much later into the evening than do northerners yet my suspicion is that they don't have higher prevalence of T2D or markedly elevated HbA1C. I am sure lot has to do with their sulfur-rich Mediterranean diet, higher UV/VitD exposure, etc. hence the actual timing of a meal may not be as important as other factors. Reply Mango Authority says: February 6, 2019 at 2:03 pm 1:06:50 Does this suggest humans should take sun bath later in the day rather than earlier? Reply Joseph Hollis says: February 18, 2019 at 11:51 am Fascinating… i like how there's no 'hard sell' in this interview. No claiming to have all the answers. Just putting their findings out there for people to experiment with. Reply Jesse Salmon says: March 14, 2019 at 9:30 pm What if I only have 6% body fat… Is it safe for me to fast? Reply Joynal Miah says: March 28, 2019 at 5:07 am I do shift work and my resting hart rate was 100pbm. Now I do 23hour fast for a 9 months & now my heart rate is averaging around 65pbm Reply Fr. Jose Maria says: April 5, 2019 at 12:00 pm Bullet proof baby Reply Gemma Hanson says: April 9, 2019 at 9:25 pm Love this, plus you’re talking so much slower, brilliant Reply 027christy says: May 22, 2019 at 5:51 am Jesus Rhondda’s let herself go. Defo not fasting lol Reply GD says: June 4, 2019 at 9:13 am Good information. And first hand information coming from a horse's (Researcher's) mouth.I am definitely going to adopt this life style. From intermittent eating method I am going to intermittent fasting. Watch this place for my updates. Reply Le Chevalier Savage says: June 17, 2019 at 6:00 pm Is there a possible placebo effect going on with some people's positive outcomes? Like maybe just because they hear this and put it into effect and their minds are constantly focused on this it changes things Reply Hamdan Saadon says: July 30, 2019 at 11:41 pm I have exhaustively studied the works of his brother, Kung Fu Panda.🤡 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.