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A | Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Doctor Sachin Panda. Doctor Sachin Panda is a professor and director of the regulatory Bi... |
B | Yeah, good to see you. |
A | We are colleagues still, but we used to be right across the street from one another in 28. |
B | Yeah, I remember those days. Yeah. |
A | Yeah. So I'm delighted that you're here. I think we're going to talk about a number of things, mainly intermittent fasting time, restricted feeding and health, but also the many other things that you're doing. Just before we started recording, we were discussing your recent paper in nature that involved recordings from... |
B | Well, you know that intermittent fasting covers many types of fasting. Actually, it started a long time ago, and it's embedded into the history of caloric restriction. Almost 100 years ago, people showed that if you reduce calorie intake in a rat, then that rat can live for a long time. And in those experiments, the ca... |
A | Was there were those studies on humans. |
B | Many of the studies started in mice, but alternate day fasting, five two and walters periodic fasting, all of them have now been done in humans. Not for longevity, of course, because you cannot do those for a long time, but for weight maintenance, for reducing some signs of aging or reversing, those things have been do... |
A | One question about the six hour versus eight hour versus twelve hour feeding window. Is it important that the feeding window begin and end at the same time? More or less, yeah. And if so, how much flexibility is there? So, for instance, I'm somebody that I am not terribly hungry in the morning. I like to drink water, u... |
B | Yeah. So the start of the feeding window, that's interesting, because the concept of time restricted feeding, when I describe animal studies, it's feeding for humans, it's eating. So the concept actually came from the science of circadian rhythm. So that means our body has an internal timetable that's present in every ... |
A | Amazing. |
B | So then, now if we think about it, so for example, when the daylight saving time changes, just 1 hour change or 1 hour change in alignment between our internal time and external time leads to kind of feeling groggy and feeling not at a peak for four months, for one or two days. So the rule of thumb is when I, the time ... |
A | You start your feeding window? When does your feeding window shut? |
B | 06:00 p.m. so I eat for around 10 hours. |
A | Okay. |
B | And then one day, if I switch to 10:00 a.m. then what happens is a clock is thinking, well, the food didn't arrive at eight, but it arrived at ten. Maybe tomorrow the food will arrive somewhere between eight and ten, so we'll be ready around nine. I see. Next day, if I come back and eat at 08:00 then I may eat, but my ... |
A | Is there evidence that those anticipatory systems, as they relate to digestion, help us better assimilate our food? I would imagine so. I mean, if you have the gastric juice that are going to help digest the proteins, fats and carbohydrates and already deployed at the time when you eat, I could imagine that food will b... |
B | The anticipatory signal is really important even from waking up. The reason why many people feel not ready completely when they wake up to an alarm clock, because the alarm clock wakes you up, but your body is not prepared. So that sleepiness after waking up to an alarm clock is due to our body is not prepared for that... |
A | In heart attacks and car accidents, and. |
B | Car accidents too, because your brain is not coordinated, so you cannot make those fine decisions. So that's a great example of anticipatory activity. But coming back to digestion, one thing is, and this is something that many people might have experienced, there are many rhythms in our digestive system, and one of the... |
A | Yeah, I've experienced that where if I've worked late or I couldn't eat dinner or something, and then I get home, I always debate whether or not to try and sleep. But if I'm too hungry, oftentimes it's challenging. And so, for me, sometimes consuming something that at least seems easily digestible, like yogurt or somet... |
B | Yeah. Now these are very interesting question. And then, unfortunately, as you can, as you might have seen in life, the most obvious questions are often unanswered because it's so hard to do these damn experiments. Because if you really want to address this in humans, you have to bring humans, put them in isolation, ju... |
A | When you say fat burning process, you mean body fat stores being burned, right? Not dietary fat, correct. |
B | Yeah. So it's all body fat means. That's why I said we don't know where that fat is being burned, because we're just measuring how much mice is breathing in and out. So, for example, it can be from the skin. So subcutaneous fat or belly fat, but not dietary fat? No. By that time, the dietary fat is already observed and... |
A | Yeah. The reason I ask is that nowadays, I think more than half of the battles about nutrition that I see online relate to this issue where I won't name names, but someone will come along and say, low carbohydrate diet allows you to burn more fat. And the more nuanced people out there will say, well, that's true, but y... |
B | So here in this case, for example, for mice, we know that as soon as they start eating, the RER goes up. Coming back to your question, what would be ideal for us to do? The experiment would be, okay, so we'll go back to that and then give the mouse maybe 100 milligrams of food and mouse runs around in the kids, and the... |
A | I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podcast. The rea... |
B | So there is a famous experiment that was published last year by Jota Kahasi's lab, and it came out in science, and that relates to caloric restriction. And we kind of started with this idea. We started discussion that the rat experiments were done with caloric restriction, and researchers gave reduced calorie consumpti... |
A | So they're sort of on the Omad diet, the one meal a day. |
B | Yeah, they're almost like in one meal a day, three to 4 hours, food is gone. Or you can sit there on 4 hours eating or feeding and 20 hours fasting. So then the question became, well, the benefit of calorie restriction, as we know, is it due to reduced calorie or time restricted feeding or timing? There is a timing com... |
A | I wonder about this, because recently there were a bunch of news headlines about intermittent fasting, and frankly, I was frustrated. If you looked at one major news outlet, they would say time restricted feeding affords no additional benefit beyond caloric restriction for weight loss. Then another popular press venue,... |
B | This example of this news article that you mentioned is really interesting because that relates to Joe Takahazi's study, because I described that if you split calories and eat throughout the day, throughout day and night, then the mice lived 10% extra. But if you now give mouse the same calorie restricted diet and feed... |
A | So 20%. |
B | 20%. |
A | Okay, so let me make sure I understand. So that I make sure I understand. If you take a certain number of calories and you distribute them throughout the 24 hours cycle. |
B | Yeah. |
A | It's caloric restriction. The mice will live 10% longer if you, however, restrict that to the active cycle. So for humans, the daytime, then 20%, then they live 20% longer. |
B | 20% longer. |
A | So it's not just total caloric intake. |
B | Yeah. |
A | Meaning it's not just important to be sub maintenance and calories for sake of longevity. It also is important as to when in the 24 hours cycle you eat those calories. Do I have that right? |
B | So now that's still the story is not over because these mice are fed during daytime when they're not supposed to eat. |
A | That's right. So for us, it would be the equivalent of being on the night shift and only eating at night. But a sub caloric, sub maintenance calorie diet, I guess, is the right way to say it. |
B | But when a fed mice during nighttime, when they're supposed to eat, and they're seeing this, getting the same number of calories within 12 hours or 2 hours, then the mice lived 35% longer than they control. |
A | 35% longer. So scale to human lifespan, which we don't know, but 35% longer would mean that. And again, no one knows but humans. Now, what is the average mortality in the United States? Somewhere around 80. |
B | Yeah, so it's around 80. It used to be 80, now slowed, reduced a little bit because of COVID but let's take 80. |
A | Okay, so people are then now living somewhere between 25 and 35 years longer. I'm putting some error bars on there. |
B | Yeah, yeah, yeah. So that was really profound. But now you pointed out biomarker and other stuff. So now if you look at any given time within that experiment. And actually, Joe went back and had a separate cohort of mice, very similar, and so that he could take tissue samples. And of course, in this case, you have to s... |
A | Does that mean that there are biomarkers related to longevity that we just haven't discovered yet? |
B | Yeah, so that's exactly. So that means whatever we know so far about biomarkers, those he could not use to predict, maybe there was a lot of noise, maybe he had to use more number of mice to get that, because biomarkers are not going to predict in every instance that there is some error. What is also very interesting i... |
A | Body composition across all these different groups. |
B | Across all these groups. |
A | So it doesn't matter when they ate, provided they were sub calories maintenance, calorie intake. So less, fewer calories than is required to maintain their weight, didn't matter what pattern of eating they were, the same weight. So that in many ways seems to mimic the human studies where they say, look, it doesn't real... |
B | Taking a snapshot of that. And then another thing with the human study that we are referring to here, in that human study, people are actually already eating within 10 hours window habitually when they selected these people to have them enroll in the study. So they were already eating for 10 hours and fasting for 14 ho... |
A | So it's just a two hour difference. |
B | It's just a 2 hours difference. |
A | Okay? So that people, I just want to make sure people can understand. So, in this human study, which is the one that I felt that the popular press venues, all except one venue, got either semi wrong or badly wrong in terms of their conclusion. That was my interpretation anyway, was that either people came into the stud... |
B | Yeah, exactly. So we have done that experiment in mice and we don't see difference in not only weight loss, many other markers. And I was telling you about this, Joe Takahashi's paper, wherever I told you that he allowed these mice to eat within 2 hours or 12 hours sub caloric diet. |
A | Two or twelve. Two or twelve, yeah, that's dramatic. |
B | But still, he did not see change in longevity even within those two. So that means when you do caloric restriction and then at least per mouse, and you are within 12 hours window, that is giving the mice the best benefit, the optimum benefit, and two, three or five or twelve per mouse doesn't matter, at least for longe... |
A | Can we conclude for humans that whether or not a feeding window is 4 hours, 6 hours, 8 hours or twelve doesn't matter, provided the calories are similar or same? |
B | Well, I won't go to that extent because we don't know many of these, particularly we don't know how this sort of eating window will affect both sexes because, you know, we always think many of these mouse experiments, even that I told you about, those are done only in male mice. |
A | But that should be changing, right? Because the NIH, I know this because I'm on study section, which is just a bunch of people who review grants, is that every grant now has to include sex as a biological variable. It's hard to get away with, or rather, I should say it the way it should be stated, which is people are r... |
B | So in this case there are many. There was also another paper in time restricted feeding that also came out a big paper showing that the thermogenesis was accounting for loss in fat mass in time restricted fed mice. That was also done only in male mice. So this is, we are paying attention to it. So we are now doing all ... |
A | Reduce their calorie intake just because of gut volume. I tried one meal per day, and I felt like I was eating so much at that one sitting that it led to a lot of gastric distress, and I got tired after the meal. And part of the reason I like to do time restricted feeding is I have more energy. And certainly in the fas... |
B | Yeah. So people will reduce energy intake, and then some people who are more active, they can actually, unconsciously, they may be spending more energy in their physical activity and basal metabolic rate, all of this combined than how much they're eating. And that can have a very adverse effect in long term, because we... |
A | Relative energy deficit in sports. Okay. |
B | Yeah. Because nearly 40% of athletes, not the NFL guys, but there are a lot of people who do track and field, and nearly 40% of athletes actually experience this. Reds, red s. Without knowing, can male. |
A | And female athletes both experience reds? So it's reds. R e D s. Relative energy. Relative energy deficit in sports. Interesting. This is the first I've heard this acronym. We have a new acronym, folks. This is good to add to a list of other acronyms so males and females can experience it. So in females, I've heard tha... |
B | Yeah. So that's so common, that so prevalent that, in fact, many women, many female athletes, they take it for granted that, yes, if they are more active, then they will lose their menstrual cycle, which may be common, but it's not normal or optimum for health. |
A | And even if they don't want to get pregnant. Yeah, yeah, yeah, yeah. We had an expert on female hormones come on and say the very same thing, that regular cycling is very important of ovulatory menstrual cycle is important to try and maintain. |
B | Yeah. So that's one. But then what is really concerning is it does affect bone health. And in this state, people actually, over a long period of time, they lose bone mass and the bone also becomes more prone to injury, micro fracture and fractures. So again, it's a risk means if some people are trying to eat within ver... |
A | So this is 12 hours of. |
B | 12 hours of feeding, 12 hours of fasting. Yeah. In humans, again, nobody has done systematically 12 hours, but there was one study in Europe from Tinhai Collet lab and Tinhai and I, we collaborate. So they used our mycircadian clock app. This is a research app. We developed just to. This is mostly used in time restrict... |
A | And people can more easily avoid reds in that way. Women. And for non athletes or recreational exercise, it sounds like women, if they distribute their calories across 12 hours, are less likely to lose their menstrual cycle. |
B | Yeah, so again, this is something that we have to look carefully. They have to be, because we do have the my circadian clock app that many people download and self monitor and they share the data for researchers. |
A | We will provide a link to that. By the way. It's a great tool. |
B | Yeah. But once in a while we do get this input from some women saying, oh, I started doing your timeless eating and I'm seeing all these problems and I asked them, okay, so what else are you doing? They typically improve their nutrition quality. So they're eating only salad and few and they're trying to increase the fi... |
A | I recall a recent study, I think it was either published in cell reports or cell reports, medicine. Forgive me for not remembering which, but both of course, cell pressed journals, excellent journals which explored time restricted feeding in the context of low carbohydrate or non low carbohydrate diet. So it was low ca... |
B | No, I totally agree that when it comes to nutrition, quality, quantity and timing, all these three matter. Nearly 40% of people who maintain healthy body weight, because 60% are overweight and obese, 40% are maintaining healthy body weight. And out of those 40%, I would say nearly majority of them are very aware about ... |
A | So you're really an optimist. You're looking at the 40% of the glass. That's, or should we say not full. That was a pun intended, but the. No, that's a very interesting way of looking at. Rather than saying, why are 60% of Americans obese? Saying, why are 40% not obese? That's a very interesting way to look at it. |
B | Yeah. I mean, subconsciously, we're always making that decision. I'm sure that you are not going and eating cheeseburger every day because you want to improve. |
A | Yeah, exactly. I wouldn't feel good. Yeah, I enjoy a cheeseburger now and again, but I. No, not. Certainly not this stage or any stage of my life. I think people. I actually think the pandemic had a lot to do with this. I think that people started to take a. A look at what they were doing to support or not support thei... |
B | Yeah. |
A | Yeah. So how do these combine with one another? And using timing that we begin and stop feeding is kind of an anchor point. Can we explore that a little bit? |
B | Yeah, so, you know, we got into this beginning and end, and then we. You asked for the calorie. How much calorie will break? The first one thing that I want the listeners and viewers to bring back to this timing of when we are breaking the fast, because we equate health with weight, body weight. And that's when we are ... |
A | Off, especially on an empty stomach, especially. |
B | On an empty stomach. So for them, again, caffeine can be a trigger. So that's why I want to kind of differentiate that there is this mental health and other aspects of health. And these are two clear examples where anxiety, panic attack related to brain health, or acid reflux related to our gut health. In those cases, ... |
A | So do you avoid caffeine in the morning? |
B | Actually, here is the interesting history about caffeine, and this is something I did not know, and I was once invited to this history of nighttime activity. And maybe we can take a little bit of detour and talk about nighttime activity, because that fascinates me as a circadian biologist, because over the last 200,000... |
A | And now we chat with our thumbs. |
B | So it's still. So we are hooked to that evening activity because that's when we are completely free from the pressure of the work and we want to express ourselves. That's our independent time. So that's why most people find it very difficult to do time restriction and stop eating at 06:00 because it's ingrained in our ... |
A | We'll provide the spelling. And the wonderful thing about social media is somebody will tell us on YouTube the proper pronunciation. So this is a great opportunity. If you know the proper pronunciation, please put it in the comments on YouTube. |
B | Actually, I'm even checking right now in my endnote library. It's not picking up. |
A | That's right. We'll provide a link. |
B | So what happened was, so coffee was introduced and people came and drank coffee and talked about politics at night, at night, at evening. And it actually started with sufi branch of Islam because they are the ones who consumed coffee in the evening. And this is the branch of Islam where they actually sing and dance and... |
A | Yeah. A few years ago, right before the pandemic 2019, I traveled to Turkey. First of all, the food is amazing. The coffee is indeed very, very thick. And I have a pretty high caffeine tolerance from drinking so much coffee and yerba mate over the years, and still do. I really enjoy it. But, yeah, it's very intense. An... |
B | But what happened was with the strong coffee that gave heartburn and acid reflux to a lot of people. So then they started eating something with coffee. And that's how the culture of breakfast started in Turkey. |
A | So coffee actually led to the development of breakfast, not the other way around. |
B | But, yeah, so it does. |
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