Intermittent Fasting to Improve Health, Cognition & Longevity | Dr. Satchin Panda

Andrew Huberman 0:00 (instrumental music) 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 Dr. Satchin Panda. Dr. Satchin Panda is a professor and director of the Regulatory Biology Laboratory at the Salk Institute of Biological Studies. His laboratory has made numerous important contributions that impact mental health, physical health, and human performance. For instance, his laboratory discovered the neurons in the eye and neurons within the brain that regulate our so-called circadian rhythms. Circadian rhythms are 24-hour rhythms in everything from gene expression to the overall functioning of tissues, our levels of mood and alertness, our ability to sleep, appetite, and much, much more. In addition, over the last decade, Dr. Panda's laboratory has made critical discoveries in terms of how our patterns of eating over time impact our biology and our health. In particular, his laboratory pioneered discoveries related to so-called intermittent fasting, also sometimes referred to as time-restricted feeding. Today, Dr. Panda and I discuss how our circadian behaviors, everything from when we wake up, to when we view light, to when we avoid viewing light, to when we eat and what we eat, and when we socialize and how we socialize impacts our biology and our psychology and how all of that has a strong impact on our health. During today's discussion, you will learn how restricting your feeding to specific periods within each 24-hour cycle, or perhaps even exploring longer patterns of fasting and eating cycles can impact everything from the health of your liver, to your gut, to your brain, and how all of that impacts things like mood and your ability to perform cognitive work. Indeed, today's discussion goes deep into all aspects of intermittent fasting, A.K.A. time-restricted feeding. We talk about the basic science, as well as the recent clinical trials that have explored time-restricted feeding in a diverse range of people, including men, women, children, people with diabetes, people who are otherwise healthy, and much, much more. I'm quite aware that intermittent fasting is a topic of much debate these days. We go deep into that debate, and by the end of today's discussion, you can be certain that you will have learned all the latest and all the details, all made very clear to you thanks to the incredible expertise, discovery, and clear communication of Dr. Panda. As some of you may already know, Dr. Panda has authored several important books on the topic of intermittent fasting and how it can benefit various aspects of health. Those books include The Circadian Code, and a more recent book, The Circadian Diabetes Code, both of which we provided links to in the show note captions. In addition, if any of you are interested in learning more about Dr. Panda's work, including seeing his publications and reading those publications, or supporting his laboratory, you can do that by going to his laboratory website, which we have also linked in the show note captions.

Andrew Huberman 3:02 Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is HVMN Ketone IQ. HVMN Ketone IQ is a supplement that increases blood ketones. I want to be clear that I am not following a ketogenic diet. Most people fall into this category. They are not following a ketogenic diet. They are omnivores, and they do eat carbohydrates. So their standard fuel source for the brain and body is not ketones. However, I found that by taking Ketone IQ, which we know increases blood ketones, I can achieve much better focus for longer periods of time, for any kind of cognitive work, and much greater energy levels for exercise, especially if I'm going into that exercise fasted and find myself a little bit hungry when I start that exercise. And this is no surprise. We know that ketones are the brain's and body's preferred fuel source, even if you're not following a ketogenic diet. So, in other words, I and many other people are now starting to leverage endogenous ketones as a fuel source for the brain and body, and yet we are not following a ketogenic diet. And, of course, if you are fol- following a ketogenic diet, Ketone IQ will further allow you to increase your blood ketones as a source of brain and body fuel. If you'd like to try Ketone IQ, you can go to hvmn.com/huberman to save 20% off your order. Again, that's hvmn.com/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. As I've talked about before on the Huberman Lab Podcast, there is a critical relationship between sleep and body temperature. That is, in order to fall asleep and stay deeply asleep, your body temperature needs to drop by about one to three degrees, and in order to wake up in the morning and feel alert, your body temperature needs to increase by about one to three degrees. The problem with most people's sleeping environment is that even if you make the room cool, the actual environment that you sleep on, that is your mattress and underneath your covers, is hard to regulate in terms of temperature. With Eight Sleep, regulating the temperature of that sleeping environment becomes incredibly easy. In fact, you can change the temperature of that environment across the night, making it a little bit cool at the beginning of the night, even cooler still a few hours into your sleep, which really helps getting into very deep sleep, and then warming it as you approach morning so that you wake up feeling most alert. I've been sleeping on an Eight Sleep mattress cover for over a year now, and it has completely transformed my sleep. If you'd like to try Eight Sleep, you can go to eightsleep.com/huberman to save up to $150 off their Pod 3 cover. Eight Sleep currently ships in the USA, Canada, UK, select countries in the EU, and Australia. Again, that's eightsleep.com/huberman. Today's episode is also brought to us by Thesis. Thesis makes custom nootropics. Now, I am not a fan of the word "nootropics" because it translates to "smart drugs," and as a neuroscientist, what I can tell you is that you have circuits in your brain that allow you to focus. You have circuits in your brain that allow you to be creative. You have circuits in your brain that allow you to task switch, and on and on. In other words, there is no specific brain circuit or even circuits for being, quote-unquote, "smart." Thesis understands this and has developed nootropics that are customized to different types of mental operations. What do I mean by that? Well, they have formulas that can put your brain into a state of increased clarity, or focus, or creativity, or that can give you more overall energy for things like physical exercise. I often take the Thesis Clarity formula prior to long bouts of cognitive work, and I'll use their Energy formula prior to doing any kind of really intense physical exercise. If you'd like to try your own personalized nootropic starter ki- go online to takethesis.com/huberman. You'll take a brief three-minute quiz, and Thesis will send you four different formulas to try in your first month. Again, that's takethesis.com/huberman, and if you use the code "Huberman" at checkout, you'll get 10% off your order.The Huberman Lab podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab podcast, you can go to livemomentous, spelled O-U-S, livemomentous.com/huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman. And now for my discussion

Andrew Huberman 7:24 with Dr. Satchin Panda. Satchin, Dr. Panda, so good to see you again.

Satchin Panda 7:28 Yeah, great to see you.

Andrew Huberman 7:29 We are colleagues still, but we used to be right across the street from one another-

Satchin Panda 7:33 Yeah.

Andrew Huberman 7:34 ... in San Diego.

Satchin Panda 7:34 I remember those days, yeah. (laughs)

Andrew Huberman 7:35 Yeah, so I'm delighted that you're here. Um, 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, uh, we were, uh, discussing your recent paper in Nature, uh, that involved recordings from post-mortem human retina. So maybe if there's time at the end, we can get back to, uh, your lab has shown that it can, uh, essentially maintain or resurrect neurons from, uh, dead people in order to potentially and eventually provide transplants to rescue vision-

Satchin Panda 8:10 Yeah.

Andrew Huberman 8:10 ... in the blind. So that's extremely exciting, but of course, not the main focus of today's discussion-

Satchin Panda 8:15 (laughs)

Andrew Huberman 8:15 ... so I'll have to, uh, split it up. Um, the first question I have is, how am I supposed to define fasting and time-restricted feeding? In meaning when I go to sleep every night, I'm not eating.

Satchin Panda 8:28 Yeah.

Andrew Huberman 8:28 So in some sense, everybody is doing time-restricted feeding to some degree or another.

Satchin Panda 8:33 Yeah.

Andrew Huberman 8:34 At what point can we start thinking about a pattern of eating as time-restricted feeding, so-called intermittent fasting? Does it have to do with how regular one is about the start and stop times? Um, how do you think about defining intermittent fasting, time-restricted feeding? And maybe just to simplify the conversation, is one term more correct than the other in terms of describing this incredible pattern of f- feeding?

Satchin Panda 9:00 Well, you know that intermittent fasting covers many types of fasting. Um, actually, it started long time ago, uh, and it's embedded into the history of caloric restriction. Um, 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 calories were reduced every single day, and that led to the idea that if we cut down our calories by 20%, say, then we can potentially live longer by doing two things. One is preventing age-related disease, or even if we fall as- uh, fall sick, maybe we can accelerate cure and keep the repair mechanism going so that we can live longer. But it was very difficult to, um, count calories every day and reduce, maintain that. Um, I must say that it's not that caloric restriction is impossible or we are not doing it. In fact, lot of us, we do, um, count calories in our subconscious mind. Means every time you took out a- you take out- we take out a soda bottle or something, I'm looking at it, "Okay, 160 kilocalorie, 30 kilocalorie, zero kilocalorie." We are doing that. So the point is, it's- it's- we are doing subconsciously some kind of calorie, uh, counting, but reducing calorie by 20, 30% every single day is not possible for many people. So then the idea came in mouse and rat experiment whether they can eat every other day. Um, and in fact, this every other day feeding, uh, also led to very similar, almost equivalent health improvement as, um, continuous calorie restriction.

Andrew Huberman 10:54 Mm.

Satchin Panda 10:55 Um, so then the idea was, well, every other day is little bit hard for humans, but just imagine I would just get to eat, uh, only one day and then another day. Then the idea came, well, for humans, can they eat less for one or two days in a week? Um, so that led to this 5:2 diet where people can eat for five days, and then two days they have to reduce calories. So that's also intermittently people are fasting. Um, then as you know, Valter Longo also came up with this idea that periodic fasting, maybe four or five days in every month or two months, three months you can fast or reduce calorie, and he also found many benefits of calorie restriction was there.

Andrew Huberman 11:40 Were those studies on humans?

Satchin Panda 11:42 Many of the studies started it in mice, but, uh, alternate-day fasting, 5:2, and Valter's periodic fast- fasting, all of them have now been done in humans. Not for longevity, of course, because cannot do those for a long time. Um, but for weight maintenance, for reducing some signs of aging or reversing, those things have been done. So all of them, uh, have been done in humans, mostly healthy humans, uh, and in some cases, people with, uh, pre-diabetes or some aspects of metabolic disease. So that led to the idea that- that all these forms of fasting in which the total caloric intake on any given day is reduced for one or more days in a week, a month, that became- that umbrella term became intermittent fasting. So if you look up the scientific literature, most intermittent fasting involves intentionally reducing calories for at least one or two days in a week or, um, few days in a month. So when we, uh, published time-restricted feeding, um, the initial mouse experiments, and even now most of the mouse experiments, we want to test what is the impact of time restriction versus calorie restriction.So in these experiments, we don't reduce calorie on any day of mouse life. So the mice eat the same number of calories as the ad libitum-fed mice, uh, but still they see health benefit. So that's why we call it time-restricted feeding. But since it involves living without food for several hours, for some people which is, um, it can be very difficult, uh, the initial experiments was done, uh, they were done for eight hours of feeding and 16 hours of fasting, that kind of became popular and, uh, so tha- that's why people use the same term as intermittent fasting. And now if you, uh, say intermittent fasting in popular literature or popular media, then people usually refer to time-restricted eating.

Andrew Huberman 13:54 Got it.

Satchin Panda 13:54 So now coming back to how do you define time-restricted feeding? Um, so the way, uh, we have been trying to define experimentally and also in, uh, literature is, um, trying to confine all your energy intake from solid and liquid food combined within a consistent window of eight to 12 hours, because that's something that doable. Of course, people have done time-restricted feeding with four hours, six hours, and some people even try to eat everything within two hours, one meal a day, um, but the point is those are n- not feasible to maintain for very long time for a lot of people.

Andrew Huberman 14:39 One question about the 6-hour versus 8-hour versus 12-hour feeding window-

Satchin Panda 14:43 Mm-hmm.

Andrew Huberman 14:45 ... is it important that the feeding window begin and end at the same time-

Satchin Panda 14:51 Yeah.

Andrew Huberman 14:51 ... more or less?

Satchin Panda 14:52 Yeah, more or less.

Andrew Huberman 14:52 Um, 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-

Satchin Panda 15:01 Mm-hmm.

Andrew Huberman 15:02 ... usually some caffeine and electrolytes-

Satchin Panda 15:04 Yeah.

Andrew Huberman 15:04 ... in the period before my first meal.

Satchin Panda 15:06 Yeah.

Andrew Huberman 15:06 And my first meal always lands sometime between 11:00 and, 11:00 AM and 12:00 noon.

Satchin Panda 15:12 Yeah.

Andrew Huberman 15:12 There are exceptions.

Satchin Panda 15:13 Yeah.

Andrew Huberman 15:14 Occasionally I'll have a breakfast, a proper breakfast as it's called. Uh, I guess-

Satchin Panda 15:18 (laughs)

Andrew Huberman 15:18 ... it would be improper if you're intermittent fasting for me. Um, but typically 11:00 AM or noon is when I first eat and my last bite of food is typically around, I don't know, 8:00-

Satchin Panda 15:28 Yeah.

Andrew Huberman 15:28 ... 8:30, 9:00 PM.

Satchin Panda 15:29 Yeah, yeah.

Andrew Huberman 15:29 That's what works for me.

Satchin Panda 15:31 Yeah.

Andrew Huberman 15:32 Is that consistency affording me any benefit sep- and let's just leave aside total caloric number, macronutrients-

Satchin Panda 15:38 Yeah.

Andrew Huberman 15:38 ... plant-based meat, et cetera. But is there any benefit to shortening that feeding window that we are aware of or extending that feeding window o- or being even more rigid about the start and end of that feeding window?

Satchin Panda 15:54 Yeah, so the start of the feeding window, um, that's interesting because it, uh, the concept of time-restricted feeding when I describe animal studies, it's feeding, for humans it's eating. Uh, so the concept actually came from (laughs) the science of circadian rhythm. So that means, um, um, our body has an internal timetable, um, that's present in every cell, in every organ, um, that pre-programs, um, many molecular aspects of the cells that leads to physiology and all that stuff. So that essentially, uh, there is a predetermined timetable for every cell, every organ to do certain things at certain time and the circadian clocks, as you and I know, are more sensitive to light. Light is the most dominant, um, time giver. Uh, so for example, when daylight saving time changes or when we travel from one time zone to another time zone, we feel kind of crappy because our daily activities are out of sync from our internal clock. So that was known for a very long time but then around the year 2000, 2002, um, there was a famous experiment by Uli Sibler from, um, Switzerland. What, uh, he did, he just fed the mice at the wrong time, mice are knocked on all their night feeders and when he fed the, uh, mice during daytime, the liver clock, instead of following its own routine, liver clock actually started following food. So that means by changing our feeding time, we can change, we can tune our liver clock. And subsequently the same experiment has been repeated many times and even we repeated that in 2009 and we figured out, yes, actually outside this brain center called suprachiasmatic nucleus or SCN, which is considered the master circadian clock, almost rest of the brain even follows when we eat. And that came out from Pierre Chambon's lab in Europe, uh, where they systematically looked at even, um, places that are very close to the SCN, um, for those who are, who know dorso-medial hypothalamus or para-ventricular nucleus, all of this within couple of, uh, four or five millimeters of the SCN but they were following food cue.

Andrew Huberman 18:35 Amazing.

Satchin Panda 18:36 So then, um, now if we think about it, so for example, when the daylight saving time changes, just one hour change, um, or one hour change in alignment between our internal time and external time leads to kind of feeling groggy and feeling not at a peak performance for one or two days. So the rule of thumb is when the time giver changes by one hour then our internal clock takes at least a day to catch up. So that means if you're flying from-... LA to New York, uh, you're moving through three time zones, then on an average, it will take three hou- three days to catch up with the New York time. For some people, it can be even slower and for some people, it can be two days. But the bottom line is, yes, there is a desynchrony. So then what does it mean for the body? So the, one of the function of clock is to anticipate when you're going to wake up, for example, so the blood pressure slightly goes up, our heart rate goes up, our breathing goes up. Similarly, for food, almost every organ that is involved in feeding or eating, digestion, uh, all of them have clocks. So even from saliva production, (laughs) that is the first phase of our digestion to secretion of all the digestive juice in the, uh, stomach and then absorption of nutrient and liver metabolism. Everything, the whole village expects when you're supposed to eat and they're getting ready for you to eat the first meal after fasting for a long time, so that's why it's breaking the fast or breakfast. Um, and when that time changes, when you change it by two or three hours from one day to another, then, um, sometimes they're like, "Oh, food didn't come. Maybe, um, we'll come at a wrong time. We, we were at the wrong time." And then they will track the new eating times. So suppose that one day you have been eating every day at 8:00 AM, um, I s- I eat at 8:00 AM, so.

Andrew Huberman 20:48 Is that when you start-

Satchin Panda 20:49 Yeah. I start.

Andrew Huberman 20:49 ... your feeding window? When do you, when does your feeding window shut?

Satchin Panda 20:53 Uh, 6:00 PM. So I eat for around 10 hours.

Andrew Huberman 20:56 Okay.

Satchin Panda 20:56 Yeah. Um, and then one day, if I switch to 10:00 AM, then what happens is the clock is thinking, "Well, the food didn't arrive at 8:00, but it arrived at 10:00. Maybe tomorrow, the food will arrive somewhere between 8:00 and 10:00, so we'll be ready around 9:00."

Andrew Huberman 21:12 I see.

Satchin Panda 21:13 So then they... And next day, if I come back and eat at eight o'clock, then I may eat, but my clock is not ready to digest that food. So that's why this idea is you have to be consistent, uh, to take advantage of this anticipatory activity of our clock and different systems to get the best out of it.

Andrew Huberman 21:34 Is there evidence that those anticipatory systems in, um, as they relate to digestion help us better assimilate our food? I would imagine so. I mean, if you have the gastric juices that are going to help digest the proteins, fats, and carbohydrates and, uh, already deployed at the time when you eat, I could imagine that food will be better utilized than if you don't. Um, so in other words, w- what is the advantage of having these anticipatory signals, um, in terms of potential health benefits?

Satchin Panda 22:02 The anticipatory s- signal is really important from even, even from waking up. Um, 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. And then the best example is when th- uh, when, um, uh, the daylight saving time changes, particularly when we have to wake up one hour early. Uh, what happens, people who have underlying heart condition, um, when they're waking up, when the body is not ready or heart is not ready and all of a sudden the heart has to start pumping a little bit harder, then there is chance of heart attack. And in fact, uh, people have looked at hospital records and they find that on those days, uh, there is a sharp rise in heart attacks, so-

Andrew Huberman 23:03 And car accidents, right?

Satchin Panda 23:04 And car accidents too, because your brain is not coordinated, so you cannot, uh, make those fine decisions. So that's a great example of anticipatory activity. But coming back to digestion, one thing is, um, and this is something that many people might have experienced, there are many rhythms in our digestive system, and one of the rhythms is our lo- our intestine has this peristaltic function, so it kind of contracts and expands and that moves food mo- food doesn't move due to gravity (laughs) so it goes back and forth. And that peristaltic action actually slows down at night, uh, few hours after our last meal. And, um, so that's why when people eat late at night, for example, uh, then that food doesn't get digested because there is not enough digestive juice, first thing. And second, even if it gets digested in the stomach, it doesn't move properly, so then the next morning people get up and think, um, of course, uh, people consume some alcohol very often and then they think that this is hangover, but those who don't, uh, consume alcohol, then they have the food hangover because it doesn't digest. So that's one extreme example where food at the wrong time can, um... So healthy food at the wrong time can be crap or junk.

Andrew Huberman 24:29 Yeah, I've, um, 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.

Satchin Panda 24:37 Yeah.

Andrew Huberman 24:37 But if I'm too hungry, oftentimes it's challenging, and so for me, sometimes consuming something that at least seems easily digestible like yogurt or something in a liquid form, um, is better for me than if I eat a meal.

Satchin Panda 24:51 Yeah.

Andrew Huberman 24:51 I've made the mistake of going to the refrigerator, being super hungry, and eating a bunch of food at 10:00 or 11:00 PM and then falling asleep. And indeed the sleep, if I'm tired enough, can be quite deep.

Satchin Panda 25:02 Yeah.

Andrew Huberman 25:02 But the next morning I feel just completely physically and, and cognitively weighed down.

Satchin Panda 25:07 Yeah.

Andrew Huberman 25:07 So I think what you just described makes a lot of sense.

Satchin Panda 25:10 Yeah.

Andrew Huberman 25:10 So is it... So if someone were to select a, a feeding window-

Satchin Panda 25:13 Mm-hmm.

Andrew Huberman 25:13 ... regardless of whether or not it...... falls-

Satchin Panda 25:16 Yeah.

Andrew Huberman 25:16 ... into classic intermittent fasting, time-restricted feeding.

Satchin Panda 25:18 Yeah, yeah, yeah.

Andrew Huberman 25:18 Sounds like s- eating your first bite of food and eating your last bite of food at more or less the same time each day-

Satchin Panda 25:25 Yeah.

Andrew Huberman 25:25 ... has benefits.

Andrew Huberman 25:28 I have this question, you mentioned feeding versus eating.

Satchin Panda 25:31 (laughs)

Andrew Huberman 25:31 And I think it's actually not just a, uh, grammatical, uh, s- semantic issue. Um, and here's why. We tend to think about when you take your first bite of food and then when you take your last bite of food. But, of course, foods digest at different rates.

Satchin Panda 25:47 Yeah.

Andrew Huberman 25:47 More fat in there is gonna digest, make carbohydrates digest slower, et cetera. I mean, there's all these adjustments to the glycemic index-

Satchin Panda 25:54 Yeah.

Andrew Huberman 25:54 ... and so forth with foods in combination. I, is it better to think about not eating, but h- your fed state and blood sugar? So for instance, I often get asked on social media, "Does blank break a fast?"

Satchin Panda 26:09 Mm-hmm.

Andrew Huberman 26:10 So, uh, and so I like to think about it scientifically, like, okay, is, does plain water break a fast? No. Does air break a fast? No.

Satchin Panda 26:18 (laughs)

Andrew Huberman 26:18 Um, does one grain of sugar, of sucrose break a fast? Well, probably not, but does one teaspoon of sugar break a fast? Well, you could say yes, but transiently.

Satchin Panda 26:28 Mm-hmm.

Andrew Huberman 26:28 Like so, I mean when we're talking about breaking a fast, are we talking about a rise in blood glucose or are there molecular signals downstream of, of a rise in blood glucose that, um, cannot be reversed? In other words, if I'm going to eat my first meal every day at noon, and I'm going to eat my last, uh, bite of food at 8:00 PM and at 9:00 AM for whatever reason, I have coffee with one teaspoon of sugar in it, I suppose in the strictest sense, I've broken my fast.

Satchin Panda 26:57 Mm-hmm.

Andrew Huberman 26:58 But maybe by n- if I went for a hard run that morning, maybe by 9:30 AM I'm back in a quote unquote "fasted state." So what is the fasted state really? Because when I'm eating-

Satchin Panda 27:07 Yeah.

Andrew Huberman 27:07 ... at 8:00 PM just to give another example, I'm start fasting at 8:01.

Satchin Panda 27:12 Mm-hmm.

Andrew Huberman 27:12 Perhaps.

Satchin Panda 27:13 Yeah.

Andrew Huberman 27:14 But I have my blood glucose is elevated, so I'm not really fasted.

Satchin Panda 27:17 No, no, no.

Andrew Huberman 27:17 I'm fed.

Satchin Panda 27:18 Yeah.

Andrew Huberman 27:18 It's just that I'm not eating, the verb, right? Okay. So, um-

Satchin Panda 27:22 (laughs)

Andrew Huberman 27:22 ... so, uh, again, I, I don't want to get overly detailed just for sake of getting detail, but I think a lot of the confusion out there about what breaks a fast-

Satchin Panda 27:29 Yeah.

Andrew Huberman 27:30 ... is related specifically to this issue.

Satchin Panda 27:32 Yeah.

Andrew Huberman 27:33 Which is if I eat a whole pizza after sitting around all day, it's very different than if I eat a whole pizza after having run a 26-mile marathon that day.

Satchin Panda 27:40 Yeah.

Andrew Huberman 27:41 Very different-

Satchin Panda 27:41 Yeah.

Andrew Huberman 27:42 ... um, metabolically speaking. So how should people think about fasted versus fed? Can we be mildly fasted versus severe fasted? Can we be, um, fed-ish versus very fed?

Satchin Panda 27:55 (laughs)

Andrew Huberman 27:55 Anyway, I'll, I'll, uh, s- stop, uh, asking questions now because they all relate to the same theme.

Satchin Panda 28:00 Yeah. No, these are, um, very interesting question. And then unfortunately as you can, as you ha- you might have seen in life, um, 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. Just like you said, I can now imagine planning five or six different experiments. Each experiment should involve eight or 10 volunteers each gender, sex, and then do it. So it's difficult. So now let's go back to see how do we, uh, let's dissect it, um, in terms of say, indirect calorimetry. So for example, indirect calorimetry is based on this principle that whatever oxygen we breathe in and carbon dioxide we, uh, breathe out, if we can measure these two, then we can figure out whether our body in total, we, we are not saying whether it's the liver, uh, gut, uh, fat or muscle, in total whether it's, uh, consuming glucose or fat as energy source. The idea is when we fast, when we are without food for several hours, then ideally our body will tap onto glycogen first and then to a little bit of fat, and then when the body's mostly running on fat, then that ratio of CO₂ to oxygen will come to 0.7. Um, but what is interesting is we can do these experiments in mice. So we can go to mice and ask, okay, so what happens in mice? So in mice, mice are a little bit, very different because mice are not simply little people, they are (laughs) their metabolism is different. They store relatively less glycogen than humans do in terms of, uh, total metabolism. So they overnight within 12 to 14 hours, the RER, respiratory exchange ratio or this ratio will go from one when they're consuming mostly glucose or carbohydrate as energy source, it'll slow down, slowly go to 0.7, 0.75. So after 12 to 14 hours, they're kind of mostly running on fat. So now as we give them food, um, within 10 or 15 minutes, they're not actually consuming couple of grams of food, they are, they might have consumed say, 100 or 200 milligram of that chow. So, which is less than say, 5% of their food. And then the RER will immediately begin to rise as if that small amount of food stopped that fat burning process and cranked up the, um...... carbohydrate-burning process.

Andrew Huberman 30:48 When you say fat-burning process, you mean body fat stores being burned, right? Not dietary fat, correct?

Satchin Panda 30:54 Yeah. So, it's all body fat. Means that, that's why I said, um, we don't know where that fat is being burned because we are just measuring how, how much mice is breathing in and out. Um, so for example, it can be from the skin, so subcutaneous fat or belly fat, uh-

Andrew Huberman 31:10 But not dietary fat.

Satchin Panda 31:11 Mm-hmm. No. By that time, the dietary fat is already absorbed and digested, and hopefully it's, uh, sitting in the liver or adipose tissue somewhere, but it's the fat-

Andrew Huberman 31:20 Okay.

Satchin Panda 31:20 ... that's body fat. Yes. Thank you for clarifying that.

Andrew Huberman 31:22 Yeah. The reason I ask is that nowadays, I think more than half of the battles about nutrition that I see online-

Satchin Panda 31:27 Yeah.

Andrew Huberman 31:27 ... relate to this issue where, I won't name names, but someone will come along and say, "A low carbohydrate diet allows you to burn more fat." Um, and the more nuanced, uh, people out there will say, "Well, that's true, but you're also talking about dietary fat." You know, the word fat-

Satchin Panda 31:44 Mm-hmm. Yeah, yeah, yeah.

Andrew Huberman 31:44 ... can confuse people.

Satchin Panda 31:45 Yeah.

Andrew Huberman 31:45 And I realize you're not doing that.

Satchin Panda 31:46 No, no.

Andrew Huberman 31:47 You, you are certainly not one of the people guilty of doing this, but indeed, you eat more fat, you'll burn-

Satchin Panda 31:50 Yeah.

Andrew Huberman 31:50 ... more fat.

Satchin Panda 31:51 Yeah.

Andrew Huberman 31:51 But that doesn't mean you'll burn more body fat.

Satchin Panda 31:52 No. Yeah.

Andrew Huberman 31:53 In fact, I think the data say that under conditions of caloric restriction, you'll actually burn less.

Satchin Panda 31:58 Yeah, yeah, because they-

Andrew Huberman 31:58 I hope I don't, I'll probably get, I'll probably get, um, pitchforks, uh, sent, uh-

Satchin Panda 32:02 (laughs)

Andrew Huberman 32:02 ... through the mail toward me on, on that one. But, but I think that's true, whereas, you know, people who consume carbohydrate can still burn body fat even though the majority of the fuel they're burning is from carbohydrates. So...

Satchin Panda 32:12 Yeah. So here in this case, for example, from mice, we know that as soon as they start eating, um, 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 milligram of food and mouse runs around in the cage. And then we'll continue to measure to see how long it takes for the mouse to come back. And then, so that's one aspect. So now let's see, um, let's stay on this and then I'll come back and talk about non-caloric food and how, whether that is considered.

Andrew Huberman 32:49 I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, 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 reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins and minerals that make sure that all of my foundational nutritional needs are met and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3 K2.

Satchin Panda 34:05 So there is a famous experiment that was published last year by Joe Takahashi's lab, and it came out in Science, and that relates to caloric restriction. And we kind of started with this idea, um, we started discussing that the rat experiments were done with caloric restriction, and researchers gave reduced calorie consumption by 20% or 30% and gave that food. The rats, and then subsequently mice, and they all lived longer. What is interesting is, um, in all those experiments, um, the researchers came and gave this bolus of food at one time, whereas the ad libitum-fed mice or rats, they had access to food all the time, so they were eating all the time, and then these rats, uh, were given 20% less. And what happens is, these mice or rats, they're not going to take that less food, which is lesser now, and just eat a little bit of, uh, lunch, and then snack after three hours, or snack after three hours. They gobble up all that food. Within two to three hours, maximum four hours, food is gone.

Andrew Huberman 35:15 So they're sort of on the OMAD diet, the one meal a day.

Satchin Panda 35:18 Yeah. They're almost like in, uh, one meal a day, three to four hours, food is gone. Or you can say they're on four hours eating or feeding and 20 hours fasting. Um, so then the question became, well, the benefit of caloric restriction as we know, is it due to reduced calorie or time-restricted feeding or timing? There is a timing component to it, that they're eating all of that within three to four hours, and then there is a long fasting. And this is a difficult question to answer because now you have to ask these poor grad students or technicians to come and split that food into 8 or 10 or 15 different, uh, small portions and then give them to mice in every two hours. Um, so Joe Takahashi, who actually published the first paper in 2017 showing that most caloric restriction study, and, I mean, he used the protocol that was used by caloric restriction field, uh, it actually creates a condition of time restriction. So he showed that, and then he went back and worked with engineers to come up with a smart cage where, um, he could actually tell, he could program how much food is given to mice at what time of the day or night, completely programmed. So then he took this, uh, for example, suppose, say, the ad libitum-fed mice eats, say, 5 grams of chow in a day.... and if you want to reduce calories by, uh, 20%, then the CR mouse would get four grams of food. And he divided this into nine or 10 meals and then gave them in every 90 minutes. So, in this case they are eating small meals throughout their night, so there is no fasting. So you can say that, well, this mouse actually is not getting into fasting because in every few hours is, uh, getting some food. And then he measured how long the mouse is going to live. Um, and he used, um, he count, I mean, this is a very standard protocol. People count how many mice are dying on which day and then examine them to see whether they died because they, there was an accident or they actually, there was a natural cause. And then they calculate at the end what is the, um, half, uh, life. So 50% survival, because that's, on an average that's a good indicator because if there is an outlier that will live for a long time, then that can skew. So what was interesting was, the ad libitum fed mice, of course, they live certain number of days and then these calorie restricted mice that never got into super fasting, but kind of eating, s- snacking throughout day and night, that also lived 10% extra, 10% longer. So that means caloric restriction extended lifespan by 10%.

Andrew Huberman 38:18 I've wondered about this because recently, you know, there's been, there were a bunch of news headlines about intermittent fasting, and I, and frankly I was frustrated, uh-

Satchin Panda 38:28 Yeah.

Andrew Huberman 38:28 ... if you looked at one major news outlet they would say, "Time-restricted feeding affords no additional benefit beyond caloric restriction for weight loss."

Satchin Panda 38:38 Yeah. Yeah.

Andrew Huberman 38:38 Then an- another popular press venue, let's call it that, same study described as, "Time-restricted feeding doesn't work."

Satchin Panda 38:50 Yeah. (laughs)

Andrew Huberman 38:50 Right. And then another one, maybe some place, um, even more extreme.

Satchin Panda 38:54 (laughs) Yeah, yeah.

Andrew Huberman 38:54 You know, "Time-restricted feeding, um n- uh, only beneficial because of caloric restriction."

Satchin Panda 39:00 Yeah, yeah, yeah.

Andrew Huberman 39:00 Or something like that. So what you've s- essentially got are three different interpretations of the same data, all of which are... well, two of which are true, one of which is false in my opinion.

Satchin Panda 39:10 Yeah.

Andrew Huberman 39:10 But what I think people take away from that is, oh, time-restricted feeding isn't valuable, which is not the case, it, I think for many people it's a convenient way to eat because at least for people like me, it's simpler to designate between portions of my day when I'm eating and portions of day, my day when I'm not eating-

Satchin Panda 39:26 Yeah. Yeah.

Andrew Huberman 39:26 ... as opposed to eat portion control.

Satchin Panda 39:28 Yeah.

Andrew Huberman 39:28 For other people, portion control can work. But all of that is related to either maintenance or loss of weight.

Satchin Panda 39:35 Mm-hmm.

Andrew Huberman 39:36 None of it deals with the lo- potential health benefits independent of weight loss.

Satchin Panda 39:41 Yeah.

Andrew Huberman 39:41 Right?

Satchin Panda 39:42 So, uh-

Andrew Huberman 39:42 Um, and so I, I think that, um, if we can segment those out, um, obviously in humans it's hard to know if a given treatment or experiment is extending life because you don't really know how long people would live anyway.

Satchin Panda 39:55 Yeah.

Andrew Huberman 39:55 Right? Whereas with mice you have some sense of when-

Satchin Panda 39:57 Yeah.

Andrew Huberman 39:57 ... the mortality was likely to occur. So w- what can we say about time-restricted feeding and longevity in terms of biomarkers or in terms of any other indication that people who start and stop their feeding window at a consistent time, somewhere between eight and 12 hours per 24 hour cycle, are tilting the scales towards living longer as opposed to living shorter?

Satchin Panda 40:21 This example of this news article that you mentioned is really interesting because that relates to Joe's, uh, Joe Takahashi's, uh, study, because I described that if you split calories and eat throughout the day, th- throughout day and night, then the mice lived 10% extra. But if you now give mouse the same calorie restricted diet and feed them during daytime, whether within 12 hours or two hours, then the mice live 10% extra.

Andrew Huberman 40:49 Beyond that?

Satchin Panda 40:50 Yes.

Andrew Huberman 40:50 So 20% longer.

Satchin Panda 40:52 20%. So-

Andrew Huberman 40:52 So, okay, so let me make sure I understand so that, uh, so that I make sure I understand. If you take a certain number of calories and you distribute them throughout the 24 hour cycle-

Satchin Panda 41:02 Yeah.

Andrew Huberman 41:03 ... it's caloric restriction, the mice will live 10% longer?

Satchin Panda 41:06 Yeah.

Andrew Huberman 41:07 If you, however, restrict that to the active cycle-

Satchin Panda 41:10 Yeah.

Andrew Huberman 41:10 ... of the, so for humans the d- daytime.

Satchin Panda 41:13 Yeah.

Andrew Huberman 41:13 Then 20% then they live 20% longer?

Satchin Panda 41:17 20% longer.

Andrew Huberman 41:18 So it's not just total caloric intake?

Satchin Panda 41:20 Yeah.

Andrew Huberman 41:21 Meaning, it's not just important to be sub-maintenance in calories for sake of longevity, it also is important as to when in the 24 hour cycle-

Satchin Panda 41:29 Yeah.

Andrew Huberman 41:29 ... you eat those calories. Do I have that right?

Satchin Panda 41:31 So now, that's, still the story is not over because these mice were fed during daytime when they're not supposed to eat.

Andrew Huberman 41:39 That's right, so for us it would be the equivalent of being on the night shift-

Satchin Panda 41:41 Only on the night shift.

Andrew Huberman 41:41 ... and only eating at night, but a sub caloric-

Satchin Panda 41:43 Yeah. Yeah.

Andrew Huberman 41:44 ... a sub-maintenance calorie diet I guess-

Satchin Panda 41:46 Yeah.

Andrew Huberman 41:46 ... is the right way to say it.

Satchin Panda 41:47 But when he fed mice during nighttime when they're supposed to eat and they're seeing the s- getting the same number of calories within 12 hours or two hours, then the mice lived 35% longer than the control.

Andrew Huberman 42:01 35% longer.

Satchin Panda 42:02 Yeah.

Andrew Huberman 42:02 So scale to human lifespan which-

Satchin Panda 42:04 Oh. (laughs)

Andrew Huberman 42:04 ... you know, we don't know, but, but a 35% longer would mean that, um... and again, no one knows, but, um, humans now, what is the average mortality in the United States? Somewhere around 80?

Satchin Panda 42:15 The U.S. life ex- yeah, so it's around 80. It used to be 80, now it's slow, uh, reduced a little bit because of COVID, but let's take 80.

Andrew Huberman 42:22 Okay. So people are then now living somewhere between 25 and 35 years longer?

Satchin Panda 42:27 Yes.

Andrew Huberman 42:27 Put, I'm putting some arrow bars on there.

Satchin Panda 42:28 Yeah, yeah, yeah, yeah.

Andrew Huberman 42:29 Amazing.

Satchin Panda 42:29 So that was, um, really profound. But now you pointed out, um, biomarker and other stuff. So now, if you look at any given time within that experiment, and actually Joe went back and, um, had a separate cohort of mice, very similar and so that he could take tissue samples, and of course in this case you have to sacrifice the mouse, and he looked for, um, he did lot of molecular analysis-... with known markers, for example, hemoglobin A1C equivalent or glucose control, cholesterol, all this stuff. He could not find anything that predicted the benefit of caloric restriction. So that means in this experiment, whatever we know so far, the predictor of longevity, none of them could predict whether this, um, CR-only mouse, which it, throughout day and night, that mouse is going to live less than the night-fed mouse that was going to live 35, 25% extra.

Andrew Huberman 43:34 Does that mean that there are biomarkers related to longevity that we just haven't discovered yet?

Satchin Panda 43:38 Yeah. So that's exactly. So that means whatever we know so far about biomarkers, uh, those he could not use to predict. Maybe there was a lot of noise, maybe he wanted, uh, he had to use more number of mice to get that because, you know, biomarkers are not going to predict in every s- instance if there is some error. What is also very interesting is if you look at the body weight and body composition of all these mice, there is no difference in body weight and body composition.

Andrew Huberman 44:10 Across all these different groups?

Satchin Panda 44:11 Across all these groups. So-

Andrew Huberman 44:12 So it doesn't matter when they ate?

Satchin Panda 44:14 Yeah.

Andrew Huberman 44:14 Provided they were sub-m- sub-

Satchin Panda 44:17 Calorie.

Andrew Huberman 44:17 ... maintenance calorie intake.

Satchin Panda 44:18 Yeah.

Andrew Huberman 44:18 So less, fewer calories than is required to maintain their weight.

Satchin Panda 44:22 Yeah.

Andrew Huberman 44:22 Didn't matter what pattern of eating, they were the same weight.

Satchin Panda 44:25 Yeah.

Andrew Huberman 44:25 So that in many ways seems to mimic the human studies-

Satchin Panda 44:27 Yeah.

Andrew Huberman 44:27 ... where they say, "Look, it doesn't really matter whether or not you use caloric restriction or, or you start your feeding window in the morning or start your feeding window in the evening, or you, um, or you portion control for sake of weight contr- weight loss."

Satchin Panda 44:40 Beca- because they're taking a snapshot of that. And then another thing with the human study that, uh, we are referring to here, um, that, in that human study, people were 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, uh, 14 hours. All participants had to reduce their caloric intake, and they reduced by almost 25%. The CR group continued with 10 hours eating window, and the CR plus time-restricted group had to eat the same number of calories within eight hours.

Andrew Huberman 45:21 So it's just a two-hour difference.

Satchin Panda 45:23 It's just a two-hours difference. So now-

Andrew Huberman 45:24 Okay, so that people... I just want to make sure people can understand. So in, in this human study, which is the one that I felt that the popular press venues, all except one venue, um, got either semi-wrong or badly wrong (laughs) in terms of their conclusion. That was my interpretation anyway, was that either people came into the study eating basically in a 10-hour feeding window.

Satchin Panda 45:44 Yeah.

Andrew Huberman 45:44 Which goes back to my first question, which is that most people are not eating in the middle of the night.

Satchin Panda 45:47 Yeah, yeah.

Andrew Huberman 45:48 Or if they're on shift work and they are, then they're sleeping during the day anyway.

Satchin Panda 45:51 Yeah.

Andrew Huberman 45:51 So they're eating in a 10 to 12-hour feeding window anyway. So you're saying they either did caloric restriction, portion control within a 10-hour window, or another group within the study ate sub-maintenance calories, so caloric restriction-

Satchin Panda 46:05 Yeah.

Andrew Huberman 46:05 ... CR, as we're calling it, the acronym CR, but restricted that to an eight-hour feeding window.

Satchin Panda 46:10 Yeah.

Andrew Huberman 46:10 And they didn't see any difference in terms of weight loss.

Satchin Panda 46:12 Yeah. Weight loss ...

Andrew Huberman 46:13 But, but it's not all that surprising, right? I mean, if it's just a two-hour difference.

Satchin Panda 46:16 Yeah, exactly. So we have done that experiment in mice and we don't see, um, difference in not only weight loss, many other markers. And I was telling you about this, um, Joe Takahashi's paper where I told you that he allowed these mice to eat within two hours or 12 hours, sub-caloric diet.

Andrew Huberman 46:36 Two or 12?

Satchin Panda 46:37 Two or 12.

Andrew Huberman 46:38 Yeah, that's dramatic.

Satchin Panda 46:39 But still, he did not see change in longevity even within those two. So that means, um, when you do caloric restriction and then, at least per mouse, and you are within 12 hours window, um, that's, that is giving the mice the best benefit, the optimum benefit. And, um, two, three or five or 12 per mouse doesn't matter, at least for longevity.

Andrew Huberman 47:05 Can we conclude for humans that whether or not a feeding window is four hours, six hours, eight hours, or 12 doesn't matter provided the calories are, are similar or same?

Satchin Panda 47:17 Well, I won't go to that extent because we don't know

Satchin Panda 47:20 many of these. Uh, particularly we don't know how this sort of, uh, 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.

Andrew Huberman 47:33 But that should be changing, right? Because the NIH, I know this 'cause I'm on study section...

Satchin Panda 47:37 (laughs)

Andrew Huberman 47:38 ... which is just a bunch of people who re- who r- review grants, is that every grant now has to include sex as a biological variable.

Satchin Panda 47:45 Yeah.

Andrew Huberman 47:45 It's hard to get away with a, um... Or rather I should say it the way it should be stated, which is, people are required and should want to look at these phenomenon in male and female mice-

Satchin Panda 47:57 Yes.

Andrew Huberman 47:58 ... especially if there are differences.

Satchin Panda 48:00 So in this case, um, there are many... I mean, there was also another paper, um, in time-restricted feeding that also came out, a big paper showing that the, um, thermogenesis was accounting for loss in fat mass in time-restricted fed mice that was also done only in male mice. Um, so this is, um... We are paying attention to it, so we are now doing all of our studies in male and female, and we do see big differences between male and female. Coming back to humans, what typically happens is when you're trying to do four hours or six hours of time-restricted eating, people will inadvertently reduce their caloric intake.

Andrew Huberman 48:39 Yeah, just because of gut volume.

Satchin Panda 48:40 Gut volume, you can... That's...

Andrew Huberman 48:40 I tried one meal per day and, and I felt like I was eating so much at that one sitting-

Satchin Panda 48:46 Yeah.

Andrew Huberman 48:46 ... that it led to a lot of gastric distress-

Satchin Panda 48:48 Yeah.

Andrew Huberman 48:48 ... and I get tired after the meal. And part of the reason I like to do time-restricted feeding is I have more energy.

Satchin Panda 48:54 Yeah.

Andrew Huberman 48:54 And certainly in the fasted state, I feel more energized-

Satchin Panda 48:58 Yeah.

Andrew Huberman 48:58 ... especially if I'm ingesting a little caffeine or something like that.

Satchin Panda 49:00 Yeah. Um, so people will reduce, um, 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 know that this energy deficit... And in fact there is a, um, scientific term for that. It's called RED-S, relative energy deficit in sports.

Andrew Huberman 49:34 Relative energy deficit in sports. Okay.

Satchin Panda 49:36 Yeah. It's because nearly 40% of athletes, um, not the NFL guys, but (laughs) you know, a lot of people who do track and field, um, and nearly 40% of athletes actually experience this REDS, RED-S, without knowing.

Andrew Huberman 49:52 Can male and female athletes both-

Satchin Panda 49:54 Both male and female.

Andrew Huberman 49:54 ... experience REDS? So it's REDS, R-E-D-S.

Satchin Panda 49:57 R-E-D-S.

Andrew Huberman 49:57 Relative-

Satchin Panda 49:58 Energy.

Andrew Huberman 49:59 Relative energy deficit in sports.

Satchin Panda 50:01 In sports.

Andrew Huberman 50:02 Interesting. This is the first I've heard this acronym. We have a new acronym, folks.

Satchin Panda 50:05 (laughs) .

Andrew Huberman 50:05 This is good (laughs) to add to a, a list of other acronyms, but I... So males and females can experience it.

Satchin Panda 50:12 Yeah.

Andrew Huberman 50:12 So w- in females, I've heard that, um, RED-S, um, can lead to, uh, amenorrhea, so loss of, of mens- of the menstrual cycle.

Satchin Panda 50:22 Yeah. So that's, uh, so common that, uh, so prevalent that, in fact, many women, many female athletes, they take it for granted that, yes, if they are more active, then they will lose their menstrual cycle, which is, uh, which may be common, but it's not normal or optimum for health. And-

Andrew Huberman 50:40 Even if they don't want to get pregnant.

Satchin Panda 50:42 Yeah.

Andrew Huberman 50:42 Yeah.

Satchin Panda 50:43 Yeah.

Andrew Huberman 50:43 Yeah. Uh, we had an expert on female hormones come on and, and say the very same thing, that-

Satchin Panda 50:47 Yeah.

Andrew Huberman 50:47 ... regular cycling is a-

Satchin Panda 50:49 Is very important.

Andrew Huberman 50:50 ... of, of, of, uh, ovulatory menstrual cycle is, is important to try and, um, maintain.

Satchin Panda 50:55 Yeah.

Andrew Huberman 50:55 Um, and then-

Satchin Panda 50:56 So that's one, but then what is really concerning is, um, it does affect bone health, and, um, in this state, people actually, over a long period of time, they lose bone mass and their bone also becomes more prone to injury, microfracture and fractures. Um, so again, it's a risk. Means if some people are trying to eat within very short time and they're physically active, that happens. And it also has impact on, uh, means the reason why these women are losing menstrual cycle is their, um, HPG axis is disrupted, hypothalamus pituitary gonadal axis. And it starts, it may start even upstream at hypothalamus or pituitary. So that means their HPA axis, hypothalamus, pituitary and adrenal axis, may also get disrupted. One of the symptoms of RED-S is also depression, anxiety, bipolar-like symptoms, and we know that many, um, many athletes experience that. We think that, well, this, this may be just peer pressure. They're always trying to compete, and we know there are... Unfortunately, there are few athletes who just can't cope it, and there are many attempted suicide or suicide. So this is a serious issue, and, um, there's also another new topic in the lab to come up with a mouse model of RED-S and then study it. Um, but this is one risk why we should not reduce our eating interval to too so- to one meal or very short time, um, because it can have adverse side effect that we don't know now. Um, maybe in future we'll figure out when we systematically study

Satchin Panda 52:40 them. There are studies that are published showing four hours and six hours time-restricted eating has benefits on weight loss, but those are on healthy individuals and they were in the studies. So the, um, you know, the study team took a... uh, were already monitoring. They made sure that there was no sudden weight loss or weight loss below, um, some safety level. Uh, so those are very different from regular people who are, who may be even normal weight or even with, uh, within the healthy range. If they do, then they can potentially... So that's why what we think is eight to 10 hours may be the ideal spot to begin with, and, um, once you are physically active and you are also spending a lot of energy in physical activity or sports, you can even go up to 12 hours, because in mice we have done that experiment, um, up to 12 hours. They do get a lot of benefits, not all, but-

Andrew Huberman 53:39 So this is 12 hours of feeding?

Satchin Panda 53:41 12 hours of feeding.

Andrew Huberman 53:42 Yeah.

Satchin Panda 53:42 12 hours of fasting.

Andrew Huberman 53:42 Yeah.

Satchin Panda 53:43 Um, in humans, um, again, nobody has done systematically 12 hours, but there was one study in Europe, um, from Tin-Hai Collette lab, and Tin-Hai and I, we collaborate. So they used our MyCircadianClock app. This is a research app we developed just to... This is mostly used in time-restricted eating studies. And, um, he had nearly... I think he started with 200 Swiss, uh, participants, but then at the end, he selected and took very small number of group, people who are very, um, meticulous about recording all their food, and divided them into usual feeding, whatever they wanted to eat whenever they wanted to eat, and they were given the, uh, advice of Swiss nutrition advice that's given to improve health and reduce blood glucose, almost like diabetes prevention program in the US. And then the other group was given advice to eat within 12 hours. Um, this was very early on in time-restricted eating, and we thought that the mice were getting some benefit. Let's try whether 12 hours has any benefit. Um, the bottom line is, at the end of, uh, three months and six months, what, um, he reported is both groups lost same amount of body weight. Um, and then there was not too much significant difference between groups, but both groups actually improved their health.... so the bottom line is, the Swiss nutritional advice that he was giving, um, which is the standard of care there, it achieved the same amount of weight loss as just giving people this advice that eat within 12 hours. So one way to look at it, look at it as only like this. And, um, then he went to more extent and actually looked at every single meal these people consumed, so there are close to, I think, close to 60 or 70,000 meal records and pictures. He went through and then classified them to say whether these are, um, good quality food, so they call it the NOVA classification one, two, three, four. One is the food that you can almost eat raw, fruits, vegetables, um, yogurt, d- dairy products that you can almost... Without any preparation. And then second, NOVA two, is kind of home pr- home-cooked food that most people will prepare in few minutes, and then three. And then fourth one is the food that you can never prepare at home, so for example, biscuit or cookies that we usually purchase and a few other things. And usually, the NOVA four are unhealthy ultra-processed foods, so which we should not be eating, so the advice is to reduce NOVA four. And what he found was, uh, people who got all this advice, um, to re- improve their nutrition quality, they actually improved their nutrition quality. They reduced their NOVA four food and people who were in time-restricted eating, they ate within 12 hours, they did not change their nutrition quality. But what is interesting is they both got the same modest weight loss, so that begs the question that in the... Maybe Jin Hai will do this experiment (laughs) again, to combine nutrition advice with time restriction and maybe reduce the time to 10 hours and that might help. Um, so 12 hours is something that I say anyone from five-year-old to 100-year-old can do, and, um, if you are trying to maintain weight, that might be a good way, and combine that with exercise, it'll be great.

Andrew Huberman 57:20 And y- and people can more easily avoid RED-S.

Satchin Panda 57:23 Yeah.

Andrew Huberman 57:23 In that way, women... And for non-athletes or recreational exercisers, it sounds like women, if they distribute their calories across 12 hours, they're less likely to lose their menstrual cycle.

Satchin Panda 57:33 Yeah, so, uh, 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 and once-

Andrew Huberman 57:44 We will provide a link to that, by the way.

Satchin Panda 57:46 Yeah.

Andrew Huberman 57:46 It's a great, it's a great tool.

Satchin Panda 57:47 Yeah.

Andrew Huberman 57:47 But-

Satchin Panda 57:48 But once in a while, we do get this input from some women saying, "Oh, I started doing your time-restricted eating and I am seeing all these problems." And then I ask them, "Okay, so what else are you doing?" They typically (laughs) improved their nutrition quality, so they're eating only salad and few... And they're trying to increase their fiber intake and it's really hard to eat so much of uncooked food because cooking helps to absorb more nutrient. And then at the same time, they're running five miles every day. And, of course, all of this combinedly can lead to RED-S-like symptom, so that's why 12, I think, is a good point if you're combining, um, physical exercise and better nutrition quality because in mice also we have seen that if mice are eating healthy food, and they're eating within 10 to 12 hours, then they also live longer than mice that are eating healthy food but distributing their calorie over a long period of time. And this is, um, Rafat Dicaba's, um, finding from NIH. He has systematically done this study with two different types of diet and in mice, and he finds the same thing, that even mice that are eating within 12 hours, they do live longer than mice that eat randomly, even healthy

Satchin Panda 59:04 food.

Andrew Huberman 59:05 I, 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 Press journals, excellent journals, which explored time-restricted feeding in the context of low carbohydrate or non-low carbohydrate diet. So it was low carbohydrate versus low carbohydrate and time-restricted.

Satchin Panda 59:25 Yeah.

Andrew Huberman 59:25 So these all caloric matched-

Satchin Panda 59:27 Yeah.

Andrew Huberman 59:27 ... right, between groups and then non-low carbohydrate diet, so a sort of more standard, uh-

Satchin Panda 59:33 Yeah.

Andrew Huberman 59:33 ... I think it was somewhere in the neighborhood of 60% of calories from complex carbohydrates.

Satchin Panda 59:36 Yeah.

Andrew Huberman 59:36 And, and as I recall, the, um, the greatest weight loss... Remember, same calories across groups, folks... Um, was achieved with low carbohydrate plus caloric restriction.

Satchin Panda 59:47 Yeah.

Andrew Huberman 59:48 Um, and I wondered why all the popular-

Satchin Panda 59:51 (laughs)

Andrew Huberman 59:51 ... news, venues didn't cover that study.

Satchin Panda 59:53 (laughs)

Andrew Huberman 59:54 Um, but that's why I'm bringing it up now. I thought this is really interesting. And, um, and I'm somebody who's, uh, cycled low carbohydrate diet, um-

Satchin Panda 1:00:00 Yeah.

Andrew Huberman 1:00:01 ... before. I find it hard to sleep after about three or four days of being on a low starch-

Satchin Panda 1:00:06 Yeah.

Andrew Huberman 1:00:07 ... diet, just personally. I, so I like to eat some starches.

Satchin Panda 1:00:09 Yeah.

Andrew Huberman 1:00:10 Especially if exercising intensely or working intensely. That's just-

Satchin Panda 1:00:13 Yeah.

Andrew Huberman 1:00:13 ... a little editorial there that, um... But look, I know many people who do just feel better on a low carbohydrate diet, but-

Satchin Panda 1:00:20 Yeah.

Andrew Huberman 1:00:20 ... well, what do you think of those data? Because it speaks to the idea that, okay, it's not just the total number of calories. It's not just the quality of those calories. It's the timing of those calories and maybe carbohydrate restriction in conjunction with time-restricted feeding might be the best path for people who are looking to lose weight.

Satchin Panda 1:00:40 No, I, I totally agree that when it comes to nutrition, quality, quantity, and timing, all these three matter. Nearly 40% of people who maintain healthy body weight, because 60% are overweight or obese, 40% are maintaining healthy body weight. And out of those 40%, I would say nearly majority of them are very aware about how much they're eating and what quality of food they're eating.

Andrew Huberman 1:01:04 Ah, so you're really an optimist. You're looking at the 40% of the glass that's, uh-

Satchin Panda 1:01:08 (laughs)

Andrew Huberman 1:01:08 ... or should we say not full to...

Satchin Panda 1:01:10 (laughs)

Andrew Huberman 1:01:10 T- uh, that was a pun intended. But the, um... No, that's a very interesting way of looking at it. Rather than saying, you know, "Why are 60% of Americans obese?"... uh, saying, "Why are 40% not obese?"

Satchin Panda 1:01:21 Yeah.

Andrew Huberman 1:01:21 That's a very interesting way to look at it.

Satchin Panda 1:01:23 Yeah. I mean, um, subconsciously, we are always making that decision, means I know- means I'm sure that you are not going and eating, um, cheeseburger every day because, um-

Andrew Huberman 1:01:33 Exactly.

Satchin Panda 1:01:33 ... you want to improve.

Andrew Huberman 1:01:34 I know. Yeah.

Satchin Panda 1:01:34 You want to get fit.

Andrew Huberman 1:01:35 No, yeah, exactly. I wouldn't feel good-

Satchin Panda 1:01:37 So essential.

Andrew Huberman 1:01:37 Yeah. I enjoy a cheeseburger now and again, but I, um-

Satchin Panda 1:01:39 Yeah.

Andrew Huberman 1:01:40 No, not- certainly not at this stage or any stage of my life. I think that, um, I think people... I actually think the pandemic had a lot to do with this. I think that people started to take a look at what they were doing to-

Satchin Panda 1:01:53 Mm-hmm.

Andrew Huberman 1:01:54 ... support or not support their health generally.

Satchin Panda 1:01:56 Yeah.

Andrew Huberman 1:01:57 I know people gained a lot of weight during the pandemic. Other people got really into fitness.

Satchin Panda 1:02:00 (laughs)

Andrew Huberman 1:02:00 I've seen some colleagues who- you've always maintained, um, th- uh, r- you've always been in good shape. Actually, this is the first time I've seen you in a while, and you seem to have aged backwards.

Satchin Panda 1:02:07 (laughs)

Andrew Huberman 1:02:07 So you are an, uh, a poster, uh, for your own, um, ideas and hypotheses-

Satchin Panda 1:02:13 Yeah.

Andrew Huberman 1:02:13 ... about time-restricted feeding, but, but I, um, I noticed that during the pandemic, a number of people emerged from the pandemic in better shape-

Satchin Panda 1:02:20 Yeah.

Andrew Huberman 1:02:20 ... other people in much worse shape. It seemed like there was a- it was a- like a bimodal distribution there.

Satchin Panda 1:02:24 Yeah.

Andrew Huberman 1:02:25 Um, so yeah, I get the sense that starting and stopping eating at more or less the same time each day, even if caloric restriction is not the main focus-

Satchin Panda 1:02:37 Yeah.

Andrew Huberman 1:02:38 ... has additional benefits. Um, can we talk about some of those benefits as they relate to the other things that impact health? So for instance, if you're starting and stopping eating at more or less the same times each day-

Satchin Panda 1:02:49 Mm-hmm.

Andrew Huberman 1:02:50 ... are you sleeping better? Are you getting more predictable, uh, shifts in alertness and sleepiness? Like, can you predict when you'll feel good enough to exercise?

Satchin Panda 1:03:00 Yeah.

Andrew Huberman 1:03:00 Uh, maybe we could talk about that because you, of course, um, are well-known for time-restricted feeding and the science around that, but also other things as well, um, not the least of which is circadian biology generally.

Satchin Panda 1:03:10 Yeah.

Andrew Huberman 1:03:10 So I always think of the main timekeepers for our system being feeding, light, activity-

Satchin Panda 1:03:17 Yep.

Andrew Huberman 1:03:18 ... and social connection.

Satchin Panda 1:03:19 Yeah.

Andrew Huberman 1:03:19 Did I miss- and maybe temp- and temperature.

Satchin Panda 1:03:21 Yeah.

Andrew Huberman 1:03:22 Yeah. So how do these combine with one another, uh, using f- timing that we begin and stop feeding as kind of an anchor point? Can we explore that a little bit?

Satchin Panda 1:03:29 Yeah, so, you know, we got into this, um, beginning and end, and then we- you asked whether calorie, how much calorie will break the fast, um, one thing that I want, um, the listeners and viewers to bring back to this timing of when we- when we are breaking the fast, because we equate health with weight, body weight, and, um, that's when, uh, we are talking about nutrition quality and quantity because both of them have impact. So now let's think about mental health 'cause a lot of people who struggle with mental health, they have anxiety or, um, depression, and also, um, so gut health because, uh, there are a lot of people who also have acid reflux or heartburn, and we know that acid reflux or heartburn can be exacerbated by caffeine intake in empty stomach. Um, those who have acid reflux or heartburn, they're prone to that, and, um, having black coffee in the morning before any food, um, can upset their stomach. So that's why in those cases, it's very clearly that caffeine for them becomes the trigger and that something, the food is supposed to come and then the stomach is not seeing the food so it's overreacting, producing excess acid, and that comes up to the esophagus and that's what they experience. Um, so if people have that kind of condition, then maybe they should consider when they drink their first coffee is breaking their overall fast or kind of putting their- putting their health at risk for acid reflux. The other thing is people who have anxiety, panic attack, um, we know that caffeine can, (laughs) jazz you up, so-

Andrew Huberman 1:05:21 Especially on an empty stomach.

Satchin Panda 1:05:22 ... especially on an empty stomach. So for them, again, caffeine can be a trigger, so that's why, um, 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. Um, in those cases, w- when we consume that caffeine in the morning can affect, so-

Andrew Huberman 1:05:53 Do you avoid caffeine in the morning?

Satchin Panda 1:05:55 No, actually, um, here is the interesting, uh, history about caffeine, and this is something I did not know, and, um, I was once invited to this, uh, history of nighttime activity, and maybe we can take a little bit of detour and talk about, uh, nighttime activity because that fascinates me as a circadian biologist 'cause over the last 200,000 years, means we assume that humans, homo sapiens evolved 200,000 years ago, so we have been, as a species, we have been living on this planet for 200,000 years, and only in the last, you can say couple of thousand or 5,000 years when we came to control fire or maybe you can even go back 100,000 years, there is some debate. Um, so then the question is, well, when we control fire and we lighted up the fire and we could light up whenever we wanted, we can add fuel and we can stop the fire when we don't want it. That's the key ability in humans that differentiates them from all the other species. No other species, we can always say, yes, there are signs of this intelligent, um, decision making, for example, we know many crows can make decision, many, many animals, they kind of figure out, strategize how to get food, but controlled use of fire is something very...... specific to human. And when we started, um, controlling fire, fire did not essentially extend the day, because fire created a evening that was very different from what people did during the day, and what people used to do during the day. They worked a lot, means gathering food (laughs) was almost everything that we did. And so in the evening, after the, after the, uh, after we brought, uh, food, mostly tubers or maybe lentils to cook or once in a while s- um, animals so that we can, we could barbecue, um, all of these things happened around fire. And fire was so expensive that, uh, it w- it was mostly communal fire. So if you go back to, for example, Maasai and, uh, all these ancestr- uh, sorry, um, uh, populations that have no access to electricity and are still living kind of that, uh, historical life, uh, fire is a communal event. And they sat around, they cooked food, and then what happened? They did not talk about work. They talked about, um, culture. They talked, they sang, they danced, they, uh, strategized. Um, that's how politics started, philosophy started, science started. All of these things that are very unique to human civilization started around fireside chat. So, um, in that way, if we think about it, we are still doing fireside chat. The only thing is we have the microwave and the t- television, uh, or social media. (laughs)

Andrew Huberman 1:09:01 And now we chat with our thumbs.

Satchin Panda 1:09:03 (laughs) Right. So it's still, so we are hooked to that evening activity, because that's when we are completely free from the pressure of the work, and we want to express ourself. That's our independent time. So that's why most people find it very difficult to do time-restricted eating and stop eating at 6:00, because it's ingrained in our, in our even DNA, that we want to eat and socialize in the evening.

Andrew Huberman 1:09:30 Right.

Satchin Panda 1:09:32 So now, uh, let's fast-forward and see what is the role of coffee in this? (laughs) And if you look at coffee consumption, particularly cafe, uh, where people can come and have a little bit of coffee and socialize, it also started as a evening activity. And, um, this is in, um... Now we can go back to Istanbul, because that's one place where coffee, cafes started in mid-16th century. So if you, we are talking about 1540 to 1570, um, and that's when, um... I'm sorry, I'm forgetting the name of historians who, (laughs) who actually invited me in. Uh, okay, his name is Cemal, uh, Ceyfettin. And, uh, um, I must be butchering the name, but I will try to find it.

Andrew Huberman 1:10:21 It's all right. We will 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.

Satchin Panda 1:10:32 Yeah. Um, I actually am even checking right now in my, uh, EndNote library. It's not picking up that.

Andrew Huberman 1:10:37 That's all right. We, we'll provide a link.

Satchin Panda 1:10:39 So I must be... Yeah.

Andrew Huberman 1:10:39 We'll provide a link.

Satchin Panda 1:10:39 So what happened was, um, so coffee was introduced, and, um, people came and, uh, drank coffee and talked about politics. (laughs)

Andrew Huberman 1:10:48 At night.

Satchin Panda 1:10:49 At night, at evening. And it actually started with, uh, with, uh, Sufi branch of Islam, because they are the ones who, uh, consumed coffee in the evening, and this is the branch of Islam where they actually sing and dance and all that happened in the evening. So singing, dancing, um, by the Sufis, and then here in Istanbul, people started congregating and having, um, uh, talk about politics. But then around the same time, um, some, you know, in Turkey, there was a good sizable number of, uh, Muslims who have to do five prayers a day, number of prayers at set time. The first prayer is very early in the morning. And then they figured out that if they wake up and immediately have coffee, then they can stay awake for the first prayer. And in that way, they felt pretty good when they woke up. So that's how it started as a morning drink, to stay awake and kind of get, get on with the day. But what happened was, I don't know whether you have ever tried Turkish coffee. It's very thick.

Andrew Huberman 1:11:58 Mm-hmm. Yeah, I ha- a few years ago, right before the pandemic, 2019, I traveled to Turkey. It was, uh, first of all, the food is amazing. The coffee is indeed very, very thick.

Satchin Panda 1:12:08 Yeah.

Andrew Huberman 1:12:09 Um, and I have a pretty high caffeine tolerance-

Satchin Panda 1:12:13 Yeah.

Andrew Huberman 1:12:13 ... um, from drinking so much coffee and yerba mate over the years, and still do. I really enjoy it. But, um, yeah, it's, it's very intense. And, uh, so what you're saying is that, um, coffee intake started as a way to extend into the night.

Satchin Panda 1:12:28 Yeah.

Andrew Huberman 1:12:28 The ability to extend into the night at all was because of the ability to harness fire. And then coffee's stimulatory properties were leveraged toward morning, uh, which is essentially, like, uh, the way I think about it, we did an episode on caffeine, and some, uh, someone else, Michael Pollan, not I, described it this way, that you're sort of taking a loan out on your energy bank account with coffee.

Satchin Panda 1:12:51 Yeah. Yeah.

Andrew Huberman 1:12:51 You're suppressing the adenosine system. Adenosine makes you sleepy.

Satchin Panda 1:12:54 Yeah. Yeah.

Andrew Huberman 1:12:54 But that adenosine system will kick in later.

Satchin Panda 1:12:55 Yeah. Yeah.

Andrew Huberman 1:12:55 So you're, you're, it's a credit card, of sorts-

Satchin Panda 1:12:57 Yeah.

Andrew Huberman 1:12:57 ... with an interest.

Satchin Panda 1:12:58 Yeah.

Andrew Huberman 1:12:58 Right?

Satchin Panda 1:12:59 Yeah.

Andrew Huberman 1:12:59 Right?

Satchin Panda 1:12:59 Yeah.

Andrew Huberman 1:12:59 And the interest being, um, an energetic lag that you're going to-

Satchin Panda 1:13:04 Yeah.

Andrew Huberman 1:13:04 ... uh, experience in the afternoon. Yeah.

Satchin Panda 1:13:06 But what happened was with the, uh, strong coffee, um, 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.

Andrew Huberman 1:13:21 Ah, so coffee actually led to the development-

Satchin Panda 1:13:24 Mm-hmm.

Andrew Huberman 1:13:24 ... of breakfast, not the other way around.

Satchin Panda 1:13:26 And that... Uh, yeah, so it does lead to-

Andrew Huberman 1:13:27 That's very heartening, uh, no, again, no pun intended, uh, for the, uh, the-... caffeine, uh, lovers among us, uh, of which I count myself-

Satchin Panda 1:13:37 Yeah.

Andrew Huberman 1:13:37 ... one of those.

Satchin Panda 1:13:38 So essentially, the food before coffee became breakfast. So you kind of give something to your f- uh, to your stomach so it's busy digesting that, and then when the coffee comes in, it's not reacting to coffee and creating, um, acid reflux.

Andrew Huberman 1:13:53 So it wasn't... It's fascinating. So it wasn't that breakfast is necessary on its own, it was essentially a buffer against the gastric distress caused by caffeine intake.

Satchin Panda 1:14:04 At least in that culture and s- in that context. Um, we cannot say that whether the same thing happened in all over the world where coffee is not consumed, but still people eat something in the morning. Um...

Andrew Huberman 1:14:15 But you said you start your, um, first meal, uh, of the day-

Satchin Panda 1:14:18 Around 8:00.

Andrew Huberman 1:14:19 ... at around 8:00. What time do you wake up?

Satchin Panda 1:14:20 I wake up around 6:00.

Andrew Huberman 1:14:21 Okay.

Satchin Panda 1:14:22 5:30 to 6:00.

Andrew Huberman 1:14:22 What time do you have your first caffeine?

Satchin Panda 1:14:24 No, actually I have... So that's why I brought up this, uh, story because I have coffee after my breakfast. (laughs)

Andrew Huberman 1:14:29 Fantastic. I'm a big proponent of delaying caffeine intake-

Satchin Panda 1:14:32 Yeah.

Andrew Huberman 1:14:32 ... for a few hours after waking-

Satchin Panda 1:14:34 Yeah.

Andrew Huberman 1:14:34 ... for other reasons that-

Satchin Panda 1:14:35 Yeah.

Andrew Huberman 1:14:35 ... my listeners have h- heard me s- talk about endlessly, so I won't bother with that now, but I think, um, allowing the, uh... just suffice to say that allowing some of the natural waking up signals to occur-

Satchin Panda 1:14:47 Yeah.

Andrew Huberman 1:14:47 ... and using light to kind of clear away and adenosine to further extend and activity, uh, is better than using a stimulant but until a few hours later. This is fascinating because, uh, I've never thought about the link between extension into the night, socialization or socializing rather, feeding, and caffeine.

Andrew Huberman 1:15:07 I'd like to take a brief break and thank our sponsor, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. The problem with a lot of blood and DNA tests out there, however, is that you get data back about metabolic factors, lipids and hormones and so forth, but you don't know what to do with those data. InsideTracker solves that problem and makes it very easy for you to understand what sorts of nutritional, behavioral, maybe even supplementation-based interventions you might want to take on in order to adjust the numbers of those metabolic factors, hormones, lipids, and other things that impact your immediate and long-term health, to bring those numbers into the ranges that are appropriate and indeed optimal for you. If you'd like to try InsideTracker, go to insidetracker.com/huberman. They have a special promotion right now through Pi Day, March 14th, where you can get 31% off their Ultimate Plan. This is their biggest promotion of the year. Again, if you go to insidetracker.com/huberman, you can get 31% off their Ultimate Plan.

Satchin Panda 1:16:20 No, actually, I'm kind of, um, speaking what many other researchers have found, and this, this particularly, this Fireside Chat, I'm forgetting again the name of the scientist. I think she's from University of Washington, Seattle. Um, she went to Africa and kind of recorded what people are talking. Of course she could not understand what they were talking.

Andrew Huberman 1:16:42 Twitter and whether or not Tesla's stock is going up, of course.

Satchin Panda 1:16:45 (laughs)

Andrew Huberman 1:16:46 No, no, no, just, just kidding folks. (laughs)

Satchin Panda 1:16:49 And then came back and tried-

Andrew Huberman 1:16:50 (laughs)

Satchin Panda 1:16:50 ... to translate it and then figured out that-

Andrew Huberman 1:16:51 Exactly.

Satchin Panda 1:16:52 ... what they were talking during daytime-

Andrew Huberman 1:16:53 (laughs)

Satchin Panda 1:16:53 ... and in the evening were very different. So-

Andrew Huberman 1:16:55 Mm-hmm.

Satchin Panda 1:16:55 ... um, so, so, uh, yeah-

Andrew Huberman 1:16:58 What are they talking about at night? Do you-

Satchin Panda 1:17:00 So, exactly. So this is, uh, like they're talking about, um, matchmaking and talking about politics and, uh, strategizing, to gather food or, or, and, uh, even singing and dancing. Uh, so this is, um, if you think, if we think about it, how we manage sunset to our bedtime, what we do between sunset and bedtime affects most of our health.

Andrew Huberman 1:17:30 I'm gonna think about that for a moment. I totally agree. Um, and by the way, I'm a huge believer and h- and I'm in, living in great hope for the idea that right now I do think that scientists understand a lot more about the different stages of sleep, slow wave sleep, REM sleep, et cetera, than we do active waking states.

Satchin Panda 1:17:50 Mm-hmm.

Andrew Huberman 1:17:50 Like, we talk about being focused or being alert, but that's not... those aren't scientific terms-

Satchin Panda 1:17:54 Yeah.

Andrew Huberman 1:17:54 ... as we know. But I do believe and I've noticed a distinct difference between the first eight hours of the day in terms of cognition. And we know that the catecholamines are at much higher levels plus cortisol, so-

Satchin Panda 1:18:07 Yeah.

Andrew Huberman 1:18:07 ... dopamine, cortisol, epinephrine, all of that is really at much higher levels than in the later evening. And so they, this evening time, it almo- certainly in the context of mental health, we know that morning and evening we are basically different creatures.

Satchin Panda 1:18:20 People. Yeah.

Andrew Huberman 1:18:20 Yeah. Completely.

Satchin Panda 1:18:21 We're different creature. Yeah. So that's why I, I think in the evening, if you think about it, um... Again, this is, uh, again, another set of research from, um, my good friend Horacio, who-

Andrew Huberman 1:18:34 Iglesias.

Satchin Panda 1:18:35 Yeah.

Andrew Huberman 1:18:35 Oh, yeah.

Satchin Panda 1:18:36 Yeah. (laughs)

Andrew Huberman 1:18:36 I'm a big fan of Horacio's.

Satchin Panda 1:18:38 (laughs) Yeah.

Andrew Huberman 1:18:38 Another, uh, he's a fellow Argentine, so occasionally we riff about things related to that. But he's a wonderful biologist, uh-

Satchin Panda 1:18:44 Yeah.

Andrew Huberman 1:18:44 ... are you guys collaborating?

Satchin Panda 1:18:45 Yeah.

Andrew Huberman 1:18:46 Okay.

Satchin Panda 1:18:46 He's, he's kind of a... I say he's very humble and keeps a low profile, but he does amazing, amazing research.

Andrew Huberman 1:18:53 Totally agree.

Satchin Panda 1:18:54 And he does research that, um, we want to know but nobody is ready to do it because field research is very difficult to go to the wilderness or go to the places where there is no electricity and then record, um, when these people are eating, sleeping, or in this case, activity, exposure to light. Uh, that's what Horacio has done. And, uh, he puts this ActiveWatch, which is kind of a modern, um, activity tracker. Um, but it's a little bit more refined because it also collects, uh, light information. What he found was most of these Argentinian Tobars who have no access to electricity-... they consistently go to bed somewhere between three to three-and-a-half hours after sunset. So, this is very important because we always think that, um, our ancestors when they didn't have electricity, as soon as the sun went down, they just went to sleep. No. The fire extended their evening, so they were staying awake for three to four hours, kind of, uh, m- you know, um, decompressing themselves that we say, and then doing all these, uh, activities, cooking, sharing meals, and then they would go to sleep. And if you look at the sleep onset variability, it was very small, like they're going to bed almost within 15 to 30 minutes standard deviations. (laughs) Standard-

Andrew Huberman 1:20:16 So, no night owls versus morning people, this kind of thing.

Satchin Panda 1:20:19 Exactly, so we'll get to that.

Andrew Huberman 1:20:20 None of this, this, uh, the m-

Satchin Panda 1:20:22 (laughs)

Andrew Huberman 1:20:23 I get attacked by m- uh, for many reasons that just goes with the business I'm in of being public facing these days. But every time I talk about viewing sunrise or low angle sunlight, you know, getting some sunlight early in the day, someone says, "Well, I'm a night owl," and they just in, it's almost like a, a protest of trying to protect identity.

Satchin Panda 1:20:41 Yeah. Yeah.

Andrew Huberman 1:20:41 It's become this ideological i- i- i- identity related thing, "I'm a night owl." "I'm a morning person." "I'm not." But you're telling me that in these cultures where there isn't electricity but there is fire, people are going to sleep within, all of them, within about 15 minutes of one another.

Satchin Panda 1:20:57 Y- yeah.

Andrew Huberman 1:20:58 So, then there is no such thing-

Satchin Panda 1:20:59 Okay, yeah.

Andrew Huberman 1:20:59 ... as a night owl or a morning person in the context of...

Satchin Panda 1:21:01 Yeah, so Horacio, I actually asked him pointedly because, um, uh, and then he said no, he, he has not seen. He actually has tracked hundreds of people and if we ask, there are many, many sleep researchers or at least the public facing sleep, um, physicians or experts, they will say, "Yeah, we can say one-third of people are night owl, one-third are morning and then one-third are in between." But...

Andrew Huberman 1:21:25 Yeah, they call them like bears, wolfs, and you know, and I'm not being disparaging of that idea. I think people really do feel as e- uh, as if they orient towards one pattern or another.

Satchin Panda 1:21:34 When I was an undergrad student, I never went to bed before midnight. And actually, midnight was my going to bed time, exactly like 11:45, I'll try to get ready to hit bed and then by 12:00, I'm in bed and I used to get up at 6:00, 6:15 with an-

Andrew Huberman 1:21:50 That's still, that's a pretty short sleep.

Satchin Panda 1:21:51 ... with an alarm, of course. And but then daytime, I used to take 45 minutes to one hour nap and that was regular, like even if, uh, whenever I got time. Of course, in college, you know, you don't have the whole day unlike in high school, you don't have (laughs) opportunity to nap but in college-

Andrew Huberman 1:22:10 Right.

Satchin Panda 1:22:10 ... you can.

Andrew Huberman 1:22:10 I might have been one of those kids with his hoodie on napping on the desk, but they come around and they wake you up.

Satchin Panda 1:22:14 Yeah.

Andrew Huberman 1:22:14 So, yeah.

Satchin Panda 1:22:14 But in, in, in this case, just come back to the dorm and, um, after lunch usually, I used to take nap. So, um, then in grad school, I remember I rarely went to bed before 2:00 AM and I could have clearly said that I'm a night owl and actually, I was a n- night owl. I was very comfortable staying up so late. I was very productive doing experiments, writing all these, um, manuscripts mostly, and... But then afterwards, um, when I look back in post-doc when I had, uh, when we had our daughter, um, then things started changing because you have to put the baby to sleep, and then after the baby sleeps, it's almost when you have a baby, your life revolves around the baby. (laughs) So, then we have to dim down the light. There is no caffeine and alcohol drinking or any other things after the baby sleeps because we cannot do too much noise. So then, I realized that, no, I'm actually not a night owl and I became kind of more normal because I could go to sleep between 10:00 and 11:00 and, um, that's how I thought, "Well, maybe this is very unique to me." But what is interesting is, uh, I have another, uh, colleague, um, good friend, uh, Ken Wright Junior-

Andrew Huberman 1:23:43 Uh, Colorado.

Satchin Panda 1:23:43 ... at Colorado.

Andrew Huberman 1:23:44 Yeah.

Satchin Panda 1:23:44 And he also had grad students and, um, and post-docs like me who strongly believed that they were night owls, um, just like everybody else, and he took, Ken took the whole lab for camping and when they were camping, of course, there is less light and lot of physical activity, hiking during the day, and they all went to bed, um, between 9:00 and 10:30 PM. So-

Andrew Huberman 1:24:10 I love that study.

Satchin Panda 1:24:11 Yeah.

Andrew Huberman 1:24:12 What Satchin just described-

Satchin Panda 1:24:13 (laughs)

Andrew Huberman 1:24:13 ... was a study. I think there were two studies of...

Satchin Panda 1:24:15 Uh, there were two, yeah.

Andrew Huberman 1:24:15 And, um, what's interesting as I recall is that after going camping for a weekend where people, uh, wake with the s- more or less with the sunrise.

Satchin Panda 1:24:24 Yeah.

Andrew Huberman 1:24:24 And go to sleep a few hours after sunset.

Satchin Panda 1:24:27 Yeah.

Andrew Huberman 1:24:28 Their melatonin rhythms and cortisol rhythms and sleep wake rhythms persisted on that schedule for several weeks-

Satchin Panda 1:24:36 Yeah.

Andrew Huberman 1:24:36 ... despite returning-

Satchin Panda 1:24:38 Yeah.

Andrew Huberman 1:24:38 ... to environments where there was a lot of artificial lighting, which I find amazing that-

Satchin Panda 1:24:42 Yeah.

Andrew Huberman 1:24:43 ... just a weekend of consistent rising and f- um, going to bed with the sunrise and sunset-

Satchin Panda 1:24:49 Yeah.

Andrew Huberman 1:24:49 ... more or less allowed a reset that was very long lasting.

Satchin Panda 1:24:53 Yeah. So, um, actually, even in Horacio's study, he found that almost all the Tobas, they wake up around, uh, sunrise time. And it's amazing when I look at the standard deviation, it's like so tight and... (laughs)

Andrew Huberman 1:25:08 So take that night owls, so-called night owls. I also did in graduate school, I would work until 2:00 AM. I loved it. I would blast music in the lab. Everyone was at home pretty much, not everyone, but they were the, the night crew.

Satchin Panda 1:25:19 Yeah.

Andrew Huberman 1:25:19 And then I'd get in sometime around, get up or sometime around 9:30, 10:00, and then get in around 11:00 and it was no problem because I was going to stay so very late. And then over time, I noticed I've become more locked to a standard schedule. So I think what we're saying is that the clock can, our internal clocks can shift-

Satchin Panda 1:25:36 Yeah.

Andrew Huberman 1:25:36 ... but this idea that we are genetically-... bias towards one schedule or another may need revisiting. That's what, that's the conclusion I'm taking from this.

Satchin Panda 1:25:45 Yes, so I guess there are a couple of aspects. One is, um, you know, some people are genetically so pre-programmed because the other flip side is, uh, what is called technically familial advanced sleep phase syndrome. So these people, um, you can give them caffeine or whatever, but they will fall asleep, say at eight o'clock. They cannot stay awake till nine or 10:00. And since it's a very strong phenotype in sleep and circadian rhythm field, they're very well-studied. So in fact, uh, Louis Ptacek and Ying-Hui Fu, they were the