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

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science and science-based tools

00:00:04.900 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.220 | and I'm a professor of neurobiology and ophthalmology

00:00:13.060 | at Stanford School of Medicine.

00:00:14.900 | Today, my guest is Dr. Sachin Panda.

00:00:17.380 | Dr. Sachin Panda is a professor

00:00:19.540 | and director of the Regulatory Biology Laboratory

00:00:21.960 | at the Salk Institute of Biological Studies.

00:00:24.940 | His laboratory has made numerous important contributions

00:00:27.500 | that impact mental health, physical health,

00:00:29.820 | and human performance.

00:00:31.420 | For instance, his laboratory discovered

00:00:33.460 | the neurons in the eye and neurons within the brain

00:00:36.620 | that regulate our so-called circadian rhythms.

00:00:38.820 | Circadian rhythms are 24-hour rhythms

00:00:41.040 | in everything from gene expression

00:00:42.420 | to the overall functioning of tissues,

00:00:44.640 | our levels of mood and alertness,

00:00:47.020 | our ability to sleep, appetite, and much, much more.

00:00:50.360 | In addition, over the last decade,

00:00:51.780 | Dr. Panda's laboratory has made critical discoveries

00:00:55.020 | in terms of how our patterns of eating over time

00:00:58.380 | impact our biology and our health.

00:01:00.720 | In particular, his laboratory pioneered discoveries

00:01:03.280 | related to so-called intermittent fasting,

00:01:05.580 | also sometimes referred to as time-restricted feeding.

00:01:08.260 | Today, Dr. Panda and I discuss how our circadian behaviors,

00:01:11.800 | everything from when we wake up to when we view light

00:01:14.660 | to when we avoid viewing light

00:01:16.600 | to when we eat and what we eat

00:01:18.860 | and when we socialize and how we socialize

00:01:22.420 | impacts our biology and our psychology

00:01:25.520 | and how all of that has a strong impact on our health.

00:01:29.820 | During today's discussion,

00:01:30.800 | you will learn how restricting your feeding

00:01:32.700 | to specific periods within each 24-hour cycle

00:01:36.120 | or perhaps even exploring longer patterns of fasting

00:01:39.340 | and eating cycles can impact everything

00:01:42.120 | from the health of your liver to your gut to your brain

00:01:45.420 | and how all of that impacts things like mood

00:01:47.680 | and your ability to perform cognitive work.

00:01:51.020 | Indeed, today's discussion goes deep

00:01:53.000 | into all aspects of intermittent fasting,

00:01:55.420 | AKA time-restricted feeding.

00:01:57.420 | We talk about the basic science

00:01:59.520 | as well as the recent clinical trials

00:02:01.660 | that have explored time-restricted feeding

00:02:03.660 | in a diverse range of people,

00:02:05.640 | including men, women, children, people with diabetes,

00:02:08.880 | people who are otherwise healthy and much, much more.

00:02:11.820 | I'm quite aware that intermittent fasting

00:02:14.300 | is a topic of much debate these days.

00:02:16.720 | We go deep into that debate

00:02:18.080 | and by the end of today's discussion,

00:02:19.880 | you can be certain that you will have learned

00:02:22.080 | all the latest and all the details,

00:02:24.620 | all made very clear to you

00:02:26.020 | thanks to the incredible expertise, discovery,

00:02:28.820 | and clear communication of Dr. Panda.

00:02:31.320 | As some of you may already know,

00:02:32.660 | Dr. Panda has authored several important books

00:02:35.240 | on the topic of intermittent fasting

00:02:36.920 | and how it can benefit various aspects of health.

00:02:40.080 | Those books include "The Circadian Code"

00:02:42.200 | and a more recent book, "The Circadian Diabetes Code,"

00:02:45.460 | both of which we've provided links to

00:02:47.120 | in the show note captions.

00:02:48.920 | In addition, if any of you are interested

00:02:50.400 | in learning more about Dr. Panda's work,

00:02:52.160 | including seeing his publications and reading

00:02:54.580 | those publications or supporting his laboratory,

00:02:57.100 | you can do that by going to his laboratory website,

00:02:59.800 | which we have also linked in the show note captions.

00:03:02.340 | Before we begin, I'd like to emphasize that this podcast

00:03:04.960 | is separate from my teaching and research roles at Stanford.

00:03:07.640 | It is, however, part of my desire and effort

00:03:09.780 | to bring zero cost to consumer information

00:03:11.660 | about science and science-related tools

00:03:13.480 | to the general public.

00:03:14.860 | In keeping with that theme,

00:03:15.860 | I'd like to thank the sponsors of today's podcast.

00:03:18.620 | Our first sponsor is HVMN Ketone IQ.

00:03:21.820 | HVMN Ketone IQ is a supplement that increases blood ketones.

00:03:26.160 | I want to be clear that I am not following a ketogenic diet.

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00:03:30.940 | They are not following a ketogenic diet.

00:03:32.840 | They are omnivores and they do eat carbohydrates.

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00:07:22.520 | And now for my discussion with Dr. Sachin Panda.

00:07:25.960 | Sachin, Dr. Panda, so good to see you again.

00:07:28.280 | - Yeah, good to see you.

00:07:29.320 | - We are colleagues still,

00:07:31.360 | but we used to be right across the street from one another.

00:07:33.520 | - Yeah, I remember those days, yeah.

00:07:35.360 | - Yeah, so I'm delighted that you're here.

00:07:37.760 | I think we're going to talk about a number of things,

00:07:39.860 | mainly intermittent fasting,

00:07:42.100 | time-restricted feeding and health,

00:07:43.580 | but also the many other things that you're doing.

00:07:46.280 | Just before we started recording,

00:07:48.160 | we were discussing your recent paper in Nature

00:07:51.040 | that involved recordings from post-mortem human retina.

00:07:54.960 | So maybe if there's time at the end, we can get back to.

00:07:57.820 | Your lab has shown that it can essentially maintain

00:08:01.120 | or resurrect neurons from dead people

00:08:06.020 | in order to potentially and eventually provide transplants

00:08:09.840 | to rescue vision in the blind.

00:08:11.340 | So that's extremely exciting.

00:08:13.040 | But of course, not the main focus of today's discussion,

00:08:15.320 | so we'll have to split it up.

00:08:17.300 | The first question I have is how am I supposed to define

00:08:22.960 | fasting and time-restricted feeding?

00:08:25.360 | Meaning when I go to sleep every night, I'm not eating.

00:08:28.600 | So in some sense, everybody is doing time-restricted feeding

00:08:32.580 | to some degree or another.

00:08:34.120 | At what point can we start thinking about

00:08:36.640 | a pattern of eating as time-restricted feeding,

00:08:38.980 | so-called intermittent fasting?

00:08:41.060 | Does it have to do with how regular one is

00:08:43.160 | about the start and stop times?

00:08:45.540 | How do you think about defining intermittent fasting,

00:08:49.980 | time-restricted feeding,

00:08:50.960 | and maybe just to simplify the conversation,

00:08:53.200 | is one term more correct than the other

00:08:56.380 | in terms of describing this incredible pattern of feeding?

00:09:00.120 | - Well, you know that intermittent fasting

00:09:02.060 | covers many types of fasting.

00:09:04.840 | Actually, it started a long time ago,

00:09:09.300 | and it's embedded into the history of caloric restriction.

00:09:12.300 | Almost 100 years ago, people showed that

00:09:16.200 | if you reduce calorie intake in a rat,

00:09:19.480 | then that rat can live for a long time.

00:09:22.420 | And in those experiments,

00:09:23.700 | the calories were reduced every single day.

00:09:27.020 | And that led to the idea that if we cut down our calories

00:09:30.480 | by 20% say, then we can potentially live longer

00:09:35.480 | by doing two things.

00:09:37.440 | One is preventing a related disease,

00:09:41.260 | or even if we fall sick, maybe we can accelerate cure

00:09:46.260 | and keep the repair mechanism going

00:09:49.460 | so that we can live longer.

00:09:50.940 | But it was very difficult to count calories every day

00:09:56.620 | and reduce, maintain that.

00:09:59.060 | I must say that it's not that calorie restriction

00:10:02.980 | is impossible or we are not doing it.

00:10:04.820 | In fact, a lot of us, we do count calories

00:10:09.820 | in our subconscious mind.

00:10:11.680 | And so every time we take out a soda bottle or something,

00:10:16.240 | I'm looking at it, okay, 160 kilocal,

00:10:18.300 | 30 kilocal, or zero kilocal, we are doing that.

00:10:21.500 | So the point is we are doing subconsciously

00:10:24.220 | some kind of calorie counting,

00:10:27.900 | but reducing calorie by 20, 30% every single day

00:10:31.760 | is not possible for many people.

00:10:33.440 | So then the idea came in mouse and rat experiment,

00:10:37.880 | whether they can eat every other day.

00:10:40.820 | And in fact, this every other day feeding

00:10:46.780 | also led to very similar,

00:10:49.220 | almost equivalent health improvement

00:10:51.400 | as continuous calorie restriction.

00:10:56.720 | So then the idea was, well,

00:10:59.060 | every other day is a little bit hard for humans,

00:11:01.480 | but just imagine I would just get to eat

00:11:04.540 | only one day and then another day.

00:11:06.340 | Then the idea came, well, for humans,

00:11:09.800 | can they eat less for one or two days in a week?

00:11:13.560 | So that led to this 5-2 diet

00:11:16.460 | where people can eat for five days

00:11:18.380 | and then two days they have to reduce calories.

00:11:20.300 | So that's also, intermittently people are fasting.

00:11:24.740 | Then as you know, Walter Longo also came with this idea

00:11:27.940 | that periodic fasting, maybe four or five days

00:11:30.320 | in every month or two months, three months,

00:11:32.620 | you can fast or reduce calorie.

00:11:35.280 | And he also found many benefits

00:11:37.840 | of calorie restriction was there.

00:11:40.420 | - Were those studies on humans?

00:11:42.600 | - Many of the studies started in mice,

00:11:45.080 | but alternate day fasting, 5-2 and Walter's periodic fasting,

00:11:50.080 | all of them have now been done in humans,

00:11:54.020 | not for longevity, of course,

00:11:55.420 | because you cannot do those for a long time,

00:11:58.480 | but for weight maintenance,

00:12:00.820 | for reducing some signs of aging or reversing,

00:12:03.820 | those things have been done.

00:12:04.760 | So all of them have been done in humans,

00:12:07.580 | mostly healthy humans, and in some cases,

00:12:10.860 | people with prediabetes or some aspects of metabolic disease.

00:12:15.100 | So that led to the idea that all these forms of fasting

00:12:20.260 | in which the total calorie can take on any given day

00:12:25.260 | is reduced for one or more days in a week, a month,

00:12:30.660 | that umbrella term became intermittent fasting.

00:12:35.520 | So if you look up the scientific literature,

00:12:39.540 | most intermittent fasting involves

00:12:41.980 | intentionally reducing calories

00:12:44.180 | for at least one or two days in a week

00:12:47.980 | or a few days in a month.

00:12:50.940 | So when we published time restricted feeding,

00:12:55.420 | the initial mouse experiments,

00:12:58.220 | and even now most of the mouse experiments,

00:13:01.040 | we want to test what is the impact of time restriction

00:13:04.460 | versus calorie restriction.

00:13:06.660 | So in these experiments,

00:13:07.660 | we don't reduce calorie on any day of mouse life.

00:13:12.080 | So the mice eat the same number of calories

00:13:14.940 | as the ad libitum fed mice,

00:13:17.780 | but still they see health benefit.

00:13:20.040 | So that's why we call it time restricted feeding.

00:13:22.820 | But since it involves living without food for several hours,

00:13:27.820 | for some people, which is, it can be very difficult.

00:13:32.460 | The initial experiments was done,

00:13:34.700 | they were done for eight hours of feeding

00:13:36.680 | and 16 hours of fasting.

00:13:38.700 | That kind of became popular.

00:13:40.600 | And so that's why people use the same term

00:13:44.100 | as intermittent fasting.

00:13:45.460 | And now if you say intermittent fasting

00:13:48.780 | in popular literature or popular media,

00:13:51.260 | then people usually refer to time restricted eating.

00:13:54.640 | So now coming back to how do you define

00:13:57.920 | time restricted feeding?

00:13:59.160 | So the way we have been trying to define experimentally

00:14:04.680 | and also in literature is trying to confine

00:14:08.680 | all your energy intake from solid and liquid food combined

00:14:15.440 | within a consistent window of eight to 12 hours,

00:14:19.880 | because that's something that's doable.

00:14:21.400 | Of course, people have done time restricted feeding

00:14:24.520 | with four hours, six hours,

00:14:26.120 | and some people even try to eat everything

00:14:27.940 | within two hours, one meal a day.

00:14:29.880 | But the point is those are not feasible

00:14:34.700 | to maintain for a very long time for a lot of people.

00:14:37.740 | - One question about the six hour versus eight hour

00:14:42.020 | versus 12 hour feeding window.

00:14:45.180 | Is it important that the feeding window

00:14:48.780 | begin and end at the same time more or less?

00:14:51.940 | - Yeah, more or less.

00:14:52.780 | - And if so, how much flexibility is there?

00:14:54.420 | So for instance, I'm somebody that

00:14:56.920 | I am not terribly hungry in the morning.

00:14:59.260 | I like to drink water, usually some caffeine

00:15:03.360 | and electrolytes in the period before my first meal.

00:15:06.780 | And my first meal always lands sometime

00:15:08.460 | between 11 a.m. and 12 noon.

00:15:12.620 | There are exceptions occasionally.

00:15:15.180 | I'll have a breakfast, a proper breakfast as it's called.

00:15:18.340 | I guess it would be improper

00:15:19.380 | if you're intermittent fasting for me.

00:15:21.520 | But typically 11 a.m. or noon is when I first eat.

00:15:25.420 | And my last bite of food is typically around,

00:15:27.600 | I don't know, 8, 39 p.m.

00:15:29.700 | That's what works for me.

00:15:30.940 | Is that consistency affording me any benefit?

00:15:35.380 | And let's just leave aside total caloric number,

00:15:37.720 | macronutrients, plant-based meat, et cetera.

00:15:40.020 | But is there any benefit to shortening that feeding window

00:15:44.500 | that we are aware of or extending that feeding window

00:15:48.100 | or being even more rigid about the start

00:15:51.540 | and end of that feeding window?

00:15:53.100 | - Yeah, so the start of the feeding window,

00:15:56.140 | that's interesting because the concept of timeless feeding,

00:16:02.320 | when I describe animal studies,

00:16:04.300 | it's feeding for humans, it's eating.

00:16:07.320 | So the concept actually came from the science

00:16:10.640 | of circadian rhythm.

00:16:11.820 | So that means our body has an internal timetable

00:16:16.820 | that's present in every cell, in every organ

00:16:20.820 | that pre-programs many molecular aspects of the cells

00:16:26.980 | that leads to physiology and all that stuff.

00:16:30.300 | So that essentially there is a predetermined timetable

00:16:34.860 | for every cell, every organ to do certain things

00:16:37.660 | at certain time.

00:16:39.240 | And the circadian clocks, as you and I know,

00:16:44.240 | are more sensitive to light.

00:16:47.120 | Light is the most dominant time giver.

00:16:51.660 | So for example, when daylight seven time changes

00:16:55.120 | or when we travel from one time zone to another time zone,

00:16:58.720 | we feel kind of crappy because our daily activities

00:17:03.020 | are out of sync from our internal clock.

00:17:06.860 | So that was known for a very long time,

00:17:10.500 | but then around the year 2000, 2002,

00:17:13.380 | there was a famous experiment by Uli Sibler from Switzerland.

00:17:19.340 | What he did, he just fed the mice at the wrong time.

00:17:23.900 | Mice are nocturnal, they're night feeders.

00:17:27.140 | And when he fed the mice during their time,

00:17:30.280 | the liver clock, instead of following its own routine,

00:17:34.480 | liver clock actually started following food.

00:17:37.120 | So that means by changing our feeding time,

00:17:41.080 | we can change, we can tune our liver clock.

00:17:45.280 | And subsequently the same experiment

00:17:47.760 | has been repeated many times,

00:17:49.580 | and we repeated that in 2009.

00:17:52.340 | And we figured out, yes, actually outside this brain center

00:17:58.000 | called suprachiasmatic nucleus or SCN,

00:18:01.160 | which is considered the master circadian clock,

00:18:05.820 | almost the rest of the brain even follows when we eat.

00:18:11.700 | And that came out from Pierre Chambon's lab in Europe,

00:18:16.240 | where they systematically looked at even places

00:18:20.380 | that are very close to the SCN.

00:18:21.980 | For those who know, there are some medial hypothalamus

00:18:26.620 | or paraventricular nucleus, all of this,

00:18:29.460 | within a couple of four or five millimeters of the SCN,

00:18:32.960 | but they were following food cue.

00:18:35.020 | - Amazing.

00:18:36.840 | - So then, now if we think about it,

00:18:40.340 | so for example, when the daylight seven time changes,

00:18:43.700 | just one hour change,

00:18:45.440 | or one hour change in alignment between our internal time

00:18:50.100 | and external time,

00:18:51.940 | leads to kind of feeling groggy

00:18:53.940 | and feeling not at a peak performance for one or two days.

00:18:58.500 | So the rule of thumb is when the time giver

00:19:01.540 | changes by one hour,

00:19:04.580 | then our internal clock takes at least a day to catch up.

00:19:08.700 | So that means if you're flying from LA to New York,

00:19:13.700 | you're moving through three time zones,

00:19:17.060 | then on an hour is it will take three days

00:19:20.920 | to catch up with the New York time.

00:19:22.380 | For some people it can be even slower,

00:19:24.940 | and for some people it can be two days,

00:19:27.040 | but the bottom line is, yes, there is a desynchrony.

00:19:30.500 | So then what does it mean for the body?

00:19:33.900 | So one of the function of clock is to anticipate

00:19:38.160 | when you're going to wake up, for example,

00:19:40.060 | so the blood pressure slightly goes up,

00:19:43.260 | our heart rate goes up, our breathing goes up.

00:19:46.060 | Similarly for food,

00:19:49.080 | almost every organ that is involved in feeding

00:19:52.520 | or eating digestion, all of them have clocks.

00:19:57.200 | So even from saliva production,

00:19:59.420 | that is the first phase of digestion

00:20:03.120 | to secretion of all the digestive juice in the stomach

00:20:06.920 | and then absorption of nutrient and liver metabolism,

00:20:10.440 | everything, the whole village expects

00:20:13.560 | when you're supposed to eat,

00:20:14.720 | and they're getting ready for you to eat the first meal

00:20:18.720 | after fasting for a long time.

00:20:20.980 | So that's why it's breaking the fast of breakfast.

00:20:23.480 | And when that time changes,

00:20:27.080 | when you change it by two or three hours

00:20:28.900 | from one day to another, then sometimes they're like,

00:20:32.240 | "Oh, food didn't come."

00:20:33.920 | Maybe it will come at a wrong time.

00:20:37.000 | We were at the wrong time,

00:20:38.600 | and then they'll track the new eating times.

00:20:42.380 | So suppose that one day you have been eating every day

00:20:44.960 | at 8 a.m., no, I ate at 8 a.m.

00:20:48.200 | - Is that when you start your feeding window?

00:20:50.520 | When does your feeding window shut?

00:20:53.300 | - 6 p.m., so I eat for around 10 hours.

00:20:56.200 | - Okay. - Yeah.

00:20:57.040 | And then one day, if I switch to 10 a.m.,

00:21:00.960 | then what happens is a clock is thinking,

00:21:04.040 | "Well, the food didn't arrive at eight,

00:21:06.000 | but it arrived at 10."

00:21:07.200 | Maybe tomorrow the food will arrive

00:21:08.840 | somewhere between eight and 10,

00:21:10.360 | so it will be ready around nine.

00:21:11.960 | So then the next day, if I come back and eat at eight o'clock

00:21:17.480 | and I may eat, but my clock is not ready to digest that food,

00:21:22.480 | so that's why this idea is you have to be consistent

00:21:27.520 | to take advantage of this anticipatory activity

00:21:30.560 | of a clock in different systems to get the best out of it.

00:21:34.360 | - Is there evidence that those anticipatory systems,

00:21:37.760 | as they relate to digestion,

00:21:39.480 | help us better assimilate our food?

00:21:41.360 | I would imagine so.

00:21:42.200 | I mean, if you have the gastric juices

00:21:43.680 | that are gonna help digest the proteins, fats,

00:21:45.680 | and carbohydrates, and already deployed

00:21:49.440 | at the time when you eat,

00:21:50.640 | I could imagine that food will be better utilized

00:21:52.960 | than if you don't.

00:21:54.840 | So in other words, what is the advantage

00:21:57.080 | of having these anticipatory signals

00:21:59.720 | in terms of potential health benefits?

00:22:01.960 | - The anticipatory signal is really important

00:22:04.960 | even from waking up.

00:22:06.800 | The reason why many people feel not ready completely

00:22:12.880 | when they wake up to an alarm clock,

00:22:15.600 | because the alarm clock wakes you up,

00:22:18.080 | but your body is not prepared,

00:22:19.760 | so that sleepiness after waking up to an alarm clock

00:22:23.360 | is due to our body is not prepared for that.

00:22:26.760 | And then the best example is when the daylight saving time

00:22:31.760 | changes, particularly when we have to wake up one hour early,

00:22:36.520 | what happens?

00:22:38.360 | People who have underlying heart condition,

00:22:40.900 | when they're waking up, when the body is not ready,

00:22:44.920 | your heart is not ready,

00:22:45.880 | and all of a sudden the heart has to start pumping

00:22:47.960 | a little bit harder,

00:22:49.360 | then there is chance of heart attack.

00:22:53.360 | And in fact, people have looked at hospital records

00:22:57.440 | and they find that on those days,

00:23:00.160 | there is a sharp rise in heart attacks.

00:23:03.120 | - And car accidents, right?

00:23:04.080 | - And car accidents too,

00:23:05.200 | because your brain is not coordinated,

00:23:06.960 | so you cannot make those fine decisions.

00:23:11.720 | So that's a great example of anticipatory activity.

00:23:14.720 | But coming back to digestion, one thing is,

00:23:17.880 | and this is something that many people

00:23:21.240 | might have experienced.

00:23:23.320 | There are many rhythms in our digestive system,

00:23:25.560 | and one of the rhythms is our intestine

00:23:29.040 | has this peristaltic function,

00:23:31.160 | so it kind of contracts and expands,

00:23:33.720 | and that moves food, food doesn't move due to gravity,

00:23:38.640 | so it goes back and forth.

00:23:40.880 | And that peristaltic action actually slows down at night.

00:23:44.960 | Few hours after our last meal.

00:23:47.480 | And so that's why when people eat late at night,

00:23:52.480 | for example, then that food doesn't get digested

00:23:56.320 | because there is not enough digestive juice, first thing.

00:23:59.720 | And second, even if it gets digested in the stomach,

00:24:02.240 | it doesn't move properly.

00:24:04.000 | So then the next morning people get up and think,

00:24:06.960 | of course, people consume some alcohol very often,

00:24:11.160 | and then they think that this is hangover,

00:24:13.120 | but those who don't consume alcohol,

00:24:15.440 | then they have the food hangover because it doesn't digest.

00:24:19.360 | So that's one extreme example where food at the wrong time,

00:24:23.800 | so healthy food at the wrong time can be crap or junk.

00:24:29.400 | - Yeah, I've experienced that where if I've worked late

00:24:32.560 | or I couldn't eat dinner or something and then I get home,

00:24:34.720 | I always debate whether or not to try and sleep.

00:24:37.920 | But if I'm too hungry, oftentimes it's challenging.

00:24:40.320 | And so for me, sometimes consuming something

00:24:42.880 | that at least seems easily digestible like yogurt

00:24:45.760 | or something in a liquid form is better for me

00:24:50.440 | than if I eat a meal.

00:24:51.960 | I've made the mistake of going to the refrigerator,

00:24:53.760 | being super hungry and eating a bunch of food

00:24:55.640 | at 10 or 11 p.m. and then falling asleep.

00:24:58.160 | And indeed the sleep, if I'm tired enough,

00:25:01.000 | can be quite deep, but the next morning I feel

00:25:03.880 | just completely physically and cognitively weighed down.

00:25:07.280 | So I think that what you just described

00:25:08.960 | makes a lot of sense.

00:25:09.880 | So if someone were to select a feeding window,

00:25:13.880 | regardless of whether or not it falls

00:25:16.080 | into classic intermittent fasting, time restricted feeding,

00:25:18.620 | sounds like eating your first bite of food

00:25:21.520 | and eating your last bite of food

00:25:23.520 | at more or less the same time each day has benefits.

00:25:26.860 | I have this question, you mentioned feeding versus eating,

00:25:31.480 | and I think it's actually not just

00:25:33.080 | a grammatical semantic issue.

00:25:36.960 | And here's why.

00:25:39.560 | We tend to think about when you take your first bite of food

00:25:43.140 | and then when you take your last bite of food,

00:25:45.100 | but of course, food's digested different rates,

00:25:47.880 | more fat in there is going to digest,

00:25:49.680 | make carbohydrates digest slower, et cetera.

00:25:51.720 | I mean, there's all these adjustments to the glycemic index

00:25:54.120 | and so forth with foods in combination.

00:25:56.220 | Is it better to think about not eating,

00:25:59.840 | but your fed state and blood sugar?

00:26:03.000 | So for instance, I often get asked on social media,

00:26:07.720 | does blank break a fast?

00:26:10.340 | So, and so I like to think about it scientifically,

00:26:13.200 | like, okay, does plain water break a fast?

00:26:15.880 | No.

00:26:16.700 | Does air break a fast?

00:26:17.540 | No.

00:26:18.360 | Does one grain of sugar of sucrose break a fast?

00:26:22.100 | Well, probably not,

00:26:23.200 | but does one teaspoon of sugar break a fast?

00:26:25.880 | Well, you could say yes, but transiently.

00:26:28.760 | Like, so, I mean, when we're talking about breaking a fast,

00:26:30.740 | are we talking about a rise in blood glucose

00:26:33.400 | or are there molecular signals downstream

00:26:36.240 | of a rise in blood glucose that cannot be reversed?

00:26:41.240 | In other words,

00:26:42.140 | if I'm going to eat my first meal every day at noon

00:26:43.880 | and I'm going to eat my last bite of food at 8 p.m.

00:26:48.040 | and at 9 a.m. for whatever reason,

00:26:50.580 | I have coffee with one teaspoon of sugar in it.

00:26:53.200 | I suppose in the strictest sense, I've broken my fast,

00:26:58.000 | but maybe by, if I went for a hard run that morning,

00:27:00.560 | maybe by 9.30 a.m. I'm back in a quote unquote fasted state.

00:27:03.920 | So what is the fasted state really?

00:27:06.000 | Because when I'm eating at 8 p.m.,

00:27:07.920 | just to give another example,

00:27:09.800 | I'm start fasting at 801 perhaps,

00:27:13.920 | but I have my blood glucose is elevated,

00:27:15.960 | so I'm not really fasted, I'm fed.

00:27:18.720 | It's just that I'm not eating the verb, right?

00:27:21.000 | Okay, so again, I don't want to get overly detailed

00:27:25.440 | just for sake of getting detailed,

00:27:26.680 | but I think a lot of the confusion out there

00:27:28.460 | about what breaks a fast is related specifically

00:27:31.880 | to this issue, which is if I eat a whole pizza

00:27:34.440 | after sitting around all day,

00:27:35.500 | it's very different than if I eat a whole pizza

00:27:37.120 | after having run a 26 mile marathon that day.

00:27:40.700 | Very different, metabolically speaking.

00:27:43.840 | So how should people think about fasted versus fed?

00:27:48.480 | Can we be mildly fasted versus severe fasted?

00:27:51.520 | Can we be fed-ish versus very fed?

00:27:55.360 | Anyway, I'll stop asking questions now,

00:27:58.740 | but 'cause they all relate to the same theme.

00:28:00.680 | - Yeah, no, these are very interesting question.

00:28:04.180 | And then unfortunately, as you might have seen in life,

00:28:08.500 | the most obvious questions are often unanswered

00:28:12.740 | because it's so hard to do these damn experiments.

00:28:16.000 | Because if you really want to address this in humans,

00:28:18.880 | you have to bring humans, put them in isolation.

00:28:21.680 | Just like you said, I can now imagine planning

00:28:26.080 | five or six different experiments.

00:28:27.560 | Each experiment should involve eight or 10 volunteers,

00:28:30.680 | each gender, sex, and then do it.

00:28:33.620 | So it's difficult.

00:28:34.520 | So now let's go back to see how do we,

00:28:38.480 | let's dissect it in terms of say indirect calorimetry.

00:28:43.080 | So for example, indirect calorimetry is based

00:28:46.840 | on this principle that whatever oxygen we breathe in

00:28:50.240 | and carbon dioxide we breathe out,

00:28:52.980 | if we can measure these two,

00:28:54.320 | then we can figure out whether our body in total,

00:28:58.000 | we are not saying whether it's the liver,

00:29:00.560 | gut, or fat, or muscle.

00:29:02.660 | In total, whether it's consuming glucose

00:29:06.040 | or fat as energy source.

00:29:08.720 | The idea is when we are without food for several hours,

00:29:14.560 | then ideally our body will tap onto glycogen first,

00:29:20.200 | and then do a little bit of fat.

00:29:22.600 | And then when the body is mostly running on fat,

00:29:25.440 | then that ratio of CO2 to oxygen will come to 0.7.

00:29:32.480 | But what is interesting is we can do these experiments

00:29:34.820 | in mice, so we can go to mice and ask,

00:29:37.060 | okay, so what happens in mice?

00:29:38.860 | So in mice, mice are a little bit very different

00:29:42.240 | because mice are not simply little people.

00:29:44.420 | They're, the metabolism is different.

00:29:47.500 | They store relatively less glycogen than humans do

00:29:52.500 | in terms of total metabolism.

00:29:55.220 | So they overnight within 12 to 14 hours,

00:29:59.660 | the RER, respiratory exchange ratio,

00:30:02.520 | or this ratio will go from one

00:30:04.460 | when they're consuming mostly glucose or carbohydrate

00:30:07.600 | as energy source, it will slow down,

00:30:09.840 | slowly go to 0.7, 0.75.

00:30:13.240 | So after 12 to 14 hours,

00:30:14.720 | they're kind of mostly running on fat.

00:30:18.040 | So now as we give them food, within 10 or 15 minutes,

00:30:24.480 | they're not actually consuming couple of grams of food.

00:30:27.680 | They might have consumed say 100 or 200 milligram

00:30:30.600 | of that chow, so which is less than say 5% of their food.

00:30:35.220 | And then the RER will immediately begin to rise

00:30:38.540 | as if that small amount of food

00:30:42.460 | stopped that fat burning process

00:30:44.680 | and cranked up the carbohydrate burning process.

00:30:48.860 | - When you say fat burning process,

00:30:50.340 | you mean body fat stores being burned, right?

00:30:53.060 | Not dietary fat, correct?

00:30:54.580 | - Yeah, so it's all body fat.

00:30:56.340 | That's why I said,

00:30:58.200 | we don't know where that fat is being burned

00:31:00.160 | because we're just measuring

00:31:01.540 | how much mice is breathing in and out.

00:31:04.620 | So for example, it can be from the skin,

00:31:07.260 | so subcutaneous fat or belly fat.

00:31:10.520 | - But not dietary fat.

00:31:12.400 | - No, by that time the dietary fat is already absorbed

00:31:14.760 | and digested and hopefully it's sitting in the liver

00:31:17.620 | or adipose tissue somewhere,

00:31:18.980 | but it's the fat that's body fat.

00:31:21.240 | Yes, thank you for that.

00:31:22.240 | - Yeah, the reason I ask is that nowadays,

00:31:23.920 | I think more than half of the battles about nutrition

00:31:26.560 | that I see online relate to this issue

00:31:28.560 | where I won't name names,

00:31:30.080 | but someone will come along and say,

00:31:32.000 | "A low carbohydrate diet allows you to burn more fat."

00:31:35.560 | And the more nuanced people out there will say,

00:31:40.220 | "Well, that's true,

00:31:41.060 | but you're also talking about dietary fat."

00:31:43.240 | You know, the word fat can confuse people.

00:31:45.440 | I realize you're not doing that.

00:31:46.900 | You are certainly not one of the people

00:31:47.980 | guilty of doing this,

00:31:48.820 | but indeed you eat more fat, you'll burn more fat,

00:31:51.040 | but that doesn't mean you'll burn more body fat.

00:31:52.960 | In fact, I think the data say

00:31:54.960 | that under conditions of caloric restriction,

00:31:57.240 | you'll actually burn less.

00:31:58.600 | I hope I don't, I'll probably get pitchforks

00:32:01.880 | sent through the mail toward me on that one,

00:32:04.420 | but I think that's true.

00:32:05.880 | Whereas, you know, people who consume carbohydrate

00:32:07.920 | can still burn body fat,

00:32:09.240 | even though the majority of the fuel they're burning

00:32:11.380 | is from carbohydrates, so.

00:32:12.600 | - Yeah, so here in this case, for example, for mice,

00:32:15.620 | we know that as soon as they start eating,

00:32:17.680 | the RER goes up.

00:32:20.560 | Coming back to your question,

00:32:21.760 | what would be ideal for us to do?

00:32:23.360 | The experiment would be, okay, so we'll go back to that

00:32:26.080 | and then give the mouse maybe 100 milligram of food,

00:32:29.020 | and mouse runs around in the case,

00:32:32.560 | and then we'll continue to measure

00:32:34.000 | to see how long it takes for the mouse to come back,

00:32:36.440 | and then, so that's one aspect.

00:32:39.400 | So now let's see, let's stay on this,

00:32:43.640 | and then I'll come back and talk about non-caloric food

00:32:46.500 | and how, whether that is considered that.

00:32:49.720 | - I'd like to take a quick break

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00:34:04.040 | - So there's a famous experiment

00:34:07.160 | that was published last year by Jotakahasi's lab,

00:34:11.220 | and it came out in science,

00:34:12.740 | and that relates to caloric restriction,

00:34:16.520 | and we kind of started with this idea,

00:34:19.680 | we started discussing that the rat experiments

00:34:22.180 | were done with caloric restriction,

00:34:23.940 | and researchers reduced calorie consumption

00:34:28.080 | by 20% or 30% and gave that food,

00:34:31.320 | the rats, and then subsequently mice,

00:34:33.660 | and they all lived longer.

00:34:35.600 | What is interesting is, in all those experiments,

00:34:42.100 | the researchers came and gave this bolus of food

00:34:45.700 | at one time, whereas the ad libitum-fed mice or rats,

00:34:49.640 | they had access to food all the time,

00:34:51.120 | so they were eating all the time,

00:34:52.860 | and then these rats were given 20% less,

00:34:56.100 | and what happens is these mice or rats,

00:35:00.080 | they're not going to take that less food,

00:35:02.320 | which is the restaurant now,

00:35:04.420 | and just eat a little bit of lunch

00:35:06.400 | and then snack after three hours or snack after three hours.

00:35:09.080 | They gobble up all that food.

00:35:10.960 | Within two to three hours, maximum four hours, food is gone.

00:35:14.960 | - So they're sort of on the OMAD diet, the one meal a day?

00:35:17.940 | - Yeah, they're almost like in one meal a day,

00:35:21.240 | three to four hours, food is gone,

00:35:23.820 | or you can say they're on four hours eating or feeding

00:35:28.160 | and 20 hours fasting, so then the question became,

00:35:32.280 | well, the benefit of caloric restriction, as we know,

00:35:36.260 | is it due to reduced calorie or time-restricted feeding,

00:35:41.260 | or there is a timing component to it,

00:35:44.160 | that they're eating all of that within three to four hours,

00:35:47.320 | and then there is a long fasting,

00:35:49.240 | and this is a difficult question to answer,

00:35:51.680 | because now you have to ask these poor grad students

00:35:55.240 | or technicians to come and split that food

00:35:58.360 | into eight or 10 or 15 different small portions

00:36:02.000 | and then give them to mice in every two hours.

00:36:05.060 | So Joe Takahashi, who actually published the first paper

00:36:09.600 | in 2017, showing that most caloric restriction,

00:36:13.640 | I mean, he used the protocol that was used

00:36:16.240 | by caloric restriction field,

00:36:18.540 | it actually creates a condition of time restriction,

00:36:22.980 | so he showed that, and then he went back

00:36:25.120 | and worked with engineers to come up with a smart case

00:36:29.160 | where he could actually tell, he could program

00:36:33.720 | how much food is given to mice

00:36:35.480 | at what time of the day or night, completely programmed.

00:36:38.940 | So then he took this, for example,

00:36:42.440 | suppose the ad libitum fed mice

00:36:44.760 | eats five grams of chow in a day,

00:36:47.960 | and if you want to reduce calories by 20%,

00:36:52.280 | then the CR mouse would get four grams of food,

00:36:56.840 | and he divided this into nine or 10 meals,

00:37:01.320 | and then gave them in every 90 minutes.

00:37:04.580 | So in this case, they're eating small meals

00:37:09.520 | throughout day and night, so there is no fasting,

00:37:11.580 | so he can say that, well, this mouse actually

00:37:13.640 | is not getting into fasting because in every few hours

00:37:17.400 | is getting some food, and then he measured

00:37:21.560 | how long the mouse is going to live,

00:37:23.360 | and he used, this is a very standard protocol,

00:37:29.080 | people count how many mice are dying on which day,

00:37:31.920 | and then examine them to see whether they died

00:37:34.880 | because there was an accident

00:37:36.400 | or there was a natural cause,

00:37:39.780 | and then they calculate at the end

00:37:42.040 | what is the half life,

00:37:46.160 | so 50% survival, because that's on an average,

00:37:49.560 | that's a good indicator because if there is an outlier

00:37:52.120 | that will live for a long time, then that can skew.

00:37:55.420 | So what was interesting was the ad libitum fed mice,

00:37:58.160 | of course, they live certain number of days,

00:38:00.800 | and then this calorie-restricted mice

00:38:04.900 | that never got into super fasting,

00:38:06.640 | but kind of eating, snacking throughout day and night,

00:38:10.800 | that also live 10% extra, 10% longer,

00:38:13.620 | so that means caloric restriction

00:38:16.060 | extended lifespan by 10%.

00:38:18.500 | - I've wondered about this because recently,

00:38:20.700 | you know, there's been,

00:38:22.900 | there were a bunch of news headlines

00:38:24.400 | about intermittent fasting,

00:38:25.860 | and frankly, I was frustrated.

00:38:28.620 | If you looked at one major news outlet,

00:38:31.060 | they would say time-restricted feeding

00:38:33.500 | affords no additional benefit beyond caloric restriction

00:38:37.400 | for weight loss.

00:38:38.900 | Then another popular press venue, let's call it that,

00:38:43.900 | same study described as time-restricted feeding doesn't work.

00:38:49.200 | - Yeah. - Right.

00:38:50.840 | And then another one that may be someplace even more extreme

00:38:54.460 | you know, time-restricted feeding only beneficial

00:38:58.920 | because of caloric restriction or something like that.

00:39:01.360 | So what you've essentially got are three different

00:39:03.520 | interpretations of the same data,

00:39:05.960 | all of which are, well, two of which are true,

00:39:08.300 | one of which is false in my opinion.

00:39:10.180 | But what I think people take away from that is,

00:39:12.560 | oh, time-restricted feeding isn't valuable,

00:39:14.960 | which is not the case.

00:39:16.620 | I think for many people, it's a convenient way to eat

00:39:19.020 | because at least for people like me,

00:39:20.900 | it's simpler to designate between portions of my day

00:39:24.460 | when I'm eating and portions of my day when I'm not eating,

00:39:26.740 | as opposed to portion control.

00:39:28.520 | For other people, portion control can work.

00:39:30.780 | But all of that is related to either maintenance

00:39:34.080 | or loss of weight.

00:39:36.260 | None of it deals with the potential health benefits

00:39:39.620 | independent of weight loss.

00:39:41.180 | - Yeah. - Right.

00:39:42.740 | And so I think that if we can segment those out,

00:39:45.680 | obviously in humans, it's hard to know

00:39:49.100 | if a given treatment or experiment is extending life

00:39:52.740 | because you don't really know

00:39:53.580 | how long people would live anyway, right?

00:39:55.640 | Whereas with mice, you have some sense

00:39:57.060 | of when the mortality was likely to occur.

00:39:59.860 | So what can we say about time-restricted feeding

00:40:03.180 | and longevity in terms of biomarkers

00:40:06.040 | or in terms of any other indication

00:40:08.300 | that people who start and stop their feeding window

00:40:10.900 | at a consistent time,

00:40:12.220 | somewhere between eight and 12 hours per 24-hour cycle,

00:40:15.820 | are tilting the scales towards living longer

00:40:19.560 | as opposed to living shorter?

00:40:21.420 | - This example of this news article that you mentioned

00:40:24.080 | is really interesting

00:40:25.060 | because that relates to Joe Takahashi's study

00:40:28.620 | because I described that if you split calories

00:40:31.220 | and eat throughout the day, throughout day and night,

00:40:33.900 | then the mice lived 10% extra.

00:40:36.620 | But if you now give mouse the same calorie-restricted diet

00:40:41.340 | and feed them during daytime,

00:40:43.000 | whether within 12 hours or two hours,

00:40:46.820 | then the mice lived 10% extra.

00:40:49.220 | - Beyond that. - Yeah.

00:40:50.340 | - So 20% longer. - 20%.

00:40:52.140 | - So, okay, so let me make sure I understand

00:40:53.860 | so that I make sure I understand.

00:40:57.700 | If you take a certain number of calories

00:40:59.440 | and you distribute them throughout the 24-hour cycle,

00:41:02.040 | it's caloric restriction, the mice will live 10% longer.

00:41:07.020 | If you, however, restrict that to the active cycle,

00:41:11.040 | so for humans, the daytime,

00:41:13.220 | then they live 20% longer. - 20% longer.

00:41:18.060 | - So it's not just total caloric intake,

00:41:21.420 | meaning it's not just important to be sub-maintenance

00:41:23.660 | in calories for sake of longevity.

00:41:25.900 | It also is important as to when in the 24-hour cycle

00:41:29.860 | you eat those calories.

00:41:30.740 | Do I have that right?

00:41:31.800 | - So now, that's still, the story is not over

00:41:35.020 | because these mice were fed during daytime

00:41:37.980 | and they're not supposed to eat.

00:41:39.240 | - That's right.

00:41:40.080 | So for us, it would be the equivalent

00:41:40.900 | of being on the night shift

00:41:41.740 | and only eating at night, but a sub-caloric,

00:41:44.220 | sub-maintenance calorie diet,

00:41:46.160 | I guess is the right way to say it.

00:41:47.720 | - But when he fed mice during nighttime,

00:41:50.140 | when they're supposed to eat,

00:41:51.540 | and they're getting the same number of calories

00:41:54.580 | within 12 hours or two hours,

00:41:57.420 | then the mice lived 35% longer than the control.

00:42:01.740 | - 35% longer.

00:42:02.820 | So scale to human lifespan, which we don't know,

00:42:06.340 | but 35% longer would mean that,

00:42:08.820 | and again, no one knows, but humans now,

00:42:12.220 | what is the average mortality in the United States?

00:42:14.720 | Somewhere around 80?

00:42:16.180 | - Yeah, so it's around 80.

00:42:17.020 | It used to be 80, now it's reduced a little bit

00:42:20.180 | because of COVID, but let's take 80.

00:42:22.420 | - Okay, so people are then now living somewhere

00:42:24.940 | between 25 and 35 years longer.

00:42:26.980 | - Yes.

00:42:27.820 | - I'm putting some error bars on there.

00:42:28.640 | - Yeah, yeah, yeah, yeah.

00:42:29.480 | - Amazing.

00:42:30.320 | - So that was really profound,

00:42:31.640 | but now you pointed out biomarker and other stuff.

00:42:36.580 | So now, if you look at any given time

00:42:40.260 | within that experiment, and actually Joe went back

00:42:42.920 | and had a separate cohort of mice, very similar,

00:42:47.300 | and so that he could take tissue samples,

00:42:49.560 | and of course, in this case,

00:42:51.140 | you have to sacrifice the mouse, and he looked for,

00:42:55.260 | he did a lot of molecular analysis with known markers.

00:43:00.260 | For example, hemoglobin A1c, covalent or glucose control,

00:43:03.580 | cholesterol, all this stuff.

00:43:04.980 | He could not find anything that predicted

00:43:10.260 | the benefit of caloric restriction.

00:43:12.420 | So that means in this experiment,

00:43:14.220 | whatever we know so far, the predictor of longevity,

00:43:18.660 | none of them could predict whether this CR-only mouse,

00:43:23.260 | which ate throughout day and night,

00:43:27.660 | that mouse is going to live less than the night fed mouse

00:43:31.660 | that was going to live 25% extra.

00:43:34.580 | - Does that mean that there are biomarkers

00:43:36.340 | related to longevity that we just haven't discovered yet?

00:43:38.740 | - Yeah, so that's exactly.

00:43:39.900 | So that means whatever we know so far about biomarkers,

00:43:45.360 | those he could not use to predict.

00:43:49.080 | Maybe there was a lot of noise.

00:43:50.420 | Maybe he wanted, he had to use more number of mice

00:43:53.340 | to get that because biomarkers are not going to predict

00:43:57.320 | in every instance that there is some error.

00:43:59.700 | What is also very interesting is if you look at the body weight

00:44:04.400 | and body composition of all these mice,

00:44:06.600 | there is no difference in body weight and body composition.

00:44:10.120 | - Across all these different groups?

00:44:10.960 | - Across all these groups.

00:44:12.640 | - So it doesn't matter when they ate,

00:44:14.680 | provided they were sub maintenance calorie intake.

00:44:18.740 | So fewer calories than is required to maintain their weight.

00:44:22.340 | It didn't matter what pattern of eating,

00:44:24.540 | they were the same weight.

00:44:25.580 | So that in many ways seems to mimic the human studies

00:44:28.000 | where they say, look, it doesn't really matter

00:44:29.420 | whether or not you use caloric restriction

00:44:31.260 | or you start your feeding window in the morning

00:44:34.000 | or start your feeding window in the evening

00:44:35.480 | or you portion control for sake of weight loss.

00:44:40.480 | - Because we're taking a snapshot of that.

00:44:42.520 | And then another thing with the human study

00:44:44.340 | that we are referring to here,

00:44:46.320 | in that human study, people are actually already eating

00:44:52.440 | within 10 hours window habitually

00:44:56.220 | when they selected these people

00:44:58.100 | to have them enroll in the study.

00:45:01.460 | So they were already eating for 10 hours

00:45:03.000 | and fasting for 14 hours.

00:45:06.120 | All participants had to reduce their calorie intake

00:45:08.860 | and they reduced by almost 25%.

00:45:12.640 | The CR group continued with 10 hours eating window

00:45:16.300 | and the CR plus time restricted group

00:45:19.000 | had to eat the same number of calories within eight hours.

00:45:21.480 | - So it's just a two hour difference.

00:45:23.120 | - It's just a two hours difference.

00:45:24.440 | - Okay, so that people,

00:45:25.320 | I just want to make sure people can understand.

00:45:26.640 | So in this human study,

00:45:28.420 | which is the one that I felt that the popular press venues,

00:45:31.840 | all except one venue,

00:45:33.760 | got either semi-wrong or badly wrong

00:45:36.160 | in terms of their conclusion.

00:45:37.080 | That was my interpretation anyway,

00:45:39.040 | was that either people came into the study

00:45:42.340 | eating basically in a 10 hour feeding window,

00:45:44.600 | which goes back to my first question,

00:45:45.880 | which is that most people are not eating

00:45:47.060 | in the middle of the night,

00:45:48.280 | where if they're on shift work and they are,

00:45:50.060 | then they're sleeping during the day anyway.

00:45:51.460 | So they're eating in a 10 to 12 hour feeding window anyway.

00:45:53.940 | So you're saying they either did caloric restriction,

00:45:56.220 | portion control within the 10 hour window

00:45:58.500 | or another group within the study,

00:46:01.200 | ate sub maintenance calories.

00:46:04.040 | So caloric restriction, CR as we're calling it,

00:46:06.480 | the acronym CR,

00:46:07.760 | but restricted that to an eight hour feeding window.

00:46:10.060 | And they didn't see any difference in terms of weight loss.

00:46:12.440 | - Yeah.

00:46:13.280 | - But it's not all that surprising, right?

00:46:14.700 | I mean, if it's just a two hour difference.

00:46:16.500 | - Yeah, exactly.

00:46:17.340 | So we have done that experiment in mice

00:46:19.480 | and we don't see a difference in not only weight loss,

00:46:22.840 | many other markers.

00:46:24.600 | And I was telling you about this Jotaka Haziz paper,

00:46:27.860 | where I told you that he allowed his mice

00:46:31.000 | to eat within two hours or 12 hours, subcaloric diet.

00:46:36.000 | - Two or 12.

00:46:37.440 | - Two or 12.

00:46:38.320 | - Yeah, that's dramatic.

00:46:39.680 | But still he did not see change in longevity

00:46:42.560 | even within those two.

00:46:44.680 | So that means when you do caloric restriction

00:46:47.980 | and then at least for mouse

00:46:50.960 | and you are within 12 hours window,

00:46:53.000 | that is giving the mice the best benefit,

00:46:57.300 | the optimum benefit.

00:46:58.940 | And two, three or five or 12 for a mouse doesn't matter,

00:47:03.940 | at least for longevity.

00:47:05.420 | - Can we conclude for humans

00:47:06.920 | that whether or not a feeding window is four hours,

00:47:10.220 | six hours, eight hours or 12 doesn't matter

00:47:13.200 | provided the calories are similar or same?

00:47:16.980 | - Well, I won't go to that extent

00:47:18.780 | because we don't know many of these,

00:47:21.140 | particularly we don't know how this eating window

00:47:25.080 | will affect both sexes

00:47:27.140 | because we always think many of these mouse experiments

00:47:30.740 | even that I told you about those are done only in male mice.

00:47:33.840 | - But that should be changing, right?

00:47:34.980 | Because the NIH, I know this

00:47:36.720 | 'cause I'm on study section,

00:47:37.900 | which is just a bunch of people who review grants

00:47:41.260 | is that every grant now has to include

00:47:43.540 | sex as a biological variable.

00:47:45.660 | It's hard to get away with,

00:47:47.740 | or rather I should say it the way it should be stated,

00:47:49.980 | which is people are required

00:47:53.200 | and should want to look at these phenomenon

00:47:55.980 | in male and female mice,

00:47:58.220 | especially if there are differences.

00:48:00.240 | - So in this case, there are many,

00:48:03.660 | there was also another paper in time-restricted feeding

00:48:06.980 | that also came out a big paper showing that the thermogenesis

00:48:11.960 | was accounting for loss in fat mass

00:48:14.460 | in time-restricted fed mice

00:48:16.220 | that was also done only in male mice.

00:48:18.520 | So this is, we are paying attention to it.

00:48:22.220 | So we are now doing all of our studies in male and female,

00:48:25.780 | and we do see big differences between male and female.

00:48:28.440 | Coming back to humans,

00:48:29.820 | what typically happens is

00:48:32.340 | when you're trying to do four hours

00:48:34.100 | or six hours of time-restricted eating,

00:48:36.420 | people will inadvertently reduce their calorie intake.

00:48:39.580 | - Yeah, just because of gut volume.

00:48:40.900 | I tried one meal per day,

00:48:42.660 | and I felt like I was eating so much at that one sitting

00:48:46.720 | that it led to a lot of gastric distress

00:48:48.740 | and I got tired after the meal.

00:48:50.100 | And part of the reason I like to do time-restricted feeding

00:48:52.780 | is I have more energy.

00:48:54.640 | And certainly in the fasted state, I feel more energized,

00:48:58.020 | especially if I'm ingesting a little caffeine

00:49:00.000 | or something like that.

00:49:02.180 | So people will reduce energy intake,

00:49:05.540 | and then some people who are more active,

00:49:08.220 | they can actually unconsciously,

00:49:11.540 | they may be spending more energy in their physical activity

00:49:15.180 | and basal metabolic rate,

00:49:16.340 | all of this combined than how much they're eating.

00:49:19.260 | And that can have a very adverse effect in long-term

00:49:22.380 | because we know that this energy deficit,

00:49:25.380 | and in fact, there is a scientific term for that.

00:49:28.800 | It's called REDD-S, relative energy deficit in sports.

00:49:33.800 | - Relative energy deficit in sports, okay.

00:49:36.220 | - Yeah, it's because nearly 40% of athletes,

00:49:39.000 | not the NFL guys, but you know,

00:49:43.040 | there are a lot of people who do track and field,

00:49:45.440 | and nearly 40% of athletes actually experience this REDD-S

00:49:51.500 | without knowing.

00:49:52.800 | - Can male and female athletes both experience REDD-S?

00:49:55.320 | So it's REDD-S, R-E-D-S, relative energy.

00:49:59.620 | - Relative energy deficit in sports.

00:50:02.200 | Interesting, it's the first I've heard this acronym.

00:50:04.240 | We have a new acronym, folks.

00:50:05.800 | This is good to add to a list of other acronyms,

00:50:09.060 | but so males and females can experience it.

00:50:12.000 | So in females, I've heard that REDD-S can lead to amenorrhea,

00:50:17.000 | so loss of the menstrual cycle.

00:50:22.100 | - Yeah, so that's so common that, so prevalent

00:50:25.380 | that in fact, many women, many female athletes,

00:50:28.660 | they take it for granted that yes,

00:50:30.960 | if they are more active,

00:50:31.940 | then they will lose their menstrual cycle,

00:50:33.680 | which may be common,

00:50:35.620 | but it's not normal or optimum for health.

00:50:39.360 | - Even if they don't want to get pregnant.

00:50:42.180 | - Yeah. - Yeah.

00:50:43.020 | - Yeah. - Yeah.

00:50:43.840 | We had an expert on female hormones come on

00:50:45.780 | and say the very same thing,

00:50:47.160 | that regular cycling is a-

00:50:48.980 | - Is very important.

00:50:49.940 | - Of ovulatory menstrual cycle

00:50:51.900 | is important to try and maintain.

00:50:55.020 | - Yeah, so that's one.

00:50:56.620 | But then what is really concerning is

00:50:58.940 | it does affect bone health.

00:51:03.080 | And in this state, people actually,

00:51:07.180 | over a long period of time, they lose bone mass

00:51:09.800 | and their bone also becomes more prone to injury,

00:51:12.960 | microfracture and fractures.

00:51:15.180 | So again, it's a risk.

00:51:18.340 | I mean, some people are trying to eat within very short time

00:51:21.180 | and they're physically active, that happens.

00:51:23.540 | And it also has impact on,

00:51:25.580 | means the reason why these women are losing menstrual cycle

00:51:30.180 | is their HPG axis is disrupted,

00:51:35.180 | hypothalamus, pituitary, gonadal axis.

00:51:39.380 | And it starts, it may start even upstream

00:51:42.740 | at hypothalamus or pituitary.

00:51:44.300 | So that means that HPA axis,

00:51:46.540 | hypothalamus, pituitary and adrenal axis

00:51:49.300 | may also get disrupted.

00:51:50.980 | One of the symptoms of reds is also depression,

00:51:53.980 | anxiety, bipolar-like symptoms.

00:51:56.420 | And we know that many, many athletes experience that.

00:52:01.180 | We think that, well, this may be just peer pressure

00:52:03.820 | that always trying to compete.

00:52:05.260 | And we know that unfortunately there are a few athletes

00:52:08.220 | who just can't cope it.

00:52:09.380 | And there are many attempted suicide or suicide.

00:52:12.520 | So this is a serious issue.

00:52:14.980 | And there's also another new topic in the lab

00:52:18.660 | to come up with a mouse model of reds and then study it.

00:52:23.360 | But this is one risk why we should not reduce

00:52:26.520 | our eating interval to one meal or very short time,

00:52:31.520 | because it can have adverse side effect

00:52:34.460 | that we don't know now.

00:52:36.780 | Maybe in future we'll figure out

00:52:38.740 | when we systematically study them.

00:52:41.180 | There are studies that are published showing four hours

00:52:44.000 | and six hours time restricted eating

00:52:45.940 | has benefits on weight loss,

00:52:48.220 | but those are on healthy individuals

00:52:50.500 | and they were in the studies.

00:52:52.060 | So the study team were already monitoring,

00:52:57.060 | they made sure that there was no certain weight loss

00:53:00.220 | or weight loss below some safety level.

00:53:05.180 | So those are very different from regular people

00:53:07.580 | who are who maybe even normal weight,

00:53:10.460 | even within the healthy range.

00:53:13.640 | If they do, then they can potentially.

00:53:15.920 | So that's why what we think is eight to 10 hours

00:53:19.160 | may be the ideal spot to begin with.

00:53:22.240 | And once you are physically active

00:53:26.120 | and you are also spending a lot of energy

00:53:28.440 | in physical activity or sports,

00:53:30.760 | you can even go up to 12 hours

00:53:32.240 | because in mice we have done that experiment.

00:53:35.480 | Up to 12 hours, they do get a lot of benefits, not all, but.

00:53:39.120 | - So this is 12 hours of feeding?

00:53:40.620 | - 12 hours of feeding, 12 hours of fasting.

00:53:42.720 | In humans, again, nobody has done systematically 12 hours,

00:53:48.960 | but there was one study in Europe

00:53:52.720 | from Tin Hai Colette Lab,

00:53:54.560 | and Tin Hai and I, we collaborate.

00:53:56.640 | So they used our micecadian clock app.

00:53:58.960 | This is a research app we developed just to,

00:54:02.000 | this is mostly used in time-restricted eating studies.

00:54:05.340 | And he had nearly,

00:54:08.560 | I think he started with 200 Swiss participants,

00:54:11.360 | but then at the end he selected

00:54:13.100 | and took very small number of groups,

00:54:15.100 | people who are very meticulous

00:54:17.840 | about recording all their food

00:54:19.560 | and divided them into usual feeding,

00:54:21.960 | whatever they wanted to eat, whenever they wanted to eat.

00:54:25.140 | And they were given the advice of Swiss,

00:54:28.200 | nutrition advice that's given to improve health

00:54:32.480 | and reduce blood glucose,

00:54:33.760 | almost like diabetes prevention program in the US.

00:54:37.440 | And then the other group was given advice

00:54:39.320 | to eat within 12 hours.

00:54:41.040 | This was very early on in time-restricted eating.

00:54:44.880 | And we thought that the mice were getting some benefit,

00:54:47.920 | let's try whether 12 hours has any benefit.

00:54:50.340 | The bottom line is at the end of three months and six months,

00:54:55.440 | what he reported is both groups

00:54:58.220 | lost same amount of body weight.

00:55:00.640 | And then there was not too much significant difference

00:55:04.640 | between groups,

00:55:05.720 | but both groups actually improved their health.

00:55:08.200 | So the bottom line is the Swiss nutritional advice

00:55:12.360 | that he was giving, which is the standard of care there,

00:55:16.240 | it achieved the same amount of weight loss

00:55:18.300 | as just giving people this advice that eat within 12 hours.

00:55:22.960 | So one way to look at the result is like this.

00:55:27.080 | And then he went to more extent

00:55:30.860 | and actually looked at every single meal

00:55:33.400 | these people consumed.

00:55:35.080 | So there are close to,

00:55:37.240 | I think close to 60 or 70,000 meal records

00:55:41.000 | and pictures he went through

00:55:42.320 | and then classified them to say

00:55:44.060 | whether these are good quality food.

00:55:47.120 | So they call it the NOVA classification.

00:55:49.280 | One, two, three, four.

00:55:50.320 | One is the food that you can almost eat raw,

00:55:53.840 | fruits, vegetables, yogurt, dairy products

00:55:58.360 | that you can almost without any preparation.

00:56:01.180 | And then second NOVA two is kind of home cooked food

00:56:05.060 | that most people will prepare in few minutes.

00:56:07.480 | And then three, and then fourth one

00:56:09.280 | is the food that you can never prepare at home.

00:56:13.400 | So for example, biscuit or cookies

00:56:16.760 | that we usually purchase and few other things.

00:56:20.120 | And usually the NOVA four are unhealthy ultra processed food

00:56:23.280 | so which we should not be eating.

00:56:24.580 | So the advice is to reduce NOVA four.

00:56:27.880 | And what he found was people who got all this advice

00:56:32.360 | to improve their nutrition quality,

00:56:34.800 | they actually improve their nutrition quality.

00:56:36.760 | They reduce their NOVA four food.

00:56:39.220 | And people who are in time-restricted eating

00:56:41.880 | they ate within 12 hours.

00:56:43.760 | They did not change their nutrition quality.

00:56:46.600 | But what is interesting is they both got the same

00:56:49.360 | modest weight loss.

00:56:51.160 | So that begs the question that in the,

00:56:53.240 | maybe Tinhai will do this experiment again

00:56:55.880 | to combine nutrition advice with time restriction

00:57:00.080 | and maybe reduce the time to 10 hours and that might help.

00:57:05.000 | So 12 hours is something that I say

00:57:09.120 | anyone from five-year-old to a hundred-year-old can do.

00:57:12.480 | And if you're trying to maintain weight

00:57:16.240 | that might be a good way and combine that with exercise.

00:57:19.180 | It'll be great.

00:57:20.520 | - And people can more easily avoid reds in that way.

00:57:24.260 | Women and for non-athletes or recreational exercises

00:57:27.200 | it sounds like women, if they distribute their calories

00:57:29.720 | across 12 hours are less likely

00:57:31.280 | to lose their menstrual cycle.

00:57:33.500 | - Yeah, so again, this is something

00:57:35.200 | that we have to look carefully.

00:57:36.580 | They have to be, because we do have the My circadian Clock app

00:57:40.180 | that many people download and self monitor

00:57:42.640 | and they share the data for researchers.

00:57:44.260 | - We will provide a link to that, by the way.

00:57:46.000 | It's a great tool.

00:57:47.960 | - But once in a while, we do get this input

00:57:49.960 | from some women saying,

00:57:51.100 | "Oh, I started doing your time ratio eating

00:57:53.280 | and I am seeing all these problems."

00:57:55.280 | And then I asked them, "Okay, so what else are you doing?"

00:57:58.080 | They typically improve their nutrition quality.

00:58:00.560 | So they're eating only salad and pew.

00:58:03.140 | And they're trying to increase the fiber intake.

00:58:05.960 | And it's really hard to eat so much of uncooked food

00:58:08.800 | because cooking helps to absorb more nutrient.

00:58:13.120 | And then at the same time,

00:58:14.120 | they're running five miles every day.

00:58:15.960 | And of course, all of this combined

00:58:17.840 | can lead to reds-like symptom.

00:58:20.800 | So that's why 12, I think, is a good point

00:58:25.560 | if you're combining physical exercise

00:58:28.760 | and better nutrition quality,

00:58:30.460 | because in mice also we have seen

00:58:32.400 | that if mice are eating healthy food

00:58:34.760 | and they're eating within 10 to 12 hours,

00:58:37.320 | then they also live longer than mice

00:58:39.660 | that are eating healthy food,

00:58:40.940 | but distributing that calorie over a long period of time.

00:58:44.280 | And this is Rafa DiCaba's finding from NIH.

00:58:49.280 | He has systematically done this study

00:58:52.100 | with two different types of diet and in mice.

00:58:55.220 | And he finds the same thing,

00:58:56.860 | that even mice that are eating within 12 hours,

00:58:59.540 | they do live longer than mice that eat randomly,

00:59:03.460 | even healthy food.

00:59:04.960 | - I recall a recent study,

00:59:06.900 | I think it was either published in Cell Reports

00:59:08.760 | or Cell Reports Medicine,

00:59:09.960 | forgive me for not remembering which,

00:59:11.260 | but both of course, Cell Press journals,

00:59:13.160 | excellent journals,

00:59:14.640 | which explored time-restricted feeding

00:59:17.200 | in the context of low carbohydrate

00:59:19.820 | or non-low carbohydrate diets.

00:59:21.240 | So it was low carbohydrate

00:59:22.440 | versus low carbohydrate and time-restricted.

00:59:25.800 | So these are all caloric matched between groups.

00:59:28.880 | And then non-low carbohydrate diets.

00:59:31.420 | So it was sort of more standard,

00:59:33.020 | I think it was somewhere in the neighborhood

00:59:34.100 | of 60% of calories from complex carbohydrates.

00:59:36.780 | And as I recall, the greatest weight loss,

00:59:40.980 | remember same calories across groups folks,

00:59:44.060 | was achieved with low carbohydrate plus caloric restriction.

00:59:48.040 | And I wondered why all the popular news venues

00:59:52.580 | didn't cover that study,

00:59:54.220 | but that's why I'm bringing it up now.

00:59:55.380 | I thought this is really interesting.

00:59:56.620 | And I'm somebody who's cycled low carbohydrate diet before,

01:00:01.620 | I find it hard to sleep after about three or four days

01:00:05.100 | of being on a low starch diet just personally.

01:00:08.500 | So I like to eat some starches,

01:00:10.020 | especially if exercising intensely or working intensely,

01:00:12.540 | that's just a little editorial there that,

01:00:15.360 | but look, I know many people who do just feel better

01:00:18.500 | on a low carbohydrate diet,

01:00:19.620 | but what do you think of those data?

01:00:21.340 | Because it speaks to the idea that,

01:00:23.240 | okay, it's not just the total number of calories,

01:00:25.620 | it's not just the quality of those calories,

01:00:28.080 | it's the timing of those calories,

01:00:30.440 | and maybe carbohydrate restriction in conjunction

01:00:33.780 | with time restricted feeding might be the best path

01:00:37.300 | for people who are looking to lose weight.

01:00:39.460 | - No, I totally agree that when it comes to nutrition,

01:00:43.820 | quality, quantity, and timing, all these three matter.

01:00:47.480 | Nearly 40% of people who maintain healthy body weight,

01:00:51.140 | because 60% are overweight and obese,

01:00:52.980 | 40% are maintaining healthy body weight.

01:00:55.580 | And out of those 40%, I would say nearly majority of them

01:00:59.960 | are very aware about how much they're eating

01:01:02.820 | and what quality of food they're eating.

01:01:04.460 | - So you're really an optimist.

01:01:05.540 | You're looking at the 40% of the glass that's,

01:01:08.620 | or should we say not full?

01:01:10.620 | Yeah, that was a pun intended.

01:01:12.220 | But the, no, that's a very interesting way of looking at,

01:01:14.600 | rather than saying, why are 60% of Americans obese,

01:01:18.940 | saying why are 40% not obese?

01:01:21.580 | That's a very interesting way to look at it.

01:01:23.300 | - Yeah, I mean, subconsciously,

01:01:26.060 | we're always making the decision.

01:01:27.460 | Means I know, means I'm sure that you are not going

01:01:30.140 | and eating cheeseburger every day

01:01:32.420 | because you want to improve.

01:01:34.460 | - Yeah, no, yeah, exactly.

01:01:35.920 | I wouldn't feel good.

01:01:37.020 | Yeah, I enjoy cheeseburger now and again,

01:01:38.980 | but I, no, not, certainly not at this stage

01:01:41.700 | or any stage of my life.

01:01:42.920 | I think that, I think people,

01:01:46.300 | actually you think the pandemic had a lot to do with this.

01:01:48.840 | I think that people started to take a look

01:01:52.060 | at what they were doing to support

01:01:55.100 | or not support their health generally.

01:01:57.020 | I know people gained a lot of weight during the pandemic.

01:01:58.980 | Other people got really into fitness.

01:02:00.460 | I've seen some colleagues,

01:02:01.380 | you've always maintained,

01:02:02.620 | you've always been in good shape.

01:02:05.060 | Actually, this is the first time I've seen you in a while

01:02:06.580 | and you've seemed to have aged backwards.

01:02:07.880 | So you are a poster for your own ideas and hypotheses

01:02:12.880 | about time-restricted feeding.

01:02:14.420 | But I noticed that during the pandemic,

01:02:17.480 | a number of people emerged from the pandemic in better shape,

01:02:20.340 | other people in much worse shape.

01:02:21.580 | It seemed like it was like a bimodal distribution there.

01:02:24.580 | So yeah, I get the sense that starting and stopping eating

01:02:30.960 | at more or less the same time each day,

01:02:33.580 | even if caloric restriction is not the main focus,

01:02:37.980 | has additional benefits.

01:02:39.660 | Can we talk about some of those benefits

01:02:42.920 | as they relate to the other things that impact health?

01:02:45.800 | So for instance, if you're starting and stopping eating

01:02:47.700 | at more or less the same times each day,

01:02:50.380 | are you sleeping better?

01:02:51.800 | Are you getting more predictable shifts

01:02:55.420 | in alertness and sleepiness?

01:02:57.580 | Like, can you predict when you'll feel good enough

01:02:59.540 | to exercise?

01:03:00.880 | Maybe we could talk about that because you, of course,

01:03:03.220 | are well-known for time-restricted feeding

01:03:05.260 | and the science around that,

01:03:06.140 | but also other things as well,

01:03:08.020 | not the least of which is circadian biology generally.

01:03:10.460 | So I always think of the main timekeepers for our system

01:03:13.680 | being feeding, light, activity, and social connection.

01:03:19.680 | Did I miss, maybe, and temperature.

01:03:21.740 | - Yeah. - Yeah.

01:03:22.760 | So how do these combine with one another?

01:03:25.040 | Using timing that we begin and stop feeding

01:03:27.720 | is kind of an anchor point.

01:03:28.640 | Can we explore that a little bit?

01:03:29.780 | - Yeah, so we got into this beginning and end,

01:03:34.320 | and then you asked for the calorie,

01:03:36.960 | how much calorie will break the fast.

01:03:39.280 | One thing that I want the listeners and viewers

01:03:43.840 | to bring back to this timing of when we are breaking the fast

01:03:49.160 | because we equate health with weight, body weight.

01:03:53.780 | And that's why we are talking about nutrition quality

01:03:58.780 | and quantity because both of them have impact.

01:04:02.620 | So now let's think about mental health

01:04:05.100 | because a lot of people do struggle with mental health.

01:04:08.300 | They have anxiety or depression,

01:04:11.980 | and also gut health because there are a lot of people

01:04:16.220 | who also have acid reflux or heartburn.

01:04:19.800 | And we know that acid reflux or heartburn

01:04:22.120 | can be exacerbated by caffeine intake in empty stomach.

01:04:27.120 | Those who have acid reflux or heartburn,

01:04:31.320 | they're prone to that.

01:04:32.240 | Then having black coffee in the morning

01:04:36.160 | before any food can upset their stomach.

01:04:39.660 | So that's why in those cases,

01:04:41.800 | it's very clearly that caffeine for them

01:04:44.600 | becomes the trigger that something,

01:04:47.720 | the food is supposed to come

01:04:49.360 | and then the stomach is not seeing the food.

01:04:51.300 | So it's overreacting, producing excess acid

01:04:54.320 | and that comes up to the esophagus

01:04:56.200 | and that's what they're experiencing.

01:04:58.840 | So if people have that kind of condition,

01:05:00.960 | then maybe they should consider

01:05:02.620 | when they drink their first coffee

01:05:05.060 | is breaking their overall fast

01:05:08.700 | or kind of putting their health at risk for acid reflux.

01:05:14.140 | The other thing is people who have anxiety,

01:05:16.460 | panic attack, we know that caffeine can judge you off.

01:05:21.260 | - Especially on an empty stomach.

01:05:22.700 | - Especially on an empty stomach.

01:05:24.020 | So for them, again, caffeine can be a trigger.

01:05:28.260 | So that's why I want to kind of differentiate

01:05:31.740 | that there is this mental health

01:05:33.160 | and other aspects of health.

01:05:35.000 | And these are two clear examples

01:05:36.580 | where anxiety, panic attack related to brain health

01:05:41.320 | or acid reflux related to our gut health.

01:05:44.300 | In those cases, when we consume that caffeine

01:05:49.620 | in the morning can affect, so.

01:05:53.280 | - Do you avoid caffeine in the morning?

01:05:55.600 | - No, actually here is the interesting history

01:05:58.960 | about caffeine and this is something I did not know.

01:06:01.680 | And I was once invited to this history of nighttime activity

01:06:06.680 | and maybe we can take a little bit of detour

01:06:10.600 | and talk about nighttime activity

01:06:12.980 | because that fascinates me as a circadian biologist.

01:06:15.900 | 'Cause over the last 200,000 years means we assume

01:06:20.860 | that humans, Homo sapiens evolved 200,000 years ago.

01:06:24.940 | So we have been, as a species,

01:06:26.420 | we have been living on this planet for 200,000 years.

01:06:29.740 | And only in the last, you can say couple of thousand

01:06:34.520 | or 5,000 years when we came to control fire

01:06:38.460 | or maybe you can even go back to 100,000 years,

01:06:40.660 | there is some debate.

01:06:41.720 | So then the question is, well, when you control fire

01:06:48.040 | and we light it up the fire

01:06:50.260 | and we could light up whenever we wanted,

01:06:53.060 | we can add fuel and we can stop the fire

01:06:55.860 | when we don't want it.

01:06:57.500 | That's the key ability in humans that differentiates them

01:07:04.300 | from all the other species.

01:07:07.900 | No other species.

01:07:09.180 | We can always say, yes, there are signs

01:07:12.020 | of this intelligent decision-making.

01:07:15.020 | For example, we know many crows can make decision.

01:07:18.300 | Many, many animals, they kind of figure out,

01:07:21.380 | strategize how to get food.

01:07:23.300 | But controlled use of fire

01:07:25.900 | is something very specific to human.

01:07:29.620 | And when we started controlling fire,

01:07:33.120 | fire did not essentially extend the day

01:07:37.420 | because fire created a evening that was very different

01:07:40.960 | from what people did during the day

01:07:43.300 | and what people used to do during the day.

01:07:45.860 | They worked a lot, means gathering food

01:07:50.140 | was almost everything that we did.

01:07:53.060 | And so in the evening after we brought food,

01:07:58.060 | mostly tubers or maybe lentils to cook

01:08:01.000 | or once in a while animals so that we could barbecue,

01:08:06.560 | all of these things happened around fire.

01:08:09.360 | And fire was so expensive that it was mostly communal fire.

01:08:13.660 | So if you go back to, for example, Maasai

01:08:16.420 | and all these populations that have no access to electricity

01:08:21.420 | and they're still living kind of that historical life,

01:08:26.800 | fire is a communal event.

01:08:29.340 | And they sat around, they cooked food.

01:08:31.340 | And then what happened?

01:08:33.300 | They did not talk about work.

01:08:34.720 | They talked about culture.

01:08:37.280 | They talked, they sang, they danced, they strategize.

01:08:42.280 | That's how politics started, philosophy started,

01:08:44.980 | science started, all of these things

01:08:47.380 | that are very unique to human civilization

01:08:50.180 | started around fireside chat.

01:08:52.660 | So in that way, if we think about it,

01:08:55.740 | we are still doing fireside chat.

01:08:57.260 | The only thing is we have the microwave

01:08:58.900 | and the television or social media.

01:09:01.900 | - And now we chat with our thumbs, right?

01:09:03.860 | - So it's still, so we are hooked to that evening activity

01:09:07.520 | because that's when we are completely free

01:09:10.460 | from the pressure of the work and we want to express ourself.

01:09:14.720 | That's our independent time.

01:09:16.380 | So that's why most people find it very difficult

01:09:20.020 | to do timeless eating and stop eating at six o'clock

01:09:22.600 | because it's ingrained in our even DNA

01:09:27.260 | that we want to eat and socialize in the evening.

01:09:31.980 | So now let's fast forward and see

01:09:34.220 | what is the role of coffee in this?

01:09:37.160 | If you look at coffee consumption, particularly cafe,

01:09:42.740 | where people can come and have a little bit of coffee

01:09:45.720 | and socialize, it also started as an evening activity.

01:09:49.820 | And this is in, now we can go back to Istanbul

01:09:54.820 | because that's one place where coffee cafes started

01:09:59.100 | in mid 16th century.

01:10:01.520 | So we are talking about 1540 to 1570.

01:10:04.800 | And that's when, I'm sorry, I'm forgetting the name

01:10:10.580 | of historians who actually invited me and okay.

01:10:15.040 | His name is Cemal Kefadar and I must be butchering the name,

01:10:20.040 | but I'll try-

01:10:21.220 | - That's right, he will provide the spelling

01:10:22.380 | and the wonderful thing about social media

01:10:24.460 | is somebody will tell us on YouTube

01:10:25.920 | the proper pronunciation.

01:10:27.160 | So this is a great opportunity.

01:10:28.600 | If you know the proper pronunciation,

01:10:30.700 | please put it in the comments on YouTube.

01:10:33.120 | - Actually, I'm even checking right now

01:10:34.780 | in my EndNote library, it's not picking up that.

01:10:37.520 | - That's right, we'll provide a link.

01:10:39.900 | - So what happened was, so coffee was introduced

01:10:43.500 | and people came and drank coffee and talked about politics.

01:10:48.500 | - At night.

01:10:49.740 | - At night, at evening.

01:10:51.020 | And it actually started with Sufi branch of Islam

01:10:54.700 | because they are the ones who consumed coffee

01:10:58.320 | in the evening and this is the branch of Islam

01:11:01.120 | where they actually sing and dance

01:11:03.600 | and all that happened in the evening.

01:11:06.000 | So singing, dancing by the Sufi

01:11:10.200 | and then here in Istanbul, people started congregating

01:11:14.240 | and having talk about politics.

01:11:17.840 | But then around the same time,

01:11:20.180 | some in Turkey, there was a good sizable number

01:11:27.420 | of Muslims who have to do five prayers a day,

01:11:30.600 | number of prayers at set time.

01:11:32.480 | The first prayer is very early in the morning.

01:11:35.220 | And then they figured out that if they wake up

01:11:37.520 | and immediately have coffee,

01:11:39.200 | then they can stay awake for the first prayer.

01:11:42.060 | And in that way, they felt pretty good.

01:11:44.680 | They woke up, so that's how it started as a morning drink

01:11:48.440 | to stay awake and kind of get on with the day.

01:11:53.440 | But what happened was,

01:11:54.920 | I don't know whether you have ever tried Turkish coffee.

01:11:57.380 | It's very thick.

01:11:58.460 | - Yeah, a few years ago, right before the pandemic, 2019,

01:12:02.600 | I traveled to Turkey, first of all, the food is amazing.

01:12:06.060 | The coffee is indeed very, very thick.

01:12:08.720 | And I have a pretty high caffeine tolerance

01:12:12.980 | from drinking so much coffee in Yerba Mate over the years

01:12:17.140 | and still do, I really enjoy it.

01:12:18.980 | But yeah, it's very intense.

01:12:21.500 | And so what you're saying is that coffee intake

01:12:25.840 | started as a way to extend into the night.

01:12:28.480 | The ability to extend into the night at all

01:12:30.420 | was because of the ability to harness fire.

01:12:32.880 | And then coffee's stimulatory properties

01:12:35.600 | were leveraged toward morning,

01:12:38.940 | which is essentially like the way I think about it,

01:12:41.880 | we did an episode on caffeine and someone else,

01:12:45.280 | Michael Pollan, not I, described it this way,

01:12:47.260 | that you're sort of taking a loan out

01:12:49.160 | on your energy bank account with coffee.

01:12:50.980 | You're suppressing the adenosine system,

01:12:52.580 | adenosine makes you sleepy,

01:12:53.980 | but that adenosine system will kick in later.

01:12:55.820 | So it's a credit card of sorts with an interest, right?

01:12:59.580 | And the interest being an energetic lag

01:13:02.620 | that you're going to experience in the afternoon.

01:13:05.980 | - But what happened was the strong coffee

01:13:09.220 | that gave heartburn and acid reflux to a lot of people.

01:13:13.300 | So then they started eating something with coffee

01:13:18.100 | and that's how the culture of breakfast started in Turkey.

01:13:21.240 | - Ah, so coffee actually led

01:13:23.700 | to the development of breakfast, not the other way around.

01:13:26.220 | - And that, yeah, so-

01:13:27.820 | - That's very heartening, again, no pun intended,

01:13:31.100 | for the caffeine lovers among us,

01:13:35.740 | which I count myself one of those.

01:13:37.980 | - So essentially the food before coffee became breakfast.

01:13:41.440 | So you kind of give something to your stomach

01:13:45.380 | so it's busy digesting that.

01:13:47.140 | And then when the coffee comes in,

01:13:49.180 | it's not reacting to coffee and creating acid reflux.

01:13:53.300 | - So it wasn't as fascinating.

01:13:54.940 | So it wasn't that breakfast is necessary on its own.

01:13:59.020 | It was essentially a buffer against the gastric distress

01:14:03.060 | caused by caffeine intake.

01:14:04.780 | - At least in that culture, in that context.

01:14:07.580 | We cannot say whether the same thing happened

01:14:09.500 | and all over the world where coffee is not consumed,

01:14:11.840 | but still people eat something in the morning.

01:14:15.060 | - You said you start your first meal of the day

01:14:18.720 | at around eight, what time do you wake up?

01:14:20.540 | - I wake up around six, I started at six.

01:14:22.580 | - What time do you have your first caffeine?

01:14:24.620 | - No, actually I have,

01:14:25.780 | so that's why I brought up this story

01:14:27.540 | because I have coffee after my breakfast.

01:14:29.820 | - Fantastic, I'm a big proponent of delaying caffeine intake

01:14:32.620 | for a few hours after waking for other reasons

01:14:35.060 | that my listeners have heard me talk about endlessly.

01:14:37.740 | So I won't bother with that now.

01:14:39.060 | But I think allowing,

01:14:43.020 | just suffice to say that allowing some of the natural

01:14:45.240 | waking up signals to occur and using light

01:14:48.260 | to kind of clear away and adenosine to further extend

01:14:52.500 | and activity is better than using a stimulant,

01:14:55.520 | but until a few hours later.

01:14:56.940 | This is fascinating because I've never thought

01:14:59.020 | about the link between extension into the night,

01:15:02.160 | socialization or socializing rather, feeding and caffeine.

01:15:07.060 | I'd like to take a brief break

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01:16:20.440 | - Now, actually, I'm kind of speaking

01:16:23.440 | what many other researchers have found

01:16:25.460 | and this particularly, this fireside chat,

01:16:28.860 | I'm forgetting again, the name of the scientist.

01:16:31.620 | I think she's from University of Washington, Seattle.

01:16:34.800 | She went to Africa and kind of recorded

01:16:38.760 | what people are talking.

01:16:39.940 | Of course, she could not understand what they were talking.

01:16:42.220 | - Twitter and whether or not Tesla's talk is going up.

01:16:45.180 | Of course, no, no, no, just kidding, folks.

01:16:48.940 | - And then came back and tried to translate

01:16:50.660 | and then figured out that what they were talking

01:16:52.680 | during daytime and in the evening were very different.

01:16:55.380 | - What are they talking about at night?

01:17:00.420 | - Exactly, so this is like they're talking about matchmaking

01:17:04.140 | and talking about politics and strategizing

01:17:08.300 | to gather food or even singing and dancing.

01:17:13.300 | So this is, if we think about it,

01:17:17.540 | how we manage sunset to our bedtime,

01:17:22.540 | what we do between sunset and bedtime

01:17:26.520 | affects most of our health.

01:17:28.740 | - I'm gonna think about that for a moment.

01:17:31.840 | I totally agree.

01:17:33.720 | And by the way, I'm a huge believer

01:17:36.980 | and I'm living in great hope for the idea that right now,

01:17:41.980 | I do think that scientists understand a lot more

01:17:45.140 | about the different stages of sleep,

01:17:46.580 | slow wave sleep, REM sleep, et cetera,

01:17:48.300 | than we do active waking states.

01:17:50.340 | Like we talk about being focused or being alert,

01:17:52.460 | but those aren't scientific terms as we know.

01:17:55.720 | But I do believe, and I've noticed a distinct difference

01:17:59.640 | between the first eight hours of the day

01:18:02.780 | in terms of cognition.

01:18:03.900 | And we know that the catecholamines

01:18:05.420 | are at much higher levels plus cortisol,

01:18:06.940 | so dopamine, cortisol, epinephrine,

01:18:08.260 | all of that is really at much higher levels

01:18:10.860 | than in the later evening.

01:18:12.640 | And so this evening time,

01:18:14.300 | it's certainly in the context of mental health,

01:18:16.660 | we know that morning and evening,

01:18:18.020 | we are basically different creatures, yeah, completely.

01:18:22.460 | - Yeah, so that's why I think in the evening,

01:18:24.840 | if you think about it, again,

01:18:27.540 | this is again, another set of research

01:18:30.000 | from my good friend Horatio who-

01:18:34.340 | - Horatio Iglesias.

01:18:35.700 | Oh yeah, I'm a big fan of Horatio.

01:18:38.660 | He's a fellow Argentine.

01:18:39.740 | So occasionally we riff about things related to that,

01:18:42.620 | but he's a wonderful biologist.

01:18:44.500 | Are you guys collaborating?

01:18:45.680 | - Yeah, he's kind of, I say he's very humble

01:18:49.380 | and keeps a low profile,

01:18:50.660 | but he does amazing, amazing research.

01:18:53.580 | And he does research that we want to know,

01:18:57.020 | but nobody is ready to do it

01:18:58.600 | because field research is very difficult

01:19:01.420 | to go to the wilderness or go to the places

01:19:05.260 | where there is no electricity and then record

01:19:08.300 | when these people are eating, sleeping,

01:19:11.980 | or in this case activity, exposure to light.

01:19:15.400 | That's what Horatio has done.

01:19:17.160 | And he puts this active watch,

01:19:19.820 | which is kind of a modern activity tracker,

01:19:23.620 | but it's a little bit more refined

01:19:26.000 | because it also collects light information.

01:19:29.740 | And what he found was most of these Argentinian tovas

01:19:32.340 | who have no access to electricity,

01:19:35.340 | they consistently go to bed somewhere

01:19:38.180 | between three to three and a half hours after sunset.

01:19:40.840 | So this is very important because we always think

01:19:42.700 | that our ancestors, when they didn't have electricity,

01:19:46.900 | as soon as the sun went down, they just went to sleep.

01:19:48.980 | No, the fire extended their evening.

01:19:52.340 | So they were staying awake for three to four hours,

01:19:56.020 | kind of decompressing themselves that we say,

01:20:01.020 | and then doing all these activities, cooking,

01:20:04.820 | sharing meals, and then they would go to sleep.

01:20:07.820 | And if you look at the sleep onset variability,

01:20:10.180 | it was very small.

01:20:11.640 | Like they're going to bed almost within 15 to 30 minutes

01:20:15.020 | standard deviation.

01:20:16.660 | - So no night owls versus morning people.

01:20:19.420 | - Exactly, so we'll get to that.

01:20:20.820 | - No, no, I get attacked for many reasons.

01:20:25.380 | It just goes with the business I'm in

01:20:27.020 | of being public facing these days.

01:20:28.780 | But every time I talk about viewing sunrise

01:20:32.060 | or low angle sunlight, getting some sunlight early

01:20:34.580 | that someone says, well, I'm a night owl.

01:20:36.780 | And they just, it's almost like a protest

01:20:39.760 | of trying to protect identity.

01:20:41.520 | It's become this ideological identity related thing.

01:20:45.740 | I'm a night owl, I'm a morning person and I'm not.

01:20:48.380 | But you're telling me that in these cultures

01:20:50.120 | where there isn't electricity, but there is fire,

01:20:51.940 | people are going to sleep within all of them,

01:20:55.340 | within about 15 minutes of one another.

01:20:58.060 | So there is no such thing as a night owl

01:20:59.940 | or a morning person in the context of-

01:21:00.780 | - Yeah, so Horacio actually asked him pointedly

01:21:03.540 | because, and then he said, no, he has not seen.

01:21:07.140 | Means he has tracked hundreds of people.

01:21:09.460 | And if we ask, there are many, many sleep researchers

01:21:13.820 | or at least the public facing sleep physicians or experts,

01:21:18.820 | they will say, yeah, we can say one third of people

01:21:21.860 | are night owl, one third are morning.

01:21:23.700 | And then one third are in between.

01:21:25.620 | - Yeah, they call them like bears, wolves,

01:21:27.260 | and I'm not being disparaging of that idea.

01:21:29.240 | I think people really do feel as if they orient

01:21:33.000 | towards one pattern or another.

01:21:34.580 | - When I was an undergrad student,

01:21:35.820 | I never went to bed before midnight.

01:21:38.300 | And actually, midnight was my going to bedtime.

01:21:41.580 | Exactly like 11, 45, I'll try to get ready to hit bed.

01:21:46.260 | And then by 12, I'm in bed.

01:21:47.680 | And I used to get up at six, 6, 15.

01:21:50.460 | - That's a pretty short sleep.

01:21:51.540 | - With an alarm, of course.

01:21:53.500 | But then daytime, I used to take 45 minutes to one hour nap.

01:21:56.860 | And that was regular.

01:21:59.200 | Like even if whenever I got time,

01:22:02.180 | of course in college, you don't have the whole day.

01:22:05.340 | Unlike in high school, you don't have opportunity to nap,

01:22:09.340 | but in college, you can.

01:22:10.500 | - I might've been one of those kids

01:22:11.580 | with his hoodie on napping on the desk,

01:22:13.180 | but they come around and they wake you up.

01:22:14.460 | - Yeah, but in this case, just come back to the dorm

01:22:17.100 | and after lunch usually, I used to take nap.

01:22:20.820 | So then in grad school,

01:22:24.680 | I remember I rarely went to bed before two a.m.

01:22:28.000 | And I could have clearly said that I'm a night owl

01:22:30.520 | and actually I was a night owl.

01:22:33.420 | I was very comfortable staying off so late.

01:22:36.500 | I was very productive doing experiments,

01:22:38.820 | writing all these manuscripts mostly.

01:22:42.900 | But then afterwards, when I look back in postdoc,

01:22:49.740 | when we had our daughter,

01:22:53.000 | then things started changing

01:22:56.460 | because you have to put the baby to sleep.

01:22:59.340 | And then after the baby sleeps,

01:23:03.180 | it's almost when you have a baby,

01:23:05.140 | your life revolves around the baby.

01:23:07.540 | So then we had to dim down the light.

01:23:11.260 | There is no caffeine and alcohol drinking

01:23:13.760 | or any other things after the baby sleeps

01:23:15.880 | because we cannot do too much noise.

01:23:17.620 | So then I realized that, no, I'm actually not a night owl.

01:23:22.300 | And I became kind of more normal

01:23:25.100 | because I could go to sleep between 10 and 11.

01:23:29.240 | And that's how I thought,

01:23:31.500 | well, maybe this was very unique to me.

01:23:34.740 | But what is interesting is I have another colleague,

01:23:40.540 | good friend, Ken Wright Jr.

01:23:43.080 | - At Colorado.

01:23:43.920 | - At Colorado.

01:23:44.820 | And he also had grad students and postdocs like me

01:23:49.820 | who strongly believed that they were night owls,

01:23:53.640 | just like everybody else.

01:23:55.680 | And Ken took the whole lab for camping.

01:23:58.780 | And when they were camping, of course, there is less light

01:24:02.400 | and a lot of physical activity, hiking during the day.

01:24:05.620 | And they all went to bed between nine and 10, 30 p.m.

01:24:10.620 | - I love that study.

01:24:11.960 | What Sachin just described was a study,

01:24:13.920 | I think there were two studies.

01:24:15.160 | - There were two, yeah.

01:24:16.000 | - And what's interesting, as I recall,

01:24:18.120 | is that after going camping for a weekend

01:24:20.220 | where people wake more or less with the sunrise

01:24:24.560 | and go to sleep a few hours after sunset,

01:24:27.340 | their melatonin rhythms and cortisol rhythms

01:24:31.160 | and sleep-wake rhythms persisted on that schedule

01:24:35.520 | for several weeks, despite returning to environments

01:24:39.600 | where there was a lot of artificial lighting,

01:24:41.160 | which I find amazing, that just a weekend

01:24:44.000 | of consistent rising and going to bed

01:24:47.680 | with the sunrise and sunset, more or less,

01:24:50.920 | allowed a reset that was very long lasting.

01:24:53.840 | - Yeah.

01:24:54.920 | So actually, even in Horacio's study,

01:24:58.480 | he found that almost all the Tobas,

01:25:01.280 | they wake up around sunrise time.

01:25:03.960 | And it's amazing when I look at the standard deviation,

01:25:06.720 | it's like so tight.

01:25:08.520 | - So take that, night owl, so-called night owls.

01:25:11.060 | - I also, in graduate school, I would work until 2 a.m.

01:25:13.760 | I loved it, I would blast music in the lab.

01:25:15.400 | Everyone was at home, pretty much, not everyone,

01:25:17.780 | but there were the night crew.

01:25:19.700 | And then I'd get in sometime around,

01:25:21.500 | get up sometime around 9.30, 10,

01:25:24.360 | and then get in around 11, and it was no problem

01:25:26.480 | because I was going to stay so very late.

01:25:29.360 | And then over time, I noticed I'd become more locked

01:25:31.840 | to a standard schedule.

01:25:32.680 | So I think what we're saying is that the clock can,

01:25:34.360 | our internal clocks can shift.

01:25:36.080 | - Yeah.

01:25:36.920 | - But this idea that we are genetically biased

01:25:40.360 | towards one schedule or another may need revisiting.

01:25:43.480 | That's what, that's the conclusion I'm taking from this.

01:25:45.240 | - There's a couple of aspects.

01:25:47.000 | One is, you know, some people are genetically so pre-programmed

01:25:51.500 | because the other flip side is what is called

01:25:54.180 | technically familial advanced sleep phase syndrome.

01:25:57.780 | So these people, you can give them caffeine or whatever,

01:26:02.780 | but they will fall asleep, say at eight o'clock.

01:26:05.980 | They cannot stay awake till nine or 10.

01:26:09.500 | And since it's a very strong phenotype

01:26:12.180 | in sleep and circadian rhythm field,

01:26:14.380 | they are very well studied.

01:26:16.060 | So in fact, Louis Patasek and Yngwie Fu,

01:26:18.980 | they were the first one to track one family like this,

01:26:22.400 | and then they figured out there was a mutation

01:26:24.820 | in one of the clock genes, period two, that clock gene,

01:26:28.560 | and that mutation allowed the clock to run in a way

01:26:33.560 | that these people went to bed very early.

01:26:36.620 | - I guess, historically, given these fireside chats,

01:26:41.300 | those people were probably not contributing much

01:26:43.740 | to the political discussion.

01:26:45.480 | Whatever was decided after they went to sleep

01:26:47.460 | is what they woke up into.

01:26:48.780 | That reminds me, because as you were describing,

01:26:50.760 | the difference between nighttime discussions

01:26:52.580 | versus morning discussions,

01:26:53.900 | is there any theme to what is discussed in the morning

01:26:56.980 | versus in the nighttime,

01:26:57.820 | or are people just sipping their,

01:26:58.980 | eating and sipping their caffeine and just waking up?

01:27:01.820 | But is there, are there any ideas

01:27:04.740 | about what morning discussions really consist of?

01:27:06.780 | - Morning discussions or daytime discussions

01:27:08.780 | are mostly about work,

01:27:11.500 | and like hunting, gathering, farming, all that stuff.

01:27:16.220 | And even these days, that's what we do.

01:27:18.420 | We, you know, you go to, I go to work,

01:27:22.180 | and it's mostly one meeting after another,

01:27:24.100 | and we're talking about how,

01:27:26.140 | means if you're in different committees

01:27:27.900 | and you're solving problems,

01:27:29.680 | or your students come with questions,

01:27:31.300 | you have your TA or the office hours,

01:27:34.080 | all these things, work-related.

01:27:35.780 | We're not talking, I mean, serious philosophy,

01:27:40.300 | unless you are in a philosophy department

01:27:41.980 | and you are talking of political science.

01:27:44.660 | And also we are not singing and dancing.

01:27:47.400 | So that's why the evening activity,

01:27:50.820 | even these days, are very different.

01:27:53.380 | And typically the evening activities

01:27:55.380 | are where we express ourselves.

01:27:58.540 | We express who we are.

01:28:00.100 | We feel like we are free.

01:28:02.220 | And, you know, you and I,

01:28:04.740 | we have this academic intellectual freedom.

01:28:07.600 | We can talk about our work just like we're talking now.

01:28:10.940 | There are a lot of people who work for,

01:28:12.680 | even in tech industry,

01:28:14.560 | they may be working for Google

01:28:16.180 | and all these big tech companies.

01:28:18.460 | They cannot talk about their work to anybody else.

01:28:21.140 | - It's all a secret.

01:28:22.060 | - It's all secret.

01:28:23.400 | So just imagine they're staying,

01:28:25.820 | so they're spending more than half of their wake-up time

01:28:31.320 | at work, thinking and doing work,

01:28:34.720 | but they cannot talk about that work,

01:28:37.300 | even sometimes to their own family members.

01:28:40.300 | So then what happens for them,

01:28:42.540 | a lot of people also do the same thing,

01:28:44.040 | like the person who is going and baking in a restaurant

01:28:47.880 | or cooking or the person who is taking truss and driving.

01:28:52.440 | - Or nurses and doctors can't talk about their patients.

01:28:54.980 | There's confidentiality.

01:28:56.540 | - Yeah. - Yeah.

01:28:57.380 | - And some people just don't want to talk about it.

01:28:59.260 | It's so stressful.

01:29:00.280 | They don't want to bring that stress home.

01:29:02.820 | So that's why I always say that from sunset

01:29:05.280 | until we go to bed,

01:29:06.880 | during that time, we try to find time for ourselves.

01:29:10.220 | People say, "This is me time."

01:29:13.180 | The me time is essentially,

01:29:15.660 | we want to truly express who we are

01:29:19.240 | or we want to entertain ourselves

01:29:22.260 | because on the fireside chart,

01:29:24.360 | it's not that everybody was a performer.

01:29:26.980 | There are also some audience.

01:29:28.640 | So we always switch our role.

01:29:30.740 | Sometimes we are performing and sometimes we are observing.

01:29:33.900 | So that's what happens with me time.

01:29:36.420 | - I love this.

01:29:37.260 | So maybe social media time should be restricted

01:29:39.900 | to just maybe a small portion of that evening time.

01:29:42.220 | 'Cause I would hope that people would also interact socially

01:29:44.900 | within the real sense. - Or maybe in a constructive

01:29:46.700 | way, or maybe you use that for,

01:29:49.100 | connect with your family members whom you love,

01:29:52.120 | or you can have some productive discussion or something.

01:29:54.720 | So it's kind of interesting.

01:29:56.620 | - I think it's extremely interesting

01:29:58.380 | because I think, again, this conversation

01:30:00.740 | about time-restricted feeding

01:30:02.240 | is really a conversation about-

01:30:03.840 | - Security and rhythms.

01:30:04.740 | - And sleep-wake activity and human evolution, right?

01:30:08.080 | - So that's why, let's go back to this night owl

01:30:11.700 | because we kind of made a comment

01:30:14.760 | that maybe it's not genetic,

01:30:16.240 | but this is where I'm still wrapping my head around

01:30:19.520 | because these days, there are some GWAS studies

01:30:24.520 | where they're trying to look at night owls

01:30:27.060 | to see whether there are some genetic linkings.

01:30:32.060 | And, you know, sometimes we always think,

01:30:34.620 | yeah, if you take half a million people,

01:30:36.420 | of course you'll find some loci.

01:30:38.340 | But going back to this idea

01:30:41.540 | that are some people more sensitive to light

01:30:45.060 | so that it's likely that the same level of light,

01:30:48.460 | even in the same household,

01:30:50.740 | may make some people stay awake late into the night,

01:30:54.020 | whereas other people are more resistant to light

01:30:56.200 | so that they can go to bed early.

01:30:59.340 | And since light has become so prevalent these days

01:31:02.700 | and this Toba story that we are talking about

01:31:05.060 | or people going on camping,

01:31:06.240 | there is, we have removed that light.

01:31:08.280 | So there is some evidence that people's light sensitivity,

01:31:14.980 | particularly the IPRGC

01:31:17.340 | or this intrinsically photosensitive retinal ganglion cell,

01:31:21.440 | or the simple speakers, the blue light sensors in our eyes,

01:31:25.880 | there seems to be even one log unit change in sensitivity

01:31:30.040 | as measured by pupil constriction.

01:31:33.080 | - So for some people,

01:31:35.760 | a small amount of artificial light at night

01:31:38.000 | could really shift their circadian clock,

01:31:40.080 | wake them up, essentially.

01:31:41.320 | - And then for some, it may not.

01:31:42.960 | - Yeah, I'm very sensitive to light at night,

01:31:45.320 | exquisitely sensitive to it.

01:31:47.000 | - Oh, so then you are like a teenager.

01:31:49.160 | - Yes, in many ways.

01:31:50.540 | I've been told this, thank you, I think.

01:31:55.100 | I have actually switched to using a red nightlight,

01:31:58.260 | but I should be clear,

01:31:59.780 | not a fancy high cost red light

01:32:02.860 | for sake of any kind of infrared simulation,

01:32:05.160 | but a red party light type light.

01:32:07.540 | And I find that that was based on reading one study

01:32:10.180 | that we covered in an episode on jet lag and shift work,

01:32:12.520 | which was that it seems to reduce

01:32:15.020 | the cortisol releasing properties of light at night

01:32:18.820 | to use red shifted light.

01:32:20.560 | So I just use a red light bulb.

01:32:22.540 | I actually travel with one.

01:32:23.460 | If I go to an Airbnb or a hotel and I switch to red light,

01:32:25.740 | and I find that I fall asleep and stay asleep

01:32:27.840 | throughout the night much more consistently,

01:32:30.080 | especially when I'm in new environments

01:32:32.020 | where it always makes it disruptive to sleep,

01:32:34.600 | it's made an enormous difference

01:32:36.880 | in the depth and duration of my sleep.

01:32:39.420 | And because oftentimes hotel lights in the bathroom,

01:32:43.380 | you'll turn them on and you're just getting beamed.

01:32:45.180 | And you're right, some people don't seem

01:32:46.640 | to be bothered by that.

01:32:48.600 | I really struggle with that.

01:32:51.260 | Yeah, and in fact, in teen age, right after puberty,

01:32:55.260 | there seems to be, I think that's when the teenagers

01:32:58.980 | become more sensitive to light.

01:33:01.340 | And it's well known that the teenage boys and girls,

01:33:06.680 | they tend to stay awake late into the night

01:33:09.220 | and they can stay up to 12 past midnight.

01:33:12.760 | Although they can stay up that late,

01:33:16.100 | that doesn't mean that their sleep schedule is reduced.

01:33:19.140 | Their body still needs the same amount of sleep

01:33:21.980 | as other teenagers.

01:33:23.040 | So that's why they are more likely not to wake up

01:33:26.380 | at 6.30 or seven when we expect them to wake up

01:33:29.900 | and go to school.

01:33:30.860 | - I have a question and I ask every circadian

01:33:35.500 | related biologist that I can come into contact with this.

01:33:38.700 | And no one has been able to give me an answer

01:33:40.360 | one way or the other.

01:33:41.660 | But I grew up hearing that every hour of sleep

01:33:44.200 | before midnight was of more value or potency

01:33:47.340 | than the hours after midnight.

01:33:49.100 | And indeed, I find that if I go to sleep at 9.30 or 10 p.m.,

01:33:53.620 | I can wake up at three or 4 a.m. feeling pretty fantastic

01:33:57.140 | and ready to lean into the day.

01:33:58.700 | But if I get the equivalent number of hours of sleep

01:34:00.980 | starting at midnight, I feel like complete garbage

01:34:04.700 | when I wake up after five, six hours.

01:34:06.780 | So is there any truth to the idea that going to sleep

01:34:11.240 | within three hours of sunset is somehow better

01:34:15.980 | for our circadian timing mechanisms?

01:34:18.040 | - Well, there are a few things.

01:34:20.220 | One, you said that you are very sensitive to light.

01:34:22.460 | So I assume that you also avoid bright light in the evening.

01:34:26.140 | - As best I can, yeah.

01:34:27.060 | - As best as you could, can.

01:34:28.980 | And then what is happening is with absence

01:34:31.780 | of that bright light, your melatonin levels begin to rise.

01:34:35.260 | So you are prepared for sleep.

01:34:37.380 | Of course, this is something that we cannot measure

01:34:40.200 | because measuring melatonin in every one hour or 30 minutes

01:34:44.700 | is very difficult and there is no consumer-facing

01:34:48.140 | product yet.

01:34:49.080 | So it's likely that your body is preparing very well

01:34:54.060 | under this dim light to fall asleep.

01:34:56.220 | And when you are trying to stay awake

01:34:58.220 | and go sleep at midnight, then maybe from midnight

01:35:02.840 | for the first three or four hours, you are sleeping well.

01:35:05.180 | But then after that, your melatonin level

01:35:07.540 | might be beginning to fall.

01:35:09.340 | And it's not only melatonin, your core body temperature

01:35:13.700 | and then your heart rate and everything is changing

01:35:15.860 | to make you awake.

01:35:17.540 | But the sleep debt that you have accumulated

01:35:20.100 | is pushing you to be in bed.

01:35:22.580 | So there is this tension between the circadian aspect

01:35:26.300 | and your sleep debt.

01:35:27.700 | And unfortunately, you cannot have good night

01:35:32.100 | of restorative sleep for the second half of the sleep

01:35:35.380 | because of the tension.

01:35:36.700 | - That makes good sense.

01:35:37.700 | - Yeah, so that's why you are not the only one.

01:35:40.940 | There are many people who experience that.

01:35:44.620 | And in fact, a lot of people think that,

01:35:46.900 | well, this may be the way I sleep.

01:35:49.320 | Maybe I'm not designed to sleep restoratively

01:35:54.260 | until I sleep one day, just like the camping trip.

01:35:58.600 | - And then they realize what it feels like

01:36:01.680 | to be empathetic. - What you're missing, yeah.

01:36:03.340 | - Absolutely.

01:36:04.740 | I want to make sure that we talk about the other aspect

01:36:07.680 | of fire, which is you had a paper that came out recently,

01:36:11.400 | very interesting paper, studying firefighters

01:36:14.040 | and time-restricted feeding in firefighters.

01:36:15.620 | Would you share with us the general contour

01:36:17.600 | and maybe even some of the specifics of that study?

01:36:19.800 | 'Cause I think it's very interesting

01:36:21.520 | for sake of shift workers,

01:36:23.120 | but for everybody really to understand these results.

01:36:26.760 | - Yeah, so let's go back to shift workers

01:36:28.460 | because this also relates to all of us

01:36:31.040 | because I always say that each of us is a shift worker

01:36:35.640 | or has lived the life of a shift worker.

01:36:38.080 | And we have experienced how terrible, difficult it is.

01:36:43.000 | And now let's start with what is the definition

01:36:46.420 | of a shift worker or shift work lifestyle?

01:36:50.560 | There is no universal definition, unfortunately,

01:36:53.320 | but there are many European countries.

01:36:55.320 | And particularly if you go

01:36:56.780 | to international labor organization,

01:36:59.000 | then you'll find some references.

01:37:02.520 | Different European countries

01:37:04.080 | have slightly different definition,

01:37:06.000 | which essentially points to if you stay awake

01:37:09.640 | for two or more hours during your habitual sleep time.

01:37:13.720 | And when they say habitual sleep time,

01:37:15.740 | they assume that we are, just like you said,

01:37:19.720 | we are kind of programmed to sleep somewhere between,

01:37:22.000 | say 10 p.m. and then stay in bed

01:37:25.860 | and kind of wake up after 5 a.m.

01:37:28.920 | So the idea is if you're staying awake

01:37:31.520 | for two or more hours between 10 p.m. and 5 a.m.,

01:37:36.360 | and you are engaged in some activity,

01:37:38.880 | whether it's physical activity or intellectual activity,

01:37:42.200 | you are not lying in bed and wondering,

01:37:45.920 | worrying about something, but actually working.

01:37:48.240 | So that defines, that's defined as shift work.

01:37:51.040 | And you don't have to do it every single day.

01:37:53.100 | Even if you do it once a week for 50 weeks,

01:37:58.160 | then that itself is enough to disrupt your physiology

01:38:03.160 | and metabolism, behavior, brain function,

01:38:06.040 | like a shift worker.

01:38:06.880 | The reason is, as you discussed,

01:38:08.920 | when you change our external timing cue,

01:38:14.340 | so in this case, when you travel jet lag

01:38:16.760 | or traveling across three days,

01:38:19.840 | three hours of jet lag will take three days to reset.

01:38:26.040 | Similarly, if you're staying awake for two hours extra,

01:38:29.180 | or if you're waking up two hours

01:38:30.800 | before your habitual wake up time,

01:38:33.660 | then we just don't get wake up

01:38:36.640 | and then be engaged in some activity in the dark.

01:38:39.580 | Most of us, unless you are wearing infrared goggles,

01:38:43.880 | we turn on light and light resets our clock.

01:38:47.380 | So in that way, every time we stay up

01:38:52.380 | for two or more hours, even for one night,

01:38:55.360 | then for the next two nights,

01:38:56.720 | our clock is kind of trying to catch up.

01:38:59.260 | So in that way, for three days,

01:39:01.300 | the day of the disruption

01:39:03.680 | and then two days following the disruption,

01:39:05.840 | our clock is trying to catch up with the outside time.

01:39:09.960 | So our clock, our body is not on time with our clock.

01:39:13.000 | So that means almost for half of the week

01:39:17.760 | or half of the year, our clock is trying to catch up.

01:39:20.720 | So that's the definition of shift work.

01:39:23.360 | So now let's come back to Department of Level Statistics,

01:39:28.360 | US government, they have not been tracking

01:39:33.360 | what percentage of people are doing shift work accurately

01:39:36.700 | because there are many difficulties in tracking too.

01:39:39.960 | But it's generally accepted that one in five working adults

01:39:44.280 | is a card carrying shift worker.

01:39:46.520 | Card carrying shift workers means they are nurses,

01:39:51.040 | doctors, firefighters, and bakers,

01:39:56.040 | truck drivers, and many in the service industry.

01:40:02.120 | So that's one in five.

01:40:04.320 | So 20% of working adults.

01:40:06.780 | Then if we think about all the college students,

01:40:11.240 | just like I was doing and you must have done,

01:40:14.400 | there are also- - Grants, deadlines.

01:40:17.600 | Grants, deadlines. - Grants, deadlines.

01:40:19.220 | Then we are also experiencing the lifestyle

01:40:22.840 | of a shift worker because we're delaying sleep.

01:40:26.280 | Even if you're delaying sleep by two hours

01:40:28.000 | for most of the college students for five days

01:40:30.080 | and then the weekend you're trying to catch up,

01:40:32.220 | that's kind of a circadian disruption going on.

01:40:34.980 | Then you take 1.5 or 1.6 million new moms

01:40:39.880 | in the US every year.

01:40:42.440 | So when the child is born,

01:40:44.260 | then that mother is a shift worker.

01:40:46.320 | And actually that mother is worse than a shift worker

01:40:48.640 | because you don't know what time of the night

01:40:52.840 | the baby will wake up and how many times,

01:40:55.900 | and there is no weekend in motherhood.

01:41:00.640 | So they're also living the life of a shift worker.

01:41:03.820 | We don't count many food delivery and Uber driver,

01:41:10.440 | Lyft drivers as shift workers,

01:41:12.500 | but many of them we know that they live.

01:41:14.760 | So in that way, we think the actual number of people

01:41:18.880 | who are experiencing the life of a shift worker

01:41:21.120 | is somewhere around 50% of the adults,

01:41:24.400 | population at any given time.

01:41:26.040 | So that's why it's also another point

01:41:30.260 | that you might have heard from people.

01:41:31.840 | They will say, "Oh, I cannot do time-restricted eating

01:41:35.080 | because my schedule is messed up

01:41:37.240 | or I work in a different way."

01:41:39.520 | And that comes into play.

01:41:43.880 | So that's why we thought,

01:41:45.460 | "Okay, so we should try something on shift worker."

01:41:48.200 | Another point is although one in five people

01:41:51.440 | are shift workers,

01:41:53.120 | they carry disproportionately heavier burden of disease

01:41:57.640 | because almost all age-related disease that we can think of,

01:42:01.360 | whether it's high blood pressure,

01:42:02.880 | usually high blood pressure starts in 40s or 50s,

01:42:06.360 | high cholesterol, gastrointestinal problem, indigestion,

01:42:12.520 | chronic inflammation of the colon,

01:42:15.520 | and then even colon cancer in many cases.

01:42:18.780 | And then of course, diabetes,

01:42:21.560 | all of these are disproportionately more prevalent

01:42:26.040 | among shift workers.

01:42:27.420 | But then when you think about clinical trials,

01:42:31.680 | whether it's a drug or a lifestyle,

01:42:35.320 | often one of the top 10 exclusion factor criteria

01:42:39.800 | is shift work.

01:42:41.140 | So people who are doing shift work,

01:42:43.220 | we exclude them from many of these trials.

01:42:46.900 | One thing is most physicians and most scientists,

01:42:50.860 | even people who do shift work,

01:42:52.300 | they know that their body and mind is so messed up

01:42:57.060 | that oftentimes even medications may not help them.

01:43:01.080 | And so that's why if we don't try new medication,

01:43:03.920 | why to take the risk when we know it may not help them.

01:43:07.360 | And then when it comes to lifestyle intervention,

01:43:09.420 | whether it's sleep extension, for example,

01:43:11.920 | we cannot do because they are supposed to stay awake

01:43:14.280 | and do their job.

01:43:15.140 | We cannot ask them to stay asleep at night.

01:43:17.760 | And then physical activity and exercise,

01:43:21.720 | some people can do,

01:43:23.520 | but some people are so tired after all night

01:43:27.360 | that they don't have the energy to do physical activity.

01:43:30.080 | And then nutrition, again,

01:43:32.360 | most nutrition studies involve the participants

01:43:36.680 | to come to the clinic and get one-on-one

01:43:41.680 | or attend group sessions, and they cannot come.

01:43:47.000 | And they cannot even sometimes come to the clinic visit

01:43:50.560 | when people have to draw blood.

01:43:54.000 | And in fact, there is another caveat that just,

01:43:59.000 | suppose I'm healthy,

01:44:00.900 | I have perfectly normal blood pressure, blood glucose,

01:44:06.040 | cholesterol, everything is normal.

01:44:08.400 | And I live the life of a shift worker just for five nights.

01:44:12.820 | That means I'm sleeping less, maybe four or five hours.

01:44:16.380 | And even if I don't eat at nighttime,

01:44:22.040 | of course, many shift workers also feel hungry

01:44:24.200 | and just to keep their work, they eat.

01:44:27.220 | Just after five days, my blood glucose level

01:44:31.200 | will read almost like I'm pre-diabetic.

01:44:33.680 | - Wow, I actually saw a study published in Prosthesis

01:44:36.800 | of the National Academy that showed

01:44:38.040 | that even 100 lux dim light present in the room

01:44:41.960 | while people are sleeping with eyes closed

01:44:44.140 | can lead to disruptions in morning blood glucose levels

01:44:48.480 | in directions that are not good.

01:44:51.040 | One night, so the faint clock in the corner

01:44:54.360 | or even a nightlight that's too bright could be problematic.

01:44:59.360 | By the way, folks, these effects are reversible.

01:45:02.520 | So whenever I say these things,

01:45:04.360 | we get a lot of comments about,

01:45:05.380 | oh my goodness, what have I been doing for years?

01:45:07.280 | But kids with nightlights, this is an issue.

01:45:10.560 | But what I'm hearing is that one in five people

01:45:13.000 | are truly shift workers in the classic sense.

01:45:16.340 | Their jobs require they work at night or into the night

01:45:19.000 | and sleep into the day.

01:45:20.420 | But far more people are shift workers

01:45:25.180 | by virtue of the fact that they're tweeting or working

01:45:27.720 | or watching movies at night, even though it's not work

01:45:30.720 | in that they're not being paid for that time.

01:45:33.040 | They are essentially operating like shift workers.

01:45:36.040 | If we add those two groups together,

01:45:37.680 | would we say it's what, a third of Americans?

01:45:41.480 | - I would say half of Americans.

01:45:42.840 | - Half of Americans.

01:45:43.680 | - Yeah, if you take teenagers,

01:45:45.280 | because high school students and college students,

01:45:48.160 | because again, going back to Horacio's study,

01:45:51.400 | because Horacio also collected activity data

01:45:54.860 | from high school students and college students,

01:45:56.800 | and we have replicated that with high school students

01:45:59.480 | and college students in San Diego.

01:46:00.960 | So that's Seattle and San Diego.

01:46:03.280 | And this study, now there are many sleep researchers

01:46:06.880 | that have been collecting this data.

01:46:09.060 | And what we find is typically the high school students,

01:46:12.780 | they are going to bed say around midnight,

01:46:16.280 | and college students, at least the UCSD students,

01:46:19.760 | we found maybe one out of 100

01:46:21.520 | who went to bed before midnight.

01:46:23.840 | - That reminds me that Horacio Iglesias

01:46:26.400 | just published this really nice paper.

01:46:29.620 | Showing that counter to what we believe students,

01:46:32.920 | now this is the University of Washington in Seattle,

01:46:34.700 | I should mention where it's very dark in the winter,

01:46:37.800 | young people, these are people in their 20s,

01:46:40.020 | are staying up later in the winter months

01:46:42.980 | compared to the summer months,

01:46:44.680 | which is totally counterintuitive.

01:46:46.580 | You think, okay, everyone stays up late in the summer

01:46:48.220 | and goes to bed early in the winter,

01:46:49.260 | but because of artificial lighting, it's the exact opposite.

01:46:51.940 | - Yeah, so another means,

01:46:54.240 | I don't know whether Horacio monitored it,

01:46:56.420 | but my other suspicion, I'm not saying whether it's true,

01:47:00.660 | in winter we are more likely to consume more coffee,

01:47:03.500 | hot chocolate in the evening,

01:47:05.340 | and that might also be delaying sleep onset.

01:47:10.140 | - That makes sense.

01:47:10.980 | - So in that way, again, here is another thing

01:47:14.980 | which can be related to policy

01:47:18.620 | or practice at educational institute.

01:47:22.500 | So what happened during COVID

01:47:24.820 | was everybody went to remote learning.

01:47:26.900 | The assignments became digital

01:47:30.460 | and assignments submission became digital.

01:47:32.900 | And there are many systems,

01:47:34.820 | online systems that came into play.

01:47:37.500 | And by default, the assignments submission deadline

01:47:41.140 | became midnight.

01:47:42.160 | So then now what is happening is,

01:47:45.020 | I don't know about Stanford,

01:47:47.300 | maybe when you are giving assignment,

01:47:49.860 | when is the deadline?

01:47:50.700 | - Midnight, typically. - Midnight.

01:47:52.220 | So then most of us, most students,

01:47:54.500 | they will try to cram as much as possible,

01:47:57.380 | try to solve as much as possible and submit at midnight.

01:48:00.260 | And it'll be really cool to go back

01:48:03.100 | to your system administrator to see,

01:48:05.680 | is there so many frequency plot of frequency distribution

01:48:09.780 | of what time people are submitting the assignment?

01:48:13.860 | Because we know, means when we submit our grant.

01:48:16.520 | - Yeah, so I mean, you hear about the obesity crisis,

01:48:20.660 | the crisis of metabolic disorders,

01:48:22.980 | not just in the US but everywhere in the world.

01:48:24.820 | I mean, it's really striking.

01:48:25.700 | I remember going to a Keystone meeting,

01:48:27.940 | scientific meeting in the early 2000s,

01:48:30.260 | and there was a map of the United States

01:48:31.620 | and it showed where the obesity rates

01:48:33.460 | were over 30% in adults.

01:48:35.140 | And the entire country basically was lighting up like crazy.

01:48:37.540 | Now it would be the entire country,

01:48:39.060 | but there were these kind of zones in the middle

01:48:41.380 | that were almost devoid of obesity.

01:48:47.220 | Colorado, namely, Idaho at that time.

01:48:50.020 | Those are now also fallen under the umbrella

01:48:52.900 | of rampant obesity.

01:48:54.500 | And everyone is speculating, okay, is it seed oils?

01:48:58.500 | Is it this, is it that?

01:49:01.380 | Is it highly processed foods?

01:49:02.820 | I'm guessing it's all of those things,

01:49:04.340 | including lack of activity.

01:49:05.780 | But one has to wonder, given everything we're talking about

01:49:08.180 | in terms of metabolic dysfunction, late shifted eating,

01:49:11.460 | all these issues with late shifted eating

01:49:13.220 | and staying up late with artificial lighting,

01:49:15.300 | whether or not that could be one of the major factors

01:49:18.020 | in the so-called obesity crisis.

01:49:19.620 | It's likely, you know, we always say freshmen 15.

01:49:22.180 | That's right.

01:49:23.220 | Because these kids are gaining 15 pounds

01:49:26.740 | in their freshman year in college.

01:49:28.420 | And this is where I think as educator or professors,

01:49:33.700 | it'll be interesting to go back and see what can we do?

01:49:37.860 | Because another thing that's also becoming

01:49:39.860 | more and more common, for example,

01:49:42.100 | I give a circadian rhythm class,

01:49:44.740 | means I just give two lectures.

01:49:47.220 | And I remember when I started 15, 17 years ago,

01:49:50.740 | that lecture used to be around 1.30 PM

01:49:55.060 | or 2.00 PM in the afternoon.

01:49:56.740 | And it's a two and a half hour lecture.

01:49:58.420 | So it's done by five.

01:49:59.780 | And for the last, before the pandemic,

01:50:03.380 | I realized that they changed the timing.

01:50:06.100 | Now the lecture was starting at 7.00 PM.

01:50:08.820 | So I was finishing by nine, 9.30 PM.

01:50:12.420 | And these kids, they had to go and eat after 9.30.

01:50:16.500 | Study, socialize.

01:50:17.140 | Study, socialize.

01:50:18.660 | Fireside chat.

01:50:19.700 | Fireside chat.

01:50:20.580 | And then to express themselves,

01:50:21.860 | like to feel free from assignments.

01:50:24.740 | When are they going to do that?

01:50:26.340 | After they submit the assignment,

01:50:28.420 | then they're going to do that.

01:50:29.460 | So that's why we had to go back and revisit this issue,

01:50:33.140 | say, okay, so for adults,

01:50:36.500 | for most of us who are working a day job,

01:50:38.820 | our deadline is 5.00 PM in most cases, right?

01:50:43.860 | Means at least in university system,

01:50:46.500 | the person who is submitting the grant,

01:50:48.260 | who is taking care of my IRB or IR clerk,

01:50:52.900 | they're all living at five o'clock.

01:50:54.180 | So for me, everything has to end by five.

01:50:56.660 | I think for most people out there,

01:50:58.100 | so this raises a kind of macroscopic question,

01:51:02.580 | which is maybe it's not so much

01:51:04.420 | about restricting the feeding window,

01:51:05.860 | but maybe it's about feeding mostly

01:51:08.660 | and being active mostly in the early part of the day.

01:51:11.060 | I mean, I could imagine a time three, four years from now

01:51:15.300 | when waking up early and going to bed

01:51:18.660 | within three hours of sunset is the protocol,

01:51:21.780 | which harnesses all other protocols, right?

01:51:24.980 | You're going to exercise,

01:51:26.180 | you're going to do it in that time.

01:51:27.300 | You're going to eat,

01:51:27.780 | you're going to do it in that time.

01:51:28.740 | You're going to socialize,

01:51:29.380 | you're going to do it in that time.

01:51:31.060 | And in doing so,

01:51:31.700 | you're also avoiding a lot of the issues

01:51:33.300 | related to disrupted sleep.

01:51:34.500 | - Yeah, so that's why all these things,

01:51:36.580 | as you said,

01:51:37.620 | time ratio feeding is just one aspect of the circadian health

01:51:41.620 | and these are all interconnected.

01:51:43.380 | And going back to the comment about

01:51:44.820 | within three hours of sunset,

01:51:47.620 | yes, that's good.

01:51:49.700 | But then what happens in say Toronto or Vancouver

01:51:54.260 | in winter time?

01:51:54.980 | - Well, I guess they're going to bed very, very early,

01:51:57.140 | but also waking up very, very early.

01:51:58.740 | One of the things that I hear all the time,

01:52:00.820 | because I'm always beating on the drum

01:52:02.340 | of getting morning sunlight,

01:52:03.700 | even if through cloud cover is people say,

01:52:05.460 | there's no sun here this time of year.

01:52:07.860 | And forgive me, but there is sun,

01:52:10.340 | unless you live in a cave,

01:52:11.220 | their sun is just coming through cloud cover.

01:52:13.220 | No matter where you live in the world,

01:52:14.660 | there's sun unless you live in a cave, of course.

01:52:17.220 | So I want to make sure that we didn't overlook,

01:52:20.020 | what was the major conclusion of the firefighter study?

01:52:22.420 | - We'll go back to the firefighter study.

01:52:23.780 | So the reason why we did this study was,

01:52:25.940 | as I said,

01:52:26.660 | there are a lot of us who are living the lifestyle

01:52:28.900 | of firefighters or shift workers

01:52:31.620 | and shift workers are excluded from studies.

01:52:34.260 | So that means whatever we are learning about lifestyle

01:52:37.220 | or even medications that may be beneficial for people

01:52:42.260 | who actually have a normal schedule,

01:52:43.700 | but not for people who have a disrupted schedule.

01:52:47.860 | And if you look up clinicaltrial.gov,

01:52:50.580 | there are more than 400,000 studies listed.

01:52:53.220 | And if you search how many studies are on shift workers,

01:52:58.020 | it's less than a thousand.

01:52:59.620 | And then if you ask,

01:53:01.700 | most of them are to see what is wrong with shift workers.

01:53:05.220 | Like that's how we know that shift work increases our risk

01:53:08.580 | for metabolic disease, cancer,

01:53:11.700 | and even some aspects of dementia.

01:53:14.500 | But if you ask how many studies are done

01:53:17.860 | to improve the health of shift worker alone,

01:53:20.420 | that's less than 50.

01:53:22.500 | Means I have to go back and check the actual number,

01:53:25.380 | but it's less than 50.

01:53:26.580 | - Wow.

01:53:27.140 | - So that's why we got super excited.

01:53:30.340 | We thought from circadian rhythm perspective,

01:53:33.860 | that's something to address.

01:53:35.620 | So this study, again, this kind of study is only possible

01:53:40.820 | because I'm at Salk and we are affiliated with UCSD

01:53:45.460 | and I can work with UCSD physicians to do this study.

01:53:50.580 | So I collaborate with Dr. Pam Togg,

01:53:53.620 | who is the director of cardiac rehab center in UCSD.

01:53:58.100 | And Pam has many firefighters as her patients.

01:54:02.420 | And we both know that the number one cause for death

01:54:06.420 | and disability on work for firefighters is not fighting fire,

01:54:10.180 | but just getting heart attack and stroke.

01:54:12.820 | So they have a very high incidence of heart attack and stroke,

01:54:16.740 | and they're also highly prone to different kinds of cancer.

01:54:19.620 | And it may be difficult to ascribe cancer to disruption,

01:54:24.340 | circadian disruption,

01:54:25.380 | because they're also exposed to a lot of toxins.

01:54:28.180 | Anytime fire burns, that smell of fire

01:54:31.620 | is essentially smell of carcinogens.

01:54:35.300 | And they're breathing, even if they have the hood on

01:54:39.300 | and respirator, they still get.

01:54:41.060 | So the idea was very simple.

01:54:43.140 | We know that firefighters, nearly 70% of firefighters

01:54:48.180 | in the US, full-time firefighters,

01:54:50.420 | because there are volunteer firefighters

01:54:52.820 | and then full-time firefighters.

01:54:54.820 | The full-time firefighters,

01:54:56.100 | 70% of them work 24 hours shift.

01:54:59.140 | So for example, in San Diego,

01:55:01.860 | they come in at,

01:55:02.900 | their shift is from 8 AM to 8 AM the next day.

01:55:05.620 | And they do, at least in San Diego,

01:55:08.580 | they do one day on, one day off, on, off,

01:55:11.860 | four cycles, and then four days off.

01:55:13.700 | And, but in some fire departments,

01:55:17.860 | they actually do 48 hours shift.

01:55:19.860 | So they come for two days, two days off,

01:55:22.900 | two days, two days off, and then four or five days off.

01:55:25.620 | Brutal. Thank you, firefighters.

01:55:27.620 | Yeah. I mean, so then the idea was,

01:55:31.700 | okay, so we'll screen firefighters

01:55:33.940 | and then find firefighters

01:55:35.300 | who are metabolically unhealthy,

01:55:38.500 | and then we'll see whether they can actually follow

01:55:40.980 | 10 hours time restricted eating.

01:55:43.540 | Because the point is if firefighters can follow it,

01:55:46.980 | then everybody else will be,

01:55:48.260 | because with all that stress, if they can.

01:55:51.780 | And this is again, where I should also acknowledge

01:55:54.660 | the San Diego Fire and Rescue Department,

01:55:56.660 | because without their help,

01:55:58.020 | we could not have even submitted the grant.

01:55:59.860 | And at that time, David Picon,

01:56:02.740 | who is the Health and Wellness Battalion Chief,

01:56:06.020 | he's the one who actually approached us

01:56:08.660 | because he's very careful.

01:56:12.340 | He knew that the job that they do

01:56:16.180 | makes them weaker in the long term

01:56:20.660 | and can kill them in long term.

01:56:22.580 | So he was always looking for new solutions.

01:56:25.540 | So he approached us and then we said,

01:56:27.780 | this is the idea.

01:56:28.980 | He said, well, I love this idea

01:56:30.500 | because we are not asking them to sleep more,

01:56:34.100 | or we are not going to cut down their overtime

01:56:36.980 | or shift or change the work schedule.

01:56:39.060 | The only thing we'll be doing is ask them

01:56:41.060 | to eat within 10 hours.

01:56:42.580 | And hopefully we can do this.

01:56:44.740 | Consistently between the days

01:56:46.340 | that they're working and not working?

01:56:47.860 | Yes.

01:56:48.340 | So that means if they're from 8 a.m. to 8 a.m. working,

01:56:51.780 | then they go home,

01:56:53.460 | then they're going to eat on the same schedule

01:56:55.940 | they did when they were at the firehouse,

01:56:57.940 | but while at home.

01:56:59.460 | So they're not allowing themselves to deviate from that.

01:57:02.180 | Yeah.

01:57:02.420 | So we thought whether they can do it or not,

01:57:05.140 | because the number one goal or the primary outcome

01:57:08.500 | in this clinical trial was feasibility.

01:57:11.300 | Can they do it?

01:57:12.100 | And then second was if they do it,

01:57:14.660 | then what happens to their blood sugar and weight

01:57:16.980 | and all this other stuff?

01:57:18.660 | And then we started the study and we hit the next hurdle.

01:57:22.020 | And that is,

01:57:22.740 | firefighters are very, very tight knit community,

01:57:29.300 | and they want to make sure that you understand their culture.

01:57:32.660 | And the best way to understand their culture

01:57:34.580 | is to live the life of a firefighter.

01:57:37.220 | So Emily Manoogian, who is the first author,

01:57:40.260 | she, and then we had Adina Jadurian,

01:57:43.140 | who is now in med school.

01:57:44.180 | She was a research coordinator at that time.

01:57:47.540 | They volunteered.

01:57:48.100 | They said, "Okay, we'll go to the biggest fire station

01:57:51.140 | in San Diego and we'll live the life of a firefighter."

01:57:54.580 | And the San Diego fire and rescue and the city,

01:57:58.340 | they all agreed.

01:58:01.380 | They reported for duty at 7.30 in the morning.

01:58:04.020 | They were assigned a bed in the station

01:58:06.660 | because all fire stations do have some beds

01:58:09.780 | for firefighters to rest and they have assigned beds.

01:58:12.500 | So they were assigned a bed.

01:58:15.140 | Yeah, so every time a 911 call came,

01:58:18.340 | and if that fire station,

01:58:19.780 | in that fire station, that fire engine was called,

01:58:22.100 | then just like other firefighters,

01:58:24.100 | they had to run, get into the gears,

01:58:26.100 | adjust the shoes and a jacket and a helmet

01:58:29.780 | and get into the seat and attend the call.

01:58:32.500 | Of course, they won't go to the side.

01:58:33.940 | They just get out of the truck, wait there and come back.

01:58:37.300 | So in that 24 hours,

01:58:40.820 | Emily got 10 calls at night that she had to run to,

01:58:46.260 | but there are more than 10 times.

01:58:47.860 | Every time the 911 call came,

01:58:52.340 | then there is a beep that goes out.

01:58:54.260 | All firefighters who are sleeping or resting,

01:58:57.060 | they'll get up or if they're doing something,

01:58:59.220 | they'll look up to see which engine is called.

01:59:01.620 | Interesting.

01:59:02.980 | So it's not just the ones that go out.

01:59:04.900 | It's everyone gets woken up.

01:59:06.500 | Everyone gets woken up.

01:59:07.620 | So that means in a night, typical night,

01:59:09.620 | they're waking up 10, 15, 20 times sometimes.

01:59:14.020 | So they're almost like, new moms are like firefighters

01:59:17.940 | because they don't have any idea

01:59:19.460 | what time the baby will cry and for what reason.

01:59:23.620 | Also, they don't know.

01:59:24.340 | So similarly, it's five.

01:59:25.940 | So that's what Emily did.

01:59:28.180 | And then next morning, once he came back, she was like, no.

01:59:31.300 | The scratch will seem easy.

01:59:32.660 | Yeah.

01:59:33.960 | So then we did the study and we essentially assigned

01:59:38.980 | all the firefighters, we recruited 150 firefighters.

01:59:41.620 | We assigned half of them to Mediterranean diet

01:59:46.580 | because you cannot do any harm.

01:59:48.020 | You have to give them something good.

01:59:49.540 | So that's another thing.

01:59:50.500 | They said, no, we want something that we know

01:59:52.500 | works for firefighters.

01:59:53.780 | And there was a Mediterranean diet study.

01:59:55.380 | So everybody was supposed to follow Mediterranean diet

01:59:59.220 | and then half, nearly 75 of them,

02:00:00.980 | were supposed to eat within 10 hours.

02:00:04.820 | We did not fix the 10 hours because we said,

02:00:08.980 | you pick your own 10 hours that you can stick to.

02:00:12.100 | But it has to be consistent from day to day.

02:00:13.940 | So if you start eating at 9 AM, you finish it at 7 PM.

02:00:18.100 | And then try to be consistent because we said, yes,

02:00:23.140 | we understand that there will be some things

02:00:25.060 | and you can take maybe half an hour here and there.

02:00:28.420 | And we'll see how many times you can do it.

02:00:30.900 | And what is interesting is how they are all doing

02:00:34.740 | 24 hour shift.

02:00:35.700 | They more or less chose to begin eating somewhere

02:00:39.540 | between 8 AM and 11 AM.

02:00:41.380 | And they did not skip any meal.

02:00:46.740 | They had their first meal or what we call breakfast.

02:00:49.460 | But it was several hours after waking up

02:00:51.940 | because they are waking up at five or six

02:00:53.860 | and they're driving to come to work at 7.30 or eight

02:00:57.460 | and they're eating the first meal, say between 8 and 11.

02:01:01.220 | And then they finished meal 10 hours later.

02:01:04.980 | And what we found is more or less most of them

02:01:10.420 | could stick to doing this at least five days

02:01:14.660 | out of seven days.

02:01:15.540 | And then at the end of the study,

02:01:18.820 | when we look at their health parameters,

02:01:21.220 | one thing that I said, we recruited everybody who can.

02:01:25.540 | So that means nearly one in three firefighters

02:01:29.700 | were completely healthy.

02:01:30.660 | They had no sign of any illness,

02:01:35.460 | no high blood pressure, high blood sugar,

02:01:37.220 | high cholesterol, depression or anything.

02:01:39.620 | So since we have one third of the population

02:01:42.580 | who are already healthy

02:01:43.700 | and then everybody has slightly different conditions.

02:01:46.820 | Some have high blood pressure,

02:01:48.340 | but they don't have high blood glucose.

02:01:50.020 | If somebody has high blood glucose,

02:01:51.860 | but not high blood pressure.

02:01:53.140 | So it is kind of heterogeneous.

02:01:55.460 | So we did not see a big difference in weight loss

02:01:59.380 | or any weight change between these two groups.

02:02:01.620 | Another thing is the firefighters actually run

02:02:05.140 | almost eight to nine miles when they're at the job

02:02:08.820 | because that's part of their exercise routine.

02:02:12.260 | But then one thing that changed significantly

02:02:17.220 | in the time-restricted eating group

02:02:18.900 | was what we call VLDL particle size and particle number

02:02:23.940 | because this is something that we know

02:02:26.180 | is very low density lipoprotein.

02:02:28.980 | These are atherogenic and if we can manage them much better

02:02:32.500 | then we reduce the risk for atherosclerosis.

02:02:35.300 | So that's one parameter that changed

02:02:37.940 | in the time-restricted feeding group

02:02:40.100 | even when you combine all healthy, unhealthy, everybody.

02:02:42.820 | Now, if we take firefighters who are beginning

02:02:48.580 | with high blood pressure,

02:02:51.300 | then we saw significant reduction in their systolic

02:02:55.140 | as well as diastolic blood pressure.

02:02:56.980 | And the change in blood pressure,

02:02:59.060 | of course, we don't claim that in the manuscript,

02:03:01.460 | but when we talk about it, some physician would get up

02:03:04.340 | and say, "Wow, that looks like almost there

02:03:06.260 | on a blood pressure lowering drug."

02:03:08.420 | So the extent of blood pressure lowering is equivalent

02:03:12.420 | to somebody taking an anti-hypertensive drug.

02:03:14.980 | Amazing.

02:03:15.540 | Yeah.

02:03:15.940 | And then those who started with high blood sugar,

02:03:18.180 | of course, we didn't have too many type 2 diabetes,

02:03:20.580 | but there are few pre-diabetic

02:03:22.820 | and they could better manage their blood glucose.

02:03:26.100 | And this is interesting because once shift workers

02:03:30.820 | become pre-diabetic or diabetic,

02:03:33.780 | they have more difficulty managing their blood sugar

02:03:37.380 | than non-shift workers because the work schedule itself

02:03:41.220 | will mess them up too much.

02:03:42.980 | Even if they're on many medications, they have difficulty.

02:03:45.780 | That's fascinating.

02:03:47.540 | And I'm really glad that you explained the study

02:03:49.860 | in such detail, because I would have thought,

02:03:52.020 | from reading the abstract, and I did look at the data,

02:03:55.220 | but if someone were to look at the abstract,

02:03:56.740 | they'd say, "Oh, firefighters."

02:03:57.700 | So they're waking up in the middle of the night

02:03:58.900 | and they're throwing on their gear

02:04:01.300 | and going out to calls and do it.

02:04:02.660 | But if I understand correctly,

02:04:04.980 | all firefighters are being woken up by the signal,

02:04:07.140 | which makes the firefighter population

02:04:09.860 | a bit more similar to the more standard population

02:04:13.300 | who's waking up in the middle of the night

02:04:14.420 | to use the bathroom, getting on social media

02:04:16.820 | for a couple of minutes or flipping on the lights.

02:04:18.660 | I mean, it's maybe not as severe

02:04:20.420 | as what firefighters are doing,

02:04:21.620 | but we know there are blood sugar regulation issues

02:04:26.260 | related to those multiple middle of the night wakings,

02:04:28.740 | especially if people are then staring at screens.

02:04:30.900 | So I think it's really important that people

02:04:34.340 | were able to hear about the deeper contours of the study.

02:04:37.460 | I mean, this result of regulating blood sugar better

02:04:41.060 | is really powerful.

02:04:41.860 | I get asked all the time, "I've got a new kid,"

02:04:44.660 | or "I'm a shift worker.

02:04:46.260 | How can I do this morning sunlight viewing?"

02:04:48.500 | What I'm hearing is that keeping

02:04:50.820 | a regular meal schedule every day-

02:04:52.820 | - At least five out of seven.

02:04:55.220 | - Five out of seven, or as close to every day.

02:04:57.220 | Sort of like sleep, I always say,

02:04:58.340 | try and get a really great night's sleep,

02:04:59.700 | 80% or more of the nights of your life.

02:05:01.780 | And on the other 20%, hopefully it's for fun reasons,

02:05:04.740 | a great party or something like that,

02:05:06.180 | or a celebration of some sort.

02:05:07.620 | That seems to me a great anchor point

02:05:13.140 | when one can't reliably control their sleep-wake cycle.

02:05:16.980 | Does that mean that if somebody is coming off

02:05:20.020 | of shift work and they're very, very tired,

02:05:22.500 | that they would be better off staying awake

02:05:24.660 | and eating than sleeping?

02:05:26.260 | - Well, yeah, so this is where we get into the nuances.

02:05:30.260 | So here, the firefighters are 24-hour shift workers.

02:05:33.140 | So that means, and they have been working the shift

02:05:36.100 | for a very long time, so they have figured out.

02:05:39.060 | And one thing is, yes, firefighters are different

02:05:42.100 | from nurses and healthcare workers

02:05:44.660 | who have to work throughout the night

02:05:46.820 | and they're staying awake throughout the night.

02:05:48.420 | Whereas firefighters, they get opportunity to sleep.

02:05:51.060 | Even with their 10 calls, they actually have opportunity

02:05:56.580 | to come back and go to sleep.

02:05:58.500 | And in fact, when Emily and Adina,

02:06:01.380 | they were in the fire station, what they observed was,

02:06:03.460 | firefighters after attending a call,

02:06:07.060 | they're not coming back and playing cards

02:06:08.740 | or trying to watch the news or get the score.

02:06:11.700 | They know, they will just go back and lie in the bed

02:06:16.580 | and switch up the light.

02:06:17.940 | So whenever they got any opportunity to sleep,

02:06:20.580 | they would try to sleep.

02:06:21.460 | So in that way, their sleep debt and sleep pressure

02:06:26.420 | during daytime is not as strong as a night shift nurse

02:06:30.980 | or a truck driver who is driving all night

02:06:35.060 | because they are staying awake throughout the night.

02:06:37.620 | So when people say, yes, you found this

02:06:40.820 | and can you extend it to other shift workers?

02:06:43.140 | My answer is no.

02:06:44.260 | We have to go back and figure out.

02:06:46.580 | That's why we went to the station

02:06:48.500 | and figured out what would work for them.

02:06:50.340 | If I have to go and do this for some nurses,

02:06:54.340 | maybe even I will go or our staff will go

02:06:57.780 | and figure out what is their work schedule?

02:06:59.700 | What happens?

02:07:00.260 | Do they have opportunity to eat?

02:07:02.340 | Do they have opportunity to even take five minutes break?

02:07:05.860 | What do they do during break?

02:07:07.460 | And all of these things come into play.

02:07:09.940 | But here, another thing is I always said

02:07:13.060 | that in other time-restricted feeding paper,

02:07:14.900 | we see change in nutrition quality and quantity.

02:07:17.620 | But here, we also saw that somehow both groups

02:07:21.860 | inadvertently improved their nutrition quality

02:07:26.420 | because everybody was told to eat Mediterranean diet.

02:07:30.340 | They increased their fruits and vegetables

02:07:32.100 | and olive oil slightly.

02:07:35.460 | And when they had to stop eating early,

02:07:40.260 | they also reduced their alcohol intake.

02:07:43.460 | And this is very significant because many shift workers,

02:07:48.020 | just to cope with the shift work,

02:07:49.620 | they tend to depend on alcohol at night

02:07:52.980 | and caffeine in the morning.

02:07:54.900 | So they begin their day with caffeine and end with alcohol.

02:07:59.220 | And now we can relate that many normal people

02:08:04.820 | who are not doing shift work,

02:08:06.340 | we also more or less begin our day with caffeine.

02:08:08.980 | And many of us end with alcohol.

02:08:11.460 | And then when they reduce that eating to 10 hours,

02:08:14.660 | and then we saw a significant reduction in alcohol intake

02:08:17.780 | in the time ratio eating group,

02:08:20.580 | but not in the standard of care or Mediterranean diet group.

02:08:24.180 | I certainly support that.

02:08:25.300 | We did an episode on alcohol,

02:08:26.580 | and I was shocked when I researched that

02:08:29.300 | to learn that zero to two drinks per week

02:08:32.980 | is essentially the threshold beyond which

02:08:34.980 | you start seeing health deficits,

02:08:38.420 | in particular cancers and metabolic disruption,

02:08:40.900 | sleep disruption, and increased anxiety

02:08:43.700 | when people aren't under the influence of alcohol.

02:08:45.540 | I mean, it's pretty incredible how alcohol

02:08:48.100 | has kind of escaped as the opposite of caffeine

02:08:51.460 | and therefore not a health hazard.

02:08:54.420 | It's, and here I'm somebody,

02:08:56.100 | I have a drink every once in a while,

02:08:57.300 | no big deal for me, I can have it or not have it,

02:08:59.700 | but it's just striking how alcohol,

02:09:03.460 | despite extensive data that it can really disrupt health,

02:09:06.260 | even at three drinks per week is just avidly consumed

02:09:10.740 | as if it was kind of like food or caffeine.

02:09:12.980 | It's really incredible.

02:09:14.100 | I want to make sure that I circle back

02:09:16.660 | to something you mentioned earlier,

02:09:17.780 | because I know there are going to be

02:09:18.740 | a number of people that asked this.

02:09:20.180 | If I recall, you said that provided

02:09:23.220 | that the feeding window is not shorter than eight hours,

02:09:28.180 | that men, women, and children can use

02:09:31.620 | time-restricted feeding, is that right?

02:09:34.580 | Yeah, so what I say is 12 hours.

02:09:38.100 | Excuse me, 12 hours.

02:09:39.860 | Thank you for that clarification.

02:09:41.220 | Because we did a study that was published in 2015.

02:09:43.940 | And again, behind many of our studies, there is a story.

02:09:48.740 | So we are publishing all these mouse stories,

02:09:51.860 | and then I would go to conferences.

02:09:53.780 | And then of course, some people would give me a look saying,

02:09:59.140 | well, you must be doing something wrong.

02:10:00.500 | We, this just breaks the X law of thermodynamics,

02:10:06.100 | because how come they're eating the same number of calories

02:10:08.100 | and not getting weight?

02:10:09.380 | And of course, by that time we figured out

02:10:11.060 | that at least in mouse,

02:10:13.140 | time-restricted feeding also changes the gut microbiome

02:10:17.860 | in a way that the mice may be pooping out

02:10:21.460 | a little bit more fat and sugar than absorbing them.

02:10:25.860 | So one thing that happens in time-restricted feeding,

02:10:28.260 | at least in mice, is the liver cholesterol metabolism

02:10:33.460 | to bile acid and bile acids excretion in the gut changes

02:10:38.980 | because the gut microbiome changes.

02:10:41.700 | So this is a very nice study.

02:10:44.500 | When Amir Jarinpar was in the lab,

02:10:46.980 | now he has his own lab in UCSD.

02:10:50.020 | And he meticulously did that.

02:10:51.860 | And we even did bomb calorimetry from the poop

02:10:55.540 | and metabolomics from the poop.

02:10:58.020 | And then we figured out that they excrete some calories

02:11:02.580 | and then that brown fat activity goes up.

02:11:05.540 | So they may be burning some of these extra calories.

02:11:08.900 | So they're more thermogenic.

02:11:10.020 | More thermogenic.

02:11:10.900 | But anyway, so one nice thing, awesome thing about Salk

02:11:16.100 | is if they see that your science is going well,

02:11:19.860 | then they will find ways to help you.

02:11:22.020 | - That's terrific.

02:11:22.900 | - Yeah.

02:11:23.400 | And this is when Bill Brody was our president.

02:11:28.020 | He was the president of Hopkins for 12 years.

02:11:31.940 | And then he was president.

02:11:33.060 | And that time he had started this innovation grant program

02:11:38.820 | which was funded by Orwin Jacob.

02:11:40.900 | Orwin is the founder of Qualcomm.

02:11:43.940 | And he was also a faculty at UCSD.

02:11:46.340 | So he understand there are very few tech leaders

02:11:49.860 | who actually spend some time in academia.

02:11:52.420 | So he understood the pain of getting grant money

02:11:56.820 | when you have some interesting idea or test some ideas.

02:11:59.460 | - Yeah, no knock on the NIH, but I'll do it anyway.

02:12:02.260 | Because I sit on study section for the NIH.

02:12:04.980 | I mean, the NIH wants to see proposals for things

02:12:07.380 | that are so certain to work that they're mostly done.

02:12:10.820 | And so really groundbreaking work can happen

02:12:14.580 | and does happen with NIH funding.

02:12:16.340 | But more often than not is it is the generosity

02:12:20.340 | of philanthropists like Orwin Jacobs and other people

02:12:22.660 | that allow the really pioneering, the new stuff,

02:12:26.420 | the cool stuff, the groundbreaking stuff,

02:12:28.820 | the stuff that really...

02:12:30.020 | No, I'm not going to say really matters.

02:12:31.220 | It all matters.

02:12:31.940 | It's all important.

02:12:32.660 | - It matters, but it's high risk.

02:12:35.300 | And NIH means NIH is not just government

02:12:39.140 | is not making money from thin air,

02:12:40.820 | means it's taxpayers' money.

02:12:42.420 | So there is a little bit responsibility or conservative

02:12:45.300 | that, okay, so we should not waste taxpayers' money

02:12:47.940 | on pie in the sky kind of project too much.

02:12:50.100 | - To be clear, we're not talking

02:12:50.980 | about politically conservative.

02:12:52.180 | We're talking about scientifically conservative.

02:12:55.300 | They'd be so careful with language nowadays.

02:12:57.380 | Pretty soon we're just going to sit and stare at one another

02:12:59.300 | at the microphones to stay safe.

02:13:00.740 | So that's interesting.

02:13:03.060 | So the-

02:13:03.460 | - So then we started this and then what we did was we...

02:13:07.220 | I had an awesome grad student and we got this funding

02:13:11.780 | from Irwin and also there are some...

02:13:13.780 | Any philanthropy matters.

02:13:16.020 | So actually the way we say is, yes, if you give me 50 bucks,

02:13:20.180 | then that 50 bucks goes towards buying the gloves

02:13:23.300 | and effing of tubes for one postdoc for maybe seven days.

02:13:27.060 | - So true.

02:13:28.580 | I think a lot of people don't realize that 99%

02:13:32.420 | of laboratory scientists just, they don't make any money

02:13:35.380 | off their discoveries.

02:13:36.260 | And even if there is a patentable discovery,

02:13:38.420 | typically the divide between the institution

02:13:40.820 | and the company that will eventually put that to market

02:13:43.220 | is so slim in favor of the others involved

02:13:46.900 | that scientists really do this as a work of passion,

02:13:50.020 | labor of love.

02:13:51.140 | - So we came up with this app, My security and clock

02:13:55.220 | at that time, and we took some lessons from tech leaders,

02:14:00.420 | particularly from Amazon, one-click checkout

02:14:03.780 | because we thought most nutrition apps actually ask people

02:14:09.780 | to detail describe what they ate, go to their food library

02:14:13.860 | and then portion size.

02:14:14.980 | We said, okay, so we'll just shortcut all of that.

02:14:17.380 | We just asked people to take a picture of the food,

02:14:19.860 | open the app, one click, take a picture, second click

02:14:24.340 | and press save, third click.

02:14:25.780 | And when they save, the picture actually came to our server,

02:14:28.020 | did not stay on their phone.

02:14:29.460 | And we asked 156 people who are not shift workers,

02:14:34.900 | just regular worker or homemakers to be part of the study.

02:14:39.380 | No student was allowed to be part of the study

02:14:41.540 | because we know that lifestyle is like shift workers.

02:14:44.900 | And we monitored for three weeks.

02:14:47.860 | And so here is some nuances and I want people to understand.

02:14:53.060 | So suppose when somebody is starting to eat at say 7 AM

02:14:59.620 | and since they're recording everything,

02:15:04.020 | we caught every single thing.

02:15:06.100 | Even if they ate half a cookie, they had to take a picture

02:15:08.740 | and they actually took picture because it's not,

02:15:11.460 | it becomes second nature after three or four days

02:15:13.540 | that every time they ate something,

02:15:15.060 | even if there was a glass of water,

02:15:16.660 | they actually took a picture because we asked them,

02:15:18.660 | take picture of everything, we'll figure out what it is.

02:15:21.140 | What is surprising was we found the median,

02:15:26.180 | so the median number of times people eat within a day,

02:15:31.300 | 24 hours a day is actually seven.

02:15:33.140 | So it's not that we are eating three times a day.

02:15:37.860 | We actually snack a little bit.

02:15:39.860 | Seven times per day.

02:15:41.060 | Seven times.

02:15:41.620 | And there are 10% of people,

02:15:43.620 | the top decile was eating 12 times a day.

02:15:47.780 | Wow.

02:15:48.280 | And it makes sense in retrospect sometimes.

02:15:52.580 | Maybe I'll fall into that seven or eight

02:15:54.740 | before I did this study because, you know,

02:15:58.180 | getting up, having coffee with cream and sugar is one.

02:16:01.780 | And then I ate my breakfast, that's two.

02:16:04.580 | Then I came to the lab and I found that cookie, that's three.

02:16:07.860 | And I went to a meeting and there was some cookie

02:16:10.820 | and something else.

02:16:12.020 | That's another one, then lunch.

02:16:14.500 | And then afternoon, somebody asked me to go out

02:16:16.900 | and have a meeting.

02:16:17.940 | And so if you think about it, it's very normal

02:16:21.060 | that we can go seven to eight times, 10 times.

02:16:23.620 | But then if we look at what time, say, I start breakfast,

02:16:29.300 | and as I said, and we see that in many people,

02:16:32.180 | they'll start at seven o'clock in one day,

02:16:33.940 | then 7.30 another day, then 8.15 another day.

02:16:37.140 | Or they go back to 6 a.m. because they had to get up early

02:16:40.260 | and go to work.

02:16:40.820 | So we took all these food data from three weeks

02:16:44.820 | and then ask, what is the time when your body system

02:16:48.500 | is expecting you to eat?

02:16:50.740 | Because it kind of averages out.

02:16:52.260 | It's kind of thinking, okay, maybe for you,

02:16:54.900 | if you're eating breakfast at, say, somewhere between 6 a.m.,

02:16:58.500 | 7.30, 7.45, 8, maybe you are expecting food

02:17:02.500 | around seven o'clock.

02:17:03.860 | Let's forget about 6.15, that's an outlier.

02:17:06.180 | And then similarly, at the end of the day,

02:17:07.780 | somebody is eating, finishing the last bite

02:17:11.220 | or the nightcap, whatever you call it,

02:17:13.060 | say, one day at 9 p.m., 9.30 p.m., 10, 11, 12.30, or one.

02:17:18.900 | Let's ignore that one and 12.30.

02:17:21.300 | But still, we got somewhere between seven to 11.30

02:17:26.340 | for that person over three weeks time.

02:17:28.580 | So this is how we kind of figure out what is the likelihood

02:17:32.260 | that your body will encounter food.

02:17:35.860 | So when we do that, what we found was nearly 50% of adults

02:17:39.700 | in our study ate for 14 hours, 45 minutes,

02:17:43.460 | that window when your body is expecting food.

02:17:46.020 | So it's easy to say that 50% of adults

02:17:50.100 | are eating within 15 hours or longer.

02:17:53.700 | Wow.

02:17:55.000 | And quite frequently throughout that year.

02:17:57.140 | Quite frequently, too.

02:17:58.180 | And then if we ask what fraction of our adults

02:18:01.940 | were actually eating the conventional within 12 hours,

02:18:06.020 | three meals a day or something like that, it was 10%.

02:18:08.580 | So snacking has gone up dramatically,

02:18:12.740 | however you want to define snacking,

02:18:14.180 | the frequency of food intake throughout the day.

02:18:16.660 | And outside this breakfast, lunch, and dinner,

02:18:19.700 | there are all these small snacks here and there.

02:18:21.460 | And also for a lot of people, the dinner is delayed.

02:18:24.340 | And we went back and looked at, okay,

02:18:26.660 | so what kind of food people are eating late at night

02:18:28.980 | and all that stuff.

02:18:30.980 | And what came out interesting, which is very counter-intuitive,

02:18:34.340 | is people who prepare their own dinner,

02:18:36.820 | they're more likely to eat later at night

02:18:40.020 | because they're coming home.

02:18:41.860 | And then they're taking some time to prepare dinner.

02:18:44.740 | And then they're sitting down and eating,

02:18:47.300 | or maybe they're eating next to the computer, whatever it is.

02:18:49.620 | So it was kind of interesting that came out.

02:18:52.340 | But coming back to your point,

02:18:55.140 | that's why I say that nearly 90% of adults

02:18:59.620 | are eating for more than 12 hours.

02:19:02.100 | So that means a lot of people can,

02:19:05.460 | there is scope or there is enough head space

02:19:09.300 | to reduce and eat within.

02:19:11.220 | So as I said, all of this are interrelated.

02:19:15.700 | So when you think about children,

02:19:17.140 | most sleep researchers agree that children and teenagers

02:19:22.260 | should sleep somewhere between nine to 10 or 11 hours,

02:19:25.620 | because young children, even five to 10 year old,

02:19:28.660 | they should sleep nine to 10 hours.

02:19:30.420 | They're just pumping out growth hormone and growing, growing, growing.

02:19:33.460 | And then the teenagers, actually the recommendation is

02:19:37.140 | they should be sleeping nine hours,

02:19:38.740 | because if you take teenagers,

02:19:41.380 | take out all the stimulatory inputs to them

02:19:44.900 | and then remove homework assignment and everything,

02:19:47.540 | and then let them kind of equilibrate to their homeostasis,

02:19:51.620 | what they're likely, how many hours they're likely to sleep,

02:19:54.340 | that turns out to be somewhere between

02:19:56.980 | eight and a half to nine and a half hours.

02:19:58.580 | Which also means that going back to sleep,

02:20:04.100 | nearly 90% of high school students in this country

02:20:10.340 | are chronically sleep deprived,

02:20:11.780 | because most high school students

02:20:13.940 | don't get nine hours of sleep on a regular basis,

02:20:16.340 | maybe in the weekend.

02:20:17.140 | Probably because of devices, they're on iPads.

02:20:20.340 | And also, as I said, this new idea

02:20:23.140 | that midnight is your assignment submission time.

02:20:27.060 | I'll come back to that again and again.

02:20:28.820 | I'm hearing that again and again.

02:20:29.940 | So teachers, take note.

02:20:31.300 | It's a very interesting idea as a way

02:20:34.020 | to kind of anchor behavior earlier in the day.

02:20:36.260 | I mean, public health is complicated

02:20:40.340 | because people are incentivized by fear,

02:20:43.300 | but you get more bees with honey, as they say, right?

02:20:46.340 | There's incentivizing people to wake earlier,

02:20:50.580 | not necessarily with the sunrise,

02:20:52.020 | but wake earlier and go to sleep earlier

02:20:54.580 | and eat within an eight to 12 hour window.

02:20:57.300 | 12 if it's children.

02:21:01.620 | Yeah.

02:21:01.940 | It sounds to me like all these health benefits

02:21:04.980 | are what I think are going to incentivize people

02:21:06.820 | more than, for instance, this idea that,

02:21:09.060 | well, if you don't do this,

02:21:09.940 | you're going to get dementia or something of that sort.

02:21:12.180 | Right.

02:21:12.820 | Like every day, people will feel more healthy

02:21:15.060 | and more productive.

02:21:16.100 | And so that's why I said that even if children

02:21:19.220 | are supposed to sleep for nine hours,

02:21:20.740 | of course, they're not eating during those nine hours.

02:21:24.100 | And we're not feeding children and putting them down to sleep

02:21:27.140 | because their core body temperature will be high,

02:21:29.380 | they cannot fall asleep.

02:21:30.740 | So at least they should have their last meal

02:21:33.220 | one or two hours before going to bed,

02:21:34.900 | because typically parents feed them

02:21:38.820 | and maybe give them a shower or a bath,

02:21:41.220 | and then they read the bedtime story.

02:21:43.300 | So it's one to two hours before bedtime,

02:21:45.860 | they're finishing food.

02:21:46.980 | Similarly, on the other hand, after they wake up,

02:21:50.260 | it's not that we're waking them up and then feeding them.

02:21:52.660 | So hopefully we're not doing that.

02:21:55.540 | So that's at 12 hours seems to be optimum.

02:22:00.180 | And it's not only I'm saying that

02:22:01.700 | if we put all the health recommendations together

02:22:04.820 | from pediatrician, then it makes sense.

02:22:07.620 | Fascinating.

02:22:10.180 | I have a question about structuring meal intake

02:22:12.740 | or food intake during the eating window.

02:22:15.620 | I have a good friend.

02:22:17.460 | Actually, he's the neurosurgeon at Neuralink now,

02:22:20.980 | but he came up through Stanford

02:22:22.580 | and he has a habit of eating,

02:22:26.020 | of skipping one meal per day within a feeding window.

02:22:29.140 | So it might be breakfast, lunch, skip dinner one day.

02:22:31.780 | Then it might be breakfast, dinner the next day,

02:22:34.180 | lunch and dinner the next one.

02:22:36.740 | So it's not in keeping with the same start time always,

02:22:39.780 | but the end time is either going to be earlier

02:22:42.580 | or there's a gate, it's never later.

02:22:45.220 | It's never later.

02:22:46.500 | What do you think about that as a strategy?

02:22:50.820 | In many ways, it feels like that fits

02:22:53.220 | with the way that a lot of people's lives run.

02:22:56.260 | So sometimes, for instance, if I'm in a podcast,

02:22:58.340 | I don't tend to eat much during the middle of the day

02:22:59.780 | 'cause it makes me a little bit groggy,

02:23:01.460 | the post-perennial dip in energy.

02:23:03.780 | So I'll do breakfast.

02:23:05.220 | Well, again, at 11 and that's the first,

02:23:07.220 | that's when I break my fast, 11-ish.

02:23:09.300 | And then dinner, maybe a snack in the middle of the day,

02:23:12.100 | but other days it's three meals.

02:23:13.860 | So does it matter overall

02:23:16.980 | as long as one isn't allowing the start time

02:23:20.900 | and the ending time to drift out?

02:23:22.660 | Is it okay if you go from 12 hours to 10 to eight,

02:23:26.260 | eight, 10, four, 12,

02:23:28.660 | as long as you don't exceed the brackets, are you okay?

02:23:32.580 | So this is where the circadian aspect come in

02:23:35.380 | because if you're moving that breakfast time

02:23:39.780 | or dinner time, three, four hours,

02:23:41.940 | you're essentially causing maybe a metabolic jet lag.

02:23:46.740 | In short term, in weeks, months, or maybe even few years,

02:23:51.780 | you may not see any change.

02:23:53.300 | But at the same time,

02:23:55.780 | we don't know what is the long-term consequences.

02:23:58.180 | One thing is we always think,

02:23:59.300 | I'll come back to this point again and again,

02:24:02.260 | we think that our body weight is a marker of health.

02:24:04.980 | Our body composition is a marker of health.

02:24:07.700 | It's not always true because as I said,

02:24:10.180 | it should reflux feeling having some pang of depression or anxiety.

02:24:17.620 | Or LDL, like high LDL.

02:24:19.300 | High LDL.

02:24:19.940 | A lot of thin people or low body fat people have very high LDL.

02:24:23.460 | Yeah.

02:24:24.020 | So those are the things that we don't connect with our habit.

02:24:28.180 | And since circadian rhythm and meal timing,

02:24:31.540 | meal structure now is a very new field,

02:24:35.540 | I think good studies will come out only in a few years

02:24:39.780 | because right now people are just going back

02:24:41.300 | and retrospectively looking at some diet record,

02:24:43.860 | one day of diet record and trying to glean too much out of it.

02:24:47.540 | But I think hopefully things will improve where it will become standard

02:24:53.220 | to at least look for one week of diet record.

02:24:56.260 | Meal time and what they're eating, all that stuff,

02:24:59.540 | because there are now mouse studies also showing

02:25:03.060 | whether front-loading carbohydrate or front-loading fat or protein

02:25:08.660 | has benefit over.

02:25:10.180 | So I think these studies are starting.

02:25:12.500 | So I should not comment whether that's good or bad.

02:25:16.340 | No, I think it's great to hold off until then we have you back on to discuss.

02:25:19.940 | I have a question about fasting on the longer term.

02:25:24.260 | And there it's a near infinite space we could explore of two days of fasting and one day.

02:25:29.700 | I know people that every once in a while they just decide, I'm fasting.

02:25:34.340 | They've either been eating too much at parties or they're not feeling well

02:25:38.260 | or whatever, they just decide, I'm fasting for 24 hours.

02:25:41.300 | And they'll still consume water and caffeine, but they'll just fast.

02:25:45.220 | Is there any health benefit or detriment?

02:25:47.540 | You mentioned the circadian clock shifting effects,

02:25:50.580 | but if somebody wakes up on Sunday and they ate too much

02:25:55.220 | or they feel they ate too much or they don't like the food they ate on Saturday,

02:25:57.940 | they're not really feeling it and they're just going to fast into Monday.

02:26:00.820 | Is there any known benefit or health detriment to doing that kind of thing?

02:26:07.140 | Yeah, there's actually a rich literature on this complete fast.

02:26:11.460 | And in fact, in many religion, people practiced complete fast as a way to

02:26:17.460 | cleanse their body and people have seen that there are benefits to that.

02:26:23.780 | So in fact, every other day eating in mouse model or even in humans,

02:26:29.540 | there are also initially some studies were done, there are many health benefits.

02:26:36.180 | And right now there are even fasting clinics in Germany where people check in

02:26:41.380 | and they're under strict supervision and then they do complete fast or maybe

02:26:47.220 | a small bowl of soup, which has 100, 200 kilocal, and that's all they get to eat.

02:26:52.980 | Sometimes two, three days, four days, five days, even they have gone up to three or four weeks.

02:26:58.820 | For sake of weight loss, is that why?

02:27:01.220 | For many different things and they come out pretty well healthy. Of course, they're under

02:27:06.660 | supervision, make sure that they're getting the micronutrients, vitamins and electrolytes.

02:27:15.700 | So those studies are pretty solid. People have observed that. And then in fact,

02:27:21.700 | there are even idea that fasting, this kind of fasting can have huge impact on brain

02:27:27.620 | and people may come out of treatment resistant depression or something.

02:27:32.020 | So those studies are very difficult to do. There are only case of one here and there

02:27:37.860 | that we hear once in a while. But hopefully in future, we'll see whether the depression,

02:27:45.220 | anxiety, the mental health aspect will benefit from fasting. Because now as there is more and

02:27:51.540 | more evidence that there's this gut-brain axis and whether the presence of food or the microbiome

02:27:58.260 | changes in the gut, if they can affect brain, then maybe long-term fasting, periodic fasting,

02:28:05.060 | a few days of low calorie diet, back-to-back will be interesting to see how it impacts brain health.

02:28:11.620 | Very interesting. What are your thoughts on fat fasting, where people try and limit their

02:28:17.380 | blood glucose by only eating mainly fats, mainly healthy. Typically they'll eat healthier fats of

02:28:25.780 | avocados, olive oils, and nuts, and some animal fats perhaps. But as a way to keep blood glucose

02:28:34.580 | low and also time restrict. This goes back to the kind of low carbohydrate thing. What are your

02:28:39.940 | thoughts on that as a general strategy for health? I mean, it combines sort of two general themes

02:28:44.980 | that are out there. I think both of which are data are still incoming, that restricting the

02:28:50.260 | feeding times, it can be beneficial as well as keeping overall blood glucose lower can be

02:28:54.500 | beneficial. Yeah, I think there is too much emphasis now on blood sugar spiking. We don't know

02:29:02.980 | this kind of eating pattern, for example. I mean, we are essentially telling pancreas that, okay,

02:29:11.460 | are the islet cells that produce insulin. It's okay, you can take a break, go on vacation for

02:29:19.300 | a month or two or three months. My question is, it will be interesting to see what happens to

02:29:28.180 | those islets. Because, for example, we know that if we disuse or unused our muscles, there's muscle

02:29:36.980 | atrophy. Muscles will become weaker. We don't know whether long-term consequences of this very low

02:29:45.940 | carbohydrate diet where you're not essentially engaging the islet cells periodically, what is

02:29:52.900 | its impact. So if there is no impact, maybe it's okay. Because, as you know, many people who

02:30:00.500 | actually work on ketogenic diet, the researchers themselves, they find it very difficult to stay

02:30:07.060 | in true ketogenic diet. Because the true ketogenic diet is consuming less than 10% of calories from

02:30:13.380 | carbohydrate. And not very many from protein. A lot of people think ketogenic diet allows them

02:30:17.860 | to eat massive amounts of meat, and that's not necessarily the case. Just one clarification for

02:30:22.100 | people, Sachin was referring to islet cells of the pancreas, which are the ones that manufacture

02:30:27.700 | insulin. So the question is whether or not taking in low levels of blood glucose by way of a low

02:30:33.460 | carbohydrate diet, those islet cells are going to shut off their production. Very interesting. I

02:30:37.700 | mean, the liver is a very plastic tissue. I mean, it tends to react very dramatically to lifestyle

02:30:43.860 | changes. Yeah. So that's why it will be interesting to see what happens. Means we know that even

02:30:47.460 | muscle disused, for example, people who become bedridden, they lose some muscle mass. But when

02:30:53.700 | they come back and exercise, they gain it back. So it'll be interesting to see what happens in

02:30:59.620 | these people who are going through long-term ketogenic diet. And of course, once in a while,

02:31:03.940 | because of social pressure or something else, if they don't have access to food or something

02:31:09.300 | happens, they may consume some sugar, some blood glucose will spike. But it's not that every spike

02:31:16.900 | is bad. I mean, the reason why we have insulin is for good reason. To buffer that spike.

02:31:23.140 | To buffer that spike and also, people always say that, well, if you have insulin produced or

02:31:28.180 | insulin-like growth factor, those are really bad and you should avoid that. And I think that's a

02:31:33.140 | little bit extreme. I mean, the insulin growth factor has evolved in muscle protein synthesis,

02:31:38.820 | tissue repair, maybe even cognition. Yeah. And it also goes back to,

02:31:44.260 | let's say, mTOR activation and all that stuff. People get really excited about how to reduce

02:31:51.860 | mTOR activation, rapamycin and all that stuff. So this is where, again, from circadian point of view,

02:31:58.260 | I ask people to think. So two very popular drug-like molecules or drugs that people think

02:32:08.980 | will increase longevity are metformin, which many people agree, not all will come to a consensus

02:32:16.420 | that it activates AMP kinase or the sensor in the cells that sense that your cells are fasting.

02:32:24.100 | So metformin activates it so that it, you can say, although it may not be scientifically accurate,

02:32:32.260 | the fasting in a pill. So it mimics fasting.

02:32:36.660 | And the thing I'd lump in there with metformin is that berberine is the poor man's metformin. It's a

02:32:42.500 | tree bark extract that also dramatically lowers blood glucose.

02:32:46.180 | Yeah. It mimics that fasting. And then rapamycin also reduces mTOR activation.

02:32:55.940 | People have shown that rapamycin and metformin can extend mouse lifespan and improve health.

02:33:09.380 | So now let's go back to the calorie restriction study that I mentioned. In calorie restriction,

02:33:15.300 | people are giving food as a lump sum, and they were essentially doing time restriction. The

02:33:20.260 | mice were doing time restriction. If we think about it, during daytime,

02:33:25.300 | when experimenters are coming to the bivariate, the mice should be sleeping and fasting.

02:33:33.140 | And they should naturally have high level of AMP kinase if they're truly fasting. And they should

02:33:40.020 | also have low level of mTOR activity because mTOR responds to insulin, and that should go off at

02:33:46.980 | night. So my suspicion is in many of these experiments where the mice were allowed to

02:33:55.780 | eat ad libitum, even normal standard chow, now we know that as mice get older, they actually

02:34:04.180 | consume a little bit more food during daytime. Which is the equivalent of human nighttime.

02:34:09.140 | Human's nighttime eating. It's like nighttime eating we know is an issue. I didn't realize

02:34:12.820 | that was more of an issue as people age, but- Yeah. So we don't know. But at least in mice,

02:34:16.980 | because we can put the mice in calorimetry, look at every single bite they're eating,

02:34:22.180 | how much they're eating. So I guess it was natural to see that researchers found that there is some

02:34:29.060 | mTOR activity during daytime when the mice were not supposed to have mTOR activity because they

02:34:34.340 | should be fasting. And since they ate a little bit, they were snacking during daytime, AMP kinase

02:34:40.900 | activity was not at its peak. So giving metformin kind of mimic their fasting state and reducing

02:34:51.700 | mTOR activity by drug like rapamycin also kind of mimic some aspect of the fasting state.

02:34:57.620 | So my suspicion is since these studies were done always in mice who are supposed to be in the

02:35:07.460 | fasting state and both mTOR, sorry, rapamycin and AMP kinase activator metformin kind of are

02:35:13.380 | mimicking that fasting state. That's why we have seen those benefits. And it'll be interesting to

02:35:19.380 | see if that experiment will be done in humans in long-term because many people are very excited

02:35:25.620 | about there is mTOR long-term metformin study. And then a lot of people are actually consuming

02:35:33.140 | good amount of rapamycin off-level. They can get their own. So that's my curiosity. I'm not saying

02:35:40.580 | whether it's good or bad or whether there is science or not. That's something that will be

02:35:43.940 | interesting to control for and see. Because recently I saw one of my, again, close friend

02:35:50.500 | and colleague at Scripps, Katya Lamia, she did a very simple, elegant study people should have

02:35:56.980 | done in metformin field. She took mice and then measured their blood glucose at different time of

02:36:03.460 | the day. And in fact, just like human blood glucose, our blood glucose fluctuates a little

02:36:09.220 | bit. She saw that rhythm. And then in every two hours or three hours on different days, of course,

02:36:17.860 | she gave the same dose of metformin to mice. And what she found was at different time of the day,

02:36:23.460 | metformin had very dramatic change in glucose reducing ability. So which means that even if

02:36:33.060 | you take metformin and give at different time of the day for the mouse or even for humans,

02:36:38.660 | in very long term, of course, in these mice, these mice were not diabetic or anything,

02:36:42.820 | they were healthy mice to begin with. So in long term, we might see benefits that are very

02:36:49.860 | different. So this brings to this idea that, well, maybe metformin, say at the end of the day,

02:36:57.300 | evening metformin may trigger that fasting state much earlier than end of digestion.

02:37:04.420 | Whereas metformin in the beginning of the day may not, at least from longevity perspective. I'm not

02:37:10.500 | talking about diabetes, type 2 diabetes here. So the same thing with mTOR. Is mTOR going to have

02:37:18.340 | much better impact if taken during evening, morning, before meal? So these are my thoughts

02:37:27.140 | that go along with all this fat story that we talked about. Do you take metformin or berberine?

02:37:34.500 | - No, I haven't taken, although, you know, I have close friend and colleague Ruben Shaw,

02:37:40.580 | who is now the director of cancer center at Salk. He extensively works on AMP kindness and

02:37:46.500 | its mechanisms. And so it's always fun to talk to him. - He's a fan. Yeah, I've taken berberine

02:37:54.900 | before and I've had two different, very distinct experiences with them. First of all, berberine,

02:38:01.060 | when ingested with carbohydrates, in particular carbohydrates that have a lot of simple sugars,

02:38:05.780 | definitely, I know this because I measured my blood glucose, I did the experiment,

02:38:09.700 | allows you to flatten out your blood glucose response. So, you know, in some sense, if you're,

02:38:16.820 | you know, there is this idea, if you're going to eat a particularly big meal or sugary meal,

02:38:20.180 | and you don't want to get a massive blood glucose rise, you take berberine or metformin.

02:38:23.780 | Metformin is prescription. That's why I went with berberine because it's, as far as I know,

02:38:28.020 | it works as well. - At least for healthy people.

02:38:31.460 | Yeah, for healthy people. That's right. When I took berberine and did not ingest

02:38:38.820 | large amounts of simple sugars or carbohydrates along with it, I experienced profound hypoglycemia.

02:38:44.980 | I felt like complete garbage for about eight hours. And I had one of the worst headaches

02:38:49.140 | of my life, which makes sense. You just got a blood sugar crash. So if you lower your blood

02:38:55.220 | sugar when you already have fairly low blood sugar and you're not ingesting carbohydrates,

02:38:58.500 | you can really bottom out your blood glucose. So just say it's, I say that for two reasons.

02:39:03.860 | One is kind of a cautionary note. And the other one that when you think about the biology of these

02:39:07.700 | compounds, it makes perfect sense. And I think that, and I did not pay attention to circadian

02:39:11.860 | effects. - Yeah. I mean,

02:39:13.220 | when I joined Salk, we know Ron Evans was the kind of the big leader in metabolism and he works on

02:39:24.340 | nuclear hormone receptors. These are the master regulator of metabolism in normal cells, cancer

02:39:29.380 | cells, and many other. And what was interesting was in the first few years, Ron did a very simple

02:39:35.940 | experiment. He just looked at what time of the day this nuclear hormone receptors are turned on

02:39:42.340 | at gene expression level and some at protein level. And he found that almost all of them

02:39:48.180 | have a circadian pattern, at least in some tissue. So he went to that length to say

02:39:56.660 | even that circadian is metabolism and metabolism is circadian. The reason why we have a circadian

02:40:03.940 | rhythm is to have a daily rhythms in food seeking behavior and eating and also go through a period

02:40:12.740 | of time when we should be fasting. And then on the other hand, all the metabolic regulators

02:40:19.700 | also have to follow that rule and almost all metabolic regulators, everything that we can

02:40:25.860 | think of connected to metabolizing, macronutrient, protein, carb, and fat, they should also have a

02:40:34.660 | circadian rhythm or diurnal cycle to align or misalign. So for example, fat oxidation should

02:40:40.820 | be in opposite phase with feeding. And in retrospect, at that time, it was kind of amazing

02:40:49.380 | to see Ron could foresee, of course, he's smart enough to foresee and predict that this is going

02:40:54.660 | to happen to circadian period. Because at that time we're thinking about the suprachiasmatic

02:40:59.300 | nucleus, sleep-wake cycle, and we are not thinking too much about metabolism. So that's the

02:41:05.700 | awesome thing about Salk, being at Salk because we have 50 PIs really crammed into two awesome

02:41:13.540 | buildings and with open lab structure. So you bump into each other and talk to yourself.

02:41:18.580 | And with an ocean view.

02:41:19.860 | With an ocean view.

02:41:20.900 | Yes. It's an amazing place. I was lucky enough to have an adjunct position there when my lab was at

02:41:25.780 | UCSD and it is an amazing place doing incredible groundbreaking work, which of course includes

02:41:33.220 | yours. Listen, Sachin, I'm clear now that we have to have you back on for another series of

02:41:41.940 | discussion, seriously speaking, if you'd be so kind and willing to do that. I want to thank you

02:41:47.860 | for several things. First of all, for your taking the time today to sit down and discuss

02:41:51.780 | these incredibly interesting ideas in detail. Much of what we talk about on the podcast

02:41:57.460 | is obviously grounded in science and often, but not always as actionable. And so much of what we

02:42:04.100 | talked about today is actionable in the sense that many people are already doing certain dimensions

02:42:10.740 | of these things. Some are not, some are hearing about it and considering it. You've given dozens,

02:42:16.580 | I've listed some out, dozens of tools and considerations based on whether or not people

02:42:22.180 | are engaging in shift work or not. I think a lot of people are going to realize that they are shift

02:42:25.540 | workers, even though they didn't think they were because of the nature of their habits now to light

02:42:30.980 | and to activity and so forth. I absolutely love the firefighter study because of its relevance

02:42:36.500 | to the general population. Also another nod to fighter fighters and shift workers everywhere.

02:42:41.460 | Thank you. And I think among the colleagues I've known for several decades now,

02:42:46.900 | you really are one of a very small few who've managed to do both animal studies and human

02:42:54.340 | studies, but also animal studies with a very clear eye and a pointer toward human health.

02:43:00.420 | And that's such a vital and rare thing, especially in this day of extremely competitive funding.

02:43:07.060 | So I want to thank you for your time today, for the knowledge you share,

02:43:10.100 | the actionable aspects of that knowledge, the science that you're doing in your laboratory.

02:43:15.380 | We will provide links for people to learn more about you and of course, to go to the app

02:43:20.100 | so people can engage in some of the science directly. And of course you have several

02:43:25.380 | wonderful books now that we will also link to both of which I've read and are wonderful,

02:43:29.060 | in particular the book, the first book, but also a book related to diabetes. And so for diabetics

02:43:34.500 | and people interested in metabolic and blood sugar regulation there. So on behalf of myself and my

02:43:41.780 | team here at the Huberman Lab podcast and all the listeners, I just want to say thank you so much.

02:43:46.100 | Your time is valuable and the fact that you share it with us and educate so many people

02:43:50.660 | is really a gift. Yeah, thank you. And actually, likewise, there are very few scientists who

02:43:56.820 | have taken this leadership role that you have taken to come and communicate science to the

02:44:03.060 | public. It's not easy because sometimes you have to distill it down to a simple soundbite

02:44:11.460 | to the point where the scientist and they'll say, "Oh, that may not be right." But we always have to

02:44:16.900 | keep in mind that we are always living in the dark is of science because the reason why I say that,

02:44:23.220 | this is not my quote actually, this is from one of my scientific hero Paul Schimmel from

02:44:27.780 | Scripps. He always says, "Think about it. 10 years ago, what you thought was right and the best

02:44:35.860 | has already changed." But one thing is the circadian rhythm and aligning it to our internal

02:44:44.100 | clock to our habit is very important. And as you mentioned, we have our MySecadianClock app,

02:44:50.820 | which is research facing, but we have also distilled all of this down to five or six

02:44:56.980 | timing component and we have a new app called OnTimeHealth or Get OnTimeHealth.

02:45:02.260 | Do people access that through the standard app stores?

02:45:04.980 | Yeah. So now it's available in Apple App Store and we want to see how, because people always

02:45:15.140 | think about fasting, but as we discussed today, feeding, fasting or eating, fasting and activity

02:45:21.940 | and sleep are kind of interlinked and we have to kind of balance both of these. So that was the

02:45:28.500 | idea behind this OnTimeHealth program. And thank you, Andy, because what you're doing is immensely

02:45:37.460 | necessary, particularly these days when science is moving at a very fast pace, there are a lot

02:45:44.260 | of results coming out. Sometimes something can be very confusing and you spending your time

02:45:50.020 | to communicate science is exceptional. So thank you, Andy.

02:45:55.380 | You're most welcome. It's days like today where I get to sit down and talk to brilliant colleagues

02:46:01.620 | like you who are doing the important work that really matters so much. And so as you

02:46:05.700 | mentioned a moment ago, there's a lot of darkness and confusion out there, but

02:46:10.980 | thank you for being one of those who's shining light.

02:46:15.380 | Thank you.

02:46:17.400 | Thank you for joining me for today's discussion with Dr. Sachin Panda,

02:46:21.300 | all about circadian biology and time restricted feeding. If you're learning from and are enjoying

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02:46:58.740 | Lab podcast. We discuss supplements while supplements aren't necessary for everybody.

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02:47:49.140 | discussed on the Huberman Lab podcast, you can go to Live Momentous, spelled O-U-S,

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02:47:57.540 | it's Huberman Lab on Instagram, Twitter, Facebook, and LinkedIn. And at all of those places,

02:48:03.620 | I cover science and science-based tools, some of which overlap with the contents of the Huberman

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02:48:11.380 | Again, it's Huberman Lab on all social media platforms. If you haven't already subscribed

02:48:15.300 | to the Huberman Lab podcast, neural network newsletter, it's a monthly newsletter that

02:48:18.980 | includes free toolkits for things like toolkit for sleep, how to enhance the quality and duration of

02:48:24.420 | your sleep, toolkit for focus, toolkit for neuroplasticity, toolkit for deliberate cold

02:48:28.740 | exposure, heat exposure, and summaries of podcast episodes. All of those toolkits can be found by

02:48:33.060 | going to HubermanLab.com, go to the menu, scroll down to newsletter, and simply give us your email.

02:48:38.260 | We do not share your email with anybody. And again, the newsletters and toolkits are completely

02:48:42.100 | zero cost, and you will also find some PDF examples of previous toolkits. Again, that's

02:48:46.820 | HubermanLab.com. Thank you once again for joining me for today's discussion with Dr. Sachin Panda.

02:48:52.340 | I hope you found the conversation to be as informative and actionable as I did.

02:48:57.300 | And last, but certainly not least, thank you for your interest in science.

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

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