All language subtitles for 230313-Intermittent Fasting to Improve Health, Cognition & Longevity-y

welcome to the huberman Lab podcast

where we discuss science and

science-based tools for everyday life

I'm Andrew huberman and I'm a professor

of neurobiology and Ophthalmology at

Stanford school of medicine today my

guest is Dr Sachin Panda Dr Sachin panda

is a professor and director of the

regulatory biology laboratory at the

Salk Institute of biological studies

his laboratory has made numerous

important contributions that impact

mental health physical health and human

performance for instance his laboratory

discovered the neurons in the eye and

neurons within the brain that regulate

our so-called circadian rhythm circadian

rhythms are 24-hour rhythms and

everything from gene expression to the

overall functioning of tissues our

levels of mood and alertness our ability

to sleep appetite and much much more in

addition over the last decade Dr Panda's

laboratory has made critical discoveries

in terms of how our patterns of eating

over time impact our biology and our

health in particular his laboratory

Pioneer discoveries related to so-called

intermittent fasting also sometimes

referred to as time restricted feeding

today Dr Panda and I discuss how our

circadian behaviors everything from when

we wake up to when we view light to when

we avoid viewing light to when we eat

and what we eat and when we socialize

and how we socialize impacts our biology

and our psychology energy and how all of

that has a strong impact on our health

during today's discussion you will learn

how restricting your feeding to specific

periods within each 24 hour cycle or

perhaps even exploring longer patterns

of fasting and eating Cycles can impact

everything from the health of your liver

to your gut to your brain and how all of

that impacts things like mood and your

ability to perform cognitive work indeed

today's discussion goes deep into all

aspects of intermittent fasting AKA time

restricted feeding we talk about the

basic science as well as the recent

clinical trials that have explored

time-restricted feeding in a diverse

range of people including men women

children people with diabetes people who

are otherwise healthy and much much more

I'm quite aware that intermittent

fasting is a topic of much debate these

days we go deep into that debate and by

the end of today's discussion you can be

certain that you will have learned all

the latest and all the details all all

made very clear to you thanks to the

incredible expertise Discovery and clear

communication of Dr Panda as some of you

may already know Dr Panda has authored

several important books on the topic of

intermittent fasting and how it can

benefit various aspects of Health those

books include the Circadian code and a

more recent book the Circadian diabetes

code both of which we've provided links

to in the show note captions in addition

if any of you are interested in learning

more about Dr Panda's work including

seeing his Publications and reading

those Publications we're supporting his

laboratory you can do that by going to

his laboratory website which we have

also linked in the show note captions

before we begin I'd like to emphasize

that this podcast is separate from my

teaching and research roles at Stanford

it is however part of my desire and

effort to bring zero cost to Consumer

information about science and science

related tools to the general public in

keeping with that theme I'd like to

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and now for my discussion with Dr Sachin

Panda Sachin Dr Panda so good to see you

again yeah good to see you we are

colleagues still but we used to be right

across the street from one another yeah

yeah you remember those days yeah yeah

so I'm delighted that you're here

um I think we're going to talk about a

number of things mainly

intermittent fasting time restricted

feeding and health but also the many

other things that you're doing just

before we started recording we were

discussing your recent paper in nature

uh that involved recordings from

post-mortem Human retina so maybe if

there's time at the end we can get back

to uh your lab has shown that you can

essentially maintain or resurrect

neurons from

uh dead people in order to potentially

and eventually provide transplants to

rescue Vision in the blind so that's

extremely exciting but of course not the

main focus of today's discussion so

we'll have to uh split it up

um the first question I have is how am I

supposed to Define

fasting and time restricted feeding in

meaning when I go to sleep every night

I'm not eating so in some sense

everybody

is doing time restricted feeding to some

degree or another yeah at what point can

we start thinking about a pattern of

eating as time restricted feeding

so-called intermittent fasting

does it have to do with how regular one

is about the start and stop times how do

you think about defining intermittent

fasting time restrictive feeding and

maybe just to simplify the conversation

is one term more correct than the other

in terms of describing this incredible

pattern of feeding

well you know that intermittent fasting

covers many types of fasting

um so actually it started long time ago

and it's embedded into the history of

caloric restriction

um almost 100 years ago people showed

that if you reduce

calorie intake in a rat then that rat

can live for a long time

and in those experiments the calories

were reduced every single day

and that led to the idea that if we cut

down our calories by 20 percent say then

we can potentially live longer by doing

two things one is preventing is related

disease or even if we follow fall sick

maybe we can accelerate cure

and keep the repair mechanism going so

that we can live longer

but it was very difficult to

count calories every day and reduce

maintain that

um

I must say that it's not that calorie

restriction is impossible or we are not

doing it in fact

a lot of us we do

um count calories in our subconscious

mind means every time you took out it

you took out we take out a soda bottle

or something I'm looking at it okay or

in 60 kilocalo or 30 kilocal or zero

kilocal we are doing that so the point

is it's it's we are doing subconsciously

some kind of calorie

counting but reducing calorie by Twenty

thirty percent every single day is not

possible for many people so then the

idea came in mouse and rat experiment

whether they can eat every other day

um and in fact this every other day

feeding

um also led to very similar almost

equivalent Health Improvement as

continuous calorie restriction

um so then the idea was well every other

day is a little bit hard for humans but

just imagine I would just get to eat

only one day and then another day

then the idea came well for humans can

they eat less for one or two days in a

week

so that led to this pipe two diet where

people can eat for five days and then

two days they have to reduce calories so

that's also

intermittently people are fasting

um then as you know Walter longer also

came with this idea that periodic

fasting maybe four or five days in every

month or two months three months you can

fast or reduce calorie

and he also found many benefits of

calorie restriction was there were those

studies on humans many of the studies

started it in mice but alternate day

fasting five two and

um Walters periodic fasting all of them

have now been done in humans not for

longevity of course because

cannot do this for a long time but for

weight maintenance for reducing some

signs of aging or reversing those things

have been done so all of them have been

done in humans mostly healthy humans and

in some cases people with pre-diabetes

or some aspects of metabolic disease so

that led to the idea that that all these

forms of fasting in which

the total caloric intake on any given

day is reduced for one or more days in a

week a month that became that umbrella

term became intermittent fasting

so if you

look up the scientific literature most

intermittent fasting involves

intentionally reducing calories

for at least one or two days in a week

or

um few days in a month

so when we publish time restricted

feeding

um the initial Mouse experiments and

even now most of the mouse experiments

we want to test what is the impact of

time restriction versus calorie

restriction

so in these experiments we don't reduce

calorie on any day of mouse life so the

mice is the same number of calories as

the adlibitum FED mice

but still they say health benefit so

that's why we call it time restricted

feeding

but since it involves

living without food for several hours

for some people which is it can be very

difficult the initial experiments was

done they were done for eight hours of

feeding and 16 hours of fasting that

kind of became popular and so that

that's why people use the same term as

intermittent fasting and now if you

say intermittent fasting and popular

literature or popular media then people

usually refer to time restricted eating

so now coming back to

how do you define time restricted

fitting

um so the way we have been trying to

Define

experimentally and also in literature is

um

trying to

confine all your energy intake from

solid and liquid food combined within a

consistent window of 8 to 12 hours

because that's something that doable of

course people have done time restrictive

trading with four hours six hours and

some people even try to eat everything

within two hours one meal a day

um but the point is those are not

feasible to maintain for very long time

for a lot of people

one question about the six hour versus

eight hour versus 12 hour feeding window

is it important that the feeding window

begin and end at the same time more or

less yeah and if so how much flexibility

is there so for instance I'm somebody

that

I am not terribly hungry in the morning

I like to drink water usually some

caffeine and electrolytes yeah in the

period before my first meal and my first

meal always lands sometime between

11 and 11 A.M and 12 noon there are

exceptions yeah occasionally I'll have a

breakfast a proper breakfast as it's

called Uh I guess it would be improper

if you're intermittent fasting for me

um but typically 11 A.M or noon is when

I first eat my last bite of food is

typically around I don't know 39 PM

that's what works for me yeah

is that consistency affording me any

benefit separate and let's just leave

aside total caloric number

macronutrients plant-based meat Etc but

is there any benefit to shortening that

feeding window that we are aware of or

extending that feeding window or being

even more rigid about the start and end

of that feeding window

yeah so the start of the fitting window

um that's interesting because the

concept of time history feeding when I

describe animal studies it's feeding for

humans it's eating so the concept

actually came from the science of

circadian rhythm so that means um

our body has an internal timetable

that's present in every cell in every

organ

that pre-programs many

molecular aspects of the cells that

leads to physiology and all that stuff

so that essentially there is a

predetermined timetable for every cell

every organ to do certain things at

certain time

and

the Circadian clocks as

you and I know are more sensitive to

light light is the most dominant

um time Giver so for example when

daylight saving time changes or when we

travel from one time zone to another

time zone we feel kind of crappy because

our daily activities uh out of sync

from our internal clock

so that was known for a very long time

but then around the year 2000 2002

there was a famous experiment by Uli

sibler from

Switzerland what he did he just

Fair demise at the wrong time mice are

nocturnal their night feeders and when

he fed the mice during their time and

the liver clock instead of

following its own routine liver clock

actually started following food so that

means by changing our feeding time we

can change we can tune our liver plot

and subsequently the same experiment has

been repeated many times and when we

repeated that in 2009

and we figured out Yes actually outside

this

brand Center called Supra chiasmatic

nucleus or scn which

is considered the master circadian clock

almost

rest of the brain even

follows when we eat and that came out

from Pierre shambon's lab in Europe

where they systematically looked at even

places that are very close to the asean

for those who are who node or some

medial hypothalamus or paraventricular

nucleus all of this

within a couple of four or five

millimeters of the scn but they were

following food queue

amazing so then

um and now if we think about it so for

example when the daylight saving time

changes just one hour change

um or one hour change in alignment

between our internal time and external

time leads to kind of feeling groggy and

filling not out of Peak Performance for

one or two days

so the rule of thumb is when the time

Giver

changes by one hour then our internal

clock takes at least a day to catch up

so that means if you're flying from

LA to New York uh you're moving through

three time zones then on an average it

will take three uh three days to catch

up with the New York Times for some

people it can be even slower and for

some people it can be two days but the

bottom line is yes there is a

decentrality so then what does it mean

for the body sorry one of the function

of clock is to anticipate when you're

going to wake up for example so the

blood pressure slightly goes up our

heart rate goes up our breathing goes up

similarly for food

almost every organ that is involved in

feeding or eating digestion all of them

have clocks

so even from saliva production that's

the first phase of digestion to

secretion of all the digestive juice and

the stomach and the absorption of

nutrients and liver metabolism

everything the whole village expects one

you're supposed to eat and they're

getting ready

for you to eat the first meal after

fasting for a long time so that's why

it's breaking the fast of breakfast

and when that time changes when you

change it by two or three hours from one

day to another then

um sometimes they're like oh food didn't

come or maybe

um will come at a wrong time we were at

the wrong time and then they will track

the new eating time so suppose say one

day you have been eating every day at

eight a.m

um I ate at 8am is that when you start

yeah

when do you when does your feeding

Windows shut uh 6 p.m so I eat for

around 10 hours okay

um and then one day if I switch to 10 am

then what happens is

a clerk is thinking well the food didn't

arrive at eight but it arrived at 10

maybe tomorrow the food will arrive

somewhere between eight and ten so we'll

be ready around nine

and next day if I come back and eat at

eight o'clock then I may eat but my

clock is not ready to digest that food

so that's why this idea is you have to

be consistent uh to take advantage of

this anticipatory activity of our cloth

in different systems to get the best out

of it is there evidence that those

anticipatory systems and as they relate

to digestion help us better assimilate

our food I would imagine so I mean if

you have the gastric juices that are

going to help digest the proteins fats

and carbohydrates and uh already

deployed at the time when you eat I

could imagine that food will be better

utilized than if you don't so in other

words what is the advantage of having

these anticipatory signals in terms of

potential health benefits the

anticipatory signal is really important

from even even from working up

um

the reason why many people feel not

ready completely when they'll wake up to

an alarm clock because the alarm clock

wakes you up but your body is not

prepared so that slippiness after waking

up to an alarm clock is due to our body

is not prepared for that and then the

best example is when the when

uh the daylight saving time changes

particularly when we have to wake up one

hour early uh what happens people who

have underlying heart condition

um when they're waking up when the body

is not ready your heart is not ready and

all operations from the heart has to

start pumping little bit harder then

there is chance of heart attack and in

fact people have looked at hospital

records and that they find that on those

days and there is a sharp rise in heart

attacks in car accidents and car

accidents too because your brain is not

coordinated so you cannot make those

fine decisions

so that's a great example of

anticipatory activity but coming back to

digestion one thing is

um

and this is something that many people

might have experienced

there are many rhythms in our digestive

system and one of the rhythms is our

look our intestine has this peristaltic

function so it kind of contracts and

expands and that moves forward more food

doesn't move due to gravity so it goes

back and forth and that peristaltic axon

actually slows down at night a few hours

after our last meal and

um so that's why when people eat late at

night for example then that food doesn't

get digested because there is not enough

digestive juice first thing and second

even if it gets digested in the stomach

it doesn't move properly so then the

next morning people get up and think

um of course people consume some alcohol

very often and then they think that this

is Hangover but those who don't consume

alcohol then they have the food hangover

because it doesn't digest so that's one

extreme example where food

at the wrong time

can

um so healthy food at the wrong time can

be crap or junk yeah I've um experienced

that where if I've worked late or I

couldn't eat dinner or something and

then I get home I always debate whether

or not to try and sleep yeah but if I'm

too hungry oftentimes it's challenging

and so for me sometimes consuming

something that at least seems easily

digestible like yogurt or something in a

liquid form

um is better for me than if I eat a meal

I've made the mistake of going to the

refrigerator being super hungry and

eating a bunch of food at 10 or 11 p.m

and then falling asleep and indeed the

sleep

if I'm tired enough can be quite deep

but the next morning I feel just

completely physically and and

cognitively weighed down so I think what

you just described makes a lot of sense

so is it so if someone were to select a

feeding window regardless of whether or

not it falls into classic intermittent

fasting time restricted feeding sounds

like eating your first bite of food and

eating your last bite of food at more or

less the same time each day yeah has

benefits

I have this question you mentioned

feeding versus eating and I think it's

actually not just a grammatical uh

semantic issue

um and here's why

we tend to think about when you take

your first bite of food and then when

you take your last bite of food but of

course Foods digest at different rates

more fat in there is going to digest

make carbohydrates digest slower Etc I

mean there's all these adjustments to

the glycemic index and so forth with

Foods in combination

I is it better to think about not eating

but your fed State and blood sugar so

for instance I often get asked on social

media does blank break a fast so uh and

so I like to think about it

scientifically like okay is does plain

water break a fast no does air break a

fast no

um does one grain of sugar

of sucrose break a fast well probably

not but does one teaspoon of sugar break

a fast well you could say yes but

transiently like so I mean when we're

talking about breaking a fast are we

talking about a rise in blood glucose or

are there molecular signals Downstream

of of a rise in blood glucose that

um cannot be reversed in other words if

I'm gonna eat my first meal every day at

noon and I'm gonna eat my last bite of

food at 8 00 pm and at 9 00 a.m for

whatever reason I have coffee with one

teaspoon of sugar in it

I suppose in the strictest sense I've

broken my fast but maybe by if I went

for a hard run that morning maybe by 9

30 a.m I'm back in a quote unquote

fasted state so what is the fasted State

really because when I'm eating at 8 pm

just to give another example

I'm start fasting at 801 perhaps yeah

but I have my blood glucose is elevated

so I'm not really fasted I'm fed yeah

it's just that I'm not eating the verb

right okay so

um so again I I don't want to get overly

detailed just for sake of getting detail

but I think a lot of the confusion out

there about what breaks a fast yeah is

related specifically to this issue yeah

which is if I eat a whole pizza after

sitting around all day it's very

different than if I eat a whole pizza

after having run a 26 mile marathon that

yeah very different yeah

um metabolically speaking so how should

people think about fasted versus fed can

we be mildly fasted versus severe fasted

can we be

um fed-ish versus very fed anyway I'll

I'll uh stop asking questions now

because they all relate to the same

theme yeah no these are um very

interesting question and then

unfortunately as you can as you have you

might have seen in life the most obvious

questions are often unanswered because

it's so hard to do these damn

experiments because if you really want

to address this in humans you have to

bring humans put them in isolation

just like you said I can now imagine

planning five or six different

experiments each experiment should

involve eight or ten volunteers it's

gender sex

and then do it so it's difficult so now

let's go back to see

how do we let's dissect it in terms of

say indirect calorimetry so for example

indirect calorimetry is based on this

principle that whatever oxygen we

breathe in and carbon dioxide we breathe

out if we can measure these two then we

can figure out whether our body

in total we are not saying whether it's

the liver gut or fat or muscle in total

whether it's consuming glucose or fat as

energy source

the idea is when we fast when we are

without food for several hours

then

ideally our body will tap onto glycogen

first and then do a little bit of fat

and then when the body is mostly running

on fat then that ratio of CO2 to oxygen

will come to 0.7

[Music]

um

but what is interesting is we can do

these experiments in mice so we can go

to mice and ask okay so what happens in

mice so

and mice mice are a little bit very

different because mice are not simply

little people they are the metabolism is

different they

store relatively less glycogen than

humans do in terms of total metabolism

so they

overnight within 12 to 14 hours the rer

respiratory exchange ratio or this ratio

will go from one when the consuming

mostly glucose or carbohydrate as energy

source it will slow down slowly go to

0.7.75

it's after 12 to 14 hours they're kind

of mostly running on fat

so now as we give them food

um within 10 or 15 minutes they are not

actually consuming couple of grams of

food they might have consumed say 100 or

200 milligram of that child so which is

less than say five percent of the food

and then the rer will immediately begin

to rise as if

that small amount of food stopped that

fat burning process and cranked up the

carbohydrate burning process when you

say fat burning process you mean body

fat stores being burned right not

dietary fat correct yeah so it's all

body fat means that that's why I said um

we don't know where that fat is being

burned because we are just measuring how

how much mice is breathing in and out

um so for example it can be from the

Skin So subcutaneous fat or belly fat

but not dietary fat no by that time the

dietary fat is already absorbed and

digested and hopefully it's sitting in

the liver or adipose tissue somewhere

but it's the fattest body fat yes thank

you yeah the reason I ask is that

nowadays I think more than half of the

battles about nutrition that I see

online relate to this issue where I

won't name names but someone will come

along and say low carbohydrate diet

allows you to burn more fat

and the more nuanced people out there

will will say well that's true but

you're also talking about dietary fat

you know the word fat can confuse people

I realize you're not doing that you are

certainly not one of the people guilty

of doing this but indeed you eat more

fat you'll burn more fat but that

doesn't mean you'll burn more body fat

in fact I think the day does say that

under conditions of caloric restriction

you'll actually burn less I hope I don't

I'll probably get I'll probably get um

pitchforks uh through the mail toward me

on on that one but but I think that's

true whereas you know people who consume

carbohydrate can still burn body fat

even though the majority of the fuel

they're burning is from carbohydrates so

yeah so here in this case for example

from mice we know that as soon as they

start eating

um the area goes up

coming back to your question what would

be ideal for us to do the experiment

would be okay so we'll go back to that

and then give the mouse maybe 100

milligram of food

and Mouse runs around in the case and

then we'll continue to measure to see

how long it takes for the mouse to come

back and then

so that's one husband so now let's say

um

let's stay on this and then I'll come

back and talk about non-caloric food and

whether that is considered

I'd like to take a quick break and

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so there is a famous experiment that was

published last year by jotakahasi Islam

and it came out in science

and that relates to caloric restriction

and

we kind of started with this idea we

started to discuss on that the rat

experiments were done with caloric

restriction and researchers get reduced

calorie consumption by 20 or 30 percent

and get that food the rats and then

subsequently mice and they all lived

longer

what is interesting is

in all those experiments the researchers

came and gave this bolus of food at one

time whereas the adlibitum FED mice or

rats they had access to food all the

time so they're eating all the time and

then these rats were given 20 percent

less

and what happens is this mice or rats

then I'm going to take that less food

which is restaurant now and just eat

little bit of lunch and then snack after

three hours or snack after three hours

they double up all that food within two

to three hours maximum four hours food

is gone so they're sort of on the omad

diet the one meal a day yeah they're

almost like in one meal a day three to

four hours food is gone

or you can sit there on

four hours eating or feeding and 20

hours fasting

um so then the question became well

the benefit of caloric restriction as we

know is it due to reduced calorie

or

time restricted feeling or timing there

is a timing component to it that they

are eating all of that within three to

four hours and then there is a long

fasting and this is a difficult question

to answer because now

you have to ask this poor grad students

or technicians to come and split that

food into eight or ten or fifteen

different small portions and then give

them to mice in every two hours

who actually published the first paper

in 2017 showing that most caloric

restrictions I mean he used the protocol

that was used by Kelly restriction field

it actually creates a condition of time

restriction

so he saw that and then he went back and

worked with Engineers to come up with

the smart kids where

he could actually tell he could program

how much food is given to mice at what

time of the day or night completely

programmed

so then he took this uh for example

suppose say the adlibitum FED mice it's

five grams of ciao in a day

and if you want to reduce calories by uh

20 percent and the CR Mouse should get

four grams of food

and it divided this into

9 or 10 meals and then give them in

every 90 minutes so in this case they're

eating small

meals

throughout day and night so there is no

fasting so you can say that well this

mouse actually is not getting into

fasting because in every few hours is

getting some food

and then he measured how long the mouse

is going to live

um and he used

um accountments this is a very standard

protocol people count how many mice have

dying on which day and then examine them

to see whether they've died because they

there was an accident or they actually

there was a natural cause

and then they calculate at the end what

is the half life so 50 survival because

that's on an average that's a good

indicator because if there is an outlier

that will live for a long time then that

can skew

so what was interesting was the limit

unfair mice of course they live certain

number of days and then this

caloric restricted mice

that never got into Super fasting but

kind of eating snacking throughout day

and night that also lift 10 percent

extra 10 percent longer so that means

caloric restriction extended lifespan by

10 percent I've wondered about this

because recently

you know there's been there were a bunch

of news headlines about intermittent

fasting and and frankly I was frustrated

if you looked at one major news outlet

they would say time restricted feeding

affords no additional benefit Beyond

caloric restriction for weight loss yeah

then another

popular press venue let's call it that

same study described as time restricted

feeding

doesn't work yeah right and then another

one maybe someplace

um even more extreme you know time

restricted feeding

um only beneficial because of caloric

restriction or something like that so

what you've essentially got are three

different interpretations of the same

data all of which are well two of which

are true one of which is false in my

opinion but what I think people take

away from that is oh time restricted

feeding isn't valuable which is not the

case it I think for many people it's a

convenient way to eat because at least

for people like me it's simpler to

designate between portions of my day

when I'm eating and portions of day my

day when I'm not eating as opposed to

eating portion control for other people

portion control can work but all of that

is related to either maintenance or loss

of weight none of it deals with the

potential health benefits independent of

weight loss yeah right so um and so I I

think that um if we can segment those

out

um obviously in humans it's hard to know

if a given treatment or experiment is

extending life because you don't really

know how long people would live anyway

yeah right whereas with mice you have

some sense of when the mortality was

likely to occur so what can we say about

time restricted feeding and longevity in

terms of biomarkers or in terms of any

other indication that people who start

and stop their feeding window at a

consistent time somewhere between 8 and

12 hours per 24 hour cycle are

tilting the scales towards living longer

as opposed to living shorter this

example of this news article that you

mentioned is really interesting because

that relates to Joe's Joe takas's study

because I described that if you split

calories and eat throughout the day

throughout day and night then the mice

lived 10 percent extra

but if you now give Mouse the same

caloric restricted diet

and fit them during day time

whether within 12 hours or two hours

then the mice lived 10 percent extra

beyond that yes so twenty percent so

okay so let me make sure I understand so

that uh so that I make sure I understand

if you take a certain number of calories

and you distribute them throughout the

24-hour cycle yeah

it's caloric restriction the mice will

live ten percent longer yeah if you

however restrict that to the active

cycle of the so for humans the daytime

then

20 then they live 20 percent long twenty

percent so it's not just total caloric

intake yeah meaning it's not just

important to be sub maintenance and

calories for sacral longevity it also is

important as to when in the 24 hour

cycle yeah you eat those calories do I

have that right so now

that's still the story is not over

because this mice were fed during

daytime and they're not supposed to eat

that's right so for us it will be the

equivalent of being on the night shift

and only eating at night but a sub color

sub maintenance calorie diet I guess is

the right way to say it but when he fed

mice during night time when they're

supposed to eat and they're seeing this

getting the same number of calories

within 12 hours or two hours

then the mice left 35 percent longer

than they control 35 longer so scale to

human lifespan which you know we don't

know but but a 35 longer would mean that

um and again no one knows but um humans

now what is the average mortality in the

United States

yeah so it's around 80 it used to be 18

hours slow uh reduce little bit because

of covet but let's take 80 okay so

people are then now living somewhere

between 25 and 35 years longer but I'm

putting some error bars on yeah yeah so

that was um really profound but now you

pointed out um biomarker and other stuff

so now

if you look at any given time within

that experiment and actually Joe went

back and

um had a separate cohort of mice very

similar and so that he could take tissue

samples and of course in this case you

have to sacrifice the mouse

and he looked for

um he did a lot of molecular analysis

with non markers for example hemoglobin

A1c equivalent or glucose control

cholesterol all this stuff

he could not find anything

[Music]

that predicted the benefit of caloric

restriction so that means in this

experiment whatever we know so far the

predictor of longevity none of them

could predict whether this

um

CR only Mouse which throughout day and

night

that Mouse is going to live less than

the night fed mouse that was going to

live 35 25 extra does that mean that

there are biomarkers related to

longevity that we just haven't

discovered yet yeah so that's exactly so

that means whatever we know so far about

biomarkers those

he could not use to predict maybe there

was a lot of noise maybe he wanted he

had to use more number of mice to get

that because you know biomarkers

are not going to predict in every

instance so there is some error

what is also very interesting is if you

look at the body weight and body

composition of all these mice there is

no difference in body weight and body

composition

across all these differences all these

groups so it doesn't matter when they

ate yeah provided they were submit sub

maintenance calorie intake so less

fewer calories than is required to

maintain their weight didn't matter what

pattern of eating they were the same way

yeah so that in many ways seems to mimic

the human studies where they say look it

doesn't really matter whether or not you

use caloric restriction or or you start

your feeding window in the morning or

start your feeding window in the evening

or you

um or you portion control for sake of

weight contr weight loss because you're

taking a snapshot of that and then

another thing with the human study that

we are referring to here

um that in that human study

people are actually already eating

within 10 hours window

habitually when they selected these

people to have them enroll in the study

so they were already eating for 10 hours

and fasting for 14 hours

all participants had to reduce that

caloric intake and they reduced by

almost 25 percent

the CR group continued with 10 hour

sitting window

and the CR plus time restricted group

had to eat the same number of calories

within eight hours so it's just a two

hour difference it's just a two hours

difference okay so that people I just

want to make sure people can understand

so in this human study which is the one

that I felt that the popular press

venues all except one venue

um got either semi-rung or badly wrong

in terms of their conclusion that was my

interpretation anyway was that

either people came into the study eating

basically in a 10 hour feeding window

which goes back to my first question

which is that most people are not eating

in the middle of the night yeah or if

they're on shift work and they are then

they're sleeping during the day anyway

so they're eating in a 10 to 12 hour

feeding window anyway so you're saying

they either did caloric restriction

portion control within the 10-hour

window or another group within the study

eight sub maintenance calories so

caloric restriction CR as we're calling

it the acronym CR but restricted to that

to an eight hour feeding window and they

didn't see any difference in terms of

weight loss yeah but but it's not all

that surprising right I mean if it's

just a two-hour difference yeah exactly

so we have done that experiment in mice

and we don't see

um difference in not only weight loss

many other markers and I was telling you

about this um paper where I told you

that he allowed this mice to eat within

two hours or 12 hours

sub calories diet 2 or 12 2 or 12. yeah

that's dramatic but still he did not see

change in longevity even within those

two so that means

um when you do caloric restriction and

then at least for months and you are

within 12 hours window

um that's that is giving the mice the

best benefit the optimum benefit and

um two three or five or twelve per Mouse

doesn't matter at least for longevity

can we conclude for humans that whether

or not a feeding window is

four hours six hours eight hours or 12

doesn't matter provided that calories

are are similar or same well I won't go

to that extent because we don't know

many of this particularly we don't know

how this sort of eating window will

affect both success because you know we

always think many of this mouse

experiments even that I told you about

those are done only in Mel mice but that

should be changing right because the NIH

I know this because I'm on study section

which is just a bunch of people who

record who review grants is that every

Grant now has to include sex as a

biological variable it's hard to get

away with

um or rather I should say it the way it

should be said which is people are

required

and should want to look at these

phenomena in male and female mice yes

especially if there are differences so

in this case

um there are many I mean there is also

another paper

um in time history repeating that also

came out a big paper showing that they

um thermogenesis was accounting for loss

in fat mass and time just to referred

mice that was also done only in male

mice

um so this is um we are paying attention

to it so we are now doing all of our

studies in male and female and we do see

big differences between male and female

coming back to humans

what typically happens is when you're

trying to do four hours or six hours of

time restricting people will

inadvertently reduce their caloric

intake yeah just because of gut volume I

tried one meal per day and and I felt

like I was eating so much at that one

sitting yeah that it led to a lot of

gastric distress and I got tired after

the meal and part of the reason I like

to do time restricted feeding is I have

more energy yeah and certainly in the

fasted State I feel more energized

especially if I'm ingesting a little

caffeine or something like that

um so people will reduce

um

energy intake and then

some people who are more active they can

actually

unconsciously they may be spending more

energy in their physical activity and

basal metabolic rate all of this

combined than homozy eating

and that can have a very adverse effect

in long term because we know that this

energy deficit and in fact there is a

scientific term for that it's called red

s relative energy deficit in sports

energy deficit in sports okay yeah it's

because nearly 40 percent of athletes

um not the NFL guys but you know a lot

of people who do track and field

um and nearly 40 percent of athletes

actually experience this Reds red S

without knowing can male and female

athletes both men remains Reds so it's

Reds Reds relative energy relative

energy deficit in sports interesting is

the first I've heard this acronym we

have a new acronym folks this is good to

add to it a list of other acronyms but I

so males and females can experience it

so in females I've heard that

um Reds

um can lead to uh eminaria so loss of of

men's of the menstrual cycle yeah so

that's uh so common that uh so prevalent

that in fact many women many female

athletes they take it for granted that

yes if they are more active then they

will lose their menstrual cycle which is

which may be common but it's not normal

or Optimum per health

and even if they don't want to get

pregnant yeah yeah yeah yeah we had an

expert on female hormones come on and

say the very same thing that regular

cycling is a is very important of

ovulatory menstrual cycle is is

important to try and

um maintain yeah yeah so that's one but

then what is really concerning is

um it does affect bone health

and

um in this state people actually over a

long period of time the loose bone mass

and the bone also becomes more prone to

injury micro fracture and fractures

um so again it's a risk means if some

people are trying to eat within very

short time and they're Physically Active

that happens and it also has impact on

means the reason why

these women are losing menstrual cycle

is the

hpg axis is disrupted hypothalamus

pituitary

gonadal axis

and it starts it may start again

Upstream at hypothalamus or pituitary so

that means that HPA axis hypothalamus

pituitary and adrenal axis may also get

disrupted one of the symptoms of Reds is

also depression anxiety bipolar like

symptoms and we know that many

um many athletes experience that we

think that well this this may be just

peer pressure that always trying to

compete and we know that I'm

unfortunately there are few authors who

just can't cope it and there are many

attempted suicide or suicide so this is

a serious issue and

there's also another new topic in the

lab to come up with a mouse model of

Reds and then study it but this is one

risk why we should not reduce our eating

interval to two such to one meal or very

short time because it can have adverse

side effects that we don't know now

um maybe in future we'll figure out when

we systematically study them

there are studies that are published

showing four hours and six hours time

restricted eating has benefits on weight

loss but those are on healthy

individuals and they were in the studies

so the um you know the study team took a

uh well already monitoring the mature

that there was no sudden weight loss or

weight loss below

um some safety level uh so those are

very different from regular people who

are who maybe even normal weight or even

with uh within the healthy range if they

do then they can potentially so that's

why

what we think is eight to ten hours

maybe the ideal spot to begin with and

um once you are physically active and

you are also spending a lot of energy in

physical activity or Sports you can even

go up to 12 hours because in mice we

have done that experiment

um after 12 hours they do get a lot of

benefits not all but so this is 12 hours

of 12 hours of feeding 12 hours of

fasting yeah

um in humans

um again nobody has done systematically

12 hours but there is one study in

Europe

um from tin High Colette lab and Tin

high and I we collaborate so they used

our my security and clock app this is a

research app we developed just to this

is mostly used in time restricted eating

studies

and he had nearly I think he started

with 200 Swiss participants but then at

the end he selected and took very small

number of groups people who are very

um meticulous about recording all their

food and divided them into usual feeling

whatever they wanted to eat whenever

they wanted to eat and they were given

the advice of Swiss nutrition advice

that's given to improved health and

reduce blood glucose almost like

diabetes prevention program in the U.S

and then the other group was given

advice to eat within 12 hours

this is very early on in time

restorating and we thought that the mice

were getting some benefit let's try with

the 12 hours has any benefit

the bottom line is

at the end of three months and six

months what he reported is both groups

lost same amount of body weight

and then there's not too much

significant difference between groups

but both groups actually improved their

health so the bottom line is the Swiss

nutritional advice that he was giving

Which is the standard of care there it

achieved the same amount of weight loss

as just giving people this advice that

eat within 12 hours so one way to look

at it look at the result is like this

and

then he went to more extent and actually

looked at every single meal these people

consumed so they're close to I think

close to 60 or 70 000 meal records and

pictures he went through and then

classified them to say whether these are

good quality food so they call it the

Nova classification one two three four

one is the food that you can almost eat

raw fruits vegetables

um yogurt and dairy products that you

can almost without any preparation

and then second Nova 2 is kind of home

home cooked food that most people will

prepare in few minutes and then three

and then fourth one is the food that you

can never prepare at home

so for example

biscuit or cookies that we usually

purchase and few other things

and usually the Nova 4 are unhealthy

Ultra processed food so which we should

not be eating so the advice is to reduce

Novak for

and what I found was people who got all

this advice

um to improve their nutrition quality

they actually improve their nutrition

quality they reduce their Nova for food

and people who were in time frustrating

the eight within 12 hours they did not

change the nutrition quality

but what is interesting is they both got

the same modest weight loss so that begs

the question that in the maybe tin high

will do this experiment again to combine

nutrition advice with time restriction

and maybe reduce the time to 10 hours

and that might help

um so

12 hours is something that I say

anyone from five-year-old to 100 year

old can do and if you are trying to

maintain weight that might be a good way

and combine that with exercise it'll be

great and and people can more easily

avoid Reds in that way women and for

non-athletes or recreational exercises

sounds like women

if they distribute their calories across

12 hours are less likely to lose their

menstrual cycle yeah so again this is

something that we have to look carefully

they have to be because

we do have the my security and clock app

that many people download and

self-monitor and they share the data for

researchers we won't provide a link to

that by the way it's a great it's a

great tool yeah but once in a while we

do get this input from some women saying

oh I started doing your Timeless routing

and I I'm seeing all these problems and

then I ask them okay so what else are

you doing they're typically improve the

nutrition quality so they're eating only

salad and few and they're trying to

increase the fiber intake and it's

really hard to eat so much of uncooked

food because cooking helps to absorb

more nutrient and then at the same time

they're running five miles every day and

of course all of this combinedly can

lead to Reds like symptom so that's why

12 I think is a good point if you're

combining physical exercise and better

nutrition quality because in mice also

we have seen that if mice are eating

healthy food and they're eating within

10 to 12 hours then they also live

longer than mice that writing healthy

food but Distributing that calorie over

a long period of time and this is um

Rafa di cabbage

finding from NIH he has systematically

done this study with two different types

of diet and in mice and he finds the

same thing that even mice that are

eating within 12 hours they do live

longer than mice that eat randomly even

healthy food

I I recall a recent study I think it was

either published in cell reports or cell

reports medicine forgive me for not

remembering which we'll both of course

cell press journals excellent journals

which explored time-restricted feeding

in the context of low carbohydrate or

non-low carbohydrate diet so it was low

carbohydrate versus low carbohydrate and

time restricted yeah so these all

caloric matched right between groups and

then non low carbohydrate diets those

are more standard uh I think it was

somewhere in the neighborhood of 60 of

calories from complex carbohydrates and

and as I recall the um the greatest

weight loss

remember same calories across groups

folks

um was achieved with low carbohydrate

plus caloric restriction yeah

um and I wondered why all the popular

news venues didn't cover that study um

but that's why I'm bringing it up now I

thought this is really interesting and

um and I'm somebody who's cycled low

carbohydrate diet

um before I find it hard to sleep after

about three or four days of being on a

low starch yeah diet just personally I

so I like to eat some starches yeah

especially if exercising intensely or

working intensely that's just a little

editorial there that

um but look I know many people who do

just feel better on a low carbohydrate

diet but what do you think of those data

because it speaks to the idea that okay

it's not just the total number of

calories it's not just the quality of

those calories

it's the timing of those calories and

maybe carbohydrate restriction in

conjunction with

time restricted feeding might be the

best path for people who are looking to

lose weight

no I I totally agree that when it comes

to nutrition quality quantity and timing

all these three matter nearly 40 percent

of people who maintain healthy body

weight because sixty percent are

overweight and rupees 40 percent of

maintaining healthy body weight and out

of those 40 I would say nearly majority

of them

are very aware about how much dieting

and what quality of food they're eating

so you're really an optimist you're

looking at the 40 of the glass that's uh

or should we say not full

there was a pun intended but the um no

it's a very interesting way of looking

at rather than saying you know why or 60

of Americans obese uh saying why are 40

not obese that's a very interesting way

to look at it yeah I mean um

subconsciously we're always making the

decision inside no means I'm sure that

you are not going and eating um

cheeseburger every day because

um you want to improve yeah right no

yeah exactly I wouldn't feel good yeah I

enjoy a cheeseburger now and again but I

um no not certainly not this stage or

any stage of my life I think that

um

I think people

actually you think the pandemic had a

lot to do with this I think that people

started to take a look at what they were

doing to support or not support their

health generally yeah I know people

gained a lot of weight during the

pandemic other people got really into

fitness I've seen some colleagues but

you've always maintained

um you've always been in good shape

actually the first time I've seen you in

a while you've seem to have aged

backwards so you are a poster uh for

your own um ideas and hypotheses about

time restricted feeding but but I um I

noticed that during the pandemic a

number of people emerged from the

pandemic in better shape other people in

much worse shape it seemed like it was a

it was like a bimodal distribution there

yeah

um

so yeah I get the sense that starting

and stopping eating at more or less the

same time each day even if caloric

restriction is not the main focus yeah

has additional benefits

um

can we talk about some of those benefits

as they relate to the other things that

impact health so for instance if you're

starting and stopping eating at more or

less the same times each day are you

sleeping better are you getting more

predictable

uh shifts in alertness and sleepiness

like can you predict when you'll feel

good enough to exercise yeah maybe we

could talk about that because you of

course

um are well known for time restricted

feeding and the science around that but

also other things as well

um not the least of which is circadian

biology generally so I always think of

the main timekeepers for our system

being feeding light

activity and social connection did I

miss maybe temp and temperature yeah

yeah so how do these combine with one

another and using timing that we begin

and stop feeding is kind of an anchor

Point can we explore that a little bit

yeah so you know we got into this

um beginning and end and then we

you asked for the calorie how much

calorie will break the fast

um

one thing that I want the listeners and

viewers to

bring back to this timing of when wait

when you're breaking the fast because we

equate Health with weight body weight

and

that's when you know we are talking

about nutrition quality and quantity

because both of them have impact

so now let's think about mental health

because a lot of people

do struggle with mental health they have

anxiety or depression

and also

um it's a gut health because there are a

lot of people who also have acid reflux

or heartburn

and we know that acid reflux or

heartburn can be exacerbated by caffeine

intake in empty stomach

those who have acid reflux of heartburn

they're prone to that then having black

coffee in the morning

before any food

um Can upset their stomach so that's why

in those cases it's very clearly that

caffeine for them becomes the trigger

and that's something the food is

supposed to come and then the stomach is

not seeing the food so it's overreacting

producing excess acid and that comes up

to the esophagus and that's what they're

experiencing

so if people have that kind of condition

then maybe they should consider when

they drink their first coffee is

breaking their

overall fast or kind of putting them

putting their health at risk for acid

reflux

the other thing is people who have

anxiety panic attack we know that

caffeine can judge you up especially on

an empty stomach especially on an empty

stomach so for them again

caffeine can be a trigger so that's why

I want to kind of differentiate that

there is this mental health and other

aspects of health and these are two

clear examples where anxiety panic

attack related to brain health

or acid reflux related to our gut health

in those cases

when we consume that caffeine in the

morning can affect so do you avoid

caffeine in the morning no actually here

is the interesting history about

caffeine and this is something I did not

know and I was once invited to this

history of nighttime activity and maybe

we can take a little bit of detour and

talk about night time activity because

that fascinates me as a circadian

biologist

because over the last 200 000 years

means we assume that humans Homo sapiens

evolved 200 000 years ago so we have

been as a species we have been living on

this planet for 200 000 years

and only in the last

you can say a couple of thousand or five

thousand years when we came to control

fire or maybe you can even go back to

100 000 years there is some debate

um so then the question is well

when you control fire and we light it up

the fire

and we could light up whenever we wanted

we can add Fuel and we can stop the fire

when we don't want it

that's the key

ability in humans that differentiates

them from all the other spaces

no other species we can always say yes

there are signs of this intelligent

decision making for example we know many

crows can make decisions many many

animals they kind of figure out

strategize how to get food but

controlled use of fire is something very

specific to Human

and when we started

um controlling fire fire did not

essentially extend the day

because fire created a evening that is

very different from what people did

during the day

and what people used to do during day

they worked a lot means Gathering food

was almost everything that we did

and so in the evening after the after

the after we brought food mostly tubers

or maybe lentils to cook or once in a

while animals so that we can we could

barbecue

um all of these things happen around

Fire and Fire was so expensive that it

was mostly communal fire so if you go

back to for example Maasai and all this

and such sorry

populations that have no access to

electricity and are still living kind of

that historical life

fire is a communal event and they sat

around the cooked food and then what

happened

they did not talk about work they talked

about

um culture they told the sang the danced

they strategize

um that's how politics started

philosophy started science started all

of this things that are very unique to

human civilization started around

fireside chat

so

um in that way if we think about it we

are still doing fireside chat the only

thing is we have the microwave and the

television or social media so now we

chat with our thumbs right so it's still

so we are hooked to that evening

activity because that's when

we are completely free from the pressure

of the work and we want to express

ourselves that's our independent kind so

that's why

most people find it very difficult to do

time resulting and stop eating at six

o'clock because it's in Grand in our in

our even DNA that we want to eat and

socialize in the evening

so now let's fast forward and see what

is the roll of coffee in this and if you

look at Coffee consumption particularly

Cafe where people can come and have

little bit of coffee and socialize it

also started as an evening activity and

this is an

um now we can go back to Istanbul

because that's one place where Coffee

Cafe is started in mid 16th century so

we are talking about 15 40 to 1570

um and that's when uh

I'm sorry I'm forgetting the name of

historians who actually invited me and

uh okay his name is

I must be butchering the name but I'll

try to provide the spelling and the

wonderful thing about social media is

somebody will tell us on YouTube the

proper pronunciation so it's a great

opportunity if you know the proper

pronunciation please put it in the

comments on YouTube I'm actually I'm

even checking right now in my endnote

library it's not picking up that that's

right we'll provide a link yeah so what

happened was

um so coffee was introduced and

um people came and drank coffee and

talked about politics at night at night

at evening and it actually started with

with Sufi branch of Islam because they

are the ones who uh consumed coffee in

the evening and this is the branch of

Islam where they actually sing and dance

and all that happened in the evening

so singing dancing

by the stupid and then here in Istanbul

people started congregating and having

um talk about politics

but then around the same time

um some you know

in Turkey there was a good sizable

number of Muslims who have to do five

prayers a day number of prayers at set

time the first prayer is very early in

the morning

and then they figured out that if they

wake up and immediately have coffee then

they can stay awake for the first prayer

and in that way they felt pretty good

and they woke up I said that's how it

started as a morning drink to stay awake

and kind of get get on with the day

but what happened was I don't know

whether you have ever tried Turkish

coffee it's very thick

yeah a few years ago right before the

pandemic 2019 I traveled to Turkey is

first of all the food is amazing the

coffee is indeed very very thick yeah

and

I have a pretty high caffeine tolerance

yeah

um from drinking so much coffee in yerba

mate over the years and still do I

really enjoy it but um yeah it's it's

very intense and so what you're saying

is that

um

coffee intake started as a way to extend

into the night the ability to extend

into the night at all was because of the

ability to harness fire and then coffee

stimulatory properties were

leverage toward morning

which is essentially like the way I

think about it we did an episode on

caffeine and some uh someone else

Michael Paul and not I described it this

way that you're sort of taking a loan

out on your energy bank account with

coffee you're suppressing the adenosine

system the density makes you sleepy but

that adenosine system will kick in later

so you're you're it's a credit card of

sorts with an interest right right and

the interest being

um an energetic lag that you're going to

experience in the afternoon yeah but

what happened was with the strong coffee

um that gave heartburn and acid reflux

to a lot of people

so then

they started eating something with

coffee and that's how the culture of

breakfast started in Turkey ah so coffee

actually led to the development of

breakfast not the other way around and

that uh yeah so that's very heartening

uh no again no pun intended uh for the

uh the caffeine lovers Among Us uh which

I count myself one of those so

essentially the food before coffee

became breakfast so you kind of

give something to your to your stomach

so it's busy digesting that and then

when the coffee comes in it's not

reacting to coffee and creating

um acid reflux so it wasn't this

fascinating so it wasn't that breakfast

is necessary on its own it was

essentially a buffer against the gastric

distress caused by caffeine at least in

that culture when in that context

um we cannot say that whether the same

thing happened in all over the world

where coffee is not consumed but still

people eat something in the morning you

said you start your um first meal uh of

the day at around eight what time do you

wake up I wake up around six if I

started to six what time do you have

your first caffeine no actually I have

so that's why I brought up this story

because I have coffee after my breakfast

fantastic I'm a big proponent of

delaying caffeine intake for a few hours

after waking for other reasons that my

listeners have heard me talk about

endlessly so I won't bother with that

now but I think um

allowing the suffice to say that

allowing some of the natural waking up

signals to occur and using light to kind

of clear away and adenosine to further

extend an activity is better than using

a stimulant but until a few hours later

this is fascinating because I've never

thought about the link between extension

into the night socialization or

socializing rather feeding and caffeine

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I'm kind of

um speaking what many other researchers

have found and this this particularly

this fireside chat I'm forgetting again

the name of the scientist I think is

from University of Washington Seattle

she went to Africa and kind of recorded

what people are talking of course you

could not understand what they were

talking Twitter and whether or not

Tesla's stock is going up of course no

no just just kidding folks and then came

back and tried to translate and then

figured out that what they're talking

during daytime and in the evening were

very different so

um so so

uh what are they talking about at night

so exactly so this is like they're

talking about matchmaking and talking

about politics and strategizing to

gather food or or

even singing and dancing uh so this is

um if you think if we think about it how

we manage

sunset

to our bedtime

what we do between Sunset and bedtime

affects most of our health

I'm going to think about that for a

moment I totally agree

um and by the way I'm a huge

believer and and I'm in living in great

hope for the idea that

right now I do think that scientists

understand a lot more about the

different stages of sleep slow wave

sleep REM sleep Etc then we do active

waking States like we talk about being

focused or being alert but that's not

those aren't scientific terms as we know

but I do

believe and I've noticed a distinct

difference between the first

eight hours of the day in terms of

cognition and we know that the

catecholamines are at much higher levels

plus court is also dopamine cortisol

epinephrine all of that is really at

much higher levels than in the later

evening

and so this evening time it all it's

certainly in the context of mental

health we know that morning and evening

we are basically different creatures

yeah yeah

so that's why I think in the evening if

you think about it um

again this is uh again another set of

research from

um my good friend Horacio who the

Iglesias yeah oh yeah yeah I'm a big fan

of horacio's another he's a fellow

Argentine so occasionally we riff about

things related to that but he's a

wonderful biologist are you guys

collaborating yeah his kind of uh I say

he's very humble and it's a low profile

but he does amazing amazing research

totally agree he does research that um

we want to know but nobody is ready to

do it because field research is very

difficult to go to the Wilderness or go

to the places where there is no

electricity and then record

um when these people are eating sleeping

or in this case activity exposure to

light that's what Horacio has done and

uh it was this active watch which is

kind of a modern

activity tracker

um but it's a little bit more refined

because it also collects light

information

what I found was most of these

Argentinian Towers who have no access to

electricity

they consistently go to bed somewhere

between three to three and a half hours

after Sunset so this is very important

because we always think that

um our ancestors when they didn't have

electricity as soon as the sun went down

they just went to sleep no

the fire extended the evening so they

were staying awake for three to four

hours

kind of

um you know

decompressing themselves that we say and

then doing all these activities cooking

sharing meals and then they would go to

sleep

and if you look at the slip onset

variability it was very small like

they're going to bed almost within 15 to

30 minutes standard deviation so no

night owls versus morning people exactly

so we'll get to that none of this this

uh I get attacked by for many reasons it

just goes with the business I'm in of

being public facing these days but every

time I talk about viewing sunrise or low

angle sunlight you know getting some

sunlight earlier someone says well I'm a

night owl and they just it's almost like

a a protest of trying to protect

identity it's become this ideological I

I identity related thing I'm a night owl

I'm a morning person and I'm not but

you're telling me that in these cultures

where there is intellectricity but there

is fire people are going to sleep within

all of them within about 15 minutes of

one another yeah so there is no such

thing as a night owl or a morning person

in the context I still actually I asked

him pointedly because uh uh and then he

said no he has not sinned and says

dragged hundreds of people and if we ask

there are many many sleep researchers or

at least the public facing sleep

Physicians or experts they will say yeah

we can say one third of people a night

hour one third of morning and then one

third are in between but yeah they call

them like Bears wolves and you know and

I'm not being disparaging of that idea I

think people really do feel as it as if

they Orient towards one pattern or

another when I was an undergrad student

I never went to bed before midnight and

actually midnight was my going to

bedtime exactly like 11 45 I'll try to

get ready to hit build and then by 12

I'm in bed and I used to get up at six

six fifteen that's a pretty short sleep

with an alarm of course and but then day

time I used to take 45 minutes to one

hour nap and that was regular

like even if uh whenever I got time of

course in college you know you don't

have the whole debt unlike in high

school you don't have opportunity to nap

but in college you can I might have been

one of those kids with this hoodie on

napping on the desk but they come around

and they wake you up yeah but in this

case just come back to the dorm and

um after lunch usually I used to take a

nap

so

um then in grad school

I remember I rarely went to bed before 2

am and I could have clearly said that

I'm a night owl and actually I was a

night owl

it was very comfortable staying up so

late I was very productive doing

experiments writing all this um

manuscripts mostly and

but then afterwards when I looked back

in postdoc when I had when we had our

daughter

um then things started changing because

you have to

put the baby to sleep

and then after the baby sleeps it's

almost when you have a baby your life

revolves around the baby so then we have

to dim down the light

there is no caffeine and alcohol

drinking or any other things after the

baby sleeps because we cannot do too

much noise and others so then I realized

that no I'm actually not a night owl and

I became kind of more normal because I

could go to sleep between 10 and 11.

and

um that's how I thought well maybe this

was very unique to me

but what is interesting is

I have another colleague good friend Ken

Wright Jr Colorado at Colorado and he

also had grad students and

um and postdocs like me who strongly

believed that there were night owls

um just like everybody else

and he took Ken took the whole Lab for

camping and when they were camping of

course there is less light and a lot of

physical activity hiking during the day

and they all went to bed between 9 and

10 30 p.m I love that study yeah what

Sachin just described was a study I

think there were two studies uh there

were two yeah and um what's interesting

as I recall is that after going camping

for a weekend where people awake with

this more or less with the sunrise yeah

and go to sleep a few hours after Sunset

yeah their melatonin rhythms and

cortisol rhythms and sleep wake rhythms

persisted on that schedule for several

weeks despite returning to environments

where there was a lot of artificial

lighting which I find amazing that just

a weekend of consistent rising and um

going to bed with the sunrise and sunset

yeah more or less

allowed a reset that was very long

lasting yeah

so

um actually even in Horatio study he

found that almost all the tobas they

wake up around sunrise time and it's

amazing when I look at the standard

deviation it's like so tight

so take that night owl so-called night

owls I also in graduate school I would

work until 2 A.M I loved it I'd blast

music in the lab everyone was at home

pretty much not everyone but there were

the the night crew and then I'd get in

sometime around

get up or sometime around 9 30 10 and

then get in around 11 and it was no

problem because I was going to stay so

very late and then over time I noticed

I've become more locked to a standard

schedule so I think what we're saying is

that the clock can our internal clocks

can shift yeah but this idea that we are

genetically

biased towards one schedule or another

may need revisiting that's what that's

the conclusion I'm taking from this a

couple of aspects one is um you know

some people are genetically so

pre-programmed because the other flip

side is what is called technically

familial Urban sleep Fest syndrome so

these people

um you can give them caffeine or

whatever but they will fall asleep say

at eight o'clock they cannot stay awake

till nine or ten

and since it's a very strong phenotype

in sleep and circadian rhythm field they

are very well studied so in fact Louis

potashek and ingwifu they were the first

one to track one family like this and

then they figured out there was a

mutation in one of the clock genes

period two that clocked in and that

mutation

um allowed the clock to run in a way

that these people went to bed very early

I guess historically

given these Fireside Chats those people

were probably not contributing much to

their political discussion whatever that

was decided after they went to sleep is

what they woke up into that reminds me

because as you were describing the

difference between nighttime discussions

versus morning discussions is there any

theme to what is discussed in the

morning versus in the nighttime where

people just sipping their eating and

sipping their caffeine and just waking

up

um but is there are there any ideas

about what morning discussions really

consistent morning discussions or

daytime discussions are mostly about

um work and like hunting Gathering or

farming all that stuff and even these

days that's what we do we you know you

go to I go to work and it's mostly one

meeting after another and we're talking

about how means if you're in different

communities and we're solving problems

or your students come with questions you

have your TA or the office hours all

these things work related we're not

talking I mean serious philosophy of

unless you are in a philosophy

department and you are talking about

political science

and also we are not singing and dancing

so that's why the evening activity even

these days are very different and

typically the evening activities uh

where we express ourselves

we express who we are we feel like we

are free and

um you know you and I we have this

academic intellectual Freedom we can

talk about our work just like we are

talking now there are a lot of people

who work for even in tech industry they

may be working for Google and all these

big tech companies

they cannot talk about their work to

anybody else it's all secret it's all

secret so just imagine that staying so

they're spending

more than half of the wake-up time at

work

thinking and doing work but they cannot

talk about that work even sometimes to

their own family members

so then what happens for them

a lot of people also do the same thing

like um the person who is going and

baking in a restaurant or cooking or the

person who is taking trust and driving

or nurses and doctors can't talk about

their patients reality yeah yeah and

some people just don't want to talk

about it it's so stressful they don't

want to bring that stress home

so that's why I always say that from

Sunset until we go to bed during that

time we try to find time for ourselves

people say this is me time the me time

is essentially we want to truly Express

who we are or we want to entertain

ourselves because on the Fireside chart

it's not that everybody was a performer

there are also some audience so we

always switch our roles sometimes we are

performing and sometimes we are

observing so that's what happens with me

time I love this so um maybe social

media time should be restricted to just

maybe a small portion of that evening

time because I would hope that people

would also interact socially within in

the room maybe in a constructive way or

maybe you use that for connect with your

family members whom you love or you can

have some productive discussion or

something so it's it's kind of

interesting I think it's extremely

interesting because I think again this

this conversation about time restricted

feeding is really conversation about

circadian rhythm and sleep wake activity

and human evolution right

um so that's why let's go back to this

um uh Night Owl because uh we we kind of

made a comment that maybe it's not

genetic but this is where I'm still

wrapping my head around because you know

these days

there's some J-1 studies where they're

trying to look at night owls to see

whether there are some genetic Lincolns

and you know sometimes we always think

yeah if you take half a million people

of course you'll find some low side

but going back to this idea that are

some people more sensitive to light

so that it's likely that the same level

of light even in the same household

may make some people stay awake late

into the night whereas other people are

more resistant to light so that they can

go to bed early and since light has

become so prevalent these days and this

tobus story that we are talking about or

people going on camping that is we have

removed that light

um so there is some

um evidence that People's Light

sensitivity particularly the iprgc or

this intrinsically photosensitive

retinal ganglion cell or the simple

speakers the blue light sensors in our

eyes

um there seems to be even one log unit

change in sensitivity as measured by

pupil constriction so for some people a

small amount of artificial light at

night could really shift their circadian

clock yeah wake them up essentially and

then for some it manner yeah I'm very

sensitive to light at night yeah

exquisitely sensitive to it oh so then

you are like a teenager yes in many ways

um I've been told this thank you

um yeah I think

um I have actually switched to using a

red night light but I should be clear

not a fancy high cost red light for sake

of any kind of infrared simulation but a

red party light type light and I find

that was based on reading one study that

we covered in an episode on jet lag and

shift work which was that it seems to

reduce the cortisol

releasing properties of light at night

to use redshifted light yeah so I just

use a red light bulb I actually travel

with one if I go to an Airbnb or a hotel

and I switch to red light and I find

that I fall asleep and stay asleep

throughout the night much more

consistently especially in when I'm in

New environments which always makes it

disruptive to sleep

um it's made an enormous difference in

the depth and duration of my sleep and

um because oftentimes Hotel lights you

know in the bathroom you'll turn them on

you're just you're just getting beam and

you're right some people don't seem to

to be bothered by that I I really

struggle with that yeah and in fact in

Tina's uh right after puberty

um there seems to be a I think that's

when the teenagers become more sensitive

sensitive to light uh and it's very it's

well known that the teenage boys and

girls they tend to stay awake late into

the night and they can stay up to 12 mid

past midnight

although they can stay of that lid that

doesn't mean that their sleep schedule

is reduced their body still needs the

same amount of sleep as other teenagers

so that's why they are more likely not

to wake up at 6 30 or 7 when we expect

them to wake up and go to school

um I have a question and I ask every

circadian related biologists that can

come into contact with this and no one

has been able to give me an answer one

way or the other but I grew up hearing

that every hour of sleep before midnight

was of more value or potency than the

hours after midnight and indeed I find

that if I go to sleep at 9 30 or 10 P.M

I can wake up at three or four a.m

feeling pretty fantastic and ready to

lean into the day but if I get the

equivalent number of hours of sleep

starting at midnight I feel like

complete garbage when I wake up after

five six hours so um is there any truth

to the idea that going to sleep Within

three hours of sunset is somehow better

for our circadian timing mechanisms

well um there are a few things one you

said that you are very sensitive to

light so I assume that you also avoid

bright light in the evening as best I

can yeah as best as you could can and

then what is happening is with a sense

of that bright light your melatonin

levels begin to rise so you are prepared

for Sleep

um of course this is something that we

cannot measure because measuring

melatonin in every one hour or 30

minutes

um is very difficult and there is no

consumer fishing product yet

so it's likely that your your body is

preparing very well under this dim light

to fall asleep and when he was trying to

stay awake and go

sleep at midnight then maybe from

Midnight for the first three or four

hours you are sleeping well but then

after that your melatonin level might be

beginning to fall and it's not only

melatonin in your core body temperature

and then your heart rate and everything

is changing to make you awake but the

Sleep debt that you have accumulated is

pushing you to be in bed so there is

this

tension between the Circadian aspect and

your sleep depth and unfortunately you

cannot have good night of restorative

sleep for the second half of the sleep

because of the tension that makes good

sense yeah so that's why

um you know you are not the only one

means there are many people who who

experience that and in fact a lot of

people think that well this may be the

way I sleep maybe I'm not um I am not

designed to sleep restoratively until

you know I sleep one day just like the

camping trip

and then they realize what it feels like

what you're missing yeah absolutely

um I want to make sure that we talk

about the other aspect of fire which is

uh you had a paper that came out

recently very interesting paper studying

firefighters and time restricted feeding

and firefighters would you share with us

the the general contour and maybe even

some of the specifics of that study

because I think it's very interesting

for for sake of shift workers but for

everybody really to understand these

results yeah so let's go back to shift

workers because

um this also relates to all of us

because

I always say that each of us is a

shipped worker or has lived the life of

a shift worker

um and we have experienced how terrible

difficult it is

um and now let's start with what is the

definition of a shift worker or

um shipped work like lifestyle there is

no Universal definition unfortunately

but there are many European countries

and particularly if you go to

International level organization

um then you'll find some references

different European countries have

slightly different definition which

essentially points to

if you stay awake for two or more hours

during your habitual sleep time and when

they say habitual sleep time they assume

that we are just like you said we are

kind of programmed to slave somewhere

between say 10

pm and then stay in bed and kind of wake

up after 5am

so the idea is if you stay if you're

staying awake for two or more hours

between 10 pm and 5 am

and you are engaged in some activity

whether it's physical activity or

intellectual activity you are not lying

in bed and wondering worrying about

something but actually working so that

defines that's defined as shift work and

you don't have to do it every single day

even if you do it once a week

for 50 weeks

then that itself is enough to disrupt

your physiology and Metabolism Behavior

brain function like a shift worker the

reason is as you discussed

when you change

our external timing queue so in this

case when you travel jet lag or or

traveling across three days

three hours of jet lag will take three

days to reset

similarly if you're staying awake for

two hours extra or if you're waking up

two hours before your habitual wake-up

time then we just don't get wake up and

then be engaged in some activity in the

dark most of us unmends unless you are

wearing a infrared goggles

we turn on light and light resets our

clock so in that way

every time we stay up for two or more

hours even for one night then for the

next two nights our clock is kind of

trying to catch up

so in that way for three days

the day of the disruption and then two

days following the disruption

um a clock is trying to catch up with

the outside time so clock our body is

not on time without clock

so that means almost for half of the

week or half of the Year our clock is

trying to catch up so that's the

definition of shift work so now let's

come back to

Department of Labor Statistics um U.S

government

um they have not been tracking what

percentage of people are doing shift

work accurately because there are many

difficulties in tracking too

but it's generally accepted that one in

five working adults is a card carrying

shift worker card carrying shift workers

means they are nurses

doctors

firefighters

um

and Bakers

um truck drivers

and many in the service industry

so that's one in five so twenty percent

of working adults

then if we think about

all the college students just like I was

doing and you must have done

um they're also deadlines grants granted

lines then we are also experiencing

experiencing the lifestyle of a shift

worker because we are delaying sleep

even if you're delaying sleep by two

hours for most of the college students

for five days and then the weekend you

are trying to catch up that's kind of a

security and disruption going on

then you take 1.5 or 1.6 million new

months

um in the US every year so when the

child is born and that mother is a shift

worker and actually that mother is worse

than a shift worker because

um you know you don't know what time of

the night the baby will wake up and how

many times and there is no weekend

in motherhood

so they're also living the life of a

ship worker

um we don't count many food delivery and

Uber drivers Lyft drivers are shift

workers but they many of them we know

that they live so in that way

we think the actual number of people who

are experiencing the life of a shift

worker is somewhere around 50 percent of

the adults population at any given time

so that's why it's also another point

that you might have heard from people

that will say oh I cannot do time

restricting

because my schedule is messed up or I

work in a different way and

um that comes into play

so that's why we thought

um okay so we should try something on

shift worker

another point is although one in five

people are shipped workers they carry

disproportionately heavier burden of

disease because almost all age-related

disease that we can think of whether

it's high blood pressure usually high

blood pressure starts in 40s or 50s

high cholesterol

um gastrointestinal problem in digestion

um chronic

inflammation of the colon and then even

colon cancer in many cases

and then of course diabetes all of these

are disproportionately more prevalent

among ship workers

but then when you think about clinical

trials whether it's a drug

or a lifestyle

often one of the top 10 exclusion Factor

criteria is shift work so people who are

doing shift work we exclude them from

many of these trials one thing is

most Physicians and most scientists even

people who do shift work they know that

they are their body and mind is so

messed up

that often time even medications may not

help them

and so that's why we don't try new

medication why to take the risk when we

know it may not help them

and then when it comes to Lifestyle

intervention whether it's sleep

extension for example we cannot do

because they are supposed to stay awake

and do their job we cannot ask them to

stay asleep at night

and then physical activity and exercise

some people can do but some people are

so tired after all night that they don't

have the energy to do physical activity

and then nutrition again most nutrition

studies involved

the participants to come to the clinic

and get

um one-on-one or one or attend group

sessions

and they cannot come

and they cannot even sometimes come to

the clinic visit

um when people have to take draw blood

and in fact there is another caveat that

just

if suppose I am healthy

perfectly normal blood pressure blood

glucose cholesterol everything is normal

and I live the life of a shift worker

just for five nights that means I'm

sleeping less maybe four or five hours

and even if I don't eat at night time

of course many shift workers also feel

hungry and just for um to keep their

work they eat

um just after five days my blood glucose

level will read almost like I'm

pre-diabetic wow I actually saw a study

in publishing procedures in the National

Academy that showed that even a hundred

Lux dim Light present in the room while

people are sleeping with eyes closed can

lead to disruptions in morning uh blood

glucose levels in directions that are

not good yeah um one night so the the

faint clock in the corner or even a a

night light that's too bright yeah could

be problematic

um by the way folks these effects are

reversible so I whenever I say these

things I we get a lot of comments about

oh my goodness what have I been doing

for years but you know kids with Night

Lights this is an issue yeah um but what

I'm hearing is that one in five people

are

truly shift workers in the classic sense

their jobs require they work at night or

into the night and sleep into the day

but far more people are shift workers by

virtue of the fact that they're Tweeting

or working or watching movies at night

even though it's not work in that

they're not being paid for that time

they are essentially operating like

shift workers if we add those two groups

together would we say it's what uh a

third of Americans I would say half of

America half of America yeah if you take

teenagers because you know high school

students and college students because

again going back to horacio's uh study

because Horatio also collected

activity data from high school students

and college students and we have

replicated that with high school

students and college students in San

Diego so that's Seattle and San Diego

and this study now there are many sleep

researchers that have been collecting

this data

and what we find is

um typically the high school students

they are going to beds around midnight

and college students at least the UCSD

students we found maybe one out of 100

who went to bed before midnight that um

reminds me that Horacio Iglesias just

published this really nice paper

um showing that counter to what we

believe students now this is the

University of Washington in Seattle I

should mention where it's very dark in

the winter

young people see other people in their

20s are staying up later in the winter

months compared to the summer months

yeah which is you know totally

counter-intuitive you think everyone

stays up late in the summer and goes to

bed early in the winter but because of

artificial lighting it's the exact

opposite yeah so and another um it's um

I don't know whether Horacio monitored

it but my other suspicion I'm not saying

whether it's true in Winter we are more

likely to consume more coffee hot

chocolate in the evening and that might

also be delaying

slip onset that makes sense so in that

way again here is another thing which

can be related to policy or practice at

Educational Institute so what happened

during uh kovid was everybody went to

remote learning

um the assignments became digital and

assignments submission became digital

and there are many systems online

systems that came into play

and by default the assignment submission

deadline became midnight

so then now what is happening is I don't

know about Stanford in maybe when you

are giving assignment um one is the

deadline in line typically midnight yeah

so then most of us most students they

will try to cram as much as possible try

to solve as much as possible and submit

at midnight

and it'll be really cool to go back to

your system administrator to see is

there so many frequency plot of

frequency distribution of what time

people are submitting the

um assignment because we know means when

we submit our grant yeah so I mean you

know you hear about the Obesity crisis

the crisis of metabolic disorders not

just in the US but everywhere in the

world I mean it's really striking I

remember going to a keystone meeting

scientific meeting in the early 2000s

and there was a map of the United States

and it showed where the Obesity rates

were over 30 percent in adults and the

entire country basically was lighting up

like crazy now it would be the entire

country but there were these kind of

zones in the middle

um that were almost devoid of of uh

obesity Colorado namely Idaho at that

time those are now also Fallen Under the

Umbrella of rampant obesity and you and

everyone is speculating okay is it uh

you know is it seed oils is it

um is it this is it that is it highly

processed foods I'm guessing it's all of

those things including lack of activity

but one has to wonder given everything

we're talking about in terms of

metabolic dysfunction late shifted

eating all these issues with late

shifted eating and staying up late with

artificial lighting whether or not that

could be one of the major factors in the

so-called obesity crisis it's likely you

know we always say Freshman 15 that's

right because this is a gaining 15

pounds in their freshman year in college

and

um this is where I think as executor

professors um it'll be interesting to go

back and see what can we do because

another thing that's also becoming more

and more common for example I I give a

security under the class means I just

give two lectures and I remember when I

started 15 17 years ago that lecture

used to be around 1 30 p.m or 2 p.m in

the afternoon and it's a two and a half

hour lecture so it's done by five

and for the last um before the pandemic

I realized that they changed the timing

now the lecture was starting at 7 pm so

I was finishing by 9 9 30 pm and these

kids they had to go and eat after 9 30.

studies socialize find aside chat

fireside chat and then to express

themselves like to feel free from

assignments what are they going to do

that after they submit the assignment

then they're going to do that

so that's why we have to go back and

revisit this issue say okay so for

adults for most of us who are working a

day job

our deadline is 5 PM in most cases

right men's at least an University

system the person who is submitting the

grant or who is doing taking care of my

IRB or I cook they are all living at

five o'clock so for me everything has to

end by five I think for most people out

there so this the race is a kind of

macroscopic question which is maybe it's

not so much about restricting the

feeding window but maybe it's about

feeding mostly in and being active

mostly in the early part of the day I

mean you know I could imagine a Time

three four years from now when it's

about when waking up early and going to

bed within three hours of sunset is the

protocol which harnesses all other

protocols right you're going to exercise

you're going to do it in that time

you're going to eat you're going to do

it in that time you're going to

socialize you're going to do it in that

time and in doing so you're also

avoiding a lot of the issues related to

disrupted sleep so that's why all these

things I just said Timeless repeating is

just one aspect of the security and

health and these are all interconnected

and going back to the comment about

um within three hours of sunset yes um

that's good but then what happens in say

Toronto or Vancouver in winter time I

guess they're going to bed very very

early but also waking up very very early

yeah you know one of the things that I

hear all the time because I'm always

beating on the drum of getting morning

sunlight even if through Cloud covers

people say there's no sun here this time

of year and I I forgive me but there is

Sun unless you live in a cave their son

is just coming through cloud cover no

matter where you live in the world their

son yeah unless you live in a cave of

course so um I want to make sure that uh

we didn't Overlook what was the major

conclusion of the firefighters

so the reason why we did this study was

as I said there are a lot of us who are

living the lifestyle of firefighters or

shipped workers and shipped workers are

excluded from studies so that means

whatever we are learning about a

lifestyle or even medications that may

be beneficial for people who actually

have a normal schedule

um but not for people who have a

disrupted schedule and if you look up

um clinicaltrial.gov there are more than

400 000 studies listed and if you search

how many studies are on shift workers

it's less than a thousand

and then if you ask most of them are to

see what is wrong with shipped workers

like that's how we know that shift work

increases our risk for metabolic disease

cancer and even some aspects of dementia

but if you ask how many studies are done

to improve the health of shift work

alone and that's less than 50 means I

mean so I have to go back and check the

actual number but it's less than 50. wow

so that's why

um we got super excited we thought

um from circadian rhythm perspective

that's something to address

so this study

again this kind of study is only

possible because I'm at Salk and we are

affiliated with UCSD and

um I can work with UCSD Physicians to do

this study so I collaborate with Dr Pam

tobb who is the director of cardiac

rehab center in UCSD and Pam has many

firefighters as her patients and we both

know that the number one cause for death

and disability on work for firefighters

is not fighting fire but just getting

heart attack and stroke uh so they have

a very high incidence of heart attack

and stroke and they're also highly prone

to different kinds of cancer and it may

be difficult to ascribe cancer to

disruption security and disruption

because they're also exposed to a lot of

toxins anytime Fire Burns that smell of

fire is essentially smell of

carcinogens and they're breathing even

if they have the

um hood on and respirator they're still

good so the idea was very simple we know

that firefighters nearly

70 percent of firefighters in the U.S

full-time firefighters because there are

volunteer firefighters and then

full-time firefighters the full-time

firefighters 70 of them work 24 hours

shift

so for example in San Diego they come in

at their shift is from 8 AM to 8 am the

next day and they do at least in San

Diego they do one day on one day off on

off four cycles and then four days off

and but in some fire departments they

actually do 48-hour shift so they come

for two days two days off two days two

days off and then four or five days

thank you firefighters yeah I mean

um so then the idea was okay so we'll

screen firefighters and then find

firefighters who are

metabolically unhealthy and then we'll

see whether they can actually follow 10

hours time restricted eating because

the point is if firefighters can follow

it then everybody else will pay for us

with all that stress if they can

and this is again where I should also

acknowledge the San Diego fire and

rescue Department because without their

health we could not have even submitted

the grant and at that time David picon

who is the health and wellness battalion

chief he's the one who actually

approached us

um because he is very careful he knew

that the job that they do

makes them weaker and long term and can

kill them in long term

so he was always looking for new

Solutions so he approached us and then

we said this is the idea he said well I

love this idea because

we are not asking them to sleep more or

we are not going to cut down their over

time or shift or change the work

schedule the only thing we'll be doing

is ask them to eat within 10 hours

and hopefully we can do this so

consistently between the days that

they're working and not working yes so

that means if they're from 8 A.M to 8

A.M working then the next day then they

go home then they're going to eat on the

same schedule they did when they were at

the fire Firehouse yeah but while at

home so they're not allowing themselves

to to deviate from that yeah so we we

thought whether they can do it or not

because the number one goal or the

primary outcome in this clinical trial

was feasibility can they do it

and then second was if they do it then

what happens to their blood sugar and

weight and all this other stuff

and then we started the study and we hit

the next hurdle and that is

um

you know firefighters are very very

tight-knit community and they want to

make sure that you understand their

culture and the best way to understand

their culture is to live the life of a

firefighter

so Emily Manoogian who is the first

author see and then we had Adina

jadurian who is now in med school she

was a research coordinator at that time

they volunteered they said okay we'll go

to the

busiest fire station in San Diego

and will live the life of a firefighter

and the San Diego fire and rescue and

the city they all agreed they reported

for duty at 7 30 in the morning they

were assigned a

bed in the station because all fire

stations do have some beds for

firefighters to rest and they have a

sign bed so they've assigned a bet

um yeah so every time a 911 call chem

and if that fire station in that fire

station that fire engine was called then

just like other firefighters they had to

run get into the gears just issues and

um a jacket and a helmet and getting the

seat and attend the call of course they

won't go to this side they just get out

of the truck wait there

then come back

so in that 24 hours MLA got 10 calls at

night that she had to run to but there

are more than 10 times the

um they got the nine one every time the

911 call came then there is a bit that

goes out

all firefighters were sleeping or

resting they would get up or if they're

doing something they'll look up to see

which engine is called and interesting

so it's not just the ones that go out

it's everyone gets woken up everyone

gets woken up so that means in a night

typical night they're waking up

um 10 15 20 times sometimes so they're

almost like

um you know new months are like

firefighters because they don't have any

idea what time the baby will cry and for

what reason also they don't know so

similarly it's five so that's what Emily

did and then next morning once you came

back she was like no it's practical seem

easy

yeah so so then we did the study and we

essentially assigned uh all the

firefighters we recruited 155 Fighters

we assigned half of them to

Mediterranean diet because you cannot do

any harm you have to give them something

good so that's another thing they said

no we want something that we know works

for firefighters and there was a

Mediterranean diet study so

everybody was supposed to follow

Mediterranean diet and then have nearly

75 of them were supposed to eat within

10 hours

we did not fix the 10 hours because we

said

um you pick your own 10 hours that you

can stick to but it has to be consistent

from day to day so if you start eating

at 9am you finish it not at uh you know

at seven PM pm and then try to be yeah

okay try to try to be consistent because

we said yes we understand that there

will be some things and you can take

maybe half an hour here and there and

we'll see how many times you can do it

and

um

what is interesting about although they

were all doing 24 hour shift

more or less chose to begin eating

somewhere between 8 AM and 11 am

and they

did not skip any meal they had their

first meal or what we call breakfast but

it was several hours after waking up

because they are waking up at five or

six and the driving to come to work at 7

30 or 8 and they're eating the first

meal say between 8 and 11. and then the

finished meal 10 hours later

and what we found is more or less

most of them could stick to doing this

at least five days out of seven days

um and then at the end of the study when

we look at their health parameters

one thing as I said

we recruited everybody who can so that

means nearly

one in three firefighters were

completely healthy they had no sign of

any

um any illness no high blood pressure

high blood sugar or high cholesterol

depression or anything

so since we have one third of the

population who are already healthy and

then everybody has slightly different

conditions some have high blood pressure

but they don't have high blood glucose

somebody has high blood glucose but not

high blood pressure

so it was kind of heterogeneous so

we did not see big difference in weight

loss or any wet change between these two

groups another thing is firefighters

actually run almost eight to nine miles

when they're at the job because that's

part of their

exercise routine

but then one thing that changed

significantly in the time restorating

group was what we call bldl particle

size and particle number because this is

something that we know this very low

density lipoprotein these are

atherogenic and if we can manage them

much better and we reduce the risk for

atherosclerosis so that's one parameter

that changed in the time restricting

group even when you combine all healthy

unhealthy everybody

now if we take firefighters who are

beginning with high blood pressure

then we saw a significant reduction in

that systolic as well as diastolic blood

pressure

and the change in blood pressure of

course we don't claim that in the

manuscript but when we talk about it

some physician would get up and say wow

that looks like almost there on a blood

pressure lowering drug so the extent of

blood pressure lowering is equivalent to

somebody taking a antihypertensive drug

amazing yeah and then those who started

with high blood sugar of course we

didn't have too many type 2 diabetic but

there were a few few pre-diabetic and

they could better manage their blood

glucose and this is interesting because

once

shift workers

become pre-diabetic or diabetic they

have more difficulty managing their

blood sugar than non-shipped workers

because the work schedule itself will

mess them up too much even if they're on

many medications they have difficulty

that's fascinating and I I'm really glad

that you explained the study in such

detail because I would have thought you

know from reading the abstract and I did

look at the data but if someone were to

look at the abstract they'd say oh

firefighters so they're waking up in the

middle of the night and they're you know

throwing on their gear and going out to

calls and doing but if I understand

correctly all firefighters are being

woken up by the signal which makes the

firefighter population a bit more

similar to the more standard population

who's waking up in the middle of the

night to use the bathroom getting on

social media for a couple of minutes or

flipping on the lights I mean it's maybe

not as severe as what firefighters are

doing

um but we know there are blood sugar

regulation issues related to those

multiple middle of the night wakings

especially if people are then staring at

screens yeah

um so I think it's really important that

people were able to hear about the the

deeper Contours of the study uh I mean

this result of regulating blood sugar

better is really powerful I get asked

all the time you know I've got a new kid

or I'm a shift worker how can I do this

morning sunlight viewing

um what I'm hearing is that keeping a

regular meal schedule every day

at least five five out of seven or as

close to every day it's sort of like

sleep I always say try and get a really

great night's sleep 80 or more of the

nights of your life and on the other 20

hopefully it's for fun reasons a great

party or something like that or a

celebration of some sort

um

that seems to me a great Anchor Point

when one can't reliably control their

sleep wake cycle does that mean that if

somebody is coming off of shift work and

they're very very tired that they would

be better off staying awake and eating

than sleeping well it's uh yeah so this

is where we get into nuances so here the

firefighters are 24-hour shipped workers

so that means and they have been working

this shift for a very long time so they

have figured out and one thing is yes

firefighters are different from nurses

and healthcare workers who have to work

throughout the night and they're staying

awake throughout the night whereas

firefighters they get opportunity to

sleep then even with their

pen calls they actually have opportunity

to come back and go to sleep and in fact

when Emily and Adina they were in the

fastest and what they observed was

firefighters after they after attending

a call they are not coming back and

playing cards or trying to watch the

news or get the score they know they

will just go back and lie in the bed and

switch off the light so whenever they

got any opportunity to sleep they would

try to sleep so in that way

their sleep debt and sleep pressure

during day time is not as strong as a

night shift nurse

or a truck driver who is driving all

night because they have they're staying

awake throughout the night so when

people say yes you found this and can

you extend it to other shift workers my

answer is no we have to go back and

figure out that's why we went to this

station and figured out what would work

for them

if I have to go and do this for some

nurses maybe even I will go or our staff

will go and figure out what is the work

schedule what happens do they have

opportunity to eat do they have

opportunity to even take five minutes

break what do they do during break and

all of these things come into play but

here another thing is um

I always said that in other time receipt

reading paper we see change in nutrition

quality and quantity but here we also

saw that somehow both groups

inadvertently the

improve the nutrition quality because

everybody was told to eat Mediterranean

diet they increase their fruits and

vegetables and olive oil and text

slightly

and when they had to stop eating early

they also reduced the alcohol intake

and this is very significant because

many shift workers just to cope with the

shift work that tend to depend on

alcohol at night and caffeine in the

morning so they begin their day with

caffeine and end with alcohol

and now we can relate that many normal

people who are not doing shift work we

also more or less begin our day with

caffeine and many of us and with alcohol

and then when they reduce that 18 to 10

hours and then we saw a significant

reduction in alcohol intake in the time

restrating group but not in the standard

of care or Mediterranean diet group I

certainly support that we did an episode

on alcohol and I was

shocked when I researched that to learn

that zero to two drinks per week is

essentially the threshold Beyond which

you start seeing health

deficits in particular Cancers and

metabolic disruption sleep disruption

and increased anxiety when people aren't

under the influence of alcohol I mean

it's a pretty incredible how alcohol has

kind of escaped as the the opposite of

caffeine and therefore

um not a health hazard it's and here I'm

somebody I have a drink every once in a

while no big deal for me I can have it

or not have it but it's just striking

how

um alcohol despite extensive data that

it can really disrupt Health even at

three drinks per week yeah is um is just

avidly consumed as if it was kind of

like food or caffeine it's really

incredible

um I I want to make sure that I Circle

back to something you mentioned earlier

because I know they're going to be a

number of people that asked this if I

recall you said that provided that the

feeding window is not shorter than eight

hours that men women and children can

use time restricted feeding

um yeah so what I say is um

12 hours 12 excuse me 12 hours thank you

for that clarifying um because we did a

study that was published in 2015 and

again

um behind many of our studies there is a

story

so we are publishing all these Mouse

stories and then I would go to

conferences and and of course the

um some some people would give me a look

saying well you must be doing something

wrong we

this just breaks the

X law of thermodynamics because how come

they're eating the same number of

calories and not getting wet and of

course by that time we figured out that

at least in Mouse

Timeless repeating also changes the gut

microbiome in a way that the mice may be

popping out a little bit more fat than

sugar than absorbing them so one thing

that happens in time restricting at

least in mice is the liver cholesterol

metabolism to bile acid and bile acids

excretion in the gut changes because

they gut microbiome changes so this is a

very nice study when Amir jarinpar was

in the lab now he has his own lab in

UCSD and he meticulously did that and we

we even did bomb calorimetry from the

poop and metabolomics from the poop and

then we figured out that they excrete

some some calories and then that brown

fat activity goes up so there may be

burning some of these extra calories so

they're more thermogenic more

thermogenic but anyway so you know one

nice thing awesome thing about Salk is

if they say that your science is going

well then they will find ways to help

you and this is terrific yeah and um

this is when

Bill Brody was our president he was the

president of um

um Hopkins for 12 years and then he was

president

and

um that time he had started this

Innovation grant program which was

funded by arvind Jacob uh Arun is the

founder of Qualcomm it was also a

faculty at UCSD so he understand there

are very few

Tech leaders who actually spent some

time in Academia so he understood the

pain of getting grant money when you

have some interesting idea or test some

ideas so yeah no knock on the NIH but

I'll do it anyway because I sit on study

section for the NIH I mean NIH wants to

see proposals for things that are so

certain to work that they're mostly done

and so really groundbreaking work can

happen and does happen with NIH funding

but more often than not is it is the

generosity of philanthropists like Irwin

Jacobs and other people that allow the

really pioneering

um the new stuff the cool stuff yeah the

groundbreaking stuff the stuff that

really no I'm not gonna say really

matters it all matters it's all

important no it matters but uh you know

it's high risk and

um NIH when San is is not just

government is not making money from thin

air means it's taxpayers money so there

is a little bit responsibility or

conservative that okay so we should not

waste tracks first money on buying this

guy

we're not talking about politically

conservative we're talking about

um scientifically conservative to be so

careful what language nowadays pretty

soon we're just gonna sit and stare at

one another at the microphones to stay

safe

um so so that's interesting so they so

that's why I started this and then what

we did was we um I had an awesome grad

student and we got this funding from

Arwin and also there are some

any philanthropy matters so actually the

way we say is yes if you give me 50

bucks then that 50 bucks towards goes

towards buying the gloves and a friend

of tubes for one postdoc for maybe seven

days so it's so true I think a lot of

people don't realize that 99 of

laboratory scientists just they they

don't make any money off their

discoveries and even if there is a

patentable discovery typically the The

Divide between the institution and the

company that will eventually put that to

Market is so slim in favor of the the

others involved that you know scientists

really do this as a work of passion

labor labor of love so so we we came up

with this app my security and clock at

that time and we took some

um you know lessons from Tech leaders um

particularly from Amazon one click

checkout

um because we thought most nutrition

apps actually ask people to detailed

describe or they add go to their food

library and then person size they said

okay so we'll just shortcut all of that

I just ask people to take a picture of

the food open the app one click take a

picture second click and press save

third click and when they said the

picture actually came to our server did

not stay on their phone

and we asked 156 people who are not

shipped workers just regular worker or

Homemakers to be part of the study

no student was allowed to be part of the

study because we know that there's a

lifestyle is like ship workers and we

monitor for three weeks and

so here is some nuances and I want

people to understand

when somebody is starting to eat at say

7 A.M and

since the recording everything we've

we've got every single thing even if

they ate half a cookie they had to take

a picture and they actually took picture

because it's not it becomes second

nature after three or four days that

every time they add something even if

there is a glass of water they actually

take a picture because we asked them

take picture of everything we'll figure

out what it is

what is surprising what we found

the median uh so the median number of

times people eat within a day 24 hours a

day is actually seven so it's not

it's not that we are eating three times

a day we actually snack a little bit

seven times per day seven times and

there are 10 percent of people the top

decile was eating

12 times a day wow

um and it makes sense in retrospect

sometimes maybe I'll fall into that

seven or eight before

um I did this study because you know

getting up having coffee with cream and

sugar is one and then I ate my breakfast

that's two then I came to the love and I

found that cookie that's three

I went to a meeting and there was some

cookie and something else that's another

one and lunch and then afternoon

somebody asked me to go out and have a

meeting and so if you think about it

it's very normal that we can go seven to

eight times ten times

but then

if we look at what time say I start

breakfast and as I said and we see that

in many people they'll start at seven

o'clock Monday then 7 30 another day

then 8 15 another day or they go back to

6 a.m because they had to get up early

and go to work so we took all this food

data from three weeks and then asked

what is the time when your body's system

is expecting it to eat because it's kind

of averages Southeast kind of thinking

okay

maybe for you if you're eating breakfast

at say somewhere between 6 AM 7 30 7 45

I eat it maybe you are expecting food

around seven o'clock let's forget about

6 15 that's an outlier and then

similarly at the end of the day

if somebody is eating finishing the last

bite or the night Gap whatever you call

it

say one day at 9 pm 9 30 p.m 10 11 12 30

or 1. Let's ignore that 1 and 12 30 but

still we got somewhere between seven to

eleven thirty for that person over three

weeks time so this is how we kind of

figure out what is the likelihood that

your body will encounter food

so when we do that what we found was

nearly 50 percent of our dogs in our

study

ate for 14 hours 45 minutes that window

when your body is expecting food

so it's easy to say that 50 of adults

are eating within 15 hours or longer

wow and and quite frequently throughout

quite frequently too and then

if we ask what fraction of our adults

were actually eating the conventional

within 12 hours three meals a day or

something like that it was 10 percent

so this snacking has gone up

dramatically however you wanted to find

snacking the frequency of food intake

throughout the day and outside this

breakfast lunch and dinner there are all

these small snacks here and there and

also for a lot of people the dinner is

delayed and we went back and looked at

okay so what kind of food people are

eating late at night and all that stuff

and what came out interesting which is

very counterintuitive is people who

prepare their own dinner

they're more likely to eat later at

night

because they're coming home and then

they're taking some time to prepare

dinner and then they're sitting down and

eating or maybe they're eating next to

the computer whatever it is

so it's kind of interesting that came

out

um but coming back to your point that's

why I say that nearly 90 percent of

adults

are eating for more than 12 hours

so that means a lot of people can

there is scope or there is enough head

space to reduce and eat within so as I

said

all of this are interrelated so when you

think about children

most sleep researchers agree that

children and teenagers should sleep

somewhere between 9 to 10 or 11 hours

because young children even five to ten

year old they should sleep nine to ten

hours they're just pumping out growth

hormone and growing growing and then the

teenagers actually the recommendation is

and they should be sleeping nine hours

because

if you take teenagers

take out all the stimulatory inputs to

them and then remove homework assignment

and everything and then let them kind of

equilibriate to their homeostasis what

are likely how many hours they're likely

to sleep

that turns out to be somewhere between

eight and a half to nine and a half

hours

which also means that going back to

sleep

nearly 90 percent of

high school students in this country are

chronically sleep deprived because most

high school students don't get nine

hours of sleep on a regular basis maybe

in the weekend probably because of

devices yeah on iPads and also as I said

this new idea that midnight is your

assignment submission time I'll come

back to that again and again I'm hearing

that again again so teachers take note

it's an issue it's a very interesting

idea as a way to kind of anchor Behavior

earlier in the day yeah learning to in I

mean Public Health

uh is complicated because people are

incentivized by fear but they you know

you get more bees with honey as they say

right you know there's uh incentivizing

people to wake earlier not necessarily

with the sunrise but wake earlier and go

to sleep earlier and eat within an 8 to

12 hour window

um 12 if it's yeah so that's my children

yeah it sounds to me like you know all

these health benefits are what I think

are going to incentivize people more

than for instance this idea that well if

you don't do this you're going to get

Dementia or something right but like

every day people will feel more healthy

and more productive

and so that's why I said that even if

children are supposed to sleep for nine

hours of course they're not eating

during those nine hours

and we're not uh feeding children and

putting them down to slay because you

know their core body temperature will be

high they cannot fall asleep so at least

they should have their last meal one or

two hours before going to bed because

typically

parents feed them and maybe give them a

shower or a butt and then they read the

bedtime story so it's one to two hours

before bedtime they're finishing food

similarly on the other end after they

wake up it's not that we're waking them

up and then feeding them so hopefully

we're not doing that so that's at 12

hours seems to be

Optimum and it's not only I'm saying

that if we put all the health

recommendations together from

pediatrists and then it makes sense

um fascinating I have a question about

structuring meal intake or food intake

um during the eating window

um I have a good friend actually he's um

he's the neurosurgeon at neurolink now

but he came up through Stanford and um

and he has a habit of eating of skipping

one meal per day within a feeding window

so it might be breakfast lunch skip

dinner one day then it might be

breakfast dinner the next day lunch and

dinner the next one so it's not in

keeping with the same start time always

but the end time is either going to be

earlier or there's a gate it's never

later yeah it's never later

um what do you think about that as a

strategy

um you know in many ways it feels like

that fits with the way that a lot of

people's lives run so sometimes for

instance if I'm in a podcast I don't

tend to eat much in the middle of the

day because it makes me a little bit

groggy the post perennial dip in energy

so I'll do breakfast well but again at

11 and that's a first that's when I

break my fast 11ish and then dinner

maybe a snack in the middle of the day

but other days it's three meals so does

it matter

um overall as long as

um one isn't allowing the start time and

the ending time to drift out is it okay

if you go from 12 hours to ten to eight

eight ten four twelve as long as you

don't exceed that the the brackets are

you okay uh so this is where the

Circadian aspect come in because if

you're going

um if you're moving that breakfast time

or dinner time three four hours

essentially

causing maybe a metabolic jet lag you

know in short term in weeks months or

maybe even few years you may not see any

change

um at the same time we don't know what

is the long term consequences one thing

is we always think I'll come back to

this point again and again we think that

a body weight is a marker of Health

or body composition is a marker of

Health it's not always true because as I

said issue drift locks

um filling

um you know having some Pang of

depression or anxiety or LDL like high

LDL a lot of thin people have or low

body fat people have very high LDL yeah

so those are the things that um we don't

connect with our habit and since

security under them and meal timing meal

structure now is a very new

um field

um I think good studies will come out

only in a few years because right now

people are just going back and

retrospectively looking at some Diet

record one day of diet record and trying

to glean too much out of it but I think

hopefully things will improve where

people will become it will become

standard to at least look for one week

of diet record meal time and what

they're eating all that stuff because uh

are now Mouse studies also showing what

a front loading carbohydrate or front

loading fat or protein has benefit over

so I think this studies are starting so

I should not comment whether that's good

or bad no I think it's great to hold off

until then we have you back on to

discuss

um I have a question about

um fasting on the longer term

um and there it's a near Infinite Space

we could explore of two days of fasting

one day I know people that every once in

a while they just decide I'm fasting

they've either been eating too much at

parties or they're not feeling well or

whatever they just decide I'm fasting

for 24 hours and um they'll still

consume water and caffeine but they'll

just fast is there any health benefit or

detriment

um you mentioned the circadian clock

shifting effects but if somebody wakes

up on Sunday and they you know they ate

too much or they feel they ate too much

or they don't like the food they ate on

Saturday they're not really feeling it

and they're just going to fast into

Monday is there any known benefit or

um Health detriment to doing that kind

of thing yeah there's a actually a rich

literature on this complete fast

um an impact in many religions people

practiced complete fast as you were to

cleanse their body and

people have seen that there are benefits

to that so in fact the every other day

eating in Mouse model or even in humans

are also initially some studies were

done there are many health benefits

and right now there are even fasting

clinics in Germany where people check in

and they're under strict supervision and

then they do complete fast or maybe a

small bowl of soup which has 100 200

kilocal and that's all they get to eat

sometimes

two three days four days five days even

they have gone up to three or four weeks

for sake of weight loss is that why from

many different things and

um they come out pretty well healthy of

course they're under supervision make

sure that they're getting macro

micronutrients sorry the micronutrients

vitamins and electrolytes

so those studies are pretty solid people

have observed that and then in fact

there are even idea that fasting this

kind of fasting can have huge impact on

brain and people may come out of

treatment resistant depression or

something but you know so those studies

are very difficult to do they're only

case of one here and there that we hear

once in a while but hopefully in future

we'll see

um whether the depression anxiety the

mental health aspect will benefit from

fasting because now as there is more and

more evidence that there's this gut

brain axis and whether the presence of

food or the microbiome changes in the

gut if they can affect brain then maybe

long-term fasting periodic fasting a few

days of low calorie diet back to back

will be interesting to see how it

impacts brain health

very interesting what are your thoughts

on fat fasting where people try and

limit their blood glucose by only eating

mainly fats mainly healthy typically

they'll eat healthier Fatso of avocados

olive oils and nuts you know and some

animal fats perhaps but

um

as a way to keep blood glucose low and

also time restrict this goes back to the

kind of low carbohydrate

um thing what are your thoughts on that

as as a general strategy for health I

mean it combines sort of two general

themes that are out there I think both

of which are you know data are still

incoming that restricting the feeding

times it can be beneficial as well as

keeping overall blood glucose lower can

be beneficial

yeah I think there is too much uh

emphasis now on blood sugar spiking or

um we don't know

um this kind of eating pattern for

example means we are essentially telling

pancreas that okay it's or the eyelid

cells that produce uh insulin and it's

okay you can take

um take a break go on vacation for you

for a month or two or three months

um my question is it will be interesting

to see what happens to those eyelets

because for example we know that if we

this user unused our muscles that is

muscle atrophy muscles will become

weaker

we don't know whether long-term

consequences of this very low

carbohydrate diet where you are not

essentially engaging the

eyelid cells periodically what is its

impact so if there is no impact maybe

it's okay maybe because

as you know many people who actually

work on ketogenic diet the researchers

themselves they find it very difficult

to stay in true ketogenic diet because

the true ketogenic diet is consuming

less than 10 percent of calories from

carbohydrate and not very many from

protein a lot of people think ketogenic

diet allows them to eat massive amounts

of meat and that's not necessarily the

case just one clarification for people

um uh Sachin was referring to islet

cells of the pancreas which are the ones

that manufacture insulin so the question

is whether or not taking in low levels

of blood glucose by way of a low

carbohydrate diet those islet cells are

going to shut off their production very

interesting I mean the liver is a very

plastic tissue I mean it tends to

um react very dramatically to to

Lifestyle Changes yeah so that's why it

was interesting to see what happens

means we know that even muscle issues

for example people who become bedridden

the loss of muscle mass but when they

come back and exercise they gain it back

so it'll be interesting to see what

happens in these people who are going

through long-term ketogenic diet and of

course once in a while

because of social pressure or something

else if they don't have access to food

or something happens they may consume

some sugar some blood glucose will Spike

but it's not that every spike is bad I

mean the reason why we have insulin is

for good reason to buffer that Spike to

buffer that Spike and also you know

people always say that well if you have

insulin produced or insulin like growth

factor those are really bad and it

should avoid that and I think that's a

little bit extreme and I mean that's the

insulin growth factors involved in

muscle protein synthesis tissue repair

yeah maybe even cognition so yeah yeah

and it also goes back to

as a m tour activation and all that

stuff people get really excited about

how to reduce them to activation

rapamycin and all that stuff so this is

where

um again from circadian point of view

um I ask people to think okay so

two very popular drug like molecules or

drugs that people think will increase

longevity or metformin which

many people agree not all will come to a

consensus that it activates

MP kinase or the sensor and the cells

that sense that your cells are fasting

so metformin kind of activates it so

that it kind of you can say although it

may not be scientifically accurate uh

the

um you know fasting and appeal so it

sort of mimics fasting yeah and the and

the thing I'd lump in there with

metformin is that berberine is kind of

the Poor Man's metformin it's a tree

bark extract that also dramatically

lowers blood glucose yeah yeah and it

mimics kind of that um fasting

and then rapamycin

um also kind of reduces Emptor

activation

and people have shown that

rapamycin and Metformin

can extend

Mouse lifespan and in improve health

okay

so now let's go back to the calorie

restriction study that I mentioned

in calorie restriction people are giving

food as a lump sum and they were

essentially doing time restriction the

mice were doing time restriction

if we think about it

during day time when experimenters are

coming to the bivarium the mice should

be sleeping and fasting

and they should naturally have high

level of MP kinase if they're truly

fasting and they should also have low

level of interactivity because M2

responds to insulin and that should go

off at night

so my suspicion is

um in many of these experiments where

the mice were allowed to eat at Louis

Vuitton even normal standard Char now we

are

we know that as mice get older they

actually consume little bit more food

during day time which is the equivalent

of human night humans nighttime it is

like nighttime eating we know is an

issue I didn't realize that was more of

an issue as people age but yeah so we

don't know but at least in mice because

you know we can put demise in

calorimetry look at every single by

dieting how much they're eating

so I guess it was natural to see that

researchers found that there is some

mtor activity during day time when the

mice were not supposed to have M3

activity because they should be fasting

and since they ate little bit they were

snacking during day time amp kinase

activity was not at its peak

so

giving metformin kind of

mimic that fasting state

and reducing M productivity by drug like

rapamycin also kind of mimics some

aspect of the fasting state

so my suspicion is

um since these studies were done always

in mice

who are supposed to be in the fasting

State and both enter sorry rapamycin and

mpkin is activated or metformin kind of

are mimicking that fasting State that's

why we have seen those benefits

and it will be interesting to see

if that experiment will be done in

humans in the long term because many

people are very excited about you know

there is M total long-term metformin

study and then a lot of people are

actually consuming good amount of

rapamycin off level they can get their

own so that's my

curiosity I'm not saying whether it's

good or bad or whether there is science

or not that's something that will be

interesting to control for and see

because recently I saw one of my again

close friend and colleague at Scripps

suited a very simple elegant study

people should have done in metformin

field so it took mice and then measured

their blood glucose at different time of

the day and in fact just like human

blood Lookers our blood glucose

fluctuates a little bit uh she saw that

rhythm and then in every two hours or

three hours

um

on different days of course so you have

the same dose of Metformin to mice and

what she found was a different time of

the day

metformin had very dramatic change in

glucose reducing ability

so which means that even if you take

metformin and give a different time of

the day for the mouse or even for humans

in very long term of course in this mice

this mice were not diabetic or anything

they were healthy mice to begin with so

in long term we might see

um benefits that are very different so

this brings to this idea that well maybe

metformin say

at the end of the day evening metformin

May trigger that fasting State much

earlier than end of digestion whereas

metformin in the beginning of the day

may not at least from longevity

perspective I'm not talking about

Diabetes Type 2 diabetes here

so the same thing with Emptor

um is mtor going to have much better

impact if taken during evening morning

before meal so

um these are my thoughts that go along

with all this fat um story that we

talked about

do you take Metformin or Burberry I know

I haven't taken although you know um I

have close uh friend and colleague um

Ruben Shaw who is now the director of

Cancer Center at salki extensively works

on MP kinase and its mechanisms and

um

so it's always fun to talk to him he's a

he's a fan yeah I've taken berberine

before and I've had two different very

distinct experiences with them first of

all

um berberine when ingested with

carbohydrates in particular

carbohydrates to have a lot of simple

sugars definitely I know this because I

measured my blood glucose I did the

experiment allows you to flatten out

your blood glucose response

so you know in some sense if you're you

know there is this idea if you're going

to eat a particularly big meal or sugary

meal and you don't want to get a massive

blood glucose rise you take berberine or

metformin metformin is yeah prescription

that's I went with berberine because

it's as far as I know it works as well

yeah um at least for healthy people yeah

for healthy people that's right

um

when I took berberine and did not ingest

large amounts of simple sugars or

carbohydrates along with it I

experienced profound hypoglycemia I felt

like complete garbage for about eight

hours and I had one of the worst

headaches of my life because which makes

sense you just got a blood sugar crash

so if you lower blood your blood sugar

when you already have fairly low blood

sugar and you're not ingesting

carbohydrates you can really bottom out

your your blood glucose so just say it's

I say that as a for two reasons one is

kind of a cautionary note and the other

one that um when you think about the

biology of these compounds it makes

perfect sense and I think that

um and I did not pay attention to

circadian effects yeah yeah I mean you

know when I joined Salk um

is the kind of the

um big liver and sick in metabolism and

he works on nuclear hormone receptors um

these are the master regulator of

metabolism and normal cells cancer cells

and many other

and what was interesting was in the

first few years Ron did a very simple

experiment he just looked at what time

of the day this nuclear hormone

receptors are turned on at gene

expression level and some are protein

level and he found that almost all of

them

have a circadian pattern at least in

some tissue

so he went to that length to say even

that circadian is metabolism and

metabolism is circadian the reason why

we have a circadian rhythm

is to have a daily rhythms in food

seeking behavior and eating

and also go through a period of time

when we should be fasting

and then on the other hand

all the metabolic Regulators also have

to follow that rule and almost all

metabolic Regulators everything that we

can think of connected to

metabolizing macronutrient protein carb

and fat they should also have a

circadian rhythm or diurnal cycle to

align or misalign so for example fat

oxidation should be in opposite phase

with feeding and

um

you know in retrospect at that time it

was kind of amazing to see Ron could

foresee of course he's smart enough to

foresee and predict that this is going

to happen to circadian field because at

that time we're thinking about the

suprachiasmatic nucleus sleep quick

cycle and we are not thinking too much

about metabolism so that's the

awesome thing about song being at Salt

because we have 50 pis really crammed

into two awesome buildings and with Open

Lab structure so you bump onto each

other and talk to you so and with an

ocean view oh it's awesome view yes it's

an amazing place I was lucky enough to

have an adjunct position there when I

when my lab was at UCSD and uh it is an

amazing Place doing incredible

groundbreaking work which of course

includes yours listen uh Sachin I I'm

clear now that um we have to have you

back on for another uh series of

discussions seriously speaking if if

you'd be so so uh kind and willing to do

that I want to thank you for several

things first of all for your taking the

time today to sit down and discuss these

um incredibly interesting ideas in

detail you know much of what we talk

about on the podcast is uh obviously

grounded in science and and often but

not always as actionable and so much of

what we talked about today

is actionable in the sense that many

people are already doing certain

dimensions of these things some are not

some are hearing about it and

considering it you've given us dozens

I've listed some out dozens of tools and

considerations based on whether or not

people are engaging in shift work or not

I think a lot of people are going to

realize that they are shift workers yeah

even though they didn't think they were

um because of the nature of their habits

now to light and activity and so forth

um I absolutely love the firefighter

study because of its relevance to the

general population

also not another nod to fighter fighters

and shift workers everywhere thank you

and you know I think among the

colleagues I've known for several

decades now you really are one of a very

small few who've managed to do both

animal studies

and human studies but also animal

studies with a very clear eye and a

pointer toward human health and um

that's such a vital and rare thing

especially in this day of

um extremely competitive funding so I

want to thank you for your time today

for the knowledge you share the

actionable aspects of that knowledge the

science that you're doing in your

laboratory we will provide links for

people to learn more about you and of

course to go to the app yeah um so

people can um engage in some of the

science directly and of course you have

several wonderful books now that we will

also link to both of which I've read and

are wonderful in particular the book

um the first book but also a book

related to diabetes and um so for

diabetics and people interested in

metabolic and blood sugar regulation

um there so yeah on behalf of myself and

my team here at The huberman Lab podcast

and all the listeners I just want to say

thank you so much your time is valuable

and the fact that you'd share it with us

and educate so many people is really a

gift yeah thank you and actually

likewise there are very few scientists

who have taken this leadership role that

you have taken to uh come and

communicate science to the public it's

not easy because

sometimes you have to distill it down to

a simple sound bite to the point where

the scientist and they'll say oh that

may not be right but we always have to

keep in mind that we are always living

in the dark is of science because the

reason why I say that this is not my

quote actually this is from one of my

scientific hero Paul simel from Scripps

Yola says think about it 10 years ago

what do you what you thought was right

and the best has already changed but one

thing is the Circadian rhythm and

aligning it to our internal clock to our

habit is very important and as you

mentioned uh we have our my security and

clock app which is research facing but

we have also distilled all of this down

to five or six timing component and we

have a new app called on time health or

get on time Health to people access that

through the standard app stores yeah so

now it's available in in app store uh

sorry uh Apple App Store and we want to

see uh how because people always think

about fasting but as we discussed today

feeding fasting or eating fasting and

activity and sleep a kind of interlinked

and we have to kind of balance both of

these so that's that was the idea behind

this on time health program and

um thank you Andy because what you're

doing is immensely necessary

particularly these days when science is

moving at a very past phase there are a

lot of results coming out sometimes

something can be very confusing and you

spending your time

to communicate science

is exceptional so thank you well you're

most welcome it's um

days like today where I get to sit down

and and talk to brilliant colleagues

like you who are doing the important

work that that really matters so much

and so as you

um mentioned a moment ago that there's

uh a lot of darkness and confusion out

there but uh thank you for being uh

one of those whose Shining Light

thank you thank you for joining me for

today's discussion with Dr Sachin Panda

all about circadian biology and time

restricted feeding if you're learning

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