2__transcript.txt

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
thank the sponsors of today's podcast
our first sponsor is hvmn Ketone IQ hvmn
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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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