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ketogenics was something it really was
transformational and as I discovered
ketogenics through you I'm very curious
to hear um you no longer feel the same
that you did what
changed well it's a broad topic I think
around that of dietary restriction so I
think my aperture has just widened
significantly so you have to take a step
way back and ask the question how does
one what are the ways in which one can
change their diet so let's come back to
your example in a moment
because I think if I recall when you
went on a ketogenic diet it wasn't in an
effort to lose weight no yeah so let's
put your case aside for a moment and
instead discuss it through the lens of
how most people think about ketogenic
diets vegan diets pick your diets it's
it's usually some form of energy
restriction so I think initially I was
like most people are pretty myopic about
my views of energy
restriction and over time that thinking
evolved into saying look there are
really broadly speaking three strategies
to reduce intake one strategy is to just
directly fixate on the reduction of
energy intake that's called caloric
restriction so bodybuilders are a great
example of this right like they really
really know how to weigh and measure
every single thing they're eating and
they certainly understand during an
anabolic phase this is how much energy I
need during a catabolic phase or cutting
phase I need this much and they've got
this down to a science and it's really
remarkable I mean it but it's a science
optimized for the reduction of fat
that's right that's right and
maintenance of muscle that's exactly
right longevity right for anybody so so
but but let's be clear like I don't
think there's a better example of any
type of person on the planet that's
figured out how to control intake up and
down and to produce a perfect result
with respect to that aesthetic MH well
said and for most people that's really
hard to do um it's hard to do because
you can't really ignore it like you
can't just eat without thinking you
always have to be paying attention to
what you're doing but it is the most
direct way to go about getting the
result you want so that's method one
method two
says how about I don't pay attention to
what I'm eating or when I'm eating um
but I pay attention pardon me how about
I don't pay attention to what I'm eating
or uh how much I'm eating but I just pay
attention to when I eat so that's called
time restriction people call that
intermittent fasting and if I make the
window in which I eat small
enough um I will reduce energy intake in
total so if I said to you you know you
can only have one meal a day chances are
you are going to lose weight um now
people thought that well there must be
something magical about intermittent
fasting beyond the caloric reduction but
that turns out to not be the case it's
been tested in several uh studies now
and it's clear that if you eat 2,000
calories in one sitting it's no better
or worse for you uh at least from a
weight perspective than if you eat 2,000
calories spread out of the course of a
day it's probably worse for you in
another way though which is you're a
little more likely to lose muscle mass
because you won't be able to get the
right amount of amino acids into your
muscles I I don't want to derail your
point but we are going to have to talk
about autophagy cuz I intermittent fast
like a fiend great we'll 35 y okay so
then we get to the third method of
caloric reduction which is the use of
what's called dietary restriction so
here we pick things within the diet and
we cut them out and the more restrictive
that is the more likely it is to produce
an energy reduction and therefore the
more likely you are to achieve the goal
of weight loss so the glib example I
always give is if you went on the no
lettuce diet you would not lose an ounce
right right it's simply not restrictive
enough if you went on the only potato
diet you would lose an insane amount of
weight you simply couldn't eat enough
potatoes to maintain now the that's not
a healthy diet right no one would think
that the all potato diet is going to
produce an ideal Health outcome but you
will lose a lot of weight right so keto
is simply a very for a restrictive form
of that diet and many people lose a lot
of weight on a ketogenic diet because
they are limiting so many things right
they're limiting so many carbs it's also
for many people much more satiating so
it actually readily reduces their hunger
and so they simply don't want to eat
more so they have fewer food choices and
they don't want to eat as much but you
can gain weight on a ketogenic diet if
you eat a lot you have to be careful
because you're generally eating more
energy-dense Foods on a ketogenic diet
and I've seen lots of people blow up on
ketogenic diets because they somehow
think it's a license to eat as much fat
as they want not the case so now let's
talk about so so that's that sort of
coming to that conclusion made me
realize oh well there's nothing really
magical about any particular diet when
it comes to energy
balance but now each of these diets has
their own tradeoffs around other metrics
of health so for example we talked about
the importance of protein protein is I
think the most important of the
macronutrients I know everybody wants to
argue about fat and carbs but I think
the the game is one and lost with
protein and you know the recommended
dietary allowance of protein is
unfortunately very low so there's most
people are being told to eat 8 grams per
kilogram of body weight and that's
literally half what you need to be
eating whoa yeah that's the amount of
protein for body mass that I carry or
ideal body mass total body weight hm
yeah so if I at 6 foot weighed 250 lb
I'm going to be wanting to eat something
like 1.6x that in protein in kilograms
so yeah so if you were if you weighed if
you were whatever 200 lb I would want
you
consuming at least 16 g of protein and
maybe closer to 200 depending on your
demand and depending on your age and
depending on the type of protein you're
getting so a lot of different diets
let's pick two that I think one has to
be they're doable but you have to be
careful about getting enough protein so
let's start with a plant-based diet so a
plant-based diet by definition you can't
have any animal protein so all of a
sudden you're doing away with the best
form of amino
acids you know one could argue that when
we eat animals or animal protein it is a
more pure synthesis of the amino acids
that are coming from Plants right so
like a cow all it's eating is plant but
you eat a cow or like venison is one of
my favorite things right so I'm eating
wild venison from Hawaii that only eats
grass and yet it's the richest source of
amino acids I can sink my teeth into in
other words its digestive system its
metabolism is doing this remarkable
thing I can't do which is turning grass
into the richest densest source of
protein if I want to go back and eat the
grass it's fine but I just have to
acknowledge I'm going to have to eat a
lot more of it because it's not a great
source of protein so the
bioavailability of plant protein is
about 70% that of animal protein and
it's not as rich in the most important
amino acids so when we have patients who
are plant-based and they say oh do I
have to give up my plant-based diet I
say not necessarily um and if it's
working for you in all other ways other
than this then there's a workaround here
but the workaround requires you being
very deliberate about your protein
quantity another example is you so we're
going to come back to the case that you
just said which is what about people who
are imminently fasting do they have to
you know is that a bad thing is that a
good thing well it depends but if a
person is intermittently fasting you're
going to see a lot of muscle loss unless
they're very thoughtful about their
protein intake so you know if a person's
intermittently fast lasting
168 you can generally get away with it
cuz in 8 hours you can get usually at
least three good servings of protein but
we have a lot of people who are
intermittently fasting and they're only
eating two meals no snacks they can't
come close to getting the right amount
of protein in because you can't have
let's just say you're on the 160 gram a
day program 80 grams twice in your day
is not going to cut it because you can't
put 80 gram to work it's too much
protein for the body to
Peter man this is so different than how
I live well no but think about it like
bodybuilders are very thoughtful of this
right if you look at bodybuilders I
thought we debunked all the like six
meals a day and you're saying no like I
actually do need to break it back up in
smaller pie if you're optimizing for
muscle mass yes and it can't be too
small so this is where it gets really
crazy if you're eating really small
amounts of protein like 20 grams at a
time you're not going to get muscle
protein synthesis because the liver is
going to the liver basically takes first
dibs on the protein and under
glucogenesis it's just going to make
glucose out of protein so if you just
trickle tiny amounts of protein in
you're not getting muscle protein
synthesis I'm turning it into glucose
really inefficient process yeah you're
just the liver is turning it into
glucose if you eat tons of protein and
the limit based on the literature seems
to be somewhere between 40 and 50 gram
in one sitting okay once you exceed 40
to 50 grams in one sitting the excess
just goes into glucogenesis
huh wow okay this is very so if you're
trying to get 140 g a day you really
need to optimize it by 4 * 40 and uh wow
okay so amazing this is amazing I'm
always game to change uh okay so I'm
breaking my protein up 4X 40 if 160 is
my goal what period of time do I need to
put between them because I would be
happy to do that like it I'm I what's
your feeding window what do you like to
eat when to when man I I usually keep it
tight like four 5 hours max okay so if
you really want to do it that way then
you're going to have to
have if I need to well but but but I'm
saying like if that's working for you
from a weight management standpoint and
a total caloric I'm a freak of
discipline I will never accidentally
gain weight you don't have to worry
about that with me what you have to
worry about with me is right now I
believe that autophagy is necessary to
avoid cancer I don't want to die of
cancer so I intermittent fast to make
sure that I'm in autophagy but there's
no evidence that 20 hours of fasting is
sufficient to induce autophagy yeah see
I thought there was man I thought
autophagy kicked in at like 15 16 hours
like uhuh but mice will die in three
days of not eating well that's bad yeah
so in other words like we're just it's
apples to oranges we have no I mean do
we know where it kicks in for humans no
because we don't have biomarkers for
autophagy uhuh my intuition which might
be as useful as a warm bucket of hamster
vomit is that it's probably three to
five days three to four days maybe do
you do any prolong fasting I don't
anymore wow um and I'm not opposed to it
like I would probably still do you know
if you were diagnosed with cancer what
would you
do yeah I would
probably get back to fasting more
evidence-based or just throwing
everything at it mechanistic yeah give
me the mechanism uh meaning deprivation
of growth factors yeah very interesting
also selective sensitization of cancer
versus non-cancer cells during chemo
right so there is some evidence from
wter Longo's work that when you're
undergoing chemotherapy doing so in a
caloric deficit can be beneficial
because the cancer cell is
differentially and disproportionately
stressed by restriction and than the
normal cell and therefore you're CU
remember chemo like the magic of chemo
is not that it kills cells or kills
cancer cells it's that it selectively
kills cancer cells anything can kill a
cancer cell it's how do you kill a
cancer cell and not a regular cell so
how do you how do you enhance the spread
between those two and it might be that
caloric restriction is a way to do it
and it renders the cancer cell even more
susceptible and at the same time that
you're hitting with chemo it becomes uh
more likely to die at the expense of the
healthy cell that's that's the mechanism
and there is some data to suggest that
that's the
case Okay so uh autophagy we know is
going to kick in at much long we hope is
kicking in at much longer periods uh
deprivation can still help with cancer
from a growth factor remember you also
kick in autophagy with exercise so if
you're looking for another absolutely
what what is autophagy right autophagy
selfing well yes yes yes but what it's
occurring in nutrient absence M and
there's a great way to induce cellular
energy reduction which is exercise when
you exercise cellular energy goes down
that's why exercise increases kinas
activity just as fasting does H so we
you you don't want to underestimate the
benefit of exercise in tricking the cell
into thinking its nutrients are scarce
okay then what kind of exercise I'm
going to guess it has to be the kind
that I hate the most most and if V2 Max
is the under the curve revealer uh it's
what we were talking about very high
intensity period of rest very high
intensity well that's how you train V2
Max but that is that what I have to do
no because that's only that's that
should only be 20% of your cardio volume
80% of your cardio volume Should Be
steady state uhhuh and moderate
intensity okay the 80% I like that a lot
better interesting that's zone two as we
call it and that's done at a level where
you could carry out a conversation if
you had to but you don't want to right
that's the that's the litmus test that
is a perfect description okay so uh
going back to protein so maybe in fact
no you're you're saying just flat out
the intermittent fasting is probably not
helping you at all and if anything it's
probably making it hard for you to get
protein and spare your muscle uh you
need to spread this out you spoke in
kilograms which really threw me off
that's okay how much do you weigh in
pounds uh 185 Okay so
160 to 180 grams per day so four meals
at 40 to 45 grams is perfect for you
okay spread out over ideally as long as
possible and to be clear these don't
have to be meals like two of my four 45
gram of protein that's a [ __ ] meal
it's not though think about it like what
is that 200 calories it's like a chicken
breast it's yeah that I mean you don't
consider that a meal that's a rounding
error um no for me like I'm doing I'll
do like I have these venison sticks that
are 10 like a little jerky venison
bought or made uh they're actually now
bought you can now buy them I like that
y okay um so each one is 10 uh grams of
protein M and 50 calories and I will
have five of those as a snack there's 50
grams of protein right there with 250
calories like it's nothing okay what
about are they highly processed anything
to avoid there no problem because
they're made they're made by company
that I'm involved in so I mean I love it
the most obviously as a guy that only
gets involved with things that I care
about think are real so it's called Maui
Nei venis okay these are um this a type
of deer called Axis deer that are
invasive to the state of Hawaii and so
they're harvested there in the most
Humane manner fashionable which is what
allows the animal to be completely
stressfree so they're harvested by
sniper at night under night vision and
whoa yeah so if you think about it like
harvesting an animal is a very stressful
thing thing for an animal uhhuh like if
you're thinking about how a cow is
harvested yeah even if it has the
most um wonderful life you know it's
grass-fed it's out in a pasture it's not
inside like all of that might be great
and it is certainly better than the
alternative but the very end of its life
is still quite stressful this is a moral
thing or does this moral no I believe I
believe I believe it impacts the quality
of the meat right so think about the
cortisol levels that are surging through
that animal's body right at the time of
its death yeah but from an evolutionary
standpoint everything got eaten oh no no
I'm not that's not a moral question I'm
saying from a health perspective yeah
but I'm saying you're a lion the gazelle
you're chewing on is freaking the [ __ ]
out as you eat it alive so there's no
way that can have some major no I think
it actually probably has an impact on
taste more than anything else um the
other thing is it's very hard I mean
this is more of an argument of why I
love Wild game yeah is Wild game eats
the best plants the best feed right so
when you go to the grocery store and
you're buying you know a regular grain
fed steak it's not eating what it
evolved to eat like it's you kind of
want things that are as close to eating
what they evolve to eat and you know for
for for deer that's like that's
basically grass right so um anyway these
things are processed in a way that
basically has nothing in them right so
you're just I'm just getting pure
protein yeah I don't want to derail this
but this is really interesting so you
snipe the deer at night using night
vision goggles so it basically dies in
its sleep it dies instantaneous yep dies
instantaneously
stressfree um and that is so interesting
how'd you find out about these guys um I
met the founder of the company five six
years ago um and we just immediately
became friends I became completely
fascinated by the problem that they were
trying to solve which was how you know
the government is trying to eradicate
this species um because it is destroying
the island so this is a species of deer
that was brought to Hawaii in the 1950s
for hunting but it had no Predator it
was brought from India where its only
Predator was the tiger you brought it to
Hawaii it had no predator and it has now
run a mck so it is kind of destroying
three islands of Hawaii are they finding
a way to do this sustainably now so that
they can keep having them the goal is by
20 30 to have it be sustainable right
now they are still not able to do it
sustainably in other words right now the
deer are still growing at a rate that is
too significant
Jesus uh head shot yes interesting wow I
don't know why I find that so
fascinating but that's very interesting
okay so back to protein intake right so
point is you could have a w prot wake up
I'm like oh Chomp Chomp into the not
necessarily like I mean again it depends
on when you like to exercise for example
so so I should exercise fasted is that
the point of that um it depends if I'm
going to exercise first thing in the
morning I do it fasted if I'm going to
wait a couple of hours I'll have a
protein meal first but it doesn't matter
because I've always heard that you've
got so much glucose if you're eating and
now you're just going to get fat and you
never going to lose doesn't matter no so
so um I generally prefer to exercise
fasted but if the workout is getting
pushed till later a couple hours later
I'm going to have something before not
because I need to but because I want to
make sure I spread out those proteins
servings enough so at least two of my
protein servings aren't meals they're
like again the jerky is not a meal it's
a snack and then like a whey protein
shake again 40 50 grams of whey protein
in some you know cashew milk you do
would you uh I'm willing to stomach the
venison snacks Andor chicken breast
Andor eggs eggs yep great cool love them
uh so if I'm willing to eat the amount
of protein that I need in eggs venison
whatever would I still do a protein
shake not necessarily no not at all and
do you cuz I have developed slowly over
time a deep aversion to anything that's
processed so I'm trying to get as close
to biting into the walking animal as
possible absolutely y That's great okay
so but you you're not stressed and then
you would have like kind of two meals
right so I'll probably also have like my
lunch would be a salad with chicken
breast or salmon and then my dinner
dinner is the easiest meal to hit your
protein Target right like that's like
falling off a lot
just because it's typical to eat a steak
Chien whatever you're going to have talk
to me red meat white meat matter again I
think it matters less the color of the
meat matters much more the source of the
meat matters much more about how that
anal grain fed yeah and and how close
can you get it to an animal that's in
its natural state truthfully it's much
easier for me to get wild game that's
red meat like I much prefer elk and axis
deer both Wild game that either I'm
killing or someone I know is killing and
it's the wild that's the important yeah
it's an animal that's eating in the
environment it's it's an animal that's
not contained right and the contained is
problematic largely because of the diet
that we know they will need yep okay uh
how much meat how much of your protein
comes from meat by
percentage
um I don't know I'd have to figure it
out but clearly the majority H yeah
because the one thing I've always I also
like Greek yogurt by the way so that's
another thing that's a hard left so
Greek yogurt has a lot of protein it
does actually it's quite high in protein
eat it because of the taste probiotics
just another way to get protein in
diversify a little bit from boredom or
diversity matters yeah just some no no
just for me diversity matters like I
like to mix things up and and it's just
again it's just a function of time like
maybe I don't have time to make an
omelet right now and I'm I got a quick
call I got to jump on so I can scarf
down a bowl of Greek yogurt with some
nuts in
it this seems
impossible it seems too good no sounds
amazing like I feel like the way that I
live right now would take a lot more
discipline than what you're
describing be interested to see if
that's true in practice
um okay so let's fit eggs into the mix
here uh i' love to get an idea knowing
that individual there's a lot of
individual variability here in fact we
should probably talk about saturated fat
at the individual level the one thing in
my diet I do not at all pay attention to
how much saturated fat I eat and go out
of my way to consume it but I make zero
attempt to avoid it and because I don't
check my blood levels nearly enough I am
always a little hesitant to push my
exact diet onto people um do I need to
worry about saturated fat potentially
yeah um saturated fat can increase your
uh synthesis of cholesterol it can also
with enough of it being consumed the
liver can sense the amount of saturated
fat and basically shut down the
clearance of cholesterol meaning the the
the bringing of cholesterol into the
liver can I quote Peter AA on
cholesterol in the book outlive if you
haven't read it I highly suggest it he
said your total cholesterol number is
about as meaningful to dying from heart
disease as your eye color that's right
so you're bringing up cholesterol so
some something matters something about
cholesterol matters but not the total
number right total cholesterol is again
not particularly relevant number
apob which is the uh con which is a
measurement a laboratory measurement
that is the
concentration of lipoproteins that carry
cholesterol into arteries that's what
you should care deeply about but when
someone says what's your total
cholesterol 200 milligrams per deciliter
who cares doesn't mean anything but
there is a type of cholesterol that is
carried in a certain well so cholesterol
for the most part that 200 migs per lit
is your total cholesterol is divided
into three types of lipoproteins a high
each has a different carrier uh no that
200 comes is the aggregation of
approximately three lipoproteins high
density lipoprotein low density
lipoprotein and very low density
lipoprotein so if you look at your lab
you get you get a blood test done if
it's done correctly a lot of them are
not but if it's done correctly and they
do a direct measurement of LDL
cholesterol you will be able to add up
the V LDL cholesterol the LDL
cholesterol the HDL cholesterol and the
sum of those three will equal the total
cholesterol so if the total cholesterol
is 200 and the HDL cholesterol is 70 and
the vldl cholesterol is 20 the LDL
cholesterol will be 110 yep and of those
three
numbers um we would say the most
important Insight you could get would be
to take total cholesterol subtract HDL
cholesterol and that number is called
non-hdl cholesterol that number starts
to become a pretty good predictor of
risk so total cholesterol because those
are damaging in some way yeah that's now
telling you the total cholesterol
content of LDL and vldl and those are
the destructive
lipoproteins now an even better number
is not how much cholesterol is contained
in those two things but how many of
those two things do you have and that's
what's captured by
apob can you explain that more
so each of those
lipoproteins the vldl and the LDL have a
protein wrapped around them that protein
is called APO lipoprotein
b00 which is a very sexy name it's
abbreviated
apob so if you measure apob because LDL
and vldl have one and only one APO
lipoprotein b00 on them the apob number
is is the concentration of those two
particles and the gradient of that the
more of those particles you have the
incre the greater the probability that
those particles are getting into your
artery walls got it so the the number of
those do matter and so if I just
subtract out my HDL subtract your HDL
from your total cholesterol you get the
cholesterol concentration of those two
particles but but and that's predictive
of risk mhm but what's more predictive
of risk is the number of those particles
okay so which a how do
you I don't know if it's going to be
fruitful but there's something in that
math that I'm not following so if I got
back my cholesterol count and I look at
them I'd be able to tell of my 200 let's
say uh 110 are the two that are bad uh
but there's some total number it sounds
like you're it's a separate measurement
you don't you wouldn't impute it from
the those CL you just have to go to apob
you have to get the apob measured that's
right yeah it's another laboratory
measurement understood understood that
is unfortunately rarely done is it can
you just ask your doctor give me an apob
measurement absolutely okay it's a
relatively inexpensive test it's about
depending on the test it's somewhere
between and $20 do they not do it
because they disagree with you or they
just they don't know they don't know
what it is troubling very okay uh so in
fact we should talk at least briefly
about this idea so in the book you talk
about medicine 3.0 versus Med medicine
2.0 medicine 2.0 is all about curing
medicine 3.0 is all about
prevention
um how do we I would call medicine 2.0
more about treating than curing okay
fair it's largely not Curative right
very good distinction uh okay so if you
were going to give me the um the little
toolkit of medicine
3.0
uh what how would you begin to bundle
that like what are the the things
that I should be going towards well
again to your point so medicine 3.0
really says we've reached the limits of
what medicine 2.0 is good for medicine
2.0 is really good at
curing uh acute problems M so it's
really good at curing um infections
traumas acute issues it's really bad at
treating chronic problems MH cancer uh
you know current heart disease
neurodegenerative disease type 2
diabetes it's really bad at treating
those things and therefore all it really
does is prolong the period of time you
have those things and I go through a lot
of explanation in the book as to why
that strategy is not the right strategy
so living longer is not accomplished by
living longer with disease living longer
is accomplished by living longer with
out disease once you realize that you
inevitably come to the obvious
conclusion that a new type of medicine
is needed which must be focused on
extending the period of time you do not
have disease and that word is prevention
which has been bastardized to mean
virtually nothing because everybody
talks about prevention but it has no
meaning right so true prevention has to
start very early true prevention needs a
set of tools that medicine 2.0 doesn't
participate in medicine 2.0 which is the
medical system that every one of us
who's trained goes through is largely A
pharmacologic playbook now you're going
to get people who sit here and say are
all pharmacology is Bad Medicine is bad
no no no that's not true at all
pharmacology is wonderful pharmacology
has done amazing things in medicine 2.0
and we would want to use all of those
pharmacologic tools needed in medicine
3.0 but it's literally you know 1 of the
equation where is nutrition where is
exercise where is sleep where is
emotional health those things are also
needed to delay the onset of chronic
disease and none of us got trained in
those tools so if if a doctor is going
to help their patient with those other
four tools they're going to have to
learn about it outside of Medical
Training that makes sense uh okay so if
we know what we're trying to do is delay
the onset of these diseases you talk
about that in the book that basically
the thing that centenarians have in
common is that they probably were able
to delay the arrival of heart disease
dementia uh because you say this um
cancer that these things are building
for oftentimes decades that you can see
heart disease in teenagers y uh which is
pretty crazy so these are people that
have probably delayed the onset of the
early symptoms of that for decades more
than the people that died say 70 or 80
exactly okay that makes sense so now
then I want to get to and we'll stay on
cholesterol here for a second so uh you
talk about in the book that dietary
cholesterol does not equal cholesterol
in your body so what does what causes
bad cholesterol being the thing that I'm
certainly more concerned about so
dietary cholesterol is very difficult
for our body to absorb it has a bulky
chemical side chain on it called an
Esther and the only way we could absorb
it is if we have an enzyme to cut the
Esther off called the deesterified and
bring it in we don't have much of that
enzyme so most of the cholesterol you
eat such as the cholesterol in you know
shellfish or eggs you poop out M okay so
we should just make sure everybody
understands that eating cholesterol has
almost zero bearing on your cholesterol
levels in your
blood that doesn't mean that your diet
has no bearing on the cholesterol in
your blood but your genes play a very
significant role in the levels of your
blood lipids so we want to always
differentiate between cholesterol and
lipoproteins cholesterol is the cargo
lipoproteins are the boat H
so um the term bad cholesterol doesn't
actually mean anything people say LDL is
the bad
cholesterol that's actually very
inaccurate right LDL low lipoprotein is
the boat that carries cholesterol and
LDL is bad but we should really say LDL
is the bad lipoprotein the cholesterol
in LDL is the same cholesterol in HDL
which people call good cholesterol so
you can see why it doesn't make any
sense now every cell in your body makes
cholesterol
so 95% of the cholesterol in your body
is cholesterol you
made the reason every cell in your body
makes cholesterol is because it is one
of the most important molecules in the
body if you couldn't make cholesterol
you would have died in
utero um and the reason for it is every
cell in your body is wrapped in a
membrane and that membrane is made of
cholesterol most of the um important
hormones in your body testosterone
estrogen progesterone cortisol are made
from cholesterol so this hormone is
absolutely this molecule is essential
for life um but not every cell can make
enough of it so we have to be able to
traffic it between cells so we have to
be able to take it back to the liver the
liver has to be able to package it back
out it has to be able to move around the
system so if your body is like a big
city the Super Highway of that body is
the blood the circulatory system and the
circulatory system is made of water so
when you cut yourself you know you see
red stuff come out but don't let the
hemoglobin and platelets and things
confuse you it's just water with a bunch
of red proteins in it um and fat doesn't
mix with water cholesterol is a fat it's
a lipid and it doesn't dissolve in water
so we can't just move cholesterol around
in the blood the way we move glucose or
the way that we move sodium or potassium
those things are dissolving in water
they're called hydrophilic and they move
around freely cholesterol is not it's
hydrophobic it repels water so that's
why we have lipoproteins we have to have
these lipo proteins to move the
cholesterol in and out of the
body and that gets to the point of there
are basically these different types of
lipoproteins some of them are very high
density they have lots of protein and a
little bit of fat in them some of them
are low
density lots of fat less protein and
some are very low density virtually no
protein and lots of fat or
cholesterol and they have different
properties and it turns out that the low
density and the very low density ones
are the ones that are arthrogenic
meaning they're the ones that promote
the destruction of your
arteries okay so something is starting
to slowly come into Focus for me so fat
in the blood is bad cholesterol or fat
which one do you mean I mean fat so when
we talk about if if I'm understanding
what you're saying correctly there are
two times now that fat getting loose has
sounded like a problem uh well let's not
so so fat is rarely FL floating around
the bloodstream for the same reason but
if A lipoprotein if the very low density
is indicated because it has very little
protein and a lot of fat well just when
I use fat there what I'm really
referring to is triglyceride and
cholesterol but they're inside the
lipoprotein why do it matter that the
ratio of protein to Fat starts getting
low it only matters in that that's how
I'm describing why they difference in
density got it so it isn't that it is
fat that makes them problematic so what
do they do what's problematic is that
the low density lipoprotein and the very
low density lipoprotein are the only
ones that seem to make their way into
coronary artery walls or artery walls in
general and they have the potential to
get stuck in there so the high density
lipo protap thing no we don't really
have a great sense of it it's something
about apob so HDL high density lipo
protein doesn't have APO on its surface
it has something called APO a on its
surface and when a high density lepo
protein goes into the artery wall it
comes back out when AN apob particle
goes into the artery wall sometimes it
comes out but sometimes it stays in
there and when it stays in there or gets
retained bad things begin to happen the
first of those things is it undergos a
chemical reaction called
oxidation that chemical reaction called
oxidation creates an inflammatory signal
and that tells inflammatory cells called
macroasia or monocytes to come they
become macrophases and they eat that
oxidized LDL
molecule that's what kicks off a
devastating Cascade in which the body
ironically and paradoxically in trying
to fix the problem creates a
catastrophic problem that ultimately
leads to the creation of a plaque that
if it ruptures will block the blood
supply of the artery and cause a heart
attack you've got the two types that end
up basically they have the apob on them
apob can get stuck in my arteries once
it's stuck in my arteries my body sends
a immune response effectively that then
ends up creating a problem uh is that
Cal ification calcification is the final
stage of the body trying to repair the
problem okay so think of it as the
concrete that gets poured on a melting
down nuclear reactor so when you get a
CT scan that's like what's called a
coronary CT scan to look for
calcification the presence of that
calcification while by itself not
problematic is predictive of something
bad that's happened I describe I think
in the book calcification is like going
through a neighborhood and seeing bars
on the windows the bars on the windows
are actually a good thing they're going
to prevent somebody from breaking in but
it tells you what kind of neighborhood
you're in yeah okay now that makes a lot
of sense going on with my diet one thing
that I'm very curious about and there's
a raging debate online a cal is just a
calorie
um where where do you come down on that
in terms of the quality of the calorie
does it matter U if I'm eating ter like
if you agree that the quality of the
calorie matters but I'm still undere
eaing do I have a
problem so the the the calorie a calorie
discussion always needs some
clarification are we talking about with
respect to energy balance are we talking
about with respect to nutrition and
health are we talking about with respect
to
satiety and and so we have to clarify
which of those we're talking about all
I'm talking about ever is longevity
so so then a calorie is not a calorie
for sure right so in other words if you
took a bunch of people and put you know
one group of them on 2 200 calories a
day of Twix bars and another group on
2500 calories of you
know one food only lettuce you know or
whatever it wouldn't be 2500 calories
lettuce but you know 200 calories of
venison sticks venison sticks and
another group on 2500 calories of some
well-rounded diet that's you know you
know blah blah they might all end up
with the same weight they might have a
different Health Quality and they I
would expect it I clearly don't expect
the guy on 2 200 calories of Twix bars
to live as long as the person on 25 200
calories of good food nor do I expect
them to feel the same so if you're
totally and by the way they might end up
at slightly different weights because of
how they feel and while you may in this
experiment control only their intake you
might not be able to to control their
energy expenditure so they might
actually expend different amounts of
energy because of how they feel
so um the the calorie as a calorie
debate I think is kind of a silly one
because a lot of times people are
talking past each other when they're
yelling at each other and they don't
understand what they're talking about
and so you you know we just have to
understand are we talking about pure
controlled you know calorimetry or are
we talking about in your case what
you're asking about which is I think
more important which is
Health we are um innately really really
bad at estimating risk and oddly enough
makes me wonder about you and race cars
so what is it that draws you to race
cars do you think you're accurately
assessing the risk on that I I I will
say you know that's not an unusual
question I get asked a lot I I think
that I feel safer in a race car than I
do in my street car really absolutely I
feel far far more frightened in the
drive I have to take tonight from here
to San Diego because I'm going to be on
the 405 and the five and I know that 80%
of people at some point on that drive
are going to be checking their phone or
losing focus or not paying attention I
don't know what percentage of them maybe
10% of them are also going to be under
the influence of alcohol and uh they
pose a infinitely greater threat to me
than I I feel like I could ever face in
a race car so other than driving what
are some just grotesque misjudgments of
the risk in terms of behaviors that
people do just on a daily
basis um I think I think Automotive is
is a very big one so yeah good that we
got that one first I think another one
that people sort of
misunderstand
is
alcohol you know I mean I I enjoy
alcohol as much as anybody but I don't
think people understand how once you get
Beyond one to two drinks like how
harmful it is on your liver
and it's sort of like Tylenol right like
at any dose Tylenol is really hard on
your liver but for most of us because
Tylenol has no good feeling associated
with it we don't really tend to use it
more than we should we you know if we
have a headache we take it and it makes
the headache go away and but but we
don't find ourselves like taking four
Tylenol every day just because of
whatever reason and yet I'm I'm
constantly amazed at how much people
drink even when there's no apparent
reason for it right so so there's always
a reason to have a drink right there's
there you can always come up with a
great reason to have a drink but there's
too many sort of blah reasons that
people are drinking so I think that um
that that to me is an asymmetric and
unnecessary risk meaning the pleasure
that they're getting from that you know
those four shitty Budweisers that they
have isn't anything worse the potential
downside it's causing in the long run
which says nothing by the way of how
often I think people do get behind the
wheel of their car when they've had a
drink in them and if there's one thing
I've learned in the simulator it's how
even one drink compromises your ability
when it matters so I remember simulator
a driving simulator yeah so I have a
driving simulator at home which is where
I do much of my learning um but I
remember one day I was like yeah I was
going to go drive the Sim after dinner
and I had a glass of wine with dinner I
remember getting in the simulator and I
was like what in the hell is wrong with
me here like I am missing every Apex my
I'm just a little bit off I'm a little
bit off and I realized oh I had a glass
of wine even one glass of wine is
compromising me um so how many times
have I gotten a car having two glasses
of wine at a restaurant the answer is
tons was I legally drunk no I was well
below
008 but if even if I'm 006 I'm legally
fine is that still a reasonable strategy
right and I think the answer is probably
not you think there are dietary things
that people are doing that have just an
asymmetric risk reward yeah you know I'm
probably kind of a a huge advocate for
caloric restriction um at least
intermittent bouts of caloric
restriction so I believe that the
short-term discomfort of not eating for
days once twice four five times a year
going through a cycle like that I think
that the
shortterm inconvenience of that that
is Trivial compared to the potential
benefit of of a true fast you know water
only fast for some period of time and I
still don't know what that minimum is I
think it's probably a minimum of three
days are necessary to start to get some
of the real benefits of autophagy
mitophagy and things like that but
what's the difference between autophagy
and mitophagy um autophagy is the cell
eating itself and mitophagy specifically
is the recycling of the mitochondria
okay
um so I think when someone says and I
have many patients or friends or family
members who have said like yeah that's
just there's no way I'm ever going to I
could never give up food even
transiently I
think that's that's that comes from like
not not even being willing to give it a
shot like what's the
emotional hangup cuz you were you used
to be literally the epitome of the
robotic eater just insanely strict and
you said about 3 years ago you were like
nope not doing that anymore and I think
to quote you exactly I no longer have
the intestinal fortitude to eat like a
robot so there was something in you that
it no longer was worth it yeah that
became much harder than what I do today
which is so so back then I wasn't doing
any Tim restricted feeding I wasn't
doing any fasting it was is a pure form
of dietary restriction so my my sort of
mental model for nutrition is everybody
is starting out on one side eating the
standard American
diet abbreviated as sad which is an
appropriate
abbreviation and the thing I always tell
patients on day one is like look the
good news is you can't get any worse
than this the only thing if you're
starting at the sad the only thing you
can do to make it worse is eat more of
the sad right but it's like the standard
American diet and I don't believe this
was deliberate right I don't think
there's a conspiracy theory here but
just through a lot of bad
luck uh has arrived at the absolute
worst combination of macronutrients you
could possibly imagine like you couldn't
come up with a way to confuse someone's
metabolism than to combine fats and
carbohydrates in the ratios that they
are combined in most of the foods that
we would eat by default if we were left
to our
brothers so from there I say look
there's kind of two introd Rory moves
which are not mutually exclusive but you
can pick one or the other the first is
time restricted feeding where now you
don't limit what you eat you just limit
when you eat it and then the second is
dietary restriction you don't restrict
when you eat you don't restrict how much
you eat which you also don't restrict in
time restri feeding but you restrict
certain elements of what you eat so for
those three years that I was on a
ketogenic diet which is I mean probably
one of the most demanding subsets of
dietary restriction
um you know I'd pulled that lever as
hard as it could be pulled then you move
into diets that sort of mimic fasting um
which is basically just another way of
saying hypocaloric diets for transient
uh periods of time and then ultimately
even beyond that is fasting just you
know water only also for limited periods
of time nowhere in there do I
include constant caloric restriction so
you know reducing by 20 30% your energy
intake in definitely I I think the data
are pretty clear that that is not a
winning strategy there's something about
the cycling into and out of catabolic
versus anabolic State you're basically
Clearing House right you're sort of
getting the cells that are themselves
defective and hopefully the ones with
the most effective mitochondria we'd
love to Target those the most for other
reasons um what you want to see is the
regrowth you want to when you refeed you
want to see The Selective repopulation
of the better cells the most robust
experiments done on this in primates did
not really suggest that as the diet got
better the benefits of caloric
restriction got better in other words
the worse the diet the better the
benefit of caloric restriction which
points us to this idea that dietary
restriction should still always be some
component of a healthy nutrition
strategy meaning like if you're eating
like [ __ ] stop eating like sh stop
eating you really really if you're if
you're committed to never eating
anywhere but McDonald's caloric
restriction will have a much bigger
effect on you positively than you know
if your Baseline intake is you know the
way you would eat for example that kind
of stuff at like the Deep cellular level
about where we're going and what this is
going to look like is is really
fascinating to me definitely not
something that I have the kind of grip
on even remotely close to what you do
but nonetheless seems like if you're um
really going to get to 100 at a high
level it seems like you're going to have
to take that pretty seriously now you've
talked a lot about
one of the tests that you want to make
real is the ability to check for
autophagy and to see in the blood um
you've thrown out a couple times that
this is like a you probably know the
people that would be creating this test
um and B that it wouldn't be you know
it's not measured in the billions so
what what would that really take um is
it something that could be
commercialized and would give people the
impetus to put the capital up for it or
what does that future look like from a
funding perspective again this is not
not like the world's hardest problem to
crack um but I'm if I'm going to be
completely truthful I don't know how
commercially interesting it is as a
general rule diagnostic tests are not
very commercially interesting um my
interests are not remotely commercial my
interest is in just knowing what to do
it's like I want this test to tell me
exactly what the right fasting protocol
needs to be should I be fasting 3 days a
month 7 Days Every 3 months 14 days when
once a year like I want to know that and
there's no amount of money that would
make it worth you know not knowing the
answer to that question um wow that's a
bold statement well think about it and
I'm not to suggest that like money
doesn't matter and money you can't do
great things with money like I want
money just as much as the next person
but never at the expense like I don't
want anything to get in the way of the
knowledge that can drive living longer
that to me is such a priority that I
would rather be
poor but know how to you know live
longer than have all the money in the
world and lose my health I totally get
that but I will say one thing I want to
talk about is you said that um one
you've said that you think that you eat
dysfunctionally even if you don't have
an eating disorder which I actually
thought was really interesting and then
you said that part of why you gave up
the robotic eating was you were worried
about how it's affecting your daughter's
view of food talk about that CU I think
certainly in this the movement that
we're all going through right now
there's a real risk of that that if I
had had kids 5 years ago when I was like
ter I was shredded I was so myopically
focused on everything that went in my
mouth and I loved it about myself and I
would Rave about how much discipline I
had so for sure if I had kids they would
have been wildly influenced by how much
pride I took in not eating and so yeah
do worry what that would have done and I
thought it was super sensitive of you to
recognize that and change
yeah I mean my brother um actually was
the he he brought this point to my
attention first but he said you know be
thoughtful about how you describe your
own interactions with food and when
you're giving you know your kids input
on what to eat or what not to eat try to
tether it less to you know body
dysmorphic ideas and Trigger it you know
Peg it more to Performance issues for
example right because those things are
still true right if you if you eat well
or eat poorly it affects your
performance it affects your cogn