Hey everyone, welcome to the Drive
podcast. I'm your host Peter Attia.
>> [music]
>> Peter, welcome to another podcast. How
you doing?
>> Very good, thank you. You?
>> Doing good. Doing good. So today we are
celebrating
400 episodes, about 8 years. So we
recently crossed this and usually what
we do is every now and then we'll look
back at kind of a reflection episode. In
the past we've always referred to them
as strong convictions loosely held. And
so I think as we start and before we get
into specific topics, do you kind of
want to remind people about what that
term means to you, where you heard about
it, and why you think it's so important?
>> Yeah, it's a term that I first heard
from a friend who ran a hedge fund. And
obviously this was through the lens of
his investment thesis. Um which was that
obviously you needed strong convictions,
but you because you're putting, you
know, real capital behind a thesis.
Um but those convictions had to be
loosely held because the moment new
information or contradictory information
showed itself, you kind of had to be
willing to um check your ego at the
door, say maybe I was wrong, and how do
I need to change things. Um but I always
thought that that frankly
was was a great, you know, view of how
to think about everything uh where
there's actual information at at at at
play. And and obviously medicine and
science are great examples of that. So
um I've been around many really really
great scientists. Um and one of the
characteristics they all have in common
is they're not married to a particular
thesis being right. They're married to
sort of getting things as right as
possible and reducing uncertainty um by
following the data wherever those
wherever those data take them. So um
Yeah. I guess uh
you know, I I think it's um important
that
we are revisiting our assumptions and as
someone asked me once um
you know, if you were to write out live
10 years from now, do you think it would
be the same book that you wrote you
know, 3 years ago and I would say no. I
in fact that would be concerning if it
were the same book in 10 years as it was
at the time it was written
cuz it would either suggest I'm too
rigid in my thinking or science has made
no progress and I think both of those
would be would be challenging. So,
um, yeah, that's loosely how we think
about this episode.
>> And Peter, when you're kind of looking
at your opinions and how you're thinking
about things and how they evolved, where
does that traditionally come from? What
are the triggers that are causing you to
potentially change your opinion or how
you look at things?
>> I think it's a combination of obviously
things that change in the literature,
um, but
you know, scientific progress is
you know, by its very nature somewhat
glacial. Um, and episodic, right? It's
not like mono, you know, it doesn't just
progress at the same rate. Um,
um, but so I think the other sources of
of learning for me and things that force
me to change maybe things I once held
uh, would be
the podcast itself, right? There's
opportunity I get most weeks to sit down
with someone who's far more of an expert
in a subject matter than I am and both
in preparing for that discussion having
a discussion, I'm learning something
that often changes, I mean almost always
changes something in how I think. Um,
and then obviously you have as every
doctor hopefully appreciate all of our
patients are kind of our teachers,
right? So,
um,
we we learn a lot because we're
we're seeing what happens in a clinic
with patients and we're
uh, and we're going to talk about some
of these things today frankly. Uh, so so
basically I think all of these things
taken together, um, whether it be
literature, conversations with experts
and seeing what what actually happens in
the in the clinic. I think um, a lot of
times these things continue to converge
and the views don't change much, and
other times the view just gets more
nuanced, and you start to carve out edge
cases and exceptions, and then sometimes
it actually causes you to change course
completely. Uh and obviously that's what
I think this episode's all about and
what what makes this type of episode for
me personally quite enjoyable.
>> I think as we start this, I think the
topic that makes the most sense to start
at, which is everyone's favorite,
nutrition.
So, kind of very early on, way back in
the day, um you were a big proponent of
the keto diet. You were also an early
adopter and advocate for kind of
extended fasting and what that could
potentially do from a longevity
perspective. And so, kind of where are
you now on those things and how has your
opinion changed?
>> Well, um my original thinking, I'll
start with the diet thing, was was
really driven by this insulin model of
obesity.
So, metabolic disease was and obviously
remains kind of um not just one of the
four horsemen of chronic disease, but
kind of the foundational problem, right?
So, it's the it's the one thing where as
as metabolic health gets worse, your
risk of all other chronic diseases
essentially goes up.
Um
and in my own journey of nutritional
experimentation, carbohydrate
restriction was proving to be very
beneficial. And as you stepwise move
down the plank of carbohydrate
restriction, you're going to pretty
quickly find yourself at a place
which is generally a line in the sand of
ketogenic diets or not, right? Because
at some point carbohydrate intake gets
so low
that you're not providing enough glucose
for your brain, but if it's still a
little high
and it's too high to um
allow your body to switch over into
ketosis, then you're not getting enough
supplemental energy for your brain, and
you're you're in that kind of no man's
land of hell. And so, I remember getting
to that point and then deciding, well,
you know, I at that point had been
reading a lot about ketogenic diets and
I said, look, I'm going to give this
thing a shot. So, anyway, so that my own
journey starts with my own experience,
which was very positive. Um I know I get
sort of uh labeled as someone who's
anti-keto diets and stuff like that um
by by various people out there and and I
I just find that to be the most comical
uh critique of me because not only was I
on a ketogenic diet for 3 years, it was
probably the best I ever felt.
Um I I
look back at, you know, what those 3
years were like and and every element of
it was was very positive for me. Uh
there were other reasons obviously I
chose to abandon it. Nevertheless,
um it reinforced the the the model in my
mind that um the relationship between
carbohydrates, insulin,
hyperinsulinemia,
uh lipogenesis, etc.
Uh
was, you know, sort of
um
it
it all made sense that then a ketogenic
diet would sort of fix these problems.
Um
I think there were also lots of
compelling um data with with animals and
humans showing the improvements in
glycemic control, insulin sensitivity,
liver liver visceral fat, etc. Um and
other metabolic markers improving. And
as I said, I, you know,
certainly reinforced that. Now, here's
what's different. Um I abandoned the
ketogenic diet basically because
I was just tired of being that
restrictive in my eating. I mean, I was
very strict in my
uh ketosis.
Um I think,
you know, I also logged unprecedented
amounts of data during this process. And
I think over a 3-year period of time,
you know, my average morning
fasting um beta-hydroxybutyrate level
was, you know, 1.8 to 2 millimoles,
something in that range. So, this wasn't
like I wasn't sort of a light ketosis
guy. And then of course it would get
much higher during the day depending on
what I was eating cuz I was mostly
eating fat. So, my abandoning the
ketogenic diet was independent of my
views of the ketogenic diet, and to this
day I still view it as an effective
diet. What has changed is my
belief as to why it works. You see, I
used to believe that the diet worked
through insulin suppression.
Um
but today I I don't think that's the
case. Today, I think the diet works
um for the same reason many restrictive
diets work, which is it makes it easier
to control energy intake. Um
even if you don't have to think about it
deliberately, which to be clear, I never
did, right? Um Now, of course, I wasn't
losing much weight on a ketogenic diet
cuz I'd already lost most of the weight
I was trying to lose just from
carbohydrate restriction.
But, when I see people who are
successful successful ketogenic diets,
they often report that they feel quite
satiated, and I think that has to do
with the type of foods that they're
consuming, which which satiate them more
than carbohydrates. Um And I also
believe there's something to be said for
when you are
um oxidizing fatty acids, that in and of
itself is providing fuel endogenously,
which is happening obviously during a
period of weight loss.
So,
it's a subtle point, but it's it's worth
making because it does reflect a change
in my viewpoint, which is that the
um the metabolic dysfunction, the
visceral fat accumulation, the ectopic
fat accumulation, the insulin
sensitivity deteriorating, all of these
things are the result of the energy
imbalance, and hyperinsulinemia is along
for the ride, but if you magically
address the hyperinsulinemia without
addressing the energy imbalance, you're
not going to fix these problems. And the
easiest way to see that is to watch a
person who's on a ketogenic diet
who, for whatever reason, is still in
energy imbalance. So, they're still
going to have lower levels of insulin,
but they're not going to lose weight,
and they could even gain weight. So, you
could gain weight on a ketogenic diet if
you're out of energy balance.
Um
so, that's that's sort of the long and
short of of my views on that.
As a result, I think it's made me less,
I mean, much less dogmatic about the
strategy or the tactics that a person
employs
when it comes to reducing, you know,
energy intake. Um I really don't have a
strong preference when a patient is at a
point where they need to reduce intake.
Once a few principles are met, and we've
obviously talked a lot about those
things, right? I really am pretty
adamant about people maintaining the the
right amount of protein, and at a
minimum, I want them hitting 1.4 g per
kilogram of body weight. But, if they
can accomplish that
on a ketogenic diet, on a low-fat diet,
on a
you know, on a mostly pescetarian diet,
I mean, again, it just doesn't really
matter as much to me
um as it as it once did. So, um
yeah, I think that's that's probably a a
big point around uh the the sort of my
previous dogmatism around nutrition.
>> And now, looking at extended fasting, do
you want to talk about kind of what was
your initial motivation there, and where
your thinking has evolved?
>> Yeah, I mean, I think it's sort of
similar. Again, a lot of things with me
begin from a place internally, right?
Where I'm doing something, and I'm
trying to push the boundaries of it
personally.
So, for about a 3-year period of time,
um
I was doing a quarterly fast, and it
would be anywhere from 7 to 10 days once
a quarter, and then on the other 2
months of the quarter, I would do a
three-day fast. Um and what was my logic
for this? I mean, to be
clearer, I was not trying to lose
weight. I was at a weight that was
perfectly reasonable. Um but I was
really fascinated by this idea that
um
with enough nutrient deprivation, we
could promote enough autophagy
uh that it would have real health
benefits. And just to remind folks what
autophagy is,
um autophagy is the process by which
cells break down and recycle um old
intracellular proteins and structures.
So, the name auto self phagy eating.
It's literally cells that are kind of
eating themselves. And And this is a
very important um
process, obviously long long conserved
in evolution because when nutrients are
scarce,
the body has to basically reuse and
recycle things.
Now, the benefit of this, of course, is
that what what is the body going to do
when it needs to reuse and recycle
things? It's not going to start with the
best stuff. It's going to start with the
worst stuff. So, if you have cells that
are heading towards senescence, if you
have cells that are developing
mutations,
the thinking goes, "Hey, that's where
we're going to start. Those are the
cells we're going to get rid of and
recycle for their constitutive
components."
And again, in preclinical models,
extended fasting
uh clearly uh does this. So, there's
there's little doubt that extended
fasting
um
uh promotes autophagy. As a little
aside, Nick, um
and I haven't looked at the literature
on this in a couple of years. So, maybe
what I'm saying someone will say, "No,
Peter, we actually, you know, look at
so-and-so study." But But it wasn't
really clear um
how many days of fasting were necessary
to get into, quote, high autophagy.
Because autophagy is not digital, it's
analog. It's not like you have no
autophagy and then you cross a threshold
and now you have autophagy in a digital
switch. It's it sort of ramps up, kind
of like ketosis.
Now in ketosis we have a threshold we
use. It's about somewhere between 0.5
and 1 mmol resting or fasting.
Um we don't even have a unit of measure
in autophagy to do that, but having
spoken with, you know, the experts on
this subject matter and looking at
preclinical data,
um
somewhere around 3 days seem to be where
where you could really sort of juice
autophagy levels beyond what you would
get from exercise or other things like
that.
Okay, so then the question becomes,
well, why aren't you doing that still,
Peter?
Um
and again, I think there were several
reasons for that, but I think what
changed most was kind of the evidence,
but also the cost.
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