0:06

Welcome to the Making Sense podcast. This

0:09

is Sam

0:09

Harris. Just a

0:11

note to say that if you're hearing this, you are not currently

0:14

on our subscriber feed and will only be

0:16

hearing the first part of this conversation. In

0:18

order to access full episodes of the Making Sense

0:20

podcast, you'll need to subscribe at SamHarris.org.

0:24

There you'll find our private RSS feed to add

0:26

to your favorite podcatcher, along with other subscriber-only

0:29

content. We don't run ads on the

0:31

podcast, and therefore it's made possible

0:33

entirely through the support of our subscribers. So

0:36

if you enjoy what we're doing here, please consider

0:38

becoming one.

0:46

Welcome to the Making Sense podcast.

0:48

This is Sam Harris. Today

0:51

I'm speaking to my friend Peter Atiyah. Peter

0:54

is a doctor and the founder

0:56

of Early Medical. He received

0:58

his medical degree from Stanford University, and

1:01

then he trained at Johns Hopkins in general

1:03

surgery. He also trained at the NIH

1:06

as a surgical oncology fellow and

1:08

at the National Cancer Institute. He's

1:11

also the host of his own podcast, The Drive.

1:14

But today we focus on his

1:16

new bestselling book. The title

1:18

is Outlive, the Science and Art

1:21

of Longevity. That really is

1:23

our focus. We talk about healthspan

1:25

as opposed to mere lifespan,

1:28

the lessons that can be learned from centenarians

1:31

and supercentenarians, diet

1:33

and nutrition, including topics

1:36

like sugar and macronutrients,

1:38

alcohol, fasting and

1:40

time-restricted eating, exercise,

1:43

heart disease, blood

1:45

pressure, cholesterol, cancer, brain

1:48

health, metabolic disorders,

1:51

proactive medical testing, medication

1:53

side effects, esoteric drugs

1:56

like rapamycin, emotional

1:58

health, and other. topics. The

2:01

full conversation runs three hours,

2:04

so it is a fairly comprehensive

2:07

look at most of the variables we might control

2:09

to maximize the chances

2:11

of living a long and healthy life. And

2:14

I bring you Peter Atiyah.

2:22

I am here with Peter Atiyah. Peter, thanks

2:24

for joining me. Yeah, Sam, thank you so much

2:26

for having me. So you have written this

2:29

amazing book, which we're going to talk

2:31

about. The

2:31

title is Outlive,

2:34

The Science and Art of Longevity. And

2:35

first of all, congratulations on the

2:37

book. It really appears to have been trumpeted

2:40

from the ramparts everywhere from

2:43

Oprah on down and it's really getting out

2:45

there. So it's got to be gratifying because when you

2:47

publish any book to say nothing of a first

2:49

book,

2:50

you really have no idea what's on the other side

2:53

of that printing press. And this

2:55

is really about as good of an

2:57

outcome as I can imagine. So it's

3:00

got to feel good. It does, yeah. And

3:03

I think this time a year ago, I get

3:05

effective at least when we're recording this, was when I really

3:08

had the thing ripped out of my hands by the publisher.

3:11

And I remember sort

3:14

of thinking to myself, like, I'm

3:16

not happy about this. It's not perfect, blah,

3:19

blah, blah. I'm sure the same thing that you've thought

3:21

of many times as you've obviously written a number

3:23

of successful books.

3:24

But then I had this thought that sort of calmed

3:27

me, which was, look, is it at the point now

3:29

where I will be proud if

3:31

my kids read this in 20 years? And

3:34

if I can answer yes to that question, then the

3:36

rest is sort of out of my hands and maybe people

3:38

will hate it and maybe people will

3:40

find a bunch of mistakes in it and all of this sort of insecurities

3:43

that I'm sure every author goes through. But

3:45

I know that once I kind of got to that point of saying,

3:47

as long as my kids will one

3:49

day be proud of it, which I know it

3:51

sounds a bit corny, it'll be okay. And

3:53

then I think the rest sort of took care of

3:55

itself.

3:56

Yeah. Well, it's quite a useful book

3:58

and it's a very canned. book

4:00

too, which you really go into your story

4:03

in considerable depth. Before

4:05

we jump into the topics at

4:07

hand, we're going to sort of track

4:09

through your book. Obviously, there's much more detail in the book and

4:11

I recommend people read it if they want

4:14

more detail on any of the topics we

4:16

touch. I should also say that you have

4:18

a podcast, The Drive,

4:21

which really goes

4:24

into extraordinary detail on all

4:26

of the topics we'll touch and many others.

4:28

So if we're going to talk for 10 minutes

4:30

about lipids for

4:33

cardiovascular health, your

4:35

podcast probably has 10 hours on

4:38

that topic. I don't think I'm exaggerating.

4:40

I

4:40

think we're going to do it. I

4:42

think I have 10, more

4:45

than 10 podcasts on each one. 30 hours, yeah. So there's quite

4:47

a wilderness of detail

4:52

awaiting anyone who wants to follow you into

4:55

it. But before we jump into the topics, perhaps

4:57

you can summarize your background

5:00

and career in medicine because you've

5:03

had a interesting story

5:05

of how you have come to

5:08

emphasize the kinds of topics

5:10

you have focused on. Yeah. So

5:13

I didn't

5:14

want to go to medical school at any point during my life.

5:16

I was not a pre-med or anything like that. In fact, I'd already

5:19

sort of finished

5:20

engineering when I had a change of heart, decided

5:22

to go back and do medicine. And in

5:24

medical school, like many others, I'm sure I was a little

5:27

undecided about what to do. Always

5:29

had an interest in oncology. And

5:31

when I showed up in med school, kind of thought I might

5:33

do pediatric oncology.

5:35

But by the end of medical school,

5:37

realized I had more of a surgical personality

5:40

and so decided to do surgery

5:42

with the plan to then go on and specialize

5:45

in surgical oncology.

5:47

And

5:48

after five years of my residency,

5:51

for a number of reasons, some of which I write about in the

5:53

book, I just became quite frustrated

5:55

with

5:56

what I've later come to call medicine 2.0,

5:58

although at the time.

5:59

of course, I had no idea that that's what

6:02

was really frustrating me. Then I just decided

6:04

to leave. I felt like

6:06

the last 10 years had been

6:09

not a good use of my time, frankly,

6:11

and I wanted to go back

6:13

and get another degree.

6:14

Probably an MBA felt

6:17

I already had enough debt. Instead, I

6:19

joined a company called McKinsey &

6:21

Company, which is a consulting firm.

6:24

It went down the path of

6:27

corporate finance and risk there, which

6:29

was very appealing to

6:31

me and to my sensibilities

6:33

around quantitative things. I

6:36

missed my background in mathematics

6:38

and

6:39

was happily marching along, doing

6:42

that, and spent

6:44

six years completely away from medicine

6:46

until my own health became

6:49

of a high enough priority to

6:51

me and a high enough interest

6:53

that the endless pursuit

6:55

of trying to understand that better gradually

6:58

led me back into the

6:59

notion of practicing medicine again, but obviously

7:02

doing it in a very different way, which is

7:04

through this lens of prevention as opposed

7:06

to

7:07

last minute treatment. You've

7:09

gone

7:10

very deep into topics

7:12

like diet and nutrition and exercise

7:15

more than the average physician, I would

7:17

say, and we will cover

7:20

that. Let's start with

7:22

what would be our first chapter here on the

7:25

topic of longevity

7:28

and really health span, I think is

7:30

your preferred word because it's

7:32

more than a matter of just not dying.

7:35

How do you think about the

7:37

main causes of mortality and the main

7:39

causes of reduced health

7:41

span? Maybe we should define health

7:43

span at the outset here.

7:45

Yeah. I think longevity

7:47

is best explained, at least for

7:49

me, conceptually, I think of longevity as

7:51

a function of these two things, lifespan

7:54

and health span.

7:55

Lifespan being the

7:57

easier to understand because it's the binary

7:59

one. It's the.

7:59

you're alive or you're dead, you're respiring or

8:02

you're not.

8:03

And the current medical system is really focused

8:05

mostly on lifespan. It's

8:07

the metric that gets measured and

8:10

it's the metric obviously that therefore gets

8:12

managed.

8:13

Healthspan,

8:15

which is obviously not binary,

8:17

is somewhat subjective as well,

8:19

really speaks to quality of life.

8:22

And while I think that everybody intuitively

8:25

gets that,

8:26

certainly I'm sure if you ask a person,

8:29

would you want to live to a hundred if

8:32

the last 20 years of your life

8:34

you were cognitively or physically

8:37

debilitated? I think most people would immediately

8:40

say no, not really.

8:41

So very long

8:43

lifespan in the absence of healthspan is not desirable.

8:46

But

8:47

similarly, wonderful healthspan

8:49

with insufficient lifespan is also undesirable.

8:52

Sam, if I said, you're going to die

8:54

at 60, but you're going to be from

8:56

now until 60, you're going to be

8:58

as strong and cognitively sharp as you were

9:00

in your 20s. I still think we would view that as tragic

9:03

as well. Your lifespan was cut short. So

9:06

what we're really trying to do is optimize both.

9:09

But I think the biggest insight

9:11

I've had in the past five years is that

9:13

if you focus relentlessly on healthspan,

9:16

you get the lifespan benefits

9:18

typically along the way.

9:20

If you do the reverse, that's not

9:22

necessarily true.

9:24

So what can we learn from

9:26

centenarians and I

9:28

guess you call them super centenarians, people who

9:31

live to be a hundred and beyond and

9:33

in many cases

9:35

really thrive. I mean, it's almost

9:37

like their healthspan is extended

9:39

by two decades

9:42

or more with respect to the average

9:45

population. What have we learned from

9:47

them? And to what

9:49

degree do you think they're the correct lens

9:52

through which to look at the goal here

9:54

and the strategy and tactics

9:56

we might use to extend longevity

9:59

and healthspan?

9:59

Well, this is a question I've been interested

10:02

in for about a decade. And

10:04

there are two people who have really done

10:06

a

10:07

lot of work on the

10:10

centenarians,

10:11

the offspring of centenarians,

10:13

and even the supracentenarians, those who live

10:15

to be 110 and beyond.

10:17

And these two folks are both here in the US. So one

10:19

is a guy named Thomas Pearls at Boston

10:22

University, and the other is near Barzillai out Albert

10:24

Einstein College in New York.

10:26

Now, understandably, most of the work that

10:29

Pearls and Barzillai have put into this have

10:31

been focused on

10:33

the more high-tech

10:35

side of the question, which is,

10:38

what are the genes that are associated

10:41

with this exceptional longevity?

10:43

Because it's pretty clear

10:45

that it's a genetic

10:48

benefit that's been bestowed on these very infrequent

10:50

individuals.

10:51

In fact,

10:52

from a behavioral standpoint,

10:54

it's kind of amusing to look

10:57

at the typical lifestyle of the average

10:59

centenarian. On average, they're more likely to

11:01

smoke,

11:02

more likely to drink to excess, less likely

11:04

to exercise,

11:05

and more likely to have poor eating habits. So

11:08

it didn't take long for people to figure

11:10

out that these guys were winning

11:13

the genetic lottery and not

11:15

living like monks.

11:17

And understandably, I think most of the

11:19

effort has been on what are those genes. I touch

11:21

on that in the book.

11:22

But for me, the big aha

11:25

moment came, roughly 2014,

11:27

when I was reading a

11:30

paper about centenarian mortality.

11:32

And I realized that if you look at the

11:35

mortality tables of centenarians,

11:37

it looks very similar to the

11:39

mortality of the rest of us. It

11:42

just has a 20-year phase shift. And

11:44

that might sound really obvious, but it's actually not.

11:46

Because what it says is,

11:48

centenarians are just as likely to die

11:51

from heart disease eventually. They're

11:53

just as likely to die from cancer eventually. And

11:55

by the way, they're just as likely to die

11:57

from cancer once they get a cancer diagnosis.

11:59

as the rest of us. What this

12:02

tells us is that their superpower, which

12:04

again is brought on genetically, is

12:06

a delay in the onset of

12:08

disease, not in a

12:11

resilience to a disease once they have

12:13

it.

12:13

I want to have a separate chapter here

12:16

on specific medications and

12:18

supplements that might be derived

12:20

from any insights we've had into the

12:22

genomes of centenarians and through

12:25

other means of things like rapamycin

12:27

and metformin.

12:28

But how do you use

12:32

what we've learned about centenarians

12:33

so far in

12:36

your thinking through the strategy

12:38

and tactics you employ

12:40

in your medical practice and just

12:42

personally? Perhaps you

12:44

want to differentiate between strategy

12:47

and tactics and how you think about longevity.

12:50

Yeah, so I think that's

12:52

a great way to lead into this, which is that insight,

12:54

which as I say it sounds relatively

12:57

so what-ish.

12:58

I think for me was a real wake-up

13:00

call and it made me realize

13:03

that the only way

13:05

one is going to somehow improve

13:08

their longevity

13:09

is to think about prevention through a much

13:12

longer lens.

13:13

So

13:14

we have to pretend

13:17

that our coronary arteries at the

13:19

age of 80,

13:20

we need to position them to look like they

13:22

would otherwise look at 60.

13:25

And the only way to do that is to

13:27

think about primordial prevention as opposed

13:29

to just quote-unquote primary prevention. So

13:32

let's use coronary artery disease as an example

13:34

of that because it is the most ubiquitous

13:36

cause of death in the United

13:38

States globally for men and

13:40

for women. It really is

13:42

the great equalizer. We

13:45

know this from as early as the

13:47

early 1970s, late 1960s when they were doing

13:50

autopsy studies on young men who were

13:52

dying in Vietnam

13:54

that even 18-year-old men have while

13:56

not grown. evidence

14:00

of atherosclerosis, i.e. you wouldn't open up

14:02

their coronary arteries and see clots, histologically

14:06

they already have the process in

14:08

embedded.

14:08

So in other words, if you look under a microscope at their coronary

14:11

arteries,

14:12

you'll see the foam cells,

14:14

you know, the macrophages that have ingested cholesterol

14:16

that's been oxidized in the arterial wall,

14:19

and you realize that that process is actually beginning

14:22

as we're children.

14:23

And the slow burn of that process

14:26

is such that for most people

14:28

it doesn't become clinically relevant until you

14:31

hit about 65. So about 50%

14:34

of men who are going to have a coronary

14:36

event in their life will have it before the

14:38

age of 65, and about a third of women

14:40

who will have a coronary event in their life will

14:43

have it before the age of 65. So that gives you a sense

14:45

of the time scale. Well,

14:47

if we want to prevent that, we can't really wait

14:49

until you're 50.

14:50

That's effectively the point here.

14:53

We have to take prevention much more

14:55

seriously, and we have to significantly

14:58

bend the arc of the disease curve

15:00

basically as soon as possible.

15:02

And we do have examples of this working already,

15:05

right? So if you take children who are born with

15:07

something called familial hypercholesterolemia,

15:10

which is a not terribly

15:12

uncommon genetic disorder

15:14

that results in unusually high levels of

15:16

cholesterol, these are indeed people

15:18

who can have, you know, MIs, myocardial infarction,

15:21

heart attack in their 20s.

15:23

And these are kids that actually have to be medicated as

15:25

youngsters. And if you do that, and if you do it aggressively,

15:28

these kids can go on to live normal lives.

15:31

Well, we'll have a separate chapter on heart

15:33

health and, you know, cardiovascular

15:36

disease here. But

15:39

let's talk about diet and nutrition. This

15:41

is really the first stop

15:43

in most people's thinking with

15:46

respect to how to prevent, you know, really

15:48

all of the diseases of aging and to

15:50

live a healthy life. You know,

15:52

I consider it one of the great scandals of medicine

15:55

and science generally that there's still any

15:58

uncertainty about

15:59

what

15:59

constitutes a healthy human diet.

16:02

I mean, it's just amazing to me that there's

16:04

such a diversity of opinion on this topic.

16:07

I mean, there are people who will tell you that whole

16:09

grains and legumes are among

16:11

the healthiest things you can eat. And there

16:13

are people who will tell you with equal

16:15

confidence that they're just pure poison

16:18

and there are whole diets marketed around

16:20

these antithetical views. And

16:23

so I had thought prior to this conversation

16:25

that the one totally uncontroversial

16:29

point in nutrition now is that refined

16:31

sugar is generally bad for

16:33

us. And maybe that's still the case. I

16:36

mean, it's generally described as the

16:38

dietary equivalent of smoking. But

16:40

right before getting on

16:42

the mic with you, I think it was yesterday,

16:46

I stumbled upon this YouTuber

16:48

who apparently spent 100 days on a diet consisting

16:52

of nothing but 2,000 calories of ice cream

16:54

and 500 calories of protein powder plus

16:57

booze. And he lost 32 pounds

16:59

and totally revamped his lipid

17:02

profile. Obviously

17:04

that's just an N of one and who knows if it's true. But

17:07

what do we absolutely know is

17:09

true about diet and nutrition

17:11

at this point? I mean, let's go through

17:14

gradations of certainty here. What are

17:17

you sure of with respect to diet

17:19

and nutrition that is generically

17:21

applicable to more or less everyone

17:24

who would listen to this? And what do

17:27

you think is just very likely to be true?

17:29

And let's just track through

17:31

with those two flags with

17:33

respect to our epistemic certainty

17:37

as we touch the various topics. How

17:39

should people think about diet

17:41

and nutrition here? And is there

17:44

anything on this landscape that is

17:46

the equivalent of a generic

17:48

certainty like it's not a good

17:51

idea to smoke cigarettes, which I

17:53

think is a piece of health wisdom

17:55

we have truly conquered at this point.

17:58

Yeah, I like the way you framed the question.

17:59

Sam, and it's sort of funny because

18:02

as

18:02

you know, you've read the book, there's like 17 chapters,

18:05

two of them are on nutrition, three of them are

18:07

on exercise, everything else gets one chapter,

18:09

right? So clearly,

18:10

exercise and nutrition get a little extra

18:13

attention, in

18:14

part due, I suppose, to their complexity in

18:16

the case of nutrition and the impact

18:18

in

18:19

the case of exercise.

18:20

However, during the first writing of the book,

18:23

I was so

18:24

annoyed by the problem you describe

18:27

that I

18:28

very sort of cheekily

18:31

sent my editor

18:32

a one page version of the nutrition

18:34

chapter and I said, this is the chapter.

18:37

And it was what you just said, it's like, here's

18:39

what we know. And it was like, I don't know,

18:41

six bullet points. And

18:43

I said, how about I just do this

18:45

and spare myself and the readers all

18:47

of the crap that follows where I have to start

18:49

getting into some uncertainty.

18:51

Needless to say, that didn't go over very well.

18:53

But

18:53

what I basically said is here's what we know.

18:56

We know that when it comes to nutrition,

18:58

too much and too little are

19:01

problematic,

19:02

though generally on different timescales.

19:04

Let's expand on that for a second.

19:06

We've been around for, depending

19:09

on where you want to draw the line in the sand of where we began

19:11

as homo sapiens versus previous

19:13

forms, let's just make it easy and say

19:16

like a couple hundred thousand years,

19:18

right?

19:19

And

19:20

for most of that period of time, food

19:23

has been relatively scarce.

19:25

So that's fact one. Fact two is, I

19:27

would

19:27

argue this, I think you would probably agree, Sam,

19:30

what separates us as humans

19:32

from every other species on this planet is

19:35

our brain. That's our

19:37

superpower, right? It's certainly not how strong

19:39

we are or how fast we are

19:42

or any other sort of physical power.

19:45

It's really our brains that

19:47

differentiate us.

19:49

That brain is an insanely energetic

19:52

organ. So roughly 25% of our caloric

19:55

need goes to servicing

19:58

that organ that constitutes two... of

20:00

our mass.

20:01

Therefore,

20:03

the trick that allowed us and

20:05

only us to leapfrog

20:07

out of the swamp ahead of every other species

20:11

was the capacity to store energy.

20:13

And it's

20:15

important to understand just how

20:17

profound that is, right? If

20:19

we couldn't store weeks

20:22

and weeks of energy, we

20:24

wouldn't be here.

20:25

Now, we store most of that as fat.

20:28

So obviously excess fat gets stored as

20:30

fat, excess carbohydrate gets stored as

20:32

fat beyond the paltry amount we can

20:34

store as glycogen, which is just a fancy word for

20:36

the storage form of glucose.

20:38

And in times of

20:40

relatively short fasts, we

20:42

just break that fat down and use it

20:45

as energy. And in relatively long periods

20:47

of fasts, we turn that fat into something

20:49

called ketones and we use those as energies. But

20:51

regardless, we can go a relatively

20:54

long time without food. By comparison, of course,

20:56

a mouse can go like

20:58

two days without food before it dies.

21:01

Even a lean person could go 20 or 30

21:03

days without eating.

21:05

So

21:06

what's the price we pay for that superpower?

21:08

Well,

21:09

up until relatively recently,

21:11

we've paid no price for that superpower.

21:13

It's only in the last hundred

21:16

or so years where we have shifted

21:19

from hundreds of thousands of years

21:21

of food scarcity to

21:23

tragic food abundance. Are

21:26

we starting to show that actually

21:28

the

21:29

drawback of this remarkable

21:31

capacity to store excess energy

21:33

is X, Y, and Z. And there are these metabolic

21:36

consequences of doing so. Now

21:38

again,

21:39

those are chronic problems, not

21:41

acute problems. And therefore,

21:44

on a relatively long time

21:46

scale, food scarcity or food shortage

21:48

is still a much greater evolutionary concern.

21:51

In fact, you would argue the

21:52

natural selection has really no interest

21:55

in the problem of over nutrition.

21:57

But to go back to your question, what is...

22:00

What can I say definitively? I can

22:02

say that too much nutrition is going to be bad chronically,

22:05

we'll go into more detail,

22:06

and too little nutrition is

22:09

going to be bad acutely. That's

22:11

fact one. Fact

22:13

two is, there are certain

22:15

amino acids

22:18

and fatty acids that are absolutely

22:21

essential for life. Meaning,

22:23

there are certain types of foods,

22:26

primarily in the form of fats and proteins,

22:29

that we must consume

22:31

in some quantity from the outside world,

22:34

and failure to do so will result in

22:36

horrific consequences.

22:38

Not just general

22:41

caloric malnourishment,

22:43

but deficiencies in cartilage,

22:46

bone, muscle, things of that nature.

22:48

There are also certain nutrients,

22:51

essential vitamins and minerals that are absolutely

22:53

essential for life. Everybody of course knows the

22:55

story of

22:57

the sailors who were not given enough vitamin

22:59

C in their rations, developed scurvy, et cetera, things

23:01

like that.

23:02

There are certain things that are toxic to us acutely.

23:05

We don't

23:07

do very well with certain types of bacteria,

23:10

so E. coli in our food,

23:13

relatively problematic.

23:14

That's about where it ends, Sam. That's

23:18

about all I can tell you

23:19

with capital T truth written all over

23:22

it.

23:22

Those are the things that are universally

23:25

true for which there's no ambiguity.

23:28

If we start to get into

23:30

how many grams of protein a day do you need,

23:33

why is it that someone can eat 2,000 calories of sugar

23:35

per day and still lose weight?

23:40

I have lots of thoughts on those things, and I

23:42

hopefully have more insight on those things

23:44

than maybe the average person on Twitter, but

23:47

we are definitely less

23:50

able to

23:51

reliably say things.

23:53

I guess that speaks to another nature, another

23:55

element of the problem, which is the human

23:57

body has a remarkable dampening.

23:59

factor quality when it comes

24:02

to nutrition. If you

24:04

think of a system like an engineering system where

24:06

you put inputs into it and then you get

24:08

the outputs out,

24:09

I think of the body as this remarkable

24:12

dampener

24:13

where when you put things in,

24:15

it sort of squashes

24:18

the output so it's very difficult to

24:20

in the short term discern how

24:22

the input affected the output.

24:24

Body weight is an example.

24:27

You know, what you ate the day before

24:29

from a caloric standpoint,

24:31

believe it or not, doesn't have an enormous impact

24:34

on your body weight the next day. That's probably more

24:36

a function of water weight and sodium

24:39

than the actual weight of the food because

24:42

most food comes with so

24:44

much water in it. So therefore, looking

24:46

at your body weight five times

24:48

a day is not really a good

24:51

way to determine energy

24:53

balance.

24:54

There's so many other movement systems in it.

24:56

Furthermore, there's so much variability

24:59

in our system with how we process

25:02

nutrients with respect to other variables

25:04

such as sleep. So we'll maybe talk

25:07

about sleep, but

25:08

a poor night of sleep

25:10

impacts insulin signaling

25:12

more than most people would appreciate and certainly several

25:15

nights of poor sleep would

25:16

have

25:17

an even bigger effect.

25:19

And the impact of that, i.e.

25:21

insulin sensitivity on fuel partitioning,

25:23

meaning how you store the nutrients you consume

25:26

them and then how you go back to the energy

25:28

well to draw them from storage is quite

25:30

significant actually.

25:32

So under two nearly identical

25:34

circumstances, food wise, two

25:36

different nights of sleep could also impact

25:39

things. So all of these things

25:40

make it very difficult to study the problem.

25:43

Yeah. Yeah. Well, so one

25:45

point about evolution and you actually

25:48

make this in the book, evolution

25:50

can't see really anything

25:53

we care about and surprisingly

25:55

to many people, it can't see

25:57

the variables that that

26:00

would determine our health span

26:02

and longevity past,

26:05

certainly past our 50s. It

26:08

just simply doesn't care about you living

26:10

to a ripe old age and being

26:12

able to swing kettlebells into your 80s.

26:16

It just cares about you spawning and

26:18

maybe helping your children

26:21

secure their spawning

26:23

period so that maybe there's

26:25

a, you can be a young grandparent

26:27

from the point of view of evolution and still

26:30

have some genetic utility. But after

26:33

that, there's just no evolution is

26:35

blind to what we care about. And

26:38

so I guess I'm

26:40

always hesitant to what, when I hear of

26:43

a diet that is using our

26:45

evolved environment as a reference

26:47

point, so like the paleo diet,

26:50

right? Where it seems to put a lot of stock

26:52

in the 200,000 years that preceded the present moment. I

26:58

just, I'm wondering about

27:00

the, how you view the limitations of

27:02

the lessons we can draw from that.

27:04

It just seems to me that we're living in

27:06

the world of science fiction now.

27:09

If we care about living to 120

27:11

with anything like a homoticum

27:13

of health span, we're, you

27:15

know, we have to figure it out on the basis

27:17

of principles that evolution has

27:20

never anticipated.

27:21

Yeah, that's a very interesting question. And it's one

27:23

I think a lot about. And you're absolutely

27:26

right, by the way, in fact, I could

27:27

just taking us back for a second, I could point to a couple

27:29

of genes

27:31

that

27:32

persisted

27:34

because of, you know,

27:36

evolutionary advantage that are a distinct

27:39

disadvantage today. So the LP little

27:41

a

27:41

phenotype, which is come comes from the LPA

27:43

gene and the APO E4 gene. So

27:46

these are both genes that are highly prevalent today

27:49

and highly associated with disease,

27:52

cardiovascular disease and Alzheimer's disease, respectively.

27:55

It might be tempting to ask the question why the heck do these

27:57

genes exist? And we know that the

27:59

the APOE gene,

28:01

the E4 isoform was the original

28:04

isoform. Well, I think the easiest

28:06

answer is one, evolution doesn't care about

28:08

Alzheimer's disease because nobody's getting it

28:10

before reproduction,

28:12

but even two, it's that the APOE4

28:14

isoform offered protection

28:17

in a world where infection ran

28:19

rampant. And the same is probably true of

28:21

LPA.

28:22

It's certainly increased blood clotting, which

28:25

would have been a huge advantage if you can think about

28:27

it, right?

28:28

Thousands of years ago, if not just a few

28:30

hundred years ago, to have a greater

28:32

likelihood of clotting

28:35

in the event of a cut would have been an enormous advantage.

28:38

Today, it's not so much an advantage and all the

28:40

negative consequences of LPA work against you. So

28:43

with all that said, lots of examples

28:45

of those situations.

28:48

When it comes to nutrition, I find

28:50

it hard to make the case that any

28:52

extreme diet is our optimal

28:54

diet, but I find myself

28:57

relying on an evolutionary example

28:59

here, which is

29:00

we were the most opportunistic omnivores

29:03

around.

29:04

So I can certainly make

29:06

the case for extreme diets to treat

29:09

disease,

29:10

meaning if a person has type 2 diabetes,

29:12

then maybe some extreme diet

29:15

or some sort of extreme dietary restriction

29:17

is the optimal diet.

29:19

But I would certainly argue that

29:21

if you don't have, if

29:24

you're just starting from a place of health,

29:26

I feel like one shouldn't have to be that restrictive.

29:29

Though

29:30

maybe I find myself making

29:32

this argument based on the fact that

29:34

we have lots of evidence that at least

29:36

to certain age,

29:38

and this of course is based on looking at

29:40

the few remaining hunter-gatherer

29:43

societies that do still manage to

29:45

make it into

29:46

old age,

29:48

consuming basically opportunistic

29:51

omnivore diets. So it's a little bit

29:53

of evolution, but it's also a little bit of looking

29:55

at, for example, certain

29:57

hunter-gatherer societies.

29:59

that still do exist, for example, in Australia

30:02

and Africa.

30:03

Okay, so let's talk about macronutrients,

30:06

right? We're talking about fat,

30:09

protein, and carbs. I guess

30:11

to come back to the crazy example I started

30:13

with of the guy who ate nothing but

30:15

ice cream, or 2,000 calories of

30:18

ice cream plus 500 calories

30:20

of protein powder and

30:22

alcohol.

30:23

So he sounded like he had fun, at least for the

30:25

first week. The fact that it was ice

30:28

cream rather than Skittles

30:31

makes me think that maybe it's

30:33

not quite as insane a story

30:36

as it might seem because I remember

30:38

the one time I tracked

30:41

my blood glucose

30:43

for 14 days, I was actually surprised

30:45

to find that ice cream, I

30:48

assume because the sugar is being mediated

30:51

by fat was not as

30:53

a high glycemic load as many

30:56

other things that were ostensibly much healthier

30:58

that I might eat, like I remember

31:00

a vegetarian burrito just

31:02

sent my blood sugar off the

31:04

charts, whereas ice cream was pretty

31:08

unspectacular. But in any

31:11

case, how do you think

31:13

about fat, protein, and

31:15

carbs in general? What

31:17

generically can you say

31:20

about what most

31:22

human beings most of the time

31:24

require on that front? And

31:27

how can you extrapolate from

31:29

those principles to

31:31

what we might assume is a, if

31:33

not the perfect diet, at the very

31:35

least, a very safe bet

31:38

for a healthy one?

31:40

So I think about this in

31:42

a formulaic way that maybe

31:44

takes a little bit of the romance out of eating,

31:46

which doesn't mean that I necessarily adhere to it

31:49

with that rigor. But if I'm going to think

31:51

about this as an engineering problem,

31:53

it's actually, I think, quite simple.

31:56

But before I do that, I think it's worth

31:58

addressing the

32:00

perhaps the mystery in the ice cream

32:02

man. So let's

32:03

assume that this is correct. And I

32:05

think that's

32:06

not an assumption one should take lightly, right?

32:08

So

32:09

I think the whole,

32:10

I did this on YouTube, therefore it's

32:12

true, one needs to have a healthy

32:15

degree of skepticism and it would

32:17

be more interesting to see that in a clinical

32:19

trial. But let's just assume there was a clinical trial

32:22

that said we took 700

32:24

overweight

32:25

people

32:29

whose average caloric intake in

32:31

the run-in period was X and

32:34

we created a 25% caloric

32:36

deficit that

32:38

consisted of what you just described.

32:40

Do you think they're going to lose weight?

32:42

My answer to that question would be yes. I would expect

32:45

them to lose weight.

32:47

In other words, I think that the single

32:50

greatest determinant

32:52

of energy balance

32:54

is indeed, or maybe a better way to say this,

32:56

the single greatest determinant of weight

32:58

loss is going to be energy imbalance would be

33:00

maybe the most accurate way I could say that.

33:02

So in other words, a caloric deficit,

33:05

no matter what you're eating.

33:06

No matter what it's constituted by, that's right. So

33:09

if we

33:10

did another

33:11

thought experiment and we said, look, we're going

33:13

to take a thousand people who are

33:15

all ostensibly overweight,

33:17

and let's just make it really elegant and say

33:19

that they're all basically genetically equivalent, so

33:21

it's just like a bunch of mice.

33:23

And they're all

33:26

coming in at 3,500 calories per day and their weight

33:29

stable at 3,500 calories per day. We're

33:31

going to divide them into two groups

33:34

and the first group is going to go on

33:36

a 2,800 calorie a

33:39

day diet

33:40

of junk food.

33:41

The other group is going to go on a 4,000

33:43

calorie a day diet of whole

33:45

foods,

33:47

right? The best, whatever, come

33:49

up with your favorite best diet.

33:51

There's no doubt in my mind that that group

33:53

eating 4,000 calories per day is going

33:55

to be heavier

33:57

when the trial is done

33:59

than the other group.

34:00

And by the way, they might also be less healthy,

34:02

that big of a gap,

34:05

right?

34:06

Because of something we should probably talk

34:08

about, which is why is it that excess

34:10

energy

34:11

is harmful? Because

34:12

it's not the aesthetics, right?

34:15

It's not because you lose your six pack that you're

34:18

unhealthy. There's something going on that's much

34:20

more important to understand.

34:22

So with all of that said, how do I

34:24

think about the problem? I think about the problem by saying,

34:27

and there's really a fourth macronutrient, Sam, that we

34:29

should at least mention, which is alcohol. And

34:31

the reason is alcohol is so calorically

34:33

dense, right? So I think most people know that

34:35

carbs and proteins are roughly four kilocalories

34:38

per gram.

34:40

Fat is nine kilocalories

34:42

per gram. Well, ethanol is seven.

34:45

So

34:45

one has to be mindful if they're in the

34:48

business of trying to lose weight, of just mindlessly

34:50

consuming alcohol

34:52

for at least two reasons. The first being the energetic

34:54

reason,

34:55

the second being if you're anything like me,

34:57

there's no greater way to reduce my inhibition

35:00

around food than to give me a couple of drinks.

35:03

So

35:04

I start with protein because protein is

35:06

the most important in my

35:08

view.

35:09

And there's different ways to think about

35:11

this, but I would just start by saying

35:13

that the RDA, the recommended dietary allowance

35:16

is clearly incorrect. And I go to great lengths

35:19

in the book to kind of explain this. I've also written about

35:21

this elsewhere. I've got multiple podcasts

35:23

on the topic.

35:24

The RDA, which

35:26

offers something to the tune of 0.5 grams of

35:29

protein

35:32

per

35:33

kilogram of body weight, or 0.5

35:35

to 0.8, I

35:35

think is the RDA. That's sort of what it

35:40

takes to not have

35:42

malnourishment. But if we want to really

35:44

talk about thriving, especially

35:46

in people over 50,

35:48

it's probably closer to 0.8 to

35:51

one gram per pound of body

35:53

weight. So again, that's a huge

35:55

difference, right? So if you take a person

35:57

who weighs 175 pounds,

35:59

or 80 kilos, the RDA

36:02

would say that person can get away with 60 grams

36:05

of protein.

36:07

I'm arguing that person should be between

36:09

about 150 and 180. So it's

36:11

a huge difference and I'm certainly not

36:13

saying this alone. Some

36:16

people much smarter than me would agree with that.

36:18

So we start with that.

36:20

The next thing I'm thinking about

36:22

in the formula is what

36:24

is your carbohydrate tolerance?

36:26

So you mentioned a moment ago that you'd

36:28

warn a glucose

36:30

tracking device, I assume a continuous glucose monitor

36:32

for a couple of weeks.

36:33

Yeah. So I think those are really helpful

36:36

tools to give people a sense of what

36:38

I mean by carbohydrate tolerance. Carbohydrates

36:41

are also very important and

36:43

I unfortunately bear a tiny

36:46

bit of responsibility in a previous life

36:48

for probably demonizing them too much. But

36:51

the reality of it is carbohydrates are

36:53

important. They're our most abundant and

36:56

quickest source of energy.

36:57

So there's nothing you can do to turn

37:00

food source into ATP quicker

37:02

than glucose.

37:04

And it is the preferred fuel of

37:06

our brains. In fact, even in a state

37:08

of total starvation, 40 days

37:10

without food,

37:11

which believe it or not was actually studied by George

37:13

Cahill at Harvard back in the 1960s,

37:15

not a study to be replicated. They had subjects

37:18

that fasted for 40 days. They

37:20

were still getting 50% of

37:23

the energy to their brain was coming from

37:25

glucose. The other 50% was coming from ketones.

37:27

If you ask where does that glucose come from when you're starving,

37:30

it's because making the ketones

37:33

and breaking down the fat to do so creates

37:35

a byproduct that gets recycled into glucose

37:37

called glycerol.

37:38

But anyway, glucose is important.

37:41

The problem with glucose is too much of it

37:43

chronically is harmful,

37:46

not acutely. Acutely, we are

37:48

much more interested in protecting against the downside

37:51

and not having enough of it. So hypoglycemia

37:54

is acutely fatal.

37:56

Hyperglycemia is not outside

37:58

of very extreme circumstances.

37:59

that can only exist if you have type 1 diabetes.

38:03

So

38:04

the body, again, going back to kind of the evolutionary

38:06

thing we talked about earlier, isn't really

38:08

working that hard

38:10

to protect you from a blood glucose of 150

38:13

milligrams per deciliter, which is about 50%

38:16

higher than normal. It doesn't truly care.

38:18

However, the

38:20

effect of that over many years is devastating.

38:23

It will destroy your kidneys, it will destroy

38:25

your heart,

38:26

it will destroy

38:27

anything in your body, including your brain, that

38:29

has small blood vessels.

38:31

That's why people with type 2 diabetes have

38:34

twice the risk of most

38:36

diseases, right? Cancer, heart

38:38

disease, Alzheimer's disease, et cetera. But

38:40

that's not a huge difference, right?

38:43

So we have to figure out

38:44

what's our limit.

38:46

And I think there's sort of two ways to think about this.

38:48

What's your average blood glucose and how much variability

38:51

is there in what you eat? And

38:53

again, you can figure this out using traditional biomarkers.

38:56

You can figure this out using a continuous glucose

38:58

monitor.

38:59

But basically once you figure out how much

39:02

protein you need, the next question is

39:04

how much carbohydrate can you tolerate

39:07

while keeping yourself in those parameters?

39:09

And I offer some suggestions for these, but

39:12

I think if you're going to be really aggressive and

39:14

have, if you want sort of an A plus on your report

39:16

card here,

39:17

I would say having an average blood glucose

39:19

below 100 milligrams per deciliter.

39:21

So that takes into account all the peaks and valleys would

39:24

be considered excellent. And that would correspond to about a hemoglobin

39:26

A1C of 5.0

39:28

Now what determines that? Well, your activity

39:30

level, how much muscle mass you have, how

39:33

insulin sensitive you are, how well you sleep, how

39:35

much hypercorticellumia is going on, genetic

39:37

factors certainly play a role in it.

39:39

All of these things will matter. And even

39:41

for a given individual, they'll change. So

39:43

when I was a

39:45

cyclist,

39:46

I could consume 800 grams of carbohydrates

39:49

a day and still be within that band.

39:51

Today it's much lower than that.

39:53

So you sort of have to know what that looks like.

39:56

And then the final point is that fat makes up

39:58

the difference.

39:59

And

39:59

And the total amount of fat that goes

40:02

in as basically a plug is to

40:04

determine where you need to be on energy balance.

40:06

So

40:07

believe it or not, in a reasonably healthy

40:09

diet, your appetite can serve

40:11

as a reasonable backstop for how much you need

40:13

to eat.

40:14

And by the way, going back to the funny

40:17

example you gave of the guy eating ice cream all

40:19

day, one thing I'm always interested in, and

40:21

I don't know if the guy talked about this in his video

40:23

is,

40:24

what was his degree of satiation?

40:26

In other words,

40:28

when you're eating 2,000 calories of ice cream a day,

40:31

what kind of cravings was he having for other food?

40:33

And was he satiated? Did he go to bed

40:35

at night feeling like I'm full?

40:37

Or did he kind of go to bed starving

40:39

because his body was actually demanding more

40:41

but he was kind of capping it artificially? Did

40:44

he comment on that? I don't remember. I

40:46

remember that the punchline was that he was

40:48

ultimately quite miserable on this diet. I

40:50

mean, he was surprised to be as

40:53

unhappy as he was

40:55

despite the improvements in his weight

40:57

and lipid profile, but he

40:59

was not having fun ultimately. But

41:02

there's another component to that, right, which I think is,

41:05

you know, I think you asked

41:07

earlier like

41:08

what would we agree on is universally true.

41:11

Another

41:12

way to ask that question is,

41:13

if you had all the experts in the room,

41:15

could they agree on what is the driver

41:18

of the modern epidemic of obesity? So it's a different

41:20

question, but they're related, right? Yeah.

41:23

Well, why have we never had an answer to that? And

41:25

I think the answer is that the nature of

41:27

science is that most people study one pathway

41:30

or one vehicle. And in obesity,

41:32

I think there are so many

41:34

that I think there are a

41:36

dozen plausible explanations

41:39

and it may be that every individual

41:41

who's obese is, you

41:43

know, their obesity may be driven by two

41:45

or three of those

41:47

as the dominant drivers versus others. So

41:50

for example,

41:51

one theory of obesity

41:53

is that our food is

41:55

so much less nutrient dense than it

41:58

used to be. And this is one thing.

41:59

I actually didn't write about in the book that I really wanted

42:02

to, but there simply wasn't enough room

42:04

to get into nutrient density

42:06

and to talk about, for example, soil health

42:08

and how soil health impacts plant health and how

42:11

that impacts animal health, etc. But

42:13

there's very little doubt that food

42:15

today, whether it be spinach or beef

42:18

or barley or whatever has fewer

42:20

nutrients in it than it did 100 years ago.

42:23

And the question is, are we

42:26

intrinsically innately wired

42:28

to seek a certain volume of

42:31

nutrient? And as the nutrient density

42:33

of our food goes down, are we

42:36

simply seeking more calories to meet

42:38

our nutrient needs? That's an argument.

42:40

There's another argument that says the same thing. We're hardwired

42:43

to get a certain amount of protein,

42:45

but as our sources of protein are getting

42:47

diluted, we're seeking out higher and

42:49

higher caloric volumes of food

42:51

to meet the same protein requirements.

42:55

Other theory, of course, is that it's all driven by

42:57

palatability. The more palatable the food,

42:59

the more likely we are to seek it out. So you get

43:01

the idea that there's multiple theories.

43:03

It's also possible they're all kind of partially

43:05

right.

43:06

So on this question of protein, I think in

43:08

your book you emphasize, as you

43:11

did here, that as you get older,

43:13

it becomes even more important to

43:15

focus on how much protein you're getting.

43:18

What are the prospects of getting sufficient protein,

43:21

as sufficient as just defined by you, something

43:24

like

43:25

a gram per

43:26

pound of body weight if you're

43:29

a vegetarian or a vegan? I

43:32

realize this is dangerous territory with respect

43:34

to getting put on the radar of the vegan

43:37

mafia, but what

43:39

are your thoughts about

43:41

cutting meat and even

43:43

all animal protein

43:45

out of one's diet and still getting the

43:47

requisite amount of protein as one

43:49

gets older? I

43:50

mean, I think it's still possible it just

43:52

gets harder. There's no question. It's

43:55

a trade-off. What you're referring to is anabolic resistance,

43:58

and that kind of, you know, starts...

44:00

Yeah, roughly in your 50s, but certainly

44:02

increases

44:03

probably non-linearly from there.

44:06

And that's where you probably have to start getting closer

44:08

to that one gram per pound

44:10

of body weight to maintain

44:13

maximal muscle protein synthesis,

44:15

the process by which

44:17

muscle gets broken down and rebuilt.

44:19

And

44:20

the reason this is so important is that

44:23

sarcopenia is an enormous

44:25

problem of the elderly. Sarcopenia

44:27

is the disorder of low muscle

44:29

mass.

44:30

And with sarcopenia and frailty

44:33

comes enormous mortality.

44:35

I think this is actually kind of the hidden

44:37

epidemic of aging. I do

44:40

write about this, but I think I write about it a little bit more in the exercise

44:42

chapter, which is

44:44

once a person reaches the age of 65, if

44:47

they fall and break their

44:49

hip, and I can't imagine there's a person

44:51

listening to us speak now, Sam, who doesn't know

44:54

somebody for whom that's happened,

44:56

right? It's like, oh, my friend's mother or somebody,

44:58

right? I've literally talked to two

45:00

patients in the last week who have

45:03

had parents go through this.

45:04

So if you're over the age of 65, you fall

45:07

and break your femoral neck or your femur.

45:09

There's a 15 to 30% chance

45:12

you will be dead in the next 12 months.

45:14

And if you don't die in the next 12 months,

45:17

of those who survive, meaning of the 70 to 85% who

45:20

survive,

45:21

there's a 50% chance you will

45:24

have a full scale reduction in

45:26

your mobility for the remainder of your life. Meaning

45:29

if before this incident you walked freely,

45:31

you will forever be using a cane.

45:33

Before this incident you were using a cane, you will be

45:36

in a walker,

45:37

et cetera, et cetera, all the way down to a wheelchair.

45:39

So accidental deaths due

45:42

to falling is the leading cause

45:44

of accidental death for people over the age

45:46

of 75 at a level

45:49

that exceeds even what

45:51

we see for accidental overdothes

45:53

for people under 65. And I think most

45:55

people are probably now aware

45:58

that

45:58

accidental death due to...

45:59

overdose has become

46:02

the most common cause of accidental death

46:04

for people under 65, eclipsing even

46:06

automotive accidents. So

46:08

with all of that said as the background, frailty

46:10

and sarcopenia are an enormous

46:12

problem, and not just because

46:15

of what they

46:16

do showing up on death certificates,

46:18

but because of how much they rob people of health

46:21

span.

46:21

Even if it doesn't kill you,

46:23

it can easily ruin the last decade of

46:25

your life.

46:26

So with all that said,

46:28

the antidote to this is to have as much

46:30

muscle as possible, to be as strong

46:33

as possible, to be as fit as possible.

46:35

I make this joke all the time,

46:37

but it's true.

46:38

How many people have existed,

46:40

Sam? Do we have a... It's like, there's eight

46:42

billion now. How many billion were there before us?

46:44

Isn't that about another? I think it's about 110 billion. Okay.

46:48

I'm willing to bet,

46:50

and I don't know how we could ever verify this, but my

46:52

bet would be

46:53

in the entire history of that 100 billion

46:56

people,

46:56

I would bet that no one

46:59

in the final days of their life said, I wish I

47:01

had less muscle. I wish I was less strong.

47:03

It's simply not possible. So

47:06

protein intake is an essential

47:09

component of maintaining muscle mass.

47:11

And of course, resistance training is

47:14

as well. So to your question,

47:16

can a person who morally or

47:18

philosophically doesn't want to consume meat

47:21

or who doesn't want to consume animal protein

47:23

still avoid sarcopenia?

47:26

I think the answer is yes,

47:27

but they have to acknowledge that they're in

47:29

for a harder ride,

47:31

meaning they're going to have to work harder at

47:33

eating than maybe you or I do, if we're

47:35

willing to consume meat and animal products.

47:38

On this issue of sparing

47:41

muscle mass, I guess there's two questions.

47:46

One actually poses

47:48

a potential puzzle with respect

47:50

to evolution. So when you just stop

47:52

eating, when you start fasting and

47:55

even start starving and

47:58

you rely on your fat stores. as

48:00

evolution has permitted, why

48:03

doesn't that reliance spare

48:05

muscle systematically

48:08

until you lose all your fat?

48:11

My understanding is if you start fasting,

48:14

there is some considerable risk that

48:16

you are going to be losing

48:18

lean muscle mass during that fast.

48:21

Why is that? It seems like evolution would

48:23

have recognized that more

48:26

muscle is generally better for all sorts of

48:28

things, and the fat store

48:31

has been put there for a reason to be

48:33

utilized under just these circumstances.

48:35

Why doesn't it just spare

48:38

muscle systematically? Yeah, it's

48:40

a great question. Below a certain

48:42

calorie threshold, we

48:44

will use protein for energy.

48:47

For example, if you went

48:49

on 1,000 calorie a day fast,

48:52

but that 1,000 calories was 250 grams of

48:56

protein, so 250 grams of protein is about 1,000 calories, you'd lose weight,

48:58

but you'd

49:02

probably lose muscle as well.

49:05

Why is that? Well,

49:07

first of all, the body does have a pretty remarkable

49:09

tool to prevent the complete emaciation

49:12

of muscle, and that is ketosis.

49:14

Earlier I mentioned glycogen, which is the storage

49:16

form of glucose.

49:18

We can store, I don't

49:20

know, somebody your size or my size, Sam,

49:23

we could probably store 400 grams

49:26

of carbohydrates. So you could probably

49:28

put 300 grams of glucose

49:31

into your muscles, so that's about 1,200

49:33

calories, and you can put another 100

49:35

into your liver.

49:36

By itself, if you

49:39

never made any other tweak to the system, that's

49:41

like a day's worth of energy.

49:43

Obviously, lots of times when we need to go more than

49:45

a day without eating,

49:47

as our ancestors

49:49

at least did.

49:50

So what you don't want to do at that

49:52

point is immediately start tapping muscle,

49:55

because if you did, you would break down muscle

49:58

in a really rapid fashion.

49:59

So in other words, if we broke down muscle for amino

50:02

acids and sent those amino acids to the

50:04

liver to undergo a process called gluconeogenesis,

50:06

we would make glucose out of the muscle. I'd

50:09

have to do the math on it. I've never done it, but

50:11

I think it would be just a matter of a

50:14

week or so until you'd be completely

50:16

broken down. So

50:18

while that is happening somewhat, it's more

50:21

happening because we are not providing

50:23

new amino acids for the muscle protein

50:26

synthesis. So

50:27

we constantly break down muscle

50:29

and replace it partially with

50:32

amino acids that we already have

50:34

broken off muscle and partially with

50:36

new amino acids that we're eating.

50:38

So

50:39

it's actually a very... The only way you can tease

50:41

this out, by the way, in research is to do labeled

50:43

studies. So you give people amino acids that

50:46

have tracers on them, and then

50:48

you can distinguish between how much of the muscle protein

50:50

synthesis is coming from the exogenous

50:53

amino acids versus the

50:55

endogenous amino acids. And what you realize

50:57

is it's actually a pool of both. So I

51:00

don't know if I'm making sense to the listener. I think

51:02

you understand what I'm saying. But basically in

51:04

a form of starvation, you've taken away half

51:07

of your amino acid pool, which

51:09

is the exogenous pool, and you're only

51:12

able to then rely on the endogenous pool for

51:14

muscle protein synthesis. And that's why you will

51:16

experience muscle wasting.

51:18

But that's far better

51:20

because at least you're not using muscle

51:23

to then make glucose via gluconeogenesis.

51:26

That would be a catastrophic problem. So I guess what

51:29

your question is, is why

51:31

hasn't the body figured out a way

51:33

to undergo muscle protein synthesis

51:35

without exogenous amino acids?

51:38

But honestly, I think that's sort of like asking, why

51:41

do we need food?

51:44

So let's touch this final topic

51:47

under nutrition of fasting and

51:49

time restricted eating because I know you've experimented

51:52

a lot with this personally. And

51:54

many people are interested in this as just

51:57

a way of

51:58

reducing...

51:59

caloric intake, I mean, just shrinking

52:02

the time window in which you eat as a strategy

52:04

for not living with

52:07

a toxic surplus of

52:09

calories. What are your

52:11

thoughts on this now? And

52:13

I guess obviously it connects

52:15

with a certain strand of

52:17

research on the topic of longevity

52:19

where caloric restriction has,

52:22

I think, across every

52:25

species in which it's been looked

52:27

at, known to be correlated with

52:30

longevity. How do you think about this

52:32

now?

52:33

So I guess I would just sort of put this all in the context

52:35

of the broader problem, right? So if the problem

52:38

is what do you do in the case

52:40

when an individual is overnourished,

52:42

which I think is just kind of a technical way to say

52:45

they have too much stored energy

52:48

and it is

52:49

exceeding the point of utility and it's now

52:51

that energy is spilling over into

52:54

other areas and causing problems. So that

52:56

fat is spilling into the

52:58

space between their organs, it's

53:00

getting into their muscles directly, it's

53:03

getting into their pancreas, and it's

53:05

toxic, right? It's inflammatory, it

53:07

increases insulin resistance, which exacerbates

53:09

the problem, all these things.

53:11

The solution to that is

53:14

reduction of energy input, right? So

53:16

you have to create a caloric deficit

53:19

in that situation.

53:21

Broadly speaking, there are three

53:23

ways to do that. The first

53:25

is to directly,

53:27

day in and day out, minute by minute,

53:29

think about reducing intake. So that's

53:31

the example, I think, of

53:33

what we've just

53:35

been talking about, right? It's like, okay, I eat 3,000

53:38

calories a day and I need to lose

53:40

fat, I have to reduce that to 2,500, I'm

53:43

going to track those macros and

53:46

count up to 2,500 calories a day.

53:48

The other way to do it is dietary restriction. Come

53:50

up with a restrictive diet

53:52

and focus on excluding

53:54

as many things as possible and

53:56

the more restrictive that diet,

53:58

the more likely you are to

53:59

to achieve energy imbalance. So

54:02

if you go on the no lettuce diet, it's not

54:04

going to be very restrictive. You're not going to lose weight.

54:07

But if you go on the potato only diet,

54:09

you almost assuredly will lose weight.

54:11

Now the third strategy is what you're talking about, which

54:13

is time restriction. Just create a narrow

54:16

enough window in which

54:18

to eat

54:19

such that at some point the window becomes

54:21

narrow enough that you're going to create an energy

54:24

deficit. So calorie

54:26

restriction is the direct way to do it. And dietary

54:28

and time restriction are the indirect ways to do it. I

54:31

was sort of,

54:32

I would say probably six, seven years

54:35

ago of the

54:37

view, because we really didn't have the data

54:39

at the time that thought there was something

54:42

beneficial to time restriction beyond

54:44

the caloric deficit. In other

54:46

words,

54:47

I believed that

54:50

the act of not eating for 18 to 20

54:52

hours per day in and of itself

54:55

brought a metabolic benefit independent

54:58

of the caloric deficit.

55:01

I would say that that view

55:03

has been refuted by at

55:06

least two studies

55:08

in the past three years, two years

55:11

that have, when controlling for

55:13

intake, demonstrated

55:16

two things. The first is that actually

55:18

all of the benefits of time restricted feeding seem

55:20

to come down to

55:22

the reduction in calories. But

55:25

a more important finding

55:27

has been that there may actually be a downside

55:30

to time restricted feeding, which

55:32

is that many people are incapable

55:34

of consuming sufficient enough protein in

55:36

that window.

55:37

And while they do lose weight,

55:40

they may disproportionately be losing muscle.

55:42

Interesting.

55:43

Just to backtrack for a second. So the

55:46

restriction of specific

55:48

foods,

55:49

do you think there's any

55:52

metabolic magic there where

55:54

you hear someone who's on an

55:56

all meat diet say and they're losing

55:59

weight? universes any other strategy.

56:02

If you are emphasizing one macro

56:05

over another, do you think it

56:07

isn't at the end of the day just

56:09

a matter of calories in with

56:11

respect to energy balance?

56:14

Is there metabolism

56:16

working above

56:17

the

56:19

mere caloric physics

56:21

that accounts for weight loss on

56:23

certain restricted diets? I don't

56:26

think so.

56:27

I do think now we're clearly, if we

56:29

go back to the way you posed the questions

56:32

at the outside of our discussion vis-a-vis nutrition,

56:34

I think we are clearly in the area where we need

56:36

to have a lot of humility

56:38

and just acknowledge we're now speaking in the unknowns.

56:41

My intuition based on the existing

56:43

body of literature

56:45

is that from an energy balance

56:47

perspective, a calorie is a calorie.

56:49

I

56:51

do not believe that we are, because

56:53

the only way that it's not is to say

56:56

you are impacting energy expenditure.

56:59

Does the body metabolize

57:02

these calories different from those calories? The

57:04

short answer, I guess, is yes, there's a

57:06

little bit of that. There's something called the thermogenic effect

57:08

of food where we require

57:11

more energy to break

57:13

down protein than we do carbohydrates and fats.

57:16

There is a slight discount metabolically

57:18

that comes from that.

57:19

Do I think that that is why a carnivore

57:22

diet being basically,

57:24

I don't know, it depends on what kind of meat

57:26

you consume, but a carnivore diet

57:29

could easily be one third protein, two

57:31

thirds fat from a macro perspective. Do

57:34

I think that that explains the

57:36

profound weight loss that people experience

57:39

when they experience it on a carnivore diet?

57:41

I don't think so. I think that really comes down

57:43

to just reduced intake.

57:44

This gets to an important point,

57:47

which is the point of satiety.

57:49

This is the hardest thing to study

57:52

because if you're

57:54

doing a really well controlled study, you actually

57:56

want to feed people

57:58

prescribed amounts of

57:59

food, thereby ignoring or

58:02

negating the benefits or

58:03

disadvantages of a change in satiety.

58:06

But in the real world,

58:08

satiety might be the single most important factor

58:11

in determining long-term compliance, right? I

58:14

don't believe that most people

58:16

can exist in a state of perpetual hunger,

58:19

day in and day out. Clearly

58:22

some people can, but I don't think that's the norm. And

58:24

therefore, whatever is at the root of

58:27

the societal energy imbalance

58:29

we have,

58:30

must have at its basis something

58:33

to do with satiety.

58:35

Unless you believe people are just mindless

58:37

eating machines, and I'm just not sure I'm

58:39

ready to fully concede that point yet. So-

58:42

You happen to know what the experience is of people who have taken

58:44

the caloric restriction principles

58:46

to a proper extreme. I know there

58:49

are

58:49

food scientists and doctors

58:52

and a few other people who have decided

58:55

that the data are in. We

58:57

know what happens to mice, we know what happens to

59:00

yeast. If you dial down

59:02

the calories to the absolute

59:06

minimum maintenance level, you

59:08

increase lifespan by an enormous

59:11

amount. And so there are people walking around, I don't

59:14

know what their caloric ceiling is, maybe

59:17

something like 1500 calories. They're

59:19

living on a diet that abstemious

59:21

for years at a stretch. Is

59:24

their experience one of being perpetually

59:27

hungry, or do they reset and

59:29

experience kind of a normal level of

59:31

satiety?

59:32

I haven't studied them. I

59:34

know anecdotally a little bit just from, I

59:37

have a couple of colleagues who

59:39

have even gone and spoken at their conferences, because

59:41

there are societies of CR out there.

59:43

Those caloric restriction societies of people who do exactly

59:46

what you're describing.

59:47

I think it's probably closer to 1800 to 2000 calories per day. But

59:51

yes, I think it's an interesting question. I mean, there's

59:53

two interesting questions there, right? So at least

59:56

two, right? So one is,

59:57

what is their subjective state of existence?

59:59

are they constantly thinking about food?

1:00:02

I will say this, I've definitely spoken

1:00:04

to a lot of body builders, and

1:00:06

that's about the amount of calories they're on

1:00:09

during a cutting phase.

1:00:11

Yeah. And Sam, I've never

1:00:13

spoken to one of them who hasn't said

1:00:15

that they don't wanna end their life during that phase.

1:00:18

Yeah, yeah.

1:00:19

So now again, you could argue, well, they're only

1:00:21

doing that for 12 weeks,

1:00:23

and maybe that's not long enough to acclimate, and they're

1:00:25

also asking a lot of themselves because they have to

1:00:27

exercise during that period of time.

1:00:29

So that's not an apples to apples comparison,

1:00:32

but that's question one.

1:00:33

I think the more important question in as

1:00:35

much as it's academically interesting is,

1:00:37

does the draconian step that they're taking

1:00:40

translate to an improvement

1:00:42

in lifespan and health span for the

1:00:44

species of interest,

1:00:46

which is humans? So everything you said is

1:00:48

true, right?

1:00:49

We know that yeast and worms and fruit flies

1:00:52

and rodents,

1:00:53

at least in a laboratory environment, will

1:00:55

live longer under CR conditions,

1:00:58

but we don't know if that's true for humans who

1:01:00

live in the real world.

1:01:02

And as I devote probably half

1:01:04

a chapter two in the book, when I go through the

1:01:06

NIH,

1:01:07

Wisconsin, NIA

1:01:09

experiment with rhesus monkeys,

1:01:11

it turned out to not even be clear that CR

1:01:13

was beneficial there.

1:01:15

Yeah. You mentioned alcohol

1:01:18

as a fourth macro here. I was gonna ask you about

1:01:20

it under the heading of lifestyle,

1:01:22

but maybe we'll just discuss it here.

1:01:25

Is, maybe it's been 10,

1:01:27

15 years since the emergence

1:01:30

of a kind of cottage

1:01:32

industry in hopeful articles

1:01:35

about the health benefits of alcohol, some

1:01:38

of which I think in retrospect were sponsored

1:01:40

by the alcohol industry.

1:01:44

It's not to say that a conflict of interest always

1:01:46

proves that the science is bad, but what

1:01:49

do we know about the health impacts

1:01:51

of alcohol? And perhaps we

1:01:53

can boil it down to kind of a personal

1:01:56

punchline. I mean, just how is it that you

1:01:58

approach this? yourself personally?

1:02:01

What have you decided is the risk-reward

1:02:04

trade-off that you're comfortable with in your

1:02:07

own life?

1:02:08

Yeah, I mean, I'll just give you my answer for me

1:02:10

but then I can sort of explain it or defend

1:02:12

it or explain why it might be illogical.

1:02:15

So my view is I do continue to consume

1:02:17

alcohol,

1:02:18

but I think from a

1:02:21

risk standpoint... If you'd like to continue

1:02:23

listening to this conversation, you'll need to subscribe

1:02:26

at SamHarris.org. Once you

1:02:28

do,

1:02:28

you'll get access to all full-length episodes of

1:02:30

the Making Sense podcast, along with other

1:02:32

subscriber-only content, including

1:02:34

bonus episodes and AMAs and

1:02:37

the conversations I've been having on the Waking Up app. The

1:02:39

Making Sense podcast is ad-free and

1:02:42

relies entirely on listener support, and

1:02:44

you can subscribe now at SamHarris.org.

1:02:57

You