0:00

What is NED? NED is a small

0:02

molecule that's the centerpiece of biology and

0:04

it really does three things in our

0:06

body. Gives us our energy, protects us

0:09

against oxygen, and it saves us from

0:11

cancer. We used to think about diseases

0:13

as being sort of these isolated instances

0:16

of bad luck. Oh, I got diabetes.

0:18

Oh my goodness, I got cancer. But

0:20

that's the 1950 ways to look. Today

0:23

we have to see these really as

0:25

an integrated whole. Why do we get

0:27

sickers we get older? The aging process

0:30

is a core fundamental derangement. spawns injury

0:32

in all these different organs. If you

0:34

happen to have an injury in your

0:36

knee, suddenly you have arthritis. But it's

0:39

really not arthritis. What it is fundamentally

0:41

is aging. I look at it like

0:43

this. If I age, it's my fault.

0:46

A lot of people think that aging

0:48

starts when you're 60 and 70, but

0:50

actually aging doesn't start when you're 65.

0:53

Given what we know with AI, with

0:55

new research, all the work you've done

0:57

in your life, You're listening to the

1:00

human upgrade with Dave

1:02

Asprey. This is going to be a

1:04

really fun episode recorded live

1:06

in the studios here in

1:09

Austin, Texas. Because I like

1:11

talking with really really smart people

1:13

who've done a lot of big

1:15

things in the world. There's so

1:18

much we can learn. The episode

1:20

today is about longevity.

1:22

It's about NAD. It's with

1:24

a guy who's only written

1:27

like a hundred and seventy

1:29

scientific publications, fifty patents, and

1:31

the guy who created the

1:33

first parp one inhibitor, which

1:35

is really, really useful in

1:37

preventing cancer. He's also the

1:39

chief medical officer for Wonderfield, which

1:42

is a new NAD focused company

1:44

making some supplements that are,

1:46

I would say, the next generation

1:49

of what's happening in the world

1:51

of NAD. If you're new to the

1:53

show and you don't know what NAD is,

1:55

we're going to go into that. This is

1:57

a compound I wrote about in my longevity

1:59

book. It's a compound that you've heard

2:01

from maybe David Sinclair on the show

2:04

talking about it. And it's something

2:06

that's very fascinating, because if you can

2:08

control your NAD levels, you can control

2:10

one of the many pathways of aging

2:12

that you need to control if you

2:15

want to live to at least 180,

2:17

like me. So let's bring one of

2:19

the luminaries in the field onto the

2:21

show to go deep on it, none

2:23

other than Dr. Andy Salzman. Andy, welcome

2:25

to the show. Thank you very much.

2:27

So you were a practicing physician, Harvard

2:29

kind of guy, and then you suddenly

2:32

one day decided I'm going to wake

2:34

up and go do research and make

2:36

drugs instead of being a doctor. Why?

2:39

I love taking care of patients and

2:41

being at the bedside and helping people,

2:43

helping children, talking to the families.

2:46

I went into intensive care because

2:48

I deeply cared about critically

2:50

ill kids. But you know, after about 10

2:53

years at the bedside, I realized that

2:55

I wasn't able to do enough. I

2:57

could work all night, I could take care of

2:59

kids, but ultimately, the real advance is when

3:01

you develop a new drug or a new

3:03

intervention that can save not one kid at

3:06

the bedside but thousands. Thousands that you haven't

3:08

even met, and so I committed myself to

3:10

research to do that. Does it have to

3:13

be drugs? I mean, could it just be

3:15

a problem? No, no, any kind of intervention,

3:17

but something different, something outside of the normal

3:19

pattern of medical behavior that we are accustomed

3:22

to in the hospital. So something that scales

3:24

better than let's send everyone to the hospital,

3:26

let's give them something that can work

3:28

even if they don't have to

3:30

go to the hospital. That's right.

3:32

You're working with a supplement company,

3:35

but you did a $600 million

3:37

deal on a cancer drug you

3:39

invented that you sold to Genentec.

3:41

So why the cutover from pharmaceuticals

3:43

to nutritionals? Well, I work in

3:45

both areas. Okay. So I don't

3:47

have a preference. Well, I will

3:49

say, I do have a preference,

3:52

actually. I think that the non-pharmaceutical

3:54

approach today has become faster. It's

3:56

richer in terms of the possibilities

3:58

you can exploit. The pharmaceutical world,

4:00

for all of the good it can do,

4:02

it's just very tedious and slow. And I

4:05

want to get a lot done. I'm ambitious.

4:07

I have a lot of things I have

4:09

to do. We're going to go deep on

4:11

NAD in a minute. Sure. You have some

4:13

interesting perspectives on this. If you wanted to

4:15

create a new pharmaceutical, and I know you

4:18

invented them on napkins in your sleep

4:20

probably, so you have this idea, how much money

4:22

would it take, on average, to get a

4:24

pharmaceutical to market in the US? Oh,

4:27

at a minimum you're talking $75 to

4:29

$100 million. Ten years. If you came

4:31

up with a new, new trusutical,

4:33

how much money would it take to

4:36

get that to market? 250

4:38

to $500,000 in six months.

4:40

Why such a difference? Regulation.

4:42

Look, the concept of the FDA

4:44

was good at the beginning in

4:46

the 1930s. They cared about people.

4:48

They didn't want anyone to get

4:51

hurt. They wanted a certain type

4:53

of procedure. and protocol to follow

4:55

every kind of new development

4:58

for the sake of the good... do

5:00

no harm, but it metastasized. It

5:02

became so extraordinarily complex and involved

5:04

that it just takes a lot

5:06

of different things to do and

5:08

it adds up costing money and

5:10

time. No way around that. Did

5:12

you just say the FDA metastasized?

5:15

I'm afraid so... I've never heard that

5:17

before and I can't disagree. And I've

5:19

been involved in longevity medicine for 25

5:21

years on the non-profit side and just

5:24

with what I do. And I've seen

5:26

so many companies just leave the United

5:28

States in order to get things done.

5:30

And it doesn't feel like it's serving

5:33

Americans or even the world when we

5:35

have this kind of resistance. And I

5:37

can see why you'd say, well, if

5:39

I can solve a problem with a

5:42

half a million dollar investment or a

5:44

hundred million dollar investment.

5:46

It's almost like they're punishing pharmaceuticals.

5:48

At some point perfection becomes

5:50

the enemy of the good. And it's a

5:53

brilliant thing to have an absolutely bulletproof drug

5:55

that's been through all of these myriad tests,

5:57

love to have it, but it takes too

5:59

long. And if we rely entirely upon

6:01

that process for the discovery of the

6:03

next generation of drugs, we're going to

6:05

be waiting a long time. I don't

6:07

have the time. There you go. And

6:09

a lot of other people don't have the

6:12

time. The people who need help, who want

6:14

interventions, who want improvements, they're not going to

6:16

wait 10 or 20 years. We need to

6:18

do it now. We have the knowledge, let's

6:21

apply it. One of the things that drives

6:23

me nuts in the world to longevity is

6:25

you'll see some of these people saying, well

6:27

we have no evidence that you can send

6:30

human life, therefore you can't, and there never

6:32

will be evidence because they would have to

6:34

die. Meanwhile we do have aging clocks and

6:36

we have the ability to measure all sorts

6:39

of aspects of aging, so we can say, well,

6:41

let's do what's most likely to be beneficial.

6:43

and let's see what happens, and I'm on

6:45

that path. What do you think about the

6:47

ability to measure someone's age and to predict

6:50

whether we can extend their lives? Well, aging

6:52

is really two things. Aging is measured in

6:54

years, which can be, as you said, a

6:56

very long process, and we have

6:58

to wait for people to succumb in

7:01

order to know whether we've made a

7:03

difference in mortality. But aging is also

7:05

reflected in the quality of our health

7:07

and our organ function. and we can

7:09

use that as a proxy for longevity.

7:11

That's where I am, and I'm saying

7:14

if I can make my organs younger,

7:16

I can make my mitochondrial work better,

7:18

and we can measure all these things. At

7:20

a minimum, I'm gonna have a really good

7:22

time when I'm 80, and if I die,

7:25

I'm 86 on average or something, I still

7:27

win, and the odds are very high that

7:29

it'll be longer than that. And I know

7:31

our current best is 120 or so years.

7:34

Given what we know with AI. with

7:36

new research, all the work you've done

7:38

in your life, how long do

7:40

you think humans could live

7:42

if we just pull at

7:44

all the stops? We have

7:46

to ask ourselves whether the

7:48

ultimate longevity of the species

7:50

is determined in some type

7:52

of inexorable and unchangeable way,

7:54

or whether it's the accumulation

7:56

of damage over time that

7:58

ultimately forces us. to succumb. If

8:00

we look at more broadly at

8:02

the ecology, we see animals that

8:05

live two weeks and we see

8:07

animals that live 400 years, like

8:09

the lake shark. What we're learning

8:11

by these experiments of nature is

8:13

to better understand what are the

8:15

underlying principles that died their ultimate

8:17

demise. And we know, for example,

8:19

in the lake shark, which is

8:21

such an interesting animal, 400 years

8:23

old, this animal has massive duplications.

8:25

of DNA repair enzymes. So they

8:28

have a tremendous investment on making

8:30

sure they don't accumulate mutations. It

8:32

takes so much energy to do

8:34

that, that the darn creature can

8:36

hardly move. He doesn't have much

8:38

energy left for anything else, but

8:40

he sure lives a long time.

8:42

So there's a tradeoff from an

8:44

evolutionary perspective where every species has

8:46

evolved either to have a wonderful

8:48

quick life. with tons of energy

8:50

like the mosquito or the house

8:53

fly or a very long and

8:55

somewhat a slow life like the

8:57

tortoise or a giant tree that

8:59

doesn't do very much or in

9:01

the case of the leg shark.

9:03

So if we understand what are

9:05

the fundamental determinants of a long

9:07

life then we can start to

9:09

make interventions to specifically interdict these

9:11

and what we've learned from these

9:13

experiments is that the leg shark

9:16

and other animals like that. have

9:18

invested massively in protection of their

9:20

genes. Because ultimately it is the

9:22

accumulation of mistakes of mutations that

9:24

will ultimately lead to dysfunction. Aging

9:26

is in the broad sense and

9:28

death. The logo for my company,

9:30

Upgrade Labs, the AI Exercise Longevity

9:32

Company, is the axilatil, which is

9:34

an animal that can regenerate limbs

9:36

or even its entire spinal cord

9:39

over and over and over. I'm

9:41

like, okay, it can be done.

9:43

How do I install that in

9:45

myself? There's the possibility. Look, everything's

9:47

based on knowledge, knowledge is power.

9:49

As we start to understand really

9:51

what are the fundamental drivers... of

9:53

longevity and of death. That will...

9:55

give us the information from a

9:57

scientific perspective to go out and

9:59

make the right interventions. So I

10:01

don't think 120 years is the

10:04

ultimate barrier. It is right now

10:06

because we really haven't made those

10:08

changes. We need to. But science

10:10

is moving very quickly. So I

10:12

would predict that in five to

10:14

10 years, we're going to start

10:16

to see changes. It's going to

10:18

be 130, 140. You know, at

10:20

some point, maybe we'll be like

10:22

the lake shark shark. I don't

10:24

think so. I certainly think we

10:27

can, and I'm totally willing to

10:29

be wrong, just have a great

10:31

life in the meantime. I've seen

10:33

in my 20s when my health

10:35

was failing. I remember my friend

10:37

Mike, who was on the board

10:39

of the anti-genon-profit, he would call

10:41

me at 1130 at night, and

10:43

he had more energy than I

10:45

did, and just... I watched people

10:47

reverse their age when they were

10:49

in pretty events. I'm like, I

10:52

wish I had that much energy.

10:54

And so I've seen it. They're

10:56

outliers. But if one person can

10:58

do it, then we got to

11:00

study them and figure out what

11:02

caused that. And your relentless curiosity

11:04

in your career, I think, is

11:06

pretty interesting because... You've done a

11:08

lot of different areas of work,

11:10

and you arrived at NAD as

11:12

something to rent attention to you.

11:15

Oh, I've been focused on NAD

11:17

since 1985. Oh, wow. You were

11:19

an early, early adopter. Oh, yes.

11:21

By 1994, my career was focused

11:23

on NAD. When I became involved

11:25

in the parp work, I recognize

11:27

that NAD was the centerpiece of

11:29

biology as far as I was

11:31

concerned in the ICU. Because NAD

11:33

power is parp. Oh it. Well,

11:35

NAD has many important functions, but

11:38

for parp, it is absolutely the

11:40

critical cofactor parp without NAD. It

11:42

doesn't work. Okay. Let's explain what

11:44

NAD is and what parp is.

11:46

So first, what is NAD and

11:48

why do we care? Well, NAD

11:50

is a small molecule, but like

11:52

I said, it's the centerpiece of

11:54

biology, and it really does three

11:56

things in our body. First of

11:58

all, NAD is absolutely. for energy.

12:00

NAD controls the production of ATP,

12:03

which is the currency we use

12:05

in order to to think, to

12:07

move our muscles, to have our

12:09

digestion work, to metabolize. So NAD

12:11

is absolutely essential for the energy

12:13

in your body. You have low

12:15

NAD, you have low energy. Okay,

12:17

so that's the first thing. Second

12:19

thing, NAD is absolutely essential. for

12:21

the production of an antioxidant defense.

12:23

We are bombarded continuously by the

12:26

environment, by cosmic rays, by accidents

12:28

we make. We are in a

12:30

bath in a world of an

12:32

oxygen. We must have an efficient

12:34

and effective antioxidant defense. NAD produces

12:36

or is converted to NAD pH.

12:38

And NAD pH is the driver

12:40

that protects us. It produces glutathion,

12:42

it produces all of the antioxidant

12:44

functionalities. So we need NAD to

12:46

survive in an oxygen-rich environment. That's

12:48

the second thing. Third, NAD is

12:51

used by PARP. PARP is the

12:53

second most abundant protein in our

12:55

nucleus. It shrouds all of our

12:57

DNA, all our genetic material. Every

12:59

minute, we are undergoing... changes in

13:01

the DNA because of the environment,

13:03

because of oxidants and cosmic rays,

13:05

and there are breaks. There are

13:07

little, you know, DNA is double

13:09

strands, the helix, though that helix

13:11

is susceptible to nix or breaks

13:14

in one of the strands, and

13:16

they're happening about 70 times a

13:18

minute. So over the day, every

13:20

day, we are having an assault

13:22

on our genetic material. If we

13:24

do not immediately recognize that and

13:26

correct it, those breaks persist. And

13:28

when the cells divide, if there

13:30

is a break, you will have

13:32

a mutation. Well, when you're 10

13:34

years old, maybe you won't have

13:37

many. By the time you're 30,

13:39

you're going to have a bunch.

13:41

By the time you're 50 or

13:43

60, if it's not corrected, you

13:45

will have loads and loads of

13:47

mutations, and that spells malignancy. If

13:49

you remove any of the DNA

13:51

repair enzymes, you are going to

13:53

get cancer. And the best example,

13:55

of course, are bracket deficiencies. So

13:57

part is the enzyme in the

13:59

nucleus that identifies the problem, the

14:02

nicked DNA, it gloms onto it,

14:04

and then twists and becomes active,

14:06

and then NAD flows into it,

14:08

and it uses the NAD to

14:10

repair. So low DNA, no DNA

14:12

repair. Mutations, ultimately malignancy. So those

14:14

are the three things that NAD

14:16

does. It gives us our energy.

14:18

It protects us against oxygen, and

14:20

it saves us from cancer. And

14:22

the protection from accidents is going

14:25

to provide cardiovascular protection, right? Oh

14:27

my goodness, yes. If you look

14:29

at the vascular system, the oxygen

14:31

that bathe our blood vessels overtime,

14:33

those lead to endothelial dysfunction. leads

14:35

to hypertension, calcification, all of the

14:37

problems we have with plaque buildup.

14:39

So yes, it is a critical

14:41

part of the vascular system. And

14:43

then of course of the cardiovascular

14:45

of the heart, the oxygen injury

14:47

to the heart impairs the heart

14:50

impairs the muscle function. So as

14:52

we get older, we have a

14:54

heart that beats less strongly and

14:56

blood vessels that are more rigid.

14:58

They don't provide the kind of...

15:00

blood flow and nutrition, we need

15:02

to sustain us. So the rule

15:04

of NAD and the cardiovascular health

15:06

cannot be underestimated. It's funny, in

15:08

the world of longevity, I talk

15:10

about there's these four killers. If

15:13

you want to live a long

15:15

time, don't die first. So that

15:17

would be don't get cancer, which

15:19

we're talking about with NAD and

15:21

PARP, and then don't get cardiovascular

15:23

disease, which is actually more deadly

15:25

than cancer. And then what's behind

15:27

both of those is don't get

15:29

diabetes. And I look at diabetes

15:31

as kind of the first of

15:33

the four, because if you get

15:36

that your risk of the other

15:38

three big things that'll kill you

15:40

goes up. We were the first

15:42

to show that in diabetes we

15:44

published in Nature that in diabetes

15:46

you get a fall in NAD.

15:48

There you go. Right. And that

15:50

leads to all the complications of

15:52

diabetes on the blood vessels on

15:54

insulin sensitivity. This is all bound

15:56

up with having a healthy level

15:58

of NAD. You've got to maintain

16:01

that indeed to maintain your health.

16:07

Long-time listeners have heard me talk

16:09

about Niacinamide, which is the very

16:11

oldest way of raising NAD. And

16:13

then the first research came out

16:15

about N.R. about 18 years ago

16:17

or something I started taking it

16:19

then, and then Neman came out,

16:21

and so I've been on these

16:23

things for a long time, I've

16:25

done the IVs and talked about

16:27

what that look like. What is

16:29

the benefit of taking NAD? There

16:31

are only two things you have

16:33

to keep in mind. One is

16:35

you have to have enough there.

16:37

You've got to have a supply.

16:39

And secondly, you need to prevent

16:41

its consumption or its depletion. So

16:43

let's look at each one of

16:45

those. You were taking supplements and

16:47

are initially then N&N. Why did

16:49

you do that? Because any D

16:52

itself cannot be swallowed and expect

16:54

to cross the gut into the

16:56

blood and get... into our cells.

16:58

NEDs, I mentioned how important it

17:00

is, but it's important inside the

17:02

cells. That's where it works. So

17:04

if it's outside the cells, it's

17:06

not going to do anything. Even

17:08

with an intravenous infusion? Even with

17:10

an intravenous infusion. It'll be in

17:12

your blood. But that doesn't mean

17:14

it's in your cells. And when

17:16

it works, it's got to be

17:18

inside the cell. That's where it

17:20

does those three things I mentioned.

17:22

So how do we get it

17:24

into the body? How do we

17:26

get it through the gut? How

17:28

do we get it from the

17:30

blood into the cells? We use

17:32

nature's own way to do it.

17:34

Nature has designed a thought about

17:36

this. So in our bodies, we

17:38

have precursors, Anem and men and

17:40

NR, and they're there for a

17:42

reason. to the inside. Remember any

17:44

idea is a very precious molecule.

17:46

God made it with charges on

17:49

it. It's a polar charge molecule.

17:51

It will not leave the cell

17:53

and it will not get into

17:55

the cell. It can't cross a

17:57

fatty lipid membrane because it's charged.

17:59

So in order to get stuff

18:01

into the... cell, there was a

18:03

jacket created around it, if you

18:05

will. That's what NR and M&M

18:07

are. They're a jacket on NAD,

18:09

and that jacket is recognized by

18:11

a shuttle which whisks it in

18:13

to the cell, and there, the

18:15

jacket comes off, and NAD is

18:17

alive and well and ready to

18:19

go inside the cell. So the

18:21

supplement industry recognizes this, and that's

18:23

why NR and N&M dominate that

18:25

industry. You have to supply those

18:27

in some manner to get enough

18:29

NAD. That's the first goal. The

18:31

second goal is you've got to

18:33

keep it there. It doesn't do

18:35

you any good to boost the

18:37

stuff and get it all in

18:39

there and then only find out

18:41

that there are depleting mechanisms that

18:43

scarf it away, that steal it

18:46

away. I think this is a

18:48

problem that I ran into. But

18:50

actually first I have to ask.

18:52

There's pretty good evidence that alcoholics

18:54

who get 10 to 20 NED

18:56

infusions have a much lower risk

18:58

of starting to drink again. And

19:00

if it can't enter the cells

19:02

at all intravenously, why are we

19:04

seeing clinical results? Because NAD in

19:06

the blood can be converted by

19:08

enzymes in the blood and in

19:10

the tissues to Neman in NNR.

19:12

So when I get an NAD

19:14

IV, my body's converting it back

19:16

to Neman? Yes. If I did

19:18

not know that. Okay. Yes. So

19:20

you can save a lot of

19:22

money by just taking the right

19:24

supplements without having to do the

19:26

IVVs. Not many people want to

19:28

walk around with an IV. Plus,

19:30

it's pretty uncomfortable. N-A-D-I-V-S, I finally

19:32

got to where I could do

19:34

a gram in about 45 minutes,

19:36

but it's like something sitting on

19:38

your chest and you're turning red,

19:40

it's a methylation thing. So we

19:43

can just stop doing that. Yes,

19:45

I would recommend good oral supplements

19:47

that make sense that provide the

19:49

precursors, these jacketed forms of N-A-D.

19:51

How much time I swim with

19:53

needles in my arm that I

19:55

didn't need to with the knowledge

19:57

that we now have that we

19:59

didn't use to? Yes. Okay. That's

20:01

fascinating. So let's say that I've

20:03

taken some NR or some NMM.

20:05

What's going to steal it? Well,

20:07

there is a lot of interesting

20:09

theories. on this, but now we

20:11

know a lot more than we

20:13

did five years ago. It turns

20:15

out that there is a major

20:17

enzyme in our body, which has

20:19

the specific role of clipping NAD

20:21

or anonymity, and cutting it in

20:23

half and destroying it. And that

20:25

is called CD38. May have heard

20:27

of this, CD38 is an enzyme

20:29

that's present in most of our

20:31

tissues. When we're young, we have

20:33

just enough that we need, but

20:35

as we age. There's more and

20:37

more and more. So by the

20:39

time we're 50 or 60 or

20:42

70, we've got way too much

20:44

of this. This enzyme is positioned

20:46

in different places in the cell.

20:48

There are actually three different places.

20:50

But the one we care about

20:52

is on the cell membrane itself.

20:54

It sticks out into the blood.

20:56

And as Neman whisks by, it

20:58

says, ha ha, there you are.

21:00

I got you. And it cuts

21:02

it cuts it in half. Why

21:04

would this exist in ourselves? Because

21:06

it needs to do that in

21:08

order to fight infection. It is

21:10

something involved in the inflammatory response.

21:12

So a little bit of this

21:14

great thing. There are three enzymes

21:16

that use NAD or ANEMN. One

21:18

of them is part, I already

21:20

mentioned, to affect DNA repair. The

21:22

second one is the sertuens, which

21:24

changes a lot of the physiology

21:26

we need, and the third one

21:28

is CD38, which uses it to

21:30

fight infection. A little bit of

21:32

something is a good thing. It's

21:34

natural. We need it. Unfortunately, as

21:36

we get older, we get more

21:39

and more inflammation. probably from leaky

21:41

gut, and CD38 responds to that

21:43

by being more and more expressed.

21:45

And as we get way too

21:47

much of it, by the time

21:49

we're 50 and 60, it is

21:51

out there and it is destroying

21:53

the NAD. So you can take

21:55

all the supplements you want, you

21:57

can load yourself up with NNR,

21:59

but this enzyme's out there when

22:01

you're 50 and 60, and it's

22:03

chewing it up. So the right

22:05

approach is give the supplement, yes,

22:07

great idea, but concomitantly with that

22:09

at the same time. slow down

22:11

CD 38. Okay. And this is

22:13

the key combination approach, which we

22:15

think is the next generation approach.

22:17

So if you were taking extra

22:19

Neman, an extra NAR, your CD-38

22:21

activity is going to go up.

22:23

C-D-38 is going up because of

22:25

your age. Well, does it go

22:27

up even more when you have

22:29

Neman and N-R? No. I thought

22:31

it consumed. It does, but it's

22:33

an enzyme. It's not used up

22:36

when it catalyzes the degradation of

22:38

NAD. It is an enzyme, it's

22:40

being regenerated, you don't lose it.

22:42

Okay. Yeah. It's just there and

22:44

it's doing its thing, which is

22:46

eating up your NAD. So if

22:48

you wanted to live a very

22:50

long time, you probably should brush

22:52

your teeth really well, because if

22:54

you have a lot of oral

22:56

bacteria, which drives your whole microbiome

22:58

and also escapes directly into the

23:00

bloodstream, you're pissing off your immune

23:02

system. You're living in a house

23:04

with toxic mold like I did

23:06

as a kid, which causes stroke

23:08

throat to grow as well. You're

23:10

pissing off your immune system. So

23:12

the more chronic infections you have,

23:14

even low grade, the more you're

23:16

going to have an aggressive immune

23:18

response. And the more likely, I'm

23:20

just, I'm kind of making this

23:22

up as I go along, but

23:24

all of the things you've said

23:26

are absolutely true. But there's it.

23:28

an even bigger gorilla in the

23:30

room here. What is it? The

23:32

real cause of the major cause

23:35

of progressive inflammation as you age

23:37

is the ability of your intestine

23:39

to seal itself and not permit

23:41

the egress of endotoxin other bacterial

23:43

constituents from inside the gut to

23:45

the blood. We know that the

23:47

major protein in the gut, which

23:49

is the seal, the gasket, is

23:51

Z01. And Z01, unfortunately, as we

23:53

get older, its levels go down.

23:55

The gut gets leakier and leakier.

23:57

Look, if you take a 25-year-old

23:59

person, they have trillions of bacteria

24:01

inside them, none of them get

24:03

into their blood. You take a

24:05

60-year-old, there's lots of garbage coming

24:07

in, and that garbage stimulates our

24:09

immune system, and it says, whoa,

24:11

time for inflammation, we have infection.

24:13

And that infection, if you took

24:15

a seven-year-old person, they're inflamed. Aging

24:17

is an inflammatory event, and that

24:19

inflammation turns on the expression of

24:21

CD 38. That's where it's coming

24:23

from. So the microbiome, and our

24:25

ability to protect our gut, is

24:27

key, proper diet. There are various

24:29

things we can do about the

24:32

microbiome. I'm sure you've talked about

24:34

that another shows. This is central

24:36

to maintaining longevity, because that starts

24:38

the whole process. Our gut is

24:40

the driver, ultimately, the initiator. The

24:42

initiator. In my longevity book, I

24:44

referenced a couple of papers that

24:46

showed taking activated charcoal, which just

24:48

binds to endotoxins in the gut,

24:50

is associated with about a 15%

24:52

lifespan increase, just from reducing some

24:54

of those. And when you look

24:56

at things like germ-free mice, where

24:58

they have no microbiome because they

25:00

live in little bubbles, they live

25:02

a long time, they're ripped, they

25:04

can eat whatever they want. This

25:06

is where I began my career,

25:08

really. In 1988, I was in

25:10

the intensive care unit. and there

25:12

was a brilliant young professor that

25:14

I teamed up with named Mitchell

25:16

Fink, and we had the idea

25:18

at that time that the barrier

25:20

of the gut might change during

25:22

disease. No one had thought about

25:24

that, and I discovered that endotoxin

25:26

can actually open up the gut,

25:29

and we published these papers from

25:31

88 to 92 showing that it

25:33

was malleable, that the gut sealed,

25:35

the barrier, is not fixed. it

25:37

can respond and we found a

25:39

lot of that we found that

25:41

hypoxia will do that we found

25:43

that acidosis would do that certain

25:45

cytokines and all of that work

25:47

show that it's dynamic that they're

25:49

opening and closing the yes yes

25:51

junction yes how would you go

25:53

about sealing as best as possible

25:55

the gut so that nothing leaks

25:57

out of it over the course

25:59

of decades that's going to require

26:01

I think understanding of diet and

26:03

the role of the microbiome Right,

26:05

that's not an area that I'm

26:07

in anymore, but there's tremendously good

26:09

research looking at that, and that's

26:11

very important. That is a major

26:13

factor in longevity that should be

26:15

emphasized. There needs to be more

26:17

research in that area. Okay. I've

26:19

been for almost the last eight

26:21

years now advising Vioam, which has

26:23

a really good data set now

26:26

where they're starting to figure that

26:28

out. I know that because I

26:30

was on antibiotics for 15 years

26:32

every month because I had chronic

26:34

sinusitis and stroke throat because I

26:36

lived in a house with toxic

26:38

mold, that I probably don't have

26:40

an advantage there. In fact, I'm

26:42

not obese right now. It's kind

26:44

of shocking given all the crap

26:46

that I went through. And so

26:48

I feel like I'm coming from

26:50

behind in my longevity journey here.

26:52

For an average person, maybe they're

26:54

a little beast, but they haven't

26:56

had that big of a problem.

26:58

Is there a pharmaceutical intervention or

27:00

is taking these NAD things like

27:02

you're making with Wonder Feel? Where

27:04

do you start? Well it's actually

27:06

interesting. Now you're talking about a

27:08

positive feedback loop. It turns out

27:10

that, and this is also work

27:12

that I did in 1992, the

27:14

energy of the cell in the

27:16

gut. is directly responsible for how

27:18

well the gut seals itself. We

27:20

published the first paper on this

27:22

where we related NAD and ATP

27:25

levels inside the gut cells to

27:27

their ability to maintain the integrity

27:29

and not let molecules slip through.

27:31

So you can imagine if that

27:33

gets out of hand, out of

27:35

whack, and then you start to

27:37

leak. and you get inflammation. CD38

27:39

expression goes up, NED goes down,

27:41

the gut now doesn't have enough

27:43

NED to maintain itself, and it

27:45

gets progressively leekier. It's a snowball

27:47

effect. So the key thing is

27:49

keep the NAD at a healthy

27:51

level, have a good healthy gut,

27:53

do whatever interventions science is telling

27:55

us to do, keep our gut

27:57

good and healthy, and then to

27:59

further augment that take NED supplements,

28:01

or actually NNN or NNR, and

28:03

find a way. which I'll talk

28:05

about a little later, to stop

28:07

the activity of CD38 depleting this

28:09

precious NAD that we have. So

28:11

even if you have immune activity.

28:13

as you age, you can stop

28:15

the CD38 so that you can

28:17

slow it down. There are two

28:19

approaches. There's the pharmaceutical approach. I

28:22

wish them well. It'll be another

28:24

10 or 15 years. I'll be

28:26

a little bit old at that

28:28

time to enjoy the benefits, but

28:30

I do wish them well because

28:32

CD38 is a target that the

28:34

pharmaceutical industry should go after. While

28:36

I'm waiting, we have botanical approaches,

28:38

natural approaches, which we include actually

28:40

in our wonderful product, which slow

28:42

down the activity of CD 38.

28:44

So that combination, I mentioned, is

28:46

so critical. Give a boost with

28:48

a supplement, but stop the depletion.

28:50

You mentioned ATP, and I think

28:52

a lot of listeners know what

28:54

ATP is. Just in case we

28:56

have some new listeners, talk about

28:58

ATP for a minute and what

29:00

it does in the gut. means

29:02

it is a currency. Think of

29:04

it as a cryptocurrency. It's a

29:06

currency in every cell that is

29:08

there and it is the final

29:10

common molecule that provides energy to

29:12

various processes, whether they're metabolic processes,

29:14

hormonal processes, movement of muscle, activity

29:16

of neurons in our brain thinking,

29:19

ultimately ATP provides the... The electron

29:21

reducing equivalent is providing the power

29:23

to do things, to make the

29:25

body work. NAD creates the ATP.

29:27

So if you don't have NAD,

29:29

you don't get ATP. And why

29:31

did I care about this as

29:33

an intensive care specialist? We're not

29:35

worried about longevity in the long

29:37

term in the ICU. We're worried

29:39

about whether you live the next

29:41

hour or two. Okay, when someone

29:43

comes in with a heart attack,

29:45

for example, they have an acute

29:47

interruption of blood flow and oxygen

29:49

to their heart. Okay. What happens

29:51

when you have no oxygen coming

29:53

into your heart? You don't have

29:55

enough NAD. PARP is activated within

29:57

about five seconds. NAD is massively

29:59

consumed and there's no ATP made.

30:01

And because there's no... ATP made,

30:03

that heart muscle which is at

30:05

risk in the first few minutes,

30:07

sadly, it goes on to die,

30:09

to infart. So if you maintain

30:11

NAD, you maintain ATP during the

30:13

heart attack, you won't get the

30:16

infart and you won't die. So

30:18

we made every effort and we

30:20

designed drugs. And this is what

30:22

I licensed to genetic. By blocking

30:24

PARP activation, it didn't consume the

30:26

NAD. during the heart attack, ATP

30:28

levels were maintained and the heart

30:30

did not get an infart. Wow.

30:32

Same with stroke. Strokes the same

30:34

way. A lot of these, and

30:36

I could go on and on

30:38

and on, but parp is very

30:40

important in these acute events. For

30:42

aging though, this is not done

30:44

over minutes. This is a problem

30:46

over decades. So the principles are

30:48

the same, but it's not as

30:50

dramatic. So parb is helpful because

30:52

it repairs your genes, but if

30:54

there's a traumatic event or an

30:56

overactivation, it stops being useful for

30:58

gene repair and it causes all

31:00

kinds of damage by stopping ATP.

31:02

So we showed this, if you

31:04

take an animal or a person

31:06

and you interrupt blood flow to

31:08

their coronary artery, so their heart

31:10

isn't deprived of... the oxygen it

31:12

needs within about one to one

31:15

and a half minutes, you get

31:17

a massive influx of oxygen in

31:19

that cell that attack the DNA,

31:21

attack your genes, cause huge numbers

31:23

of DNA single strand breaks, millions

31:25

in the cell of the heart.

31:27

Those activate parp like crazy. Suddenly,

31:29

parp consumes NAD within about two

31:31

to three minutes. If you measure

31:33

the NAD levels in the heart

31:35

after two to three minutes after

31:37

heart attack, zero. Undetectable. And of

31:39

course you wait one more minute,

31:41

no ATP. You wait another five

31:43

minutes, dead, cell. So yes, parp

31:45

overactivation in the acute setting is

31:47

a killer. Would it make sense

31:49

to block parp before you play

31:51

a football game? Because you're never

31:53

going to get hit an ad?

31:55

That is something I never heard

31:57

anybody suggest. It's a wild idea,

31:59

but... It's an interesting concept. We

32:01

did prophylax animals, many. Afterhead, we

32:03

did traumatic brain injury studies with

32:05

parbat, and yes, you can preserve

32:07

brain function, reduce neuronal injury. I'm

32:09

not suggesting anyone do this. I

32:12

am. But, well, okay. Okay, I'm

32:14

with you. But if you're an

32:16

MMA fighter or professional football player,

32:18

I have protocols for what to

32:20

do before. Oh, it would go

32:22

down. No, it would help there.

32:24

Yes. Yes. We have done dozens

32:26

of studies in traumatic brain injury.

32:28

We've done them in cheap. We've

32:30

done them in mice and rats.

32:32

And we have shown conclusively that

32:34

you can immelurate and prevent. the

32:36

sequeli of a concussive or a

32:38

worse event, yes, it is protective in

32:40

that sense. Not making a recommendation, but

32:43

it works. No one that I'm aware

32:45

of is using parb drugs like the

32:47

one you invented for this, and there

32:49

may be side effects, I don't even

32:52

know about, but what I do know,

32:54

having had a titanium knee to the

32:56

head at high speed and gotten a

32:58

brain injury, I'm fortunate that I know

33:01

what to do for that, and I

33:03

have a neurosidence and all. But the

33:05

incidence of brain injury even in kids

33:07

or in highly functioning adults, you get

33:10

in a car accident, you get whiplash,

33:12

and it ruins marriages, it messes

33:14

with puts a major killer in the, and

33:16

not just killer, but it leads to very

33:18

sad situations where people have

33:20

chronic brain injury that just doesn't...

33:22

get better. I know six weeks after

33:25

I took that need of the head,

33:27

I sent Tim Ferris an angry email

33:29

about something he didn't even do. Like

33:31

I was out of my mind. I

33:33

was squiring all the time and you're

33:36

like, what is going on? And some

33:38

of this has to do with the

33:40

fact that my brain, which actually at

33:42

the time, especially didn't even have enough

33:45

blood flow regularly according to Ammon clinics.

33:47

And then I ran out of ATP for

33:49

the parts where I scrambled to a

33:51

you can recover. Yes. But I look

33:53

at people who are at risk of

33:55

these things and saying, all right, I

33:58

know having ketones present reduces oxygen. There's

34:00

all sorts of different strategies that

34:02

are all mitochondrial enhancing. And when

34:04

you peel all that stuff away,

34:06

ultimately it seems like NAD is

34:08

the most important of all of

34:10

those. It's the centerpiece. It's the

34:12

miniature player. Wow. All right. So what about liposomal

34:15

NAD? I've seen some formulations of

34:17

that. Does that work? Well, there's

34:19

liposomal namen. That's been looked at

34:21

because people want to optimize the

34:23

amount of nr or namen that's

34:26

coming in. I'm all for that,

34:28

but it needs to be done

34:30

in a way that's effective. So

34:32

far, we haven't seen studies that

34:34

really prove to me that liposomel

34:37

namen is better than just regular

34:39

namen. It might be, but I

34:41

haven't seen the studies. I will

34:43

say that liposomes are not easy

34:46

to work with. They leak over time,

34:48

so there's stability issues, even on

34:50

the shelf. So it's a difficult modality

34:52

to work with, more power to them,

34:55

that they should do great research, and

34:57

maybe that will improve it in the

34:59

long run, but I haven't seen that

35:01

yet. Got it. And I realize I'm

35:04

using big words, if you're listening, well,

35:06

lipo, whatever. A liposome is a little,

35:08

call it a bubble of fat, that

35:11

you can use to put a pharmaceutical

35:13

or a pharmaceutical, or a pharmaceuticals. The

35:15

very first liposomal glutathion on the market,

35:17

I hope to bring that to market

35:20

years and years ago, and then I

35:22

had a dry liposome at bulletproof, and

35:24

like you said, they're very hard to

35:26

work with. My friends at Quicksilver make

35:28

some cool stuff. There's even like liposomal

35:30

testosterone formulations and things now. So it's

35:33

a cool delivery system that's very finicky.

35:35

That's the right word. Yeah, difficult, difficult,

35:37

unstable. And what you have with the

35:39

stuff you're doing in a wonderful feel

35:41

is you're doing in-em-em-em-em-em-em-en.

35:44

Plus you're blocking CD 38 at the

35:46

same time. We have two natural products

35:48

in their ingredients, if you will, in

35:50

our solution. One of them is resveratrol,

35:52

which of course is from red grapes,

35:54

and that has been, and is in

35:56

wine, red wine, and that has been

35:58

shown to block CD 38. Very interesting.

36:00

And the other is from

36:02

olive oil, hydroxy tyrosol,

36:05

okay, in the Mediterranean diet there.

36:07

And that is also a blocker

36:09

of CD 38. So that's why

36:11

we took those two and we

36:14

added those to NEMN so that

36:16

we would increased the supply, but

36:18

we would block the depletion simultaneously.

36:20

You're the only person who's ever

36:23

talked about hydroxy tyrosol on the show.

36:25

And I looked at a lot of the

36:27

research around olive oil. and there's plenty

36:30

of evidence that says 30

36:32

grams of olive oil a

36:34

day is good for you. Above that,

36:36

it's a bit challenging. If

36:38

you take a lot of

36:40

oleic acid, the primary fat

36:43

in there, it increases something

36:45

called D5D and D6D, which

36:47

means that your body way

36:49

more easily oxidizes all the

36:51

other omega sixes. So, olive

36:53

oil good, excessive olive

36:55

oil drives oxidation. Well, we don't provide

36:57

olive oil because we just purify the

37:00

hydroxy tire results. Exactly. Right. So hydroxy

37:02

tire is all is the most likely

37:04

beneficial compound in olive oil. So when

37:06

I put together one of my, if

37:09

it goes my fat, my Omega 3

37:11

formula back when I was a bulletproof

37:13

and guys, I don't have anything to

37:15

do a bulletproof. I don't, I don't

37:17

believe there. following my formulas, I don't

37:20

even track it, so no commentary there

37:22

I can offer you. But the thing

37:24

I formulated years ago, I put hydroxy

37:26

tyrosol on it. And my formulators were

37:29

like... What is this? Another is a

37:31

supplier, we've got to do this because

37:33

I wanted the benefits of drinking a

37:35

gallon of olive oil. I just don't

37:38

want to drink the olive oil because

37:40

I don't think it's good for you

37:42

at high doses. Hydroxy Tyrosol of course

37:45

is an antioxidant, has lots of different

37:47

functions. One of them is the CD38

37:49

blockade, blockade, effect, is also important. And

37:52

to that end, by the way, we've

37:54

added another ingredient in our wonder field,

37:56

which is ergothionine. So this is ergothion.

37:59

At the reason did that was that

38:01

we didn't want to have

38:03

a lot of DNA damage.

38:05

DNA damage activates PARP, PARP

38:07

consumes NAD. So by giving

38:10

that heavy hit with Ergothining,

38:12

we have a lot of antioxidant

38:14

power in there now that

38:16

reduces the amount of DNA

38:18

damage and reduces the need

38:21

for PARP to... fix something

38:23

which would consume NAD. So

38:25

all of this was focused

38:27

on keeping NAD levels high,

38:29

using antioxidants in conjunction with

38:31

boosting the NAD, very important.

38:33

And that's why it was

38:35

necessary to include Ergothionine. Ergothionineine

38:37

is another one of these

38:39

longevity molecules that most people

38:41

haven't even heard of. And

38:44

I look at this as foundational as glutathion.

38:46

And when I started the whole

38:48

biohacking movement, glutathion was the rock

38:50

star, and it still is. You

38:52

need this for your liver, if

38:54

your brain inside all your cells,

38:56

an organ is as potent via

38:59

different mechanisms. Yes, it's any most

39:01

people know that. I should also

39:03

add that glutathion, just to make

39:05

a full circle, here, where does

39:07

that come from? Lutithion is produced

39:09

by a glutathion reductase, and the

39:11

energy to make glutathion comes from

39:14

NADadp from NADepage. True. And where's

39:16

NAD pH? What is that? That's

39:18

from NAD. So NAD is acted

39:21

on by NAD-Kines. It makes NAD-P-H,

39:23

which then creates glutathion, which is

39:26

a major, major important antioxidant. If

39:28

you can, if you take animals

39:30

that can't make glutathion, they die.

39:33

they do not do well, okay?

39:35

And any kind of limited injury,

39:37

even a minor trivial injury, becomes

39:40

a major problem. So glutathion is

39:42

one of the most important natural

39:45

antioxidants that we have, and that's

39:47

all dependent on having NAD there

39:49

to make it. Without NAD, you

39:51

cannot make glutathion. Wow. Be very

39:54

clear about that. Yeah. So NAD

39:56

has a very important antioxidant functionality

39:58

in that way. One of the... concerns that

40:01

I've had, and this goes back to

40:03

when I started in longevity, it was

40:05

actually the late 90s, where I'm in

40:07

my 20s and I'm learning from people

40:09

in their 80s, and we were

40:11

taking a lot of antioxidants, sort

40:13

of like oxidation's, the devil. And

40:15

the problem is, we have this

40:17

ox, redox reaction that makes ATP.

40:19

How do we know that when

40:21

we take Wonder Feel, and now

40:24

we're getting Urgithyanine, and we're getting

40:26

Resferrotrol. and we're getting all the

40:28

other antioxidants, like hydroxyl, Tarsol.

40:30

How do we know that

40:32

we're not suppressing oxidation to

40:34

the point that it's a

40:36

problem? You do need some

40:38

redox stress. It's very important

40:40

in terms of signaling. We

40:42

were the first to show

40:44

that oxy radical signaling is

40:46

very important in terms of

40:48

oxy radical signaling. It's important

40:50

you need a limited amount

40:52

of redox stress, of oxygen

40:54

stress. Too much of course

40:56

causes all these other problems. How

40:58

do we know that we're not

41:00

giving too many antioxidants? Well, we

41:02

listen to our customers. We have

41:04

a registry where every single person

41:06

who takes our product writes back

41:08

to us, and most of them

41:10

do, because they repeat customers. We

41:13

don't really advertise. We don't need

41:15

two people like the product. They

41:17

come back, they buy more, and

41:19

so they generously give us their

41:21

thoughts and their feedback. And we've

41:23

seen no evidence of... a problem

41:25

with the material of the solution

41:27

that would get us concerned. We're always

41:29

watching though. We have a respect for listening

41:31

to the patients, to the customers. So

41:33

if we do see any problem, we

41:35

would quickly, you know, investigate that. So

41:37

far, we haven't seen that. What we do

41:39

see are numerous reports coming back that

41:42

exemplify just how effective this is. It's

41:44

really surprised me. You know, I was

41:46

a little bit cynical before about supplements.

41:49

I was in the pharmaceutical industry, so

41:51

I was on the bad side, right.

41:53

So I was kind of suspicious, what are these

41:55

guys doing? But when you read these reports,

41:57

you have to stand up and pay attention.

42:00

We had a 60-year-old person with arthritis.

42:02

She used to be a tennis player.

42:04

She could hardly get off her couch.

42:06

And she's back and she's playing tennis

42:09

now. We had a 75-year-old lady who

42:11

unfortunately had pretty advanced vascular dementia. Her

42:13

husband was having to take care of

42:15

her. She loved to do crossword puzzles

42:18

before all of this. She was doing

42:20

maybe one every day or two. She's

42:22

now doing four a day. Her husband's

42:25

crazy. He's the one buying it. Sexual

42:27

Health, all of the nitric oxide metabolism

42:29

in sexual health is driven by the

42:31

need to have any DPH activate EC-NOS.

42:34

So we found people, both men and

42:36

when we had a woman who was

42:38

61, who was reporting much stronger orgasms

42:41

and vaginal lubrication. We published, we're the

42:43

first to publish on vaginal lubrication. I

42:45

did that in 2004, showing that this

42:47

whole mechanism. Causes increased blood flow to

42:50

the vagina and increased lubrication and that's

42:52

entirely dependent on NED being there. So

42:54

NED drives sexual function? Oh, yes erectile

42:57

dysfunction is based on ECNOS. Look at

42:59

Viagra. Viagra do it prevents the breakdown,

43:01

okay, of cyclic GMP. But what is

43:03

making cyclic GMP? Nitric oxide is formed

43:06

by the activity of the EC... N.O.

43:08

synthase, the nitric oxide synthase. That enzyme,

43:10

which is present in the cavernosa of

43:13

the penis, that enzyme requires NAD pH

43:15

in order to work. The electron, which

43:17

comes onto nitrogen to make nitric oxide,

43:19

that comes, that literally comes from NAD.

43:22

NAD pH is formed from NAD. So

43:24

if you have NAD deficiency, you can

43:26

take all the Viagra you want in

43:28

the world, it will not help. No

43:31

kidding. No. Viagra is great if you're

43:33

making nitric oxide because it prevents the

43:35

cyclic GMP from being wiped out. If

43:38

you don't have nitric oxide, forget it.

43:40

The Viagra just doesn't work. And we

43:42

know that Viagra... Viagra works in maybe

43:44

half the population that needs help doesn't

43:47

work in everybody because some people cannot

43:49

make nitric oxide. Wow. So this NAD

43:51

is interesting because it will facilitate making

43:54

nitric oxide. So it would be very

43:56

interesting actually to look at our product

43:58

in conjunction with Viagra. We haven't done

44:00

that yet, but the reports we're getting

44:03

of sexual health from our customers suggest

44:05

that something important is going on and

44:07

that deserves more attention. This is fascinating.

44:10

One of the longevity pharmaceuticals that I

44:12

take is low dose cellists. I take

44:14

five milligrams, most days, right? And this

44:16

isn't for sexual function. It's for vascular

44:19

function because I don't want to get

44:21

Alzheimer's disease and because I like having

44:23

veins. It works very, very well. So

44:26

low levels of nitric oxide are absolutely

44:28

essential. to the preservation of your vascular

44:30

system in several ways. First of all,

44:32

nitric oxide causes vasodilitation, not just of

44:35

the large vessels, but of the micro

44:37

vessels. The micro vessels are what nourish,

44:39

the intestine, the gut, the liver, and

44:42

especially the brain. You have to have

44:44

good, healthy blood flow. As we get

44:46

older, we get calcifications and other changes,

44:48

the vessels get stiffer. is that nitric

44:51

oxide, it inhibits platelet activation by increasing

44:53

the cyclic GMP in the platelets. So

44:55

platelets are great, if you get a

44:57

cut, you don't want to bleed, you

45:00

need your platelets, but platelets can also

45:02

add here to the vessels, especially in

45:04

the heart and in the brain, it

45:07

can cause a stroke or a myocardial

45:09

infarction. So you don't want... Excessive platelet

45:11

activation that happens as we get older.

45:13

Again, nitric oxide is key in keeping

45:16

the platelets quiescent, keeping them happy and

45:18

non-activated. So again, NAD, by facilitating NO

45:20

expression, is. critical to vascular health. And

45:23

that's been shown now even in clinical

45:25

studies with an immense supplementation. They've shown,

45:27

for example, an improvement in blood pressure.

45:29

In fact, if you remove CD 38,

45:32

which as I mentioned, breaks down NAD,

45:34

so you have more NAD, you see

45:36

a fallen blood pressure. Interesting. Yeah. So

45:39

nitric oxide, CD 38, NAD, they're all

45:41

connected. But the centerpiece is NAD. Yes,

45:43

that's been shown now. If you take

45:45

people who are on heavy and immense

45:48

supplementation... The Buck Institute of Aging and

45:50

a number of the NIH places have

45:52

recommended 900 milligrams total per day. Some

45:55

of the studies have used much less

45:57

and they haven't seen this good results.

45:59

There was one study when you do

46:01

have histogram. Yes, there was a study

46:04

with 250 milligrams in patients. They had

46:06

an inkling of something good happening, but

46:08

it was not the right dose. But

46:10

when you get to the right dose,

46:13

you can see changes that are favorable

46:15

not only in blood pressure falling, but

46:17

you get better insulin sensitivity, so less

46:20

diabetes. All of these things are happening

46:22

because any of the levels are rising

46:24

to the level where they can produce

46:26

nitric oxide and relax the blood vessel

46:29

and provide a defense against oxygen stress

46:31

in the blood vessel. If someone is

46:33

at normal blood pressure and they increase

46:36

your entity levels, is it going to

46:38

drop even further? No, it wouldn't do

46:40

that excessively, but when you measure your

46:42

blood pressure with a cuff on your

46:45

arm, you're looking at the... You're not

46:47

looking at blood flow, you're looking at

46:49

blood pressure. What we really care about

46:52

is not really just the pressure, we're

46:54

looking at the blood getting to where

46:56

it's supposed to go. And that can

46:58

happen in a number of ways with

47:01

NAD. First of all, as it opens

47:03

up the small blood vessels that allows

47:05

it to go everywhere in capital areas.

47:08

But in the longer term, NAD, higher

47:10

levels of NAD increase mitochondrial supply. And

47:12

the blood vessels therefore are able to

47:14

enlarge and large in form. So a

47:17

person like a mask. player, someone who's

47:19

out there going back and forth on

47:21

the court, he has far more mitochondria

47:24

than I do. And that's because he's

47:26

been exercising, he has NAD being produced,

47:28

you get more mitochondria, so in the

47:30

long run not only does it help

47:33

your immediate health but it makes you

47:35

in better shape. You actually condition a

47:37

runner will have much more blood supply

47:39

throughout his muscles because of this NAD

47:42

increase. It makes so much sense. There

47:44

are about 30 million people in the

47:46

US alone who have a COVID vaccine

47:49

injury, also known as long COVID. Yes,

47:51

I know. I just trolled a bunch

47:53

of people with that. But what's the

47:55

rule of NAD in long COVID? Actually,

47:58

there was a study looking at the

48:00

effect of NEMN in people who had

48:02

had COVID. in terms of their vascular

48:05

function, and it actually was much better.

48:07

So that's a population that is at

48:09

risk. People who have had the vaccine

48:11

or COVID, you know, they've had the

48:14

spike protein, the vaccine has the spike

48:16

protein, COVID has the spike protein. So

48:18

that is an activator of endothelial damage

48:21

potentially. And so N-O and N-A-D will

48:23

protect the blood vessels. So if you've

48:25

got COVID, it's recommended from this article

48:27

as an NIH publication. It's something to

48:30

think about, and certainly if you have

48:32

long COVID, it's something also to think

48:34

about. I had chronic fatigue syndrome and

48:37

fibromyalgia diagnosed in my 20s. Those are

48:39

exactly the same thing as long COVID.

48:41

You can have different things that trigger

48:43

the whole cascade of mass cells and

48:46

all the stuff that's involved in those.

48:48

So this has been an area where

48:50

I was able to recover from that

48:53

and I did get COVID and did

48:55

not get long COVID because I take

48:57

care of my mitochondria. So I look

48:59

at all of those conditions as... mitochondrial

49:02

and inflammatory things. And if you want

49:04

to turn off inflammation, you turn on

49:06

mitochondria, and as you just described, NAD's

49:08

most important at the scene. You know,

49:11

we used to think about diseases as

49:13

being sort of these isolated instances of

49:15

bad luck. Oh, I got diabetes. Oh

49:18

my goodness, I got cancer. Oh my

49:20

gosh, I have fatty liver disease. Oh,

49:22

I'm having a renal problem. Oh, I'm

49:24

having Alzheimer's. And we had departments set

49:27

up and then we had doctors who

49:29

had specialized their entire lives in each

49:31

of these very distinct areas. And that's

49:34

one way to look at medicine, but

49:36

that's the 1950 ways to look. Today

49:38

we have to see these really as

49:40

an integrated whole. Why do we get

49:43

sickers we get older? Is it just

49:45

bad luck? No. The aging process is

49:47

a core fundamental derangement that then spawns

49:50

injury in all these different organs. If

49:52

you happen to have an injury in

49:54

your knee, suddenly you have arthritis. But

49:56

if it's really not arthritis, really what

49:59

it is fundamentally is aging. And so

50:01

we can spend all our time trying

50:03

to treat arthritis or maybe we need

50:06

to go upstream to spend our time

50:08

thinking about the aging process itself. I

50:10

look at it like this. I age,

50:12

it's my fault. It means I haven't

50:15

figured out what I could be doing

50:17

or I could have done to do

50:19

a better job of it. Right? We

50:21

know all these different pathways and maybe

50:24

there's some things we don't know. Well,

50:26

that means I haven't discovered them yet.

50:28

Or you haven't discovered them yet. That's

50:31

right. And it's never too early. You

50:33

know, a lot of people think that

50:35

aging starts when you're 60 and 70.

50:37

They're elderly, right? You get your senior

50:40

discount. I just got mine. I just

50:42

got mine. I just got mine. I

50:44

was so excited. I was so excited.

50:47

I was so excited. I was so

50:49

excited. I was so excited. I was

50:51

so excited. I was. I was so

50:53

excited. I was. I was. I was.

50:56

I was. I was. I was. I

50:58

was. I was. I was. I was.

51:00

I was. I was. I was. I

51:03

was. I was. I was. I was.

51:05

I was. I was. I was But

51:07

actually aging doesn't start when you're 65.

51:09

Aging actually starts in your early 20s.

51:12

I'm sorry to say that, but it's

51:14

true. If you look at a baseball

51:16

player, the rookies are great, 20 years

51:19

old. By the time they're 30, they're

51:21

kind of not rookies. By the time

51:23

they're 36, they can't run as fast.

51:25

They can't slide as fast. It's not

51:28

the same person. So if you care,

51:30

if you're in your early 30s or

51:32

in your late 20s, and you want

51:35

to maintain vigor. You're an ambitious person,

51:37

you know, you want to master your

51:39

skills, you want to, you want to

51:41

exceed and, you know, do everything you

51:44

can and you're in your profession, do

51:46

really well there, succeed there. You want

51:48

to have good pleasure in your life.

51:50

and good sexual health, it is not

51:53

sensible to wait till you're 60 to

51:55

70 to wake up. Wake up now.

51:57

When you're in your 20s, start thinking,

52:00

what can I do to maintain my

52:02

NAD at a healthy level so that

52:04

I don't develop these problems? I don't

52:06

have to work backwards to fix them.

52:09

Let's prevent them. The reason that I

52:11

called what I do biohacking is that

52:13

I learned, because I had the unfortunate

52:16

problem of being old when I was

52:18

young. the things that make old people

52:20

young make young people powerful. And all

52:22

of a sudden, I think, what if

52:25

I talk about it in a way

52:27

I would have listened when I was

52:29

19? Wow, I get to choose to

52:32

not be obese. I get to choose

52:34

the skin I want. I get to

52:36

choose the brain function I want. And

52:38

as a side effect, you have way

52:41

more stamina and you have a better

52:43

life and you don't age the way

52:45

everyone else does. That's right. I mean,

52:48

people in their 20s care really about

52:50

three things, I would say. They want

52:52

to be mastering things, whether it's at

52:54

work or in sports, they want to

52:57

master things. They're ambitious, they have drive,

52:59

they have energy, they want to flourish,

53:01

whether it's in sports or whether it's

53:04

at work, and they want to have

53:06

fun, they want to have pleasure, they

53:08

want to have a good life with

53:10

their family. This is what, well, all

53:13

of these things will be derailed if

53:15

you don't have an NAD level that

53:17

can support you. in your endeavors and

53:19

your goals. I mean you've got to

53:22

be alert, you've got to be sharp

53:24

at work, you've got to be, if

53:26

you're on the tennis court, you've got

53:29

to win, you've got to have muscle,

53:31

you have to have power, you have

53:33

to have pleasure and fun, you have

53:35

to have a normal sexual life, so

53:38

all of these things can be derailed,

53:40

but you don't have to let that

53:42

happen, you have a choice. Because I

53:45

know now what it does. What is

53:47

the role of alcohol in NAD? Well,

53:49

alcohol first of all can spawn the

53:51

generation of oxygen stress. It directly damages

53:54

tissues with the alcohol because it gets

53:56

into the membranes. but more than that

53:58

it can lead to a lot of

54:01

oxygen injury. And so that damages DNA

54:03

activates. Parp consumes NAD. So NAD levels

54:05

in an alcoholic are suboptimal. Best thing,

54:07

of course, is to stop the alcohol.

54:10

But over and above that, you want

54:12

to maintain your levels of NAD in

54:14

the face of alcoholism. Got it. So

54:17

the best thing is to stop the

54:19

alcohol. Yeah. Do you drink? I drink

54:21

on Shabbat. I have a glass of

54:23

wine. Okay, I live with it as

54:26

that. Yeah, I have a rule. I

54:28

drink if it's older than I am.

54:30

Okay. So there's an economic reason to

54:32

not drink, right? So maybe once a

54:35

year I'll have, you know, good socket

54:37

with sushi or something. But it's for

54:39

me not even a monthly thing because

54:42

I'm into cognitive function longevity and I

54:44

know what it does. And frankly, it's

54:46

just about the worst thing you can

54:48

do for brain function. It just is

54:51

a neuronal injurious agent, pure and simple.

54:57

My experience is a long-time burning

54:59

man guy and I have a

55:01

ketamine as an offering through a

55:03

medical doctor up at my neuroscience

55:05

clinic. In fact, a lot of

55:07

my new book, I have a

55:09

big section on psychedelics. Any psychedelic

55:11

journey or deep meditation or breath

55:13

work, it doesn't really matter what,

55:15

getting you into these altered states.

55:17

If you can upregulate mitochondrial function,

55:19

you have a much deeper, more

55:21

powerful experience. And it follows then

55:23

that having adequate NAD, when you're

55:25

calling on the brain to go

55:27

into these altered states, whether they're

55:29

self-induced or chemically induced, It's a

55:31

very, very big difference in the

55:33

quality and intensity of the experience.

55:35

Well, we know that, I mean,

55:37

now I'm thinking about it in

55:39

light of what you're saying there.

55:41

The psychedelics upregulate in a very

55:43

acute fashion the metabolic activity of

55:45

the brain. And the brain actually

55:47

is the most metabolically active organ

55:49

in our body. It uses 25%

55:51

of our blood supply. The oxygen

55:53

demand by the brain outstrips everything,

55:55

including the heart. that anything that

55:57

you are doing that causes increased

55:59

brain activity and function will require

56:01

a commensurate amount of oxygen to

56:03

support that and NEDs. So I

56:06

guess if this psychedelic experience you're

56:08

describing is energy demanding then it's

56:10

obligatory that you have sufficient NED

56:12

to support that. So when I'm

56:14

going to go on a journey,

56:16

and because I'm not recommending any

56:18

of this stuff, I'm just talking

56:20

about my practice and what I've

56:22

found works best, I want to

56:24

have some ketones present, and I

56:26

don't care if it's from MCT

56:28

or ketone dials, which are, I

56:30

think, my preferred way to do

56:32

that at this point, and human

56:34

makes out HPMN. And then I

56:36

take a bunch of mitochondrial answers

56:38

and wonderful feel, of course. Because

56:40

what you want is for every

56:42

cell in your body to be

56:44

able to do everything that it's

56:46

capable of doing effortlessly. Because there's

56:48

this beautiful thing that I've noticed

56:50

in biology. I'm a distributed systems

56:52

computer hacker guy. And like, well,

56:54

if you don't have enough compute

56:56

power, you stop doing some things

56:58

that aren't critical. And the body's

57:00

the same thing. If I don't

57:02

have enough metabolic power in the

57:04

form of NAD, ATP, mitochondrial function,

57:06

well, what are the things that

57:08

aren't necessary to be alive right

57:10

now? Let's not do those. So

57:12

if I can stack all of

57:14

my energy metabolism and all of

57:16

my antioxidant metabolism to their fullest.

57:18

then when I'm doing something, whether

57:20

it's an athletic thing or it's

57:22

a spiritual journey kind of thing,

57:24

then I'm going to have the

57:26

full experience. And my body... That

57:28

leads me to... I want to

57:30

add something there because there is

57:32

a positive feedback loop, which of

57:34

course you being a computer engineer,

57:36

you know what I'm talking about,

57:38

when you are in a situation

57:40

where you have a fall in

57:42

the amount of NAD and systems

57:44

start to go awry... Those will

57:46

actually increase the damage in the

57:48

gut that allows leakiness, which increases

57:50

CD38, which further lowers NEDs. So

57:52

it is a positive feedback loop

57:54

in the bad way. It gets

57:56

worse and worse and worse. In

57:58

contrast, if you can do the

58:00

proper things in terms of your

58:02

health. maintain NAD, you will have

58:04

a positive feedback loop in the

58:06

other direction in terms of restoration

58:08

and prevention of disease. So it's

58:10

a very highly amplified system. It's

58:12

sensitive. If you are taking, say,

58:14

any NMM supplements or our product,

58:16

for example, and all is going

58:18

well, and we've had all of

58:20

these people comment about other lives

58:22

have changed, we've had several people

58:24

who went traveling and forgot their

58:26

stuff. Now those people... seem to

58:28

regress pretty quickly after about two

58:30

to three weeks. And so it

58:32

can get better quickly, but it

58:34

can get worse if you're not

58:36

doing these right things. So it's

58:38

the sort of thing where you

58:40

need to be mindful to do

58:42

it every day. I mean, this

58:44

is a journey. Longevity treatments are

58:46

not something you can do. now

58:49

and then. If you're committed to

58:51

taking care of your health, it's

58:53

something that you've got to do

58:55

every day. We recommend, for example,

58:57

that our capsule is taken at

58:59

the time we brush your teeth,

59:01

because you remember that in the

59:03

morning. And you want to do

59:05

this every day. All of these

59:07

things you're discussing. We're talking about

59:09

here today, require commitment. It's life

59:11

long. If you want to make

59:13

a difference, you have to maintain

59:15

that momentum and you can't be

59:17

skipping out, you've got to be

59:19

consistent. You saw my supplement room.

59:21

Yes. Where I take about 150

59:23

pills a day. I never saw

59:25

anything like this before. I've been

59:27

doing this for 20 plus years.

59:29

Wow. Because just hanging out with

59:31

people in their 80s when I

59:33

was in my 20s, I know

59:35

what's possible. And also because I

59:37

was pretty sick at the beginning

59:39

of this. And the benefits keep

59:41

coming in where I'm not slowing

59:43

down. My brain works. Look, the

59:45

evidence is out there for us

59:47

to see. We all know people.

59:49

My mother, for example, God bless

59:51

her. She's 92 and a half.

59:53

Her house burnt down last week.

59:55

Oh no. But she ran out

59:57

of the house and she's already

59:59

to rebuild the new house. She's

1:00:01

excited. She can't wait. That's a

1:00:03

92-year-old with energy, with activity, with

1:00:05

drive. But I know a lot

1:00:07

of other people, the same age,

1:00:09

and they're shuffling, they can hardly

1:00:11

walk, they have limited activity, they

1:00:13

don't, my mother's out there running

1:00:15

down buses to go to the

1:00:17

symphony, go to the museum, and

1:00:19

other people, they need care, they're

1:00:21

at home. So 92 is not

1:00:23

92. 92 is not 92. 92

1:00:25

is just a number. If you

1:00:27

want to maintain your health and

1:00:29

you're good about this, you can

1:00:31

be a very vigorous active citizen

1:00:33

well into your 90s, maybe longer.

1:00:35

But it requires a lifelong commitment

1:00:37

to stay in good health and

1:00:39

some good genes. That doesn't hurt.

1:00:41

Jeans do not hurt. How much

1:00:43

wonder if you'll, does your mom

1:00:45

take? She doesn't take it yet.

1:00:47

She doesn't? And she's just naturally

1:00:49

doing this. Well, all her relatives

1:00:51

live to be 100. I'm sure

1:00:53

her parp activity is probably off

1:00:55

the wall compared to most people,

1:00:57

so she's not getting these genetic

1:00:59

damage accumulations. But not all of

1:01:01

us have. We all know people

1:01:03

who live to be very old.

1:01:05

But there are a lot of

1:01:07

people who are in their 60s.

1:01:09

Frankly, they look like they're 80

1:01:11

or 90. I have friends like

1:01:13

that. They're not doing anything wrong,

1:01:15

they feel. But really, they could

1:01:17

be doing more. They could prevent

1:01:19

this. What are the biggest mistakes

1:01:21

that people make with NAD supplements?

1:01:23

But I think the mistake is

1:01:25

not recognizing that depletion of the

1:01:27

material is just as important as

1:01:29

its supply. I really believe in

1:01:31

the concept of combination therapy. So

1:01:34

I think I wouldn't call it

1:01:36

a mistake. I'd recognize that things

1:01:38

like CD38 over activation are going

1:01:40

to cause a problem. So I

1:01:42

think that's very important. Second thing

1:01:44

is consistency, like I said. This

1:01:46

is not occasional, let me try

1:01:48

some supplement. It's a commitment. So

1:01:50

that's a mistake if you don't

1:01:52

maintain that reliability and compliance and

1:01:54

take it every day. Other mistakes,

1:01:56

they are not recognizing that the

1:01:58

NAD story is part of a

1:02:00

systems biology thing. You have to.

1:02:02

exercise. You have to keep your

1:02:04

weight down. You have to be

1:02:06

doing all the other important things

1:02:08

with your diet and all the

1:02:10

important things with your nutrition and

1:02:12

taking care of yourself. So it's

1:02:14

part of a program. It is

1:02:16

not a solution by itself. What

1:02:18

do we know about NAD and

1:02:20

the brain? Well, there are studies

1:02:22

actually looking very carefully at this,

1:02:24

and clinical studies even showing that

1:02:26

NMM supplementation or NNR supplementation have

1:02:28

a real effect on memory, on

1:02:30

the rapidity of your thinking, they

1:02:32

get rid of brain fog, they

1:02:34

allow you to be sharper, all

1:02:36

of the things that you would

1:02:38

expect from a molecule that is

1:02:40

at the centerpiece of the energy

1:02:42

of the brain. I mean, the

1:02:44

brain is a motor. It's like

1:02:46

a computer. It runs on, it

1:02:48

doesn't run on electricity. Well, it

1:02:50

does run on electricity actually, but

1:02:52

it has power. And if you

1:02:54

strip the power away, you turn

1:02:56

it down 50%, what do you

1:02:58

expect? You're not going to be

1:03:00

sharp. So NAD is absolutely front

1:03:02

and center. In fact, it is

1:03:04

the organ most demanding of NAD.

1:03:06

Why do I say that? If

1:03:08

you lose, if you have a

1:03:10

traumatic brain injury or a stroke,

1:03:12

or there's any kind of interruption

1:03:14

to blood flow in the brain.

1:03:16

You had eight minutes. Wow. That's

1:03:18

it. Eight minutes go by without

1:03:20

oxygen. You have irreversible neuronal injury

1:03:22

and severe brain injury. So there

1:03:24

is no time and no tolerance

1:03:26

for a lack of NAD. Minutes

1:03:28

are life-threatening. So great that you

1:03:30

brought that up. The most important

1:03:32

orchid in the body dependent on

1:03:34

NAD. Are there synergies between NAD

1:03:36

and coffee or caffeine my favorite

1:03:38

biochemical? Well caffeine is a stimulant

1:03:40

and it's going to activate the

1:03:42

metabolism of cells and by when

1:03:44

I say activate what does that

1:03:46

mean? It means that it increases

1:03:48

the energy production and consumption in

1:03:50

the cell. It's like being in

1:03:52

a car driving 20 miles an

1:03:54

hour or 100 miles an hour.

1:03:56

500 miles an hour your car

1:03:58

engine is working like crazy you're

1:04:00

using more gas you're going faster

1:04:02

all of those things happen when

1:04:04

you take caffeine. So your need

1:04:06

for NAD and those situations is

1:04:08

heightened. Right. If you take caffeine

1:04:10

and you don't have the NAD

1:04:12

that you should have, you will

1:04:14

have a relative deficiency and it

1:04:17

could probably cause you some harm.

1:04:19

So if you're going to be

1:04:21

a heavy coffee drinker, make sure

1:04:23

that you're youthful in your cells

1:04:25

and that you have your NAD

1:04:27

maintained. We know there's dozens of

1:04:29

studies now associating coffee consumption, not

1:04:31

necessarily caffeine, but coffee consumption with

1:04:33

longer life. And I think some

1:04:35

of that is because of the

1:04:37

antioxidants that are present in the

1:04:39

coffee. But if you were to

1:04:41

stack those with ergothionine and the

1:04:43

other compounds you have in wonderful

1:04:45

and you have adequate NAD, you're

1:04:47

going to get more benefits. And

1:04:49

I think either one by themselves

1:04:51

work, the combination together seems like

1:04:53

a better idea. Yes, we're actually

1:04:55

doing research in this area right

1:04:57

now because we think that adding

1:04:59

a stimulant to our products may

1:05:01

be important not in the long

1:05:03

run, but in the short term

1:05:05

it allows you to be sharper,

1:05:07

faster, better during the day. Everybody

1:05:09

wants that if you're an ambitious

1:05:11

young guy or girl. You want

1:05:13

to be full of energy and

1:05:15

do what you need to do.

1:05:17

But at the same time we

1:05:19

know that like you said stimulation

1:05:21

without... The commensurate increases in energy

1:05:23

supply is asking for trouble. So

1:05:25

that's why we're thinking about a

1:05:27

further combination therapy like that. What

1:05:29

does NAD do for ketosis? Well,

1:05:31

fat metabolism is a, of course,

1:05:33

ketones are produced when fat is

1:05:35

metabolized. Right. And when fat is

1:05:37

metabolized, that requires energy. Okay, because

1:05:39

the process of beta oxidation of

1:05:41

fats, that's how fats are removed

1:05:43

in adipocytes in the fat cells,

1:05:45

it's an energetic process when insulin

1:05:47

isn't present, and that process requires

1:05:49

energy in order to process the

1:05:51

processing of fats. to degrade them.

1:05:53

So when you are ketotic, because

1:05:55

you're breaking down fats, you need

1:05:57

energy to facilitate that process. So

1:05:59

NAD can help with breaking down

1:06:01

fats, you can be in ketosis.

1:06:03

The other thing to keep in

1:06:05

mind is that NAD is very

1:06:07

important in the creb cycle. Okay,

1:06:09

there are two molecules of NAD

1:06:11

which enter into the creb cycle,

1:06:13

and the creb cycle is using

1:06:15

ketones. and incorporating them. So it

1:06:17

is a very central part of

1:06:19

intermediary metabolism. So yes, you do

1:06:21

need to have good NAD levels

1:06:23

when you're ketotic. There are a

1:06:25

lot of different longevity pathways that

1:06:27

we cover on the show and

1:06:29

I'm trying to manage all of

1:06:31

them for myself. We have things

1:06:33

like Mtor, AMPK, and sertuents. How

1:06:35

does NAD compare to each of

1:06:37

those? Well, the NAD and the

1:06:39

sertuans, of course, are related because

1:06:41

sertuans use NAD. They use it

1:06:43

to ribosolate proteins, which cause a

1:06:45

deacetylation. So sertuans and NAD are

1:06:47

intrinsically connected with each other. For

1:06:49

other pathways, all of them will

1:06:51

interact with metabolic machinery. and oxygen

1:06:53

flux and all of these things,

1:06:55

more or less, depending on the

1:06:57

specifics. So I don't know, I

1:07:00

can't answer that generally, but on

1:07:02

the specifics, yes, there will be

1:07:04

research that we are doing and

1:07:06

other people are doing to make

1:07:08

those connections. The Mtor front is

1:07:10

really fascinating to me, because for

1:07:12

listeners, Mtor causes tissue growth, which

1:07:14

is good, unless it's on all

1:07:16

the time, in which case you

1:07:18

might get cancer. So what I

1:07:20

like to do is suppress my

1:07:22

M-tor because the more you suppress

1:07:24

it, then the stronger it rebounds.

1:07:26

So the three things that we

1:07:28

know suppress it are, let's see,

1:07:30

coffee, suppresses M-tor, exercise suppresses M-tor,

1:07:32

and fasting suppresses M-tor. So the

1:07:34

tripling down on M-tor thing is,

1:07:36

well, wake up in the morning,

1:07:38

have some coffee, don't eat breakfast,

1:07:40

exercise. that point you've smashed Emtor

1:07:42

down and then you have some

1:07:44

protein and some carbs which raise

1:07:46

Emtor. So then you get a

1:07:48

big surge right when you want

1:07:50

to put on muscle after the

1:07:52

exercise. But if you want to

1:07:54

put on muscle and you don't

1:07:56

have enough metabolic energy because you're

1:07:58

low in NAD you simply won't

1:08:00

be able to put on muscle

1:08:02

you just get the systemic stress

1:08:04

of all that behavior but you

1:08:06

can't adapt to it. You've got

1:08:08

to have your minerals, you've got

1:08:10

to have your substraterate in the

1:08:12

cells to be able to be

1:08:14

able to do this. and that

1:08:16

means you're getting more results and

1:08:18

less time from the exercise. So

1:08:20

there might not be a study,

1:08:22

but mechanistically we know if you're

1:08:24

going to build any protein in

1:08:26

the body, what's powering that? It's

1:08:28

NAD through ATP, right? That's right.

1:08:30

When your weight lifting or when

1:08:32

you're doing any kind of regular

1:08:34

exercise, there's a period of stress

1:08:36

where your muscles are undergoing hypoxia,

1:08:38

they're not getting enough oxygen because

1:08:40

you're vigorously exercising, lifting weights, whatever,

1:08:42

and that is a stimulus. for

1:08:44

growth of new muscle, for growth

1:08:46

of new protein, and for fission

1:08:48

and production, by fission I mean

1:08:50

separate reproduction of mitochondrial, right? So

1:08:52

someone who's an active runner or

1:08:54

a weightlifter or a bicycler is

1:08:56

causing stress to his system during

1:08:58

the activity and then when he

1:09:00

waits a day or two before

1:09:02

he does it again during that

1:09:04

time, there's regrowth and new growth

1:09:06

of muscle. All of that requires

1:09:08

an incredible amount of energy in

1:09:10

order to facilitate protein production. Protein

1:09:12

synthesis is a highly energy-dependent process.

1:09:14

So you've got to have adequate

1:09:16

levels of ATP and NAD to

1:09:18

sustain and support that. So that

1:09:20

is why the good nutrition is

1:09:22

critical to have the ingredients for

1:09:24

protein. You need amino acids. You

1:09:26

need to have the right diet.

1:09:28

But then you have to have

1:09:30

a steady state level maintained of

1:09:32

NAD. in your cell to facilitate

1:09:34

the expansion of the muscle. Wow.

1:09:36

What do you know about NAD

1:09:38

and willpower? I mean in terms

1:09:40

of your mind, in terms of

1:09:43

your energy, I've never explored, that's

1:09:45

a great question, I go ahead.

1:09:47

Can I share something with you?

1:09:49

This is just my favorite study,

1:09:51

maybe of all the studies ever.

1:09:53

And I wrote about this in

1:09:55

my brain enhancement book. And it's

1:09:57

a study from Israel, where you

1:09:59

live. And a group of scientists

1:10:01

got together and they said, what

1:10:03

predicts whether someone's going to get

1:10:05

parole to get out of prison?

1:10:07

Is it their gender? Is it

1:10:09

where they're from, socioeconomic? What crime

1:10:11

they committed? All of that. And

1:10:13

after they combed through the data.

1:10:15

What predicts whether you get parole

1:10:17

or you get sent back to

1:10:19

prison is what time is your

1:10:21

meeting with a parole board? Because

1:10:23

decisions take mitochondrial energy. So in

1:10:25

the morning, if you get your

1:10:27

meeting, you're very likely to get

1:10:29

out, because they'll consider your case,

1:10:31

okay, you can go. And if

1:10:33

they're tired at the end of

1:10:35

the day, blood trigger levels are

1:10:37

lower, mitochondrial activity is lower, brain

1:10:39

function is lower, it's just too

1:10:41

much work to think about it,

1:10:43

stay in prison. And there was

1:10:45

a brief spike right after lunch

1:10:47

when their blood sugar peaked and

1:10:49

then dropped again and you're screwed

1:10:51

if you have an afghanier meaning.

1:10:53

Right. And so I found the

1:10:55

studies. There was two studies that

1:10:57

directly associate mitochondrial function with willpower,

1:10:59

which only makes sense because this

1:11:01

drives everything. Well, I think that

1:11:03

the whole issue about NAD level

1:11:05

being susceptible both to or influenced

1:11:07

both by supply and depletion is

1:11:09

important. If you take a supplement

1:11:11

in the morning... And this has

1:11:13

been shown in animals as well

1:11:15

as in humans. When you take

1:11:17

a supplement, you will get a

1:11:19

boost in your blood levels of

1:11:21

NAD and NMN. It goes up.

1:11:23

But it's not going to stay

1:11:25

up because over time, the activity

1:11:27

of CD38 on the outside of

1:11:29

these cells will chew it up

1:11:31

as well as it being used

1:11:33

up. So that is why we

1:11:35

feel so important. It's so important

1:11:37

to have this combination so that...

1:11:39

you have a sustainable level of

1:11:41

NAD throughout the day and it's

1:11:43

not just a brief burst or

1:11:45

episode in the morning after you've

1:11:47

taken the supplement. So this would

1:11:49

be wonderful. in the morning and

1:11:51

at lunch? No, you take it

1:11:53

once a day, but by blocking

1:11:55

CD 38 activation, by inhibiting CD

1:11:57

38, you prevent the subsequent breakdown

1:11:59

that would occur later in the

1:12:01

day. So think of it as

1:12:03

a bathtub. You have water going

1:12:05

in and you have a drain

1:12:07

with water going out. You can

1:12:09

fill up the bathtub in the

1:12:11

morning, but if there's a big

1:12:13

hole in it, during the day,

1:12:15

it's going to run down. The

1:12:17

only way to maintain a steady

1:12:19

state level of something is to

1:12:21

make sure that the water going

1:12:23

in is good and that the

1:12:25

whole letting it out is small.

1:12:28

Right. And this is the point

1:12:30

of having that combination. That's why

1:12:32

I think you'd have a more

1:12:34

sustainable level when you're blocking CD

1:12:36

38 and not just giving the

1:12:38

supplement. That makes so much sense.

1:12:40

The other process that's driven by

1:12:42

mitochondria is the Glenphatic system. which

1:12:44

is something that happens when you're

1:12:46

asleep at night, and your brain

1:12:48

basically washes itself out via a

1:12:50

recently discovered mechanism. And I did

1:12:52

find a couple studies showing that

1:12:54

that's also derived from mitochondrial things.

1:12:56

You have to pump this stuff

1:12:58

out, and this isn't the kind

1:13:00

of pumping that happens when you're

1:13:02

asleep. Is there a case for

1:13:04

increasing NAD for sleep efficiency? We

1:13:06

have had, and not just we,

1:13:08

many people have commented, that NED

1:13:10

supplementation has a very profound effect

1:13:12

on the quality of sleep. We

1:13:14

have seen this from our customers,

1:13:16

many anecdotes. This is one of

1:13:18

the most common things to come

1:13:20

back, but not just us. There

1:13:22

are numerous reports with NED supplements

1:13:24

like the Neman and NNR commenting

1:13:26

on exactly this point. I don't

1:13:28

know why that is the case.

1:13:30

We don't, I mean, there's very

1:13:32

little research really on the... type

1:13:34

of energy requirement during sleep and

1:13:36

where and how it's done. But

1:13:38

let's face it, sleep is a

1:13:40

process which is removing adenosine. That's

1:13:42

one of the main, I mean,

1:13:44

does many things. There's neuronal plasticity,

1:13:46

there's a corporal. of events into

1:13:48

long-term memory, but fundamentally during the

1:13:50

day, the brain, like any organ,

1:13:52

is having to consume energy in

1:13:54

order to do its job, and

1:13:56

as a consequence of that, the

1:13:58

brain is accumulating metabolites of ATP

1:14:00

that break down. It uses ATP

1:14:02

to make it go, the ATP

1:14:04

becomes ADP, and AMP, and ultimately

1:14:06

adenosine. So when that all happens

1:14:08

by the end of the day,

1:14:10

say 10, 11 o'clock at night,

1:14:12

your brain is chockful of adenosine.

1:14:14

It's exhausted, to put it in

1:14:16

another way, during the night. And

1:14:18

the adenosine, by the way, is

1:14:20

what makes you sleepy. And that's

1:14:22

why coffee keeps you away, because

1:14:24

coffee is an antagonist of the

1:14:26

receptor of adenosine. So a person

1:14:28

who takes coffee and takes caffeine

1:14:30

doesn't allow the adenosine within their

1:14:32

brain to make them sleepy. Adenosine

1:14:34

says to you, I'm sleepy, go

1:14:36

to sleep. Okay, so when you

1:14:38

start to go to sleep, the

1:14:40

adenosine is then take it up

1:14:42

into the cells and ATP with

1:14:44

help of NAD regenerates the ATP

1:14:46

for the next day. When you

1:14:48

wake up in the morning, you're

1:14:50

feeling pretty good. You're getting pretty

1:14:52

good. So NED during the night

1:14:54

is the key driver of the

1:14:56

process, which is restoring your ATP

1:14:58

levels and lowering your identity. So

1:15:00

you're using NED at night to

1:15:02

get back to where you were

1:15:04

for the next morning. You always

1:15:06

take wonderful in the morning? We

1:15:08

take it in the morning. What

1:15:11

happens if you take it at

1:15:13

night? Well... It probably would be

1:15:15

okay, but think about it. You're

1:15:17

going to have some type of

1:15:19

burst of activity or levels. I

1:15:21

mean, when you take any molecule,

1:15:23

whether it's a drug or a

1:15:25

supplement, whatever, you take it in

1:15:27

the morning at 8 o'clock, your

1:15:29

peak level will typically occur between

1:15:31

30 minutes and two hours. I'm

1:15:33

almost all drug. There are a

1:15:35

few exceptions, but most take Tylenol

1:15:37

for example, 15 to 20 minute

1:15:39

peak, Advil, 30 minute peak. So

1:15:41

when you take Wonderfield in the

1:15:43

morning, you're going to get your

1:15:45

peak early. When you want to

1:15:47

have the highest levels, because you're

1:15:49

moving around, you're active, you're going

1:15:51

to work, you're bicycling, you're thinking

1:15:53

a lot, so you want to

1:15:55

have super high levels right then.

1:15:57

To take it right before you

1:15:59

go to sleep seems like kind

1:16:01

of a waste of time. You

1:16:03

need a steady state level while

1:16:05

you're sleeping, but you don't need

1:16:07

a big burst. You're not doing

1:16:09

a huge amount of activity when

1:16:11

you're sleeping in general. One of

1:16:13

the things that a lot of

1:16:15

humans will do is something's good

1:16:17

for you more is better. I

1:16:19

believe this about exercise. For 18

1:16:21

months, I worked out 90 minutes

1:16:23

a day, six days a week

1:16:25

religiously. I never lost a pound

1:16:27

because I was over training and

1:16:29

under recovering. Right. Is there such

1:16:31

a thing as having too much

1:16:33

NAD because you're just popping supplements

1:16:35

all the time? Well, there have

1:16:37

been studies of this going up

1:16:39

to 900 milligrams a day, and

1:16:41

about four or five studies now

1:16:43

have all shown that the best

1:16:45

effects were at 900 milligrams. There

1:16:47

was one study that showed also

1:16:49

a good effect at 600 milligrams,

1:16:51

but slightly better at 900. And

1:16:53

there is actually courtesy of Dr.

1:16:55

Sinclaira study of where he actually

1:16:57

went up to grams. Several grams.

1:16:59

He claims in that study that

1:17:01

no one was hurt, which is

1:17:03

good. It means there's a nice

1:17:05

safety factor so we can all

1:17:07

step back and relax a bit.

1:17:09

Whether you need more than 900

1:17:11

milligrams to be effective has not

1:17:13

been examined. There has not been

1:17:15

a careful comparison between 900 milligrams

1:17:17

and 2 grams. It might be

1:17:19

better. At some point, though, having

1:17:21

said that, too much of something

1:17:23

may not be a good thing.

1:17:25

And all of the, when you

1:17:27

think about biology as a whole

1:17:29

and the way our system works,

1:17:31

the entire organism in the human

1:17:33

biology, in any kind of biology,

1:17:35

is based on having the foot

1:17:37

on the gas and the foot

1:17:39

on the break simultaneously. This is

1:17:41

how we create control. We don't

1:17:43

have a system where just the

1:17:45

gas is on or just the

1:17:47

break is. So you need to

1:17:49

have a certain amount of something,

1:17:51

but if it becomes grossly excessive...

1:17:54

you're going to have other factors

1:17:56

involved. If NAD is spinning the

1:17:58

creb cycle too fast, that could

1:18:00

create byproducts that can't be handled.

1:18:02

So there could be a lot

1:18:04

of things where excessive NAD is

1:18:06

not needed, certainly, and could actually

1:18:08

be injurious. Okay. So you like

1:18:10

the recommended dose? Or the moment.

1:18:12

There should be research examining all

1:18:14

doses, but this is where the

1:18:16

research currently tells us it's best.

1:18:18

Okay. Anecdotally, I did notice, especially

1:18:20

with NR, which I started taking

1:18:22

a long time ago, I felt

1:18:24

a difference at two grams I

1:18:26

didn't feel at a gram or

1:18:28

less, but especially in the early

1:18:30

days, that stuff was really expensive.

1:18:32

It was like $500 a month

1:18:34

to take that much, which is

1:18:36

kind of absurd for most people.

1:18:38

Keep in mind that when you're

1:18:40

taking NR, you're going to get

1:18:42

a boost. But then it's going

1:18:44

to come down because of the

1:18:46

CD 38. And we don't know

1:18:48

the CD 38 and done all

1:18:50

the research. And so these are

1:18:52

old days. So maybe now the

1:18:54

lower dose with blocking CD 38

1:18:56

is. And I want to emphasize

1:18:58

that at Wonderfield at least, and

1:19:00

just in my life, I'm a

1:19:02

deep believer in the importance of

1:19:04

doing research. I don't just like

1:19:06

to recommend something or even think

1:19:08

about it. My entire career has

1:19:10

been based on researching everything. I'm

1:19:12

not just curious, but it can

1:19:14

help people. with NAD. I'm telling

1:19:16

you what I know today, I

1:19:18

hope we'll know a lot more

1:19:20

next year, and that'll be from

1:19:22

research. Well, thank you. We're carrying

1:19:24

out that research. By the way,

1:19:26

we have a big biology lab

1:19:28

where we conduct research activities constantly

1:19:30

in the cellular level, at the

1:19:32

animal level, we're asking questions about

1:19:34

this all the time. Well, thanks

1:19:36

for your relentless curiosity. That's what

1:19:38

it takes to really discover this

1:19:40

instead of just deciding something works

1:19:42

and then sticking to your guns.

1:19:44

The final question for you as

1:19:46

we wrap up the interview, and

1:19:48

you've studied all the different biochemists.

1:19:50

you've treated people in hospitals. Is

1:19:52

there a hard truth about biological

1:19:54

aging that even biomarkers wouldn't want

1:19:56

to accept? I don't think that

1:19:58

pessimism or cynicism or resignation, capitulation,

1:20:00

is appropriate for people. If you

1:20:02

just look historically where we were

1:20:04

200 years ago, where very few

1:20:06

people live beyond the age of

1:20:08

49, If we go back 5,000

1:20:10

years ago where very few people

1:20:12

lived ever beyond the age of

1:20:14

25, all I see are good

1:20:16

things happening. And I don't think,

1:20:18

just like the four-minute mile, you

1:20:20

know, there was that whole debate

1:20:22

before Roger Bannister ran, and they

1:20:24

asked him afterwards, did you think

1:20:26

there was a physical impossibility to

1:20:28

run a four-minute mile? He said,

1:20:30

no, I just had to work

1:20:32

hard to train. So I don't

1:20:34

think there is a barrier as

1:20:37

long as we... are wedded to

1:20:39

the commitment to do the research

1:20:41

to understand why we're aging. We

1:20:43

need to do a lot of

1:20:45

research, but I am gun-ho, I'm

1:20:47

ready to be part of that

1:20:49

research, and I think the sky's

1:20:51

the limit. We just have to,

1:20:53

we have to push hard, be

1:20:55

optimistic. Well, Dr. Andy Salzman, thanks

1:20:57

for your lifetime of just incredible

1:20:59

work and going out there and

1:21:01

saying, how do I do stuff

1:21:03

that affects more people? I think

1:21:05

you've had a meaningful impact on

1:21:07

our understanding of biology and aging

1:21:09

and cell metabolism and a bunch

1:21:11

of other stuff, cancer. So you

1:21:13

have an impact, and I love

1:21:15

it that you're not slowing down.

1:21:17

So I appreciate you. Thank you.

1:21:19

It was a pleasure to be

1:21:21

here. Thank you. Guys, wonderfield.com is

1:21:23

where you can learn about all

1:21:25

this stuff and a lot of

1:21:27

your writing is on that web

1:21:29

page as well or you can

1:21:31

just read as 170 publications if

1:21:33

you want to. There's that. If

1:21:35

you like this episode, you know

1:21:37

what to do. Have more NAD

1:21:39

in your life. It seems like

1:21:41

that's a good strategy. It's not

1:21:43

the first time you've heard it

1:21:45

on the show, but this is

1:21:47

the first time we've gone deep

1:21:49

on CD38, CD38, Ergothion, Eureth. combination.

1:21:51

And as you know, if you

1:21:53

listen to the show for the

1:21:55

last 10 plus years, I take

1:21:57

150 supplements a day and they're

1:21:59

carefully designed for my metabolism. I

1:22:01

don't publish the entire list because

1:22:03

if you did what I did,

1:22:05

you'd probably get disaster pants or

1:22:07

as my daughter calls it, underwear

1:22:09

surprise. So you want to figure

1:22:11

out what is the load on

1:22:13

your life? What kind of stress

1:22:15

are you under? What kind of

1:22:17

aging do you want to have

1:22:19

in your in your brain right

1:22:21

now? And you try things. I'm

1:22:23

going to try Wonderfield. So you

1:22:25

try it for, I would say,

1:22:27

at least three months and see

1:22:29

what happens. And we're great at

1:22:31

understanding. I felt good today. I

1:22:33

felt good tomorrow. But some of

1:22:35

these effects build up over the

1:22:37

course of weeks and we're terrible

1:22:39

as a species at noticing effects

1:22:41

that are just downstream. So this

1:22:43

is one of those things. Get

1:22:45

your NAD up in your CD3838

1:22:47

down and just watch what happens

1:22:49

over time. And you might say,

1:22:51

I've always felt this good. And

1:22:53

then, let's say, you stop it

1:22:55

for a month. And you go,

1:22:57

oh, look, my aura ring, or

1:22:59

in this case, not my ultra-human

1:23:01

ring, I'm wearing both, it says,

1:23:03

oh, wow, my heart rate of

1:23:05

variability started to drop. I didn't

1:23:07

get as much sleep. My morning

1:23:09

readiness score isn't where it was.

1:23:11

And you realize, oh, there's these

1:23:13

gentle patterns that happen over time.

1:23:15

And you want to live a

1:23:17

very long time. You want to

1:23:19

watch those as well, and there's

1:23:22

so much evidence at this point.

1:23:24

This is probably the 10th episode

1:23:26

on NAD, and the first one

1:23:28

to go on this level, that

1:23:30

this should be a part of

1:23:32

your longevity strategy. And maybe say,

1:23:34

I can't live longer. I'm a

1:23:36

Peter Atia fan who believes you

1:23:38

can't extend human life. That's okay.

1:23:40

You can still improve human performance

1:23:42

and the quality of your health

1:23:44

span, if that's your only goal.

1:23:46

I think your goal should be

1:23:48

lifespan. plus health span. And that's

1:23:50

my goal. So if you share

1:23:52

that, get your NED levels up

1:23:54

via any means necessary. Thanks for

1:23:56

listening. See you next time on

1:23:58

the Human Upgrade podcast.