Let's let's talk about the

multivitamins. So, this was the COSMOS

trial. I've talked a lot about the

COSMOS trial in the context of brain

aging. So, the larger there's, you know,

the larger trials and there was three

randomized controlled trials where these

older adults were given a standard

Centrum Silver multivitamin a day

every day and it was what is it about

3.6 years for this trial?

And

they were looking at I mean, there's a

lot of endpoints of this trial, but one

of them was cognitive function and brain

aging. And at the end of the trial, the

the people that were given the

multivitamin had slowed their brain

aging by 2.1 years. There's a battery of

tests that were done there and I'm not

sure if in fact some clocks were used as

well.

But I know that the global brain aging

was slowed by 2.1 years and their

episodic brain aging, so episodic memory

is the kind of memory where you're

remembering experiences, people, right?

Like those sorts of things. Um that was

slowed by almost 5 years compared to the

placebo group, which is quite

significant and they did better on a

battery of cognition tests.

And so that was very that's very

encouraging, you know, and it's

something that I do talk about a lot

because I feel like it's a very easy

safe intervention that people can take a

standard multivitamin. These have a

variety of

vitamins and minerals, trace elements

that people are not getting from their

diets. And so they're kind of filling

that nutritional gap. And

and so, you know, who doesn't want their

parents and grandparents to have better

brain aging? I think so. I'm my parents

are on a multivitamin, right?

Um when it comes to looking at these

epigenetic aging clocks,

the PhenoAge GrimAge clocks were the

ones that stood out to me. As you

mentioned, there was a battery of clocks

that were that were looked at, but it

seemed as though they were slowing or at

least

I I'm not exactly sure all the

calculations that go into this, but 2.7

months to 5 months, right? Like they

were basically

they're they're slowing the aging by

roughly that amount.

>> Yes.

>> Um

which to me is if you think about now

this this trial that was done

with the aging clocks, I think it was

like a subset of it of the larger trial.

Was it 2 years or did they do the 3.6

years for that? Do you

>> It was Yeah, I think it was 2 years.

>> 2 years, yeah. And and so um to me

the question is now this wasn't the you

said the duodenum paste didn't change.

>> No, it it it changed in the right

direction. It just wasn't statistically

significant.

>> Oh, I see. So

>> No, um

in the right direction, you know. Maybe

a larger sample size would have um led

to a significant finding. It was

definitely in the right direction.

>> Well, the question I have for you is if

you're changing it by, you know, 3 to 5

months within that 2-year range

according to the the GrimAge and

PhenoAge clocks

and you're to keep doing that, you know,

you know, for years. So now we're

talking not just 2 years, we're talking

20, we're talking 30, 40 years.

>> Yes.

>> How do you think that Do you think that

you get this accumulative effect?

>> Yes, I think so. I um I think so. I um

maybe to step back, if you tell an

80-year-old that um a multivitamin will

reduce his or her age by 3 months, they

will roll their eyes. They will say,

"Hey, give me something that reverses my

age by 30 years, you know."

Um

um so fair enough. The effect

it we just need to acknowledge the

effect is very minor, you know. However,

I like the way you conceptualize it. If

you

um really use it for 30 years, right?

You're a 50-year-old and you use it

until you're age 80,

my expectation is that suddenly these uh

3 months benefit they accumulate and

suddenly you have a benefit of maybe 2

and 1/2 years, you know? It's still not

great, you know, but there is a benefit,

you know, so um

>> But think of the effort you have to put

into just taking a multivitamin. Right?

I I think it's pretty great for that

amount of effort, you know, if you're if

you're just having to take one vitamin

supplement

>> Yes.

>> and it's going to delay your your brain

aging, you know, by 2.1 years just

after,

you know, in that trial it was 3.6 year

trial, but you know, that's pretty

robust. 5 years delaying brain episodic

brain aging.

>> Yes.

>> And and now we're talking about like

globally like

biological aging. If it's if it's

slowing it by, let's say, on the high

end 5 months after 2 years,

>> Yes.

>> I don't know. That seems like a pretty

great effect. If you're just taking a

vitamin supplement for 2 years it's

doing that, well, let's continue on and

and then combine them the things and

we'll get into some of the other trials

that do show synergy, but

>> Yes.

>> Um I think it's interesting. The other

question is that and this is where

um you know, the COSMOS trials, people

but they're looking at everything,

right? Cancer mortality, cardiovascular

mortality, all-cause mortality, and

those didn't really seem to change

>> Yes.

>> at least within the time frame

>> Yes.

>> that was looked at. And so,

you know, we see these epigenetic clocks

giving us a signal. We see the brain

aging effects and the question is why

are why are those showing up before

perhaps

>> I tell you my reading of it and um to me

this whole study was

one triumph for epigenetic clocks and I

explain to you why.

Assume you knew nothing um about

multivitamins. Um you would think that

there is a benefit, you know? Um clearly

vitamins are important. It's a trivial a

tautology.

>> Avoiding deficiencies are important.

>> especially, you know? So, you would say,

"Okay, I administer that to the US

population. I would hope [snorts] to see

an effect." and that of course is the

reason why these large-scale studies

were even initiated. Think about how

difficult it is to raise the funding for

such a large-scale study.

Clearly

there must be very compelling reasons.

Okay, but there's a problem now and

these hard endpoints, mortality,

cardiovascular disease, they didn't

detect an effect. It's deeply

frustrating.

>> Well, there was a trend, it wasn't

statistically significant.

>> Yeah, I I let you summarize it but to

me, you know, it um

I I I I just looked at it from the point

of view as a consumer. 5 years ago, you

know, I wouldn't take a multivitamin. I

looked at the literature, no benefit. I

won't take it, you know.

Now

um so um

a person can now make their own

judgment, you know, so what does it

mean?

To me, I take it as a wonderful triumph

of genetic clocks that they did pick up

the the signal.

And I um call this testing the test. You

have an intervention where um

you really think it's got to move the

needle, you know, and then if a readout

doesn't show it

one interpretation is well, maybe the

readout is too crude. Maybe

um all cause mortality is a real I mean,

we I like it as a readout. I used it for

GrimAge, don't get me wrong. I I like

that it's hard and definitive. You can't

argue with it. However, people die for a

hundred different reasons, you know,

that may really not relate to the uh

biology of aging, you know, and um so

now that we have actually biomarkers

that did pick up that signal even though

it's very weak is to me um

really reassuring, you know.

>> Yeah, and I think it's reassuring in

combination with the the the brain aging

signal that it picked up. And just

knowing that, you know, so many

globally people are not getting enough

of these important vitamins and minerals

and trace elements and essential fatty

acids from their diet, then it's kind of

like a an insurance. Like, okay, I'm

going to fill some of these nutritional

gaps. They won't all get filled because

you can't stuff everything into one

pill. I mean, you know,

you can only get a little bit of some

things in there, right?

>> Yes.

>> But I do think that it's it's again, I

agree with you. I think it is a triumph

and it's something that I do think that

is safe. I mean, it's really been shown

to be safe and so so maybe maybe you pee

a little bit more, but out. So what?

It's it's it seems to be doing something

beneficial for the brain and at least

for you know, looking at these aging

clocks, it seems like for the way your

aging as well.

>> Yes. Yeah, so what have you got to lose,

you know? Yeah.