AMA #12: Thoughts on Longevity Supplements (Resveratrol, NR, NMN, Etc.) & How to Improve Memory

ANDREW HUBERMAN: Welcome to the Huberman Lab podcast

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I'm Andrew Huberman, and I'm a professor

of neurobiology and ophthalmology

at Stanford School of Medicine.

Today is an Ask Me Anything episode, or AMA.

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So without further ado, let's get

to answering your questions.

The first question is about resveratrol.

The question specifically is, and I

quote, "there seems to be a lot of conjecture about resveratrol

and whether or not it can extend lifespan.

Could you please tell us your thoughts on this subject?"

OK, well, I will indeed tell you my thoughts on this subject.

And I'll use it as an opportunity

to also give you my thoughts about supplementation

for sake of longevity, that is, for extending lifespan,

more generally.

So resveratrol got a lot of attention

some years back because, at the time,

it was believed that supplementing with resveratrol

could impact certain cellular pathways that would extend not

just the lifespan of those individual cells

but perhaps the lifespan of the entire organism, meaning us,

humans.

And as a consequence, supplements

such as resveratrol supplements but also grape seed extracts,

which we know contain a fair amount of resveratrol

or can be converted into resveratrol, also

received a lot of attention for their potential

to increase lifespan.

I think by now, 2023, it's fair to say

that most of that thinking has been, let's just say, debunked.

I think that most people understand

that while indeed resveratrol might

have some positive effects on the functioning of our cells

that there is very little, if any,

direct evidence that resveratrol can increase lifespan.

If you are aware of any data to the contrary that is modern,

is highly controlled, and even better,

was carried out in human studies or non-human primate

studies or even mouse studies, please

put links to those in the comments on YouTube,

because I'd love to see those studies, especially

recent studies.

But my current line of thinking is

that resveratrol while it may have certain health benefits

does not seem to increase lifespan.

Now, with that said, that doesn't

mean that things like resveratrol or grape seed

extract are of zero utility.

In fact, I take 400 to 800 milligrams of grape seed

extract, usually with a meal.

It's just part of my standard supplementation

stack every single day.

But I do that mainly for its effects on vascular function

and blood flow and a few other effects

that grape seed extract has been related to.

The data there, I would say, are reasonably strong, strong

enough certainly that when weighed

against the potential downsides of taking grape seed extract,

including the cost of grape seed extract,

lead me to take 400 to 800 milligrams

grape seed extract per day.

I just do that as a kind of general insurance policy

against a number of things.

And it's part of a small kit of supplements

that I take that fall into that category,

meaning supplements that appear to be very safe, certainly

at the dosages that I just referred to,

supplements that potentially are having

positive effects on our cells, and that are

fairly if not very low cost.

So that's why I take grape seed extract.

I do not take it for its potential impact

on resveratrol and resveratrol-related pathways

per se and certainly not to extend my lifespan.

So that basically answers the question that I was asked,

which is what are your thoughts on resveratrol

for extending lifespan.

My answer was I don't think it extends lifespan.

But I take something related to resveratrol for other health

purposes.

And by the way, I certainly wouldn't

place grape seed extract in my list of top five

or even top 10 supplements if somebody, for instance,

said I want to take anywhere from one to 10 supplements,

and I have x amount of budget to devote to supplementation.

And I'm thinking about taking grape seed extract.

Would that be one of the top 10 supplements

you would recommend?

I certainly wouldn't put it in the top 10.

And by the way, at some point in the not too distant future,

I will put online--

so I'll probably do a podcast episode-- listing

out all the supplements that I take and the rationale

behind those and how long I've taken them and the effects

that I've observed both subjectively and in my blood

work and what I recommend to other people, what I don't

recommend to other people, what's specific to me,

and so on and so forth.

But meanwhile, that's my answer to the question.

I don't think resveratrol increases longevity.

At least, I'm not aware of any direct evidence

for that in humans.

Now, with that said, let's use this as an opportunity

to talk about some of the other so-called longevity

supplements and drugs that are often discussed online

and elsewhere in terms of their efficacy to increase lifespan.

About four or five years ago, there

was a sudden and increased attention

on NAD-related pathways for increasing longevity.

So the NAD pathway, as some of you may already know,

is a pathway within all of our cells.

This is a pathway that is highly active in young animals

and humans.

But all animals and humans across the entire lifespan

make NAD in their cells.

It's related to cellular energetics.

That is the production of energy in cells.

It has direct relevance to mitochondrial

function and mitochondrial function to it.

And that's a discussion unto itself.

But suffice it to say that the pathway leading to NAD

includes things such as NR and NMN.

NR and NMN are considered by many to be precursors to NAD.

OK, so why am I telling you all these acronyms?

Here's the deal.

The argument was made, in fact, by some prior guests

on the Huberman Lab podcast and elsewhere that by increasing

NAD levels in our cells that one could potentially

extend lifespan.

And there are generally three ways in which people

have attempted to do that.

OK, we'll talk about whether or not increasing NAD in our cells

actually increases lifespan in a moment.

But for the time being, let's just talk about some

of the ways that people have tried to increase NAD

within their brain and body.

The most typical ways that people have done that

is through, until very recently, supplementation.

And so there are supplements out there such as NR which we

know can increase NAD levels.

So this is taken as a pill or a powder,

typically as a capsule or a powder.

Or by taking NMN which, and here there's been some,

let's just say, debate as to whether

or not taking NMN actually leads to increases

in NAD within our cells, whether or not

it can get into our cells, whether or not

it's converted into NAD, and so on and so on.

But there again, the idea was by taking NAD either

in capsule form, or it's sometimes taken

as a sublingual powder, that one could increase NAD levels

and thereby potentially increase lifespan.

And then there's a third way that's commonly

used to try and increase NAD levels,

and that's by infusing by intravenous infusion,

or in some cases, by oral administration, either liquid

or pill form, NAD itself.

Now, I confess that I have tried all three of these approaches.

OK, so I do indeed take an NR supplement every day.

I take 500 milligrams of NR.

I also and have separately taken an NMN supplement.

I take sublingual NMN.

So I'll take anywhere from 1 to 2 grams of NMN

as a sublingual powder, which as the name suggests,

you put it under your tongue, and it dissolves there.

It's got this kind of tangy flavor.

And the goal for me in taking an NR and NMN each day--

and I should mention that sometimes I have just

taken NMN or just NR to do the comparison between NR and NMN

for me in a subjective way, just comparing what are my energy

levels, how do I feel, whether or not

there are any side effects.

And then I've also taken them together.

And I've arrived at a protocol where I take

NR and NMN every single day.

And the goal of that is indeed to increase NAD levels

within my system.

However, and I really want to emphasize this,

I do not take NR and NMN in order to increase my lifespan.

In fact, at this point in history,

it's unclear and seems somewhat unlikely that increasing NAD is

going to increase lifespan.

But I think we should always keep our minds open.

There may be data to arrive in the future that

shows that actually does happen in humans.

Now, there are some animal data suggesting that increasing NAD

either by taking NR and/or NMN can increase lifespan.

But frankly, that is not why I take NR and NMN.

I take NR and NMN in an effort to increase NAD.

And now I realize what I'm about to say is entirely subjective.

And I really want to highlight that.

What I'm about to describe is my experience.

It is not based on any peer-reviewed studies.

When I take NR and NMN at the dosages

I talked about a little bit earlier,

it gives me a lot of sustained mental and physical energy

throughout the day.

Now, I've always had a lot of mental and physical energy.

But I'm 48 years old now.

And I'm interested in doing anything

that I safely can to keep those levels of energy

as high as is reasonable, right?

I don't want to have so much energy

that I can't sit still or so much energy

that I can't sleep at night.

But I find that when I take NR and NMN in the morning--

so typically, I'll do this before my first meal.

I don't really regulate how close it is to that first meal.

So I'll wake up, use the bathroom,

hydrate, get my sunlight, do all the things I've

talked about on other podcasts.

But I'll take my NR and NMN sometime

usually within about an hour or two

of waking up and typically at least 30 minutes

to two hours before my first meal, which for me usually

arrives around 11:00 a.m.

So sometimes I'll take it long before my first meal.

In any event, it gives me a lot of energy.

And I seem to have that energy throughout the day.

I have gone periods of time where

I stopped taking NR and/or NMN.

And while I didn't feel as if I was completely

depleted of energy, I did notice a decrement in energy

compared to when I took NR and NMN.

Now, I want to be very, very clear.

I have no, zero, financial relationship

to any company that manufactures NR.

And while I used to have a relationship to a company that

made NMN, as of recently, there's

an FDA ruling that has made NMN not available as a supplement

in the wider world.

So earlier this year-- that is in 2023--

there was a filing for NMN as a experimental drug

in a clinical trial.

And as a consequence, NMN was listed as a banned or not

allowed to be commercially sold supplement.

And that has to do with some of the legality

around clinical trials.

And when something is listed as an experimental drug,

it can't be listed as a supplement.

Nonetheless, you can still find NMN on the open market.

You can find it on Amazon.

I can't really speak to the purity

of one source versus another.

You'll have to explore that on your own.

But I will say this, even though I said it before.

I have zero financial relationship

to any company that manufactures and sells NMN at this time

or NR at this time.

So the short summary to this whole discussion

about NR and NMN is that I take NR and NMN,

but I take it because I like how it makes me feel.

It increases my energy levels in the morning

and throughout the day.

And it does so in a way that tapers

off nicely in the evening, and I can still

fall asleep, et cetera.

I do not take it with any expectation

that it's going to increase my lifespan,

simply because I don't think the data substantiating

the extension and lifespan are here yet.

They may arrive at some point.

But I don't think that they are here yet.

So there are a good number of people out there

that still take NR and/or NMN and are doing so in efforts

to increase NAD.

And so let's take a moment and talk about increasing NAD

directly, because that's something

that I have some recent experience with, and that's

becoming more common and is, yes, still FDA approved,

at least as far as I know.

There are companies that can come to your house,

or you can go to a facility, and they

will give you an NAD infusion.

So they will infuse you directly with NAD into the vein.

I've done this twice now.

And I will say, as most people experience

when they do an NAD infusion, it's pretty darn uncomfortable.

In fact, so much so that a lot of people

have to take anti-nausea meds in order to get the NAD infusion.

I opted to not take the anti-nausea meds,

not because I'm particularly tough,

but because I don't like taking additional medication if I can.

But I've taken anywhere from 500 to 1,000 milligrams of NAD

by infusion.

I did that at times when I was feeling particularly

rundown or post-illness.

And I did indeed find that after the NAD infusion was complete,

I felt much, much better in a number of different ways--

improved sleep, improved vigor, coming off those illnesses.

I felt much better.

But again, there is no clinical trial

exploring NAD infusion for sake of vigor,

et cetera, that I am aware of.

I just happen to be somebody who is

interested in exploring these tools and techniques from time

to time.

And I deemed this as safe.

Whether or not it's safe for you,

you have to explore with your physician.

Also, I do want to reemphasize what I said a moment ago.

Those NAD infusions are pretty darn uncomfortable.

You can have the person administering

the infusion adjust the rate of the infusion

so that the drip is slower, which

makes it more tolerable as opposed to trying

to get the whole infusion bag in there in 45 minutes or less.

I just wanted to get the whole thing over with.

So I just said, put it in as quickly as you reasonably

and safely can.

It took about an hour, maybe 45 minutes to an hour.

Initially, I felt nauseous.

I felt like someone was stepping on my chest.

I felt like someone was stepping on my legs.

I felt like, well, I just felt lousy.

I felt so awful.

And then after about 10 minutes, it passed.

And I felt fine.

And then after the infusion was done, as I mentioned before,

I felt terrific.

I was still able to fall asleep that night just fine,

although I did make it a point to do this earlier in the day.

I have heard of some people doing NAD infusions later

in the day and having challenges with sleep.

But again, that's just anecdotal.

Or we could call it anecdata, if you want, but it's anecdotal.

It's generally assumed for obvious reasons

that NAD infusions are more effective at increasing

cellular levels of NAD than NR or NMN or both

together, although the direct comparison has not been made,

as far as I know.

And there's still this general question as to

whether or not any of this stuff is getting into cells directly

and impacting NAD levels in specific cells,

although I think most people assume that the NAD

infusions certainly are.

Now, there are a number of different experts out there

who debate all the fine points of everything that I just said,

people like Dr. Charles Brenner and people

like Dr. David Sinclair, people like Matt Kaeberlein.

There are people who really actively,

and let's just say, heatedly debate all the issues

that I just talked about.

I think the greatest debate is around whether or not

increasing NAD levels in cells actually increases lifespan.

But there's also a debate around whether or not

NR is more advantageous than NMN, whether or not all of this

is too premature to explore yet already.

Again, I just want to restate for the third time.

I don't do any of this stuff in these NAD pathways

for sake of increasing lifespan.

I do it for sake of the vitality and energy effects

that I subjectively experience.

I must say that the NAD infusions are expensive enough,

inconvenient enough, and let's just say uncomfortable enough

that I don't see myself doing them very often,

although perhaps maybe doing them a couple of times a year

or more makes sense should I find myself

feeling run down or post-illness fatigue or things of that sort.

I would be very curious to learn from any of you,

the audience, what sorts of things

you've experienced if perhaps you've

explored NR supplementation, NMN supplementation, or NAD

infusions.

And as I mentioned earlier, there's

now a growing number of different products

that claim that you can take NAD orally,

so either in pill, tincture or other forms,

so no requirement for an infusion.

But I'm not aware of any studies that have directly

linked oral NAD to NAD levels in cells

and how those two things relate.

So lots more important science to be done in this area, lots

more debate surely to be had, and any time we

talk about supplements, I just want

to emphasize several times that I do see supplements as indeed

supplements.

I think only by getting your light exposure, sunshine,

movement, nutrition, stress modulation,

social relationships, et cetera, correct should you even

begin to consider supplementation,

because supplementation is just not

at the foundation of mental health, physical health,

and performance.

It is indeed something that, provided

it fits within your safety and economic frameworks,

could potentially enhance mental health,

physical health, performance in certain ways.

But it's certainly not the foundation

from which you build mental health, physical health,

and performance.

So now we've talked about resveratrol, a little bit

about grape seed extract.

We've talked about NR and NMN and NAD and the NAD pathway.

There are a few other things that are commonly

discussed in the longevity sphere, let's call

it, things such as metformin.

I'll just be very direct and say I do not take metformin.

And I also don't take what some people

call the poor man's version of metformin, which is berberine.

Berberine gives me brutal headaches.

Berberine lowers blood glucose.

That's why I think it's giving me brutal headaches.

A lot of people have explored or are

thinking about exploring taking metformin or berberine for sake

of lowering blood glucose and lowering a particular cellular,

let's just say, pathway or a set of molecules, mTOR

being the most common of them.

mTOR, mammalian Target of Rapamycin,

is abundant in developing cells.

It's responsible for the growth of individual cells.

And the amount of mTOR in our cells

tapers off across our lifespan.

mTOR and its pathways is something

that I've actually worked on fairly extensively

in my laboratory in the context of the regeneration

of the visual system.

So I'm very familiar with it.

And for sake of convenience and ease in this conversation,

we can just think of mTOR as something

that's abundant in cells during development

and any time cells are growing, including

the growth of tumor cells, and cellular growth

at any stage of the lifespan.

So the logic that people have waged

is that drugs like metformin or compounds like berberine

that reduce mTOR levels or impact the mTOR pathway in ways

that lead to net decreases in mTOR,

the logic is that could somehow increase lifespan.

There's also the logic that fasting can reduce mTOR

which can increase lifespan.

I don't think there's any direct evidence for that

yet, however, at least not in humans.

So I'll tell you.

I don't take berberine for the reasons I mentioned before.

It makes me feel uncomfortable.

Not psychologically uncomfortable,

it makes me feel physically uncomfortable.

I don't take metformin because expert colleagues of mine,

including Dr. Peter Attia, have come on this podcast.

In fact, we did a collaboration journal club podcast

that we'll provide a link to in the show

note captions during which we, meaning mainly Peter,

reviewed the peer-reviewed data on metformin and lifespan.

And at least to my understanding,

at present, there isn't sufficient data

to support taking metformin for increasing lifespan.

So that's why I don't take it.

I may in the future if more data come out and things change.

But right now, I see no reason to take metformin

to increase my lifespan.

So I don't take metformin.

Similarly, there's a lot of discussion

out there about rapamycin.

Remember mTOR, mammalian Target of Rapamycin,

is so named because it's a target of this drug, which

is used largely as an anticancer drug

but has other purposes as well.

Rapamycin is actively under investigation,

which makes it sound like there was a crime committed.

But as far as I know, there wasn't.

Under active scientific exploration

would be the more accurate way to say it,

by excellent researchers such as Dr. Matt Kaeberlein up

at the University of Washington in Seattle.

He's been looking at rapamycin for its ability

to extend lifespan, focusing on many different species,

including dogs.

So he has a dog longevity project.

So that's really interesting.

Dr. Peter Attia has talked a lot about rapamycin

and did a recent podcast about rapamycin

with not only Matt Kaeberlein but one

of the experts in the world on mTOR.

So I invite you to check out that podcast if you

want to learn about rapamycin.

So there is a fair amount of understanding

about the biological pathways of rapamycin and mTOR and so on.

And there are clinician physicians,

like Peter as well as others, who

are quite excited about the potential for rapamycin

to extend lifespan, although you have to go directly

to Peter to find out exactly what he's doing,

whether or not he's taking rapamycin or not.

I certainly can't speak for him.

But at present, I don't take rapamycin.

Why don't I take rapamycin?

Well, I don't take rapamycin because at least to my eye,

the data at present don't justify

that for sake of increasing lifespan.

That is not to say that rapamycin

isn't an effective drug for the treatment of various cancers

and for other purposes.

But for me, at this point in time,

I just don't see a good reason for me

to take rapamycin relative to some of the, let's just say,

substantiated potential side effects of rapamycin.

It is a drug that I think can be taken safely

under certain conditions but has enough of a side effect profile

that I'm not interested in taking it

for sake of increasing lifespan at this time.

So no metformin, no rapamycin for me right now,

perhaps in the future.

I've listed out the things that I'm

perfectly willing and happy to do, grape seed extract, NR

and NMN, the occasional NAD infusion

to increase NAD directly, and for the time being,

I've decided to stay away from metformin and rapamycin.

But of course, any and all of that

could change going forward depending

on the data that are published and my own experiences.

As a final point on this, I want to again emphasize

that the foundation of a quality life and a long life

is most certainly going to come from the basics, perhaps

the most fundamental and important of which

is to get sufficient amounts of quality sleep each night.

We know that not doing that can indeed

reduce your lifespan if not directly, then certainly

indirectly by increased number of accidents

and certainly being far less happy and energetic

during the day.

So that's fundamental.

Also, and this is very important to emphasize--

and here I'm essentially borrowing the words straight

out of Dr. Peter Attia's mouth.

So forgive me, Peter.

This won't be nearly as eloquent or succinct

as Peter would make it.

But it is very, very clear that at present there

is no supplement or drug for increasing longevity

that even comes close to the known improvements in health

metrics that relate to longevity that come from getting quality

sleep and especially from getting sufficient amounts

of quality exercise.

So that means both a combination of cardiovascular exercise,

a minimum of 180 to 220 minutes of so-called zone 2 cardio

per week.

So that's cardio that you can carry out

while still maintaining a conversation

but should you increase the intensity any more,

you would have a hard time completing your sentences.

But in addition to that also doing some VO2 max work,

so getting your heart rate way, way up at least once per week,

and also, of course, doing resistance training either

with weights, machines or bodyweight,

doing that at sufficient intensity,

six sets minimum per body part per week

to maintain not just muscular size and strength

but equally important, perhaps even more important,

maintaining nerve to muscle connectivity,

which correlates with cognitive function

and a number of other important longevity metrics.

So again exercise, sleep, quality nutrition, quality

social connection, which means eliminating

as best you can toxic social connection

and increasing quality social connection, people that you

like and enjoy spending time with and feel enriched by,

stress modulation, all of these things are so key.

And of course, getting morning sunlight, all of those things

combine to have a huge out-sized effect compared to anything

that you could take in pill, capsule or infusion.

So before even considering taking any supplement or drug

to increase your longevity or even for increasing vitality

for that matter, get those basics of sleep, sunlight,

nutrition, movement, stress modulation, or stress control,

I should say, and relationships down.

Get those right.

And get that morning sunlight to set your circadian rhythm,

because of course, your circadian rhythm

is what anchors it all.

And I'd be completely remiss if I didn't emphasize

yet again that any time you're thinking of adding a supplement

or removing a supplement from your regimen

or adding a prescription drug or removing a prescription drug,

you absolutely should consult you're

board-certified physician.

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