Welcome to the huberman live podcast where we discuss science and science based tools for everyday life. 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. This
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Mm and download the premium subscription feed. And for those of you that are not huberman Lab podcast premium subscribers. You can still hear the first 20 minutes of today's episode and determine whether or not becoming a premium subscriber is for you. 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?
Act. Okay. 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 of 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
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 20:23, it's fair to say that most of that thinking has been let's just say debunked. I think that most people
And that while indeed Resveratrol might have some positive effects on the functioning of ourselves 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 or 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 are 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 400 800 milligrams of grape seed extract per day. I just do that as a 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. Okay, 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?
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, you know, I want to take anywhere from one to ten 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 ten supplements you would recommend ice
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 in the rationale behind those and how long I've taken them in the effects that I've observed both subjectively and in my blood work and what I recommend other people what I don't recommend to other people what 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,
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 and cells it has direct relevance to mitochondrial function and mitochondrial function to it. And that's a discussion into itself. But suffice to say that the pathway leading to NAD includes things such as NR + NM n + r + MN are
Heard by many to be precursors to NAD.
Okay. 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. Okay, we'll talk about whether or not increasing NAD in our cells actually increases lifespan and 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 so typically as a
capsule or a powder or by taking n MN 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 ourselves whether or not can get into ourselves with a KT converted into NAD and so on and so on But there again the idea was by taking an ID either in capsule form or it 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.
In either liquid or pill form NAD
itself. Now I confess that I have tried all three of these approaches. Okay, so I
do indeed take an our supplement every
day. I take 500 mg of NR. I also and have separately taken and and then
men supplement I take sublingual
nmn. So I'll take anywhere from one to two grams of nmn as a sublingual powder which as the name suggest you
put it under your tongue and it dissolves there.
At this kind of Tangy flavor
and the goal for me and taking an r and N MN each day, and I should mention that sometimes I
have just taken n MN or just an R to do the comparison between NR + n MN for me in a subjective way. Just comparing one of my energy levels. How do I feel whether or not there any side effects? And then I'm also taking them together and I've arrived at a protocol where I take n r and N MN every single
day and the goal of that is indeed to increase
NAD
levels within my system.
However, really want to emphasize this I do not take
n r and N MN in order
to increase my life span. In fact at this point in history. It's unclear
and seems somewhat unlikely to increasing NAD is going to increase lifespan, but I think we should always, you know,
keep our minds open there may be data to arrive in the future that shows that that actually does
happen in humans. Now, there are some
animal data
suggesting the increasing NAD either by
Taking NR and or nmn can increase
lifespan, but frankly that is
not why I take an RN M.
Ni Take n r and N MN 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 n r and N MN 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 n r and N MN 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.
Other podcast but I'll take my NR n MN some
time usually within about an hour or two of waking up and typically at least 30 minutes to 2 hours before my first meal which for me usually arrives around 11 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 an r and or nmn
and while I didn't feel as if I was completely
Lee depleted of energy I did notice
a decrement in energy compared to when I took an r and N MN
now, I want to be very very clear.
I have no 0 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.
Was a filing for nmn as a experimental drug in a clinical trial and as a consequence nmn was listed as a band 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 Anna men on the open market you find on Amazon. I can't really speak to the purity of one
source for
it has 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 an RN n MN is that I take n
r and N MN 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 at
cetera. I do not.
Take it with any expectation that it's going to increase
my life span 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 and are 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
they 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
Your 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 1000 mg of NAD by infusion. I did that at times when I was feeling particularly run down. It will 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 improve sleep improve Vigor coming off those illnesses.
Mrs. I
felt much better. But again, there is no clinical
trial exploring NAD infusion for sake of vigor Etc that I am aware of. I just happen to be somebody who's interested in exploring these tools and techniques from time to time and I deemed this
as safe whether or not safe for you. You
have to explore with your
physician. Also, I do want to re-emphasize what I said a moment ago those NAD
infusions are pretty darn uncomfortable. You
can have the the person administering the infusion adjust the rate of the
Fusion 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 want to get the
whole thing over with so I just said put 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've just felt lousy mood 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 call it and it data if you want but it's
anecdotal. It's generally assumed for obvious reasons that NAD infusions are more effective at increasing seller levels of NAD
then RNR.
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 infusion certainly are
now there are number of different experts out there who debate all the fine points of everything that I just said people like,
dr. Charles Brenner people like dr. David Sinclair
people like Matt caber line. There are people who really
We 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 and 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 and 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 video.
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 may be doing them a couple 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 when
if perhaps you've explored NR supplementation and immense 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 of no requirement for an infusion, but I'm not aware of any studies that have directly linked oral NAD to nadh
levels in cells and how those two things relate so
lots more important science to be done in this
Serie lots more debate surely to be had and anytime 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 Etc.
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 economical frame.
Works 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 little bit about grape seed extract. We talked
about nrmn 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.
It 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 thinking about exploring taking metformin or berberine for sake of lowering blood glucose and lowering a particular seller. Let's just say pathway or set of
molecules mtor being the most
common of them mtor. Mammalian. Target of rapamycin is a
Engine 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 it's 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 and this conversation we could just think of mtor something that's abundant in cells during development and anytime cells are growing including the growth of tumor cells
and
and cellular growth at any stage of the lifespan.
So the
logic that people have waged is that
drugs like metformin are 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 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
I'll tell you I don't take berberine for the reasons. I
mentioned before makes me feel uncomfortable. I don't not psychologically uncomfortable makes me feel physically uncomfortable.
I don't take Metformin because expert colleagues of mine including dr. Peter Tia have come on this podcast. In fact, we did a collaboration
Journal Club podcast that will provide a link to in the show no
captions during which we meaning mainly Peter reviewed the data the peer review 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 met 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 as a target of this drug, which is used largely as an anti-cancer,
Her 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 caber line 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 a TIA has talked a lot about rapamycin and did a recent
podcast about rapamycin with
not only Matt caber line, but one of the
experts in the world on mtor, so 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
clinicians Physicians like Peter as well as others who are quite excited about
the potential for rapamycin to
Span 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'm 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
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. Okay, so no
metformin no rapamycin for
me right now perhaps in the future. I've listed out the things that I'm
He willing and happy to do
grape seed extract and are 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 in 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 word straight out of dr. Peter atilla's mouth. So forgive me Peter. This won't be nearly
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
to cardio per week. Okay. So that's cardio that you can carry out while still maintaining a conversation but should you increase the intensity anymore? You would have a hard
time completing your sentences. But in addition to that also doing some
vo2max works are getting a heart rate way
way up at least once per week. And also of course doing resistance
training either with weights machines or body
weight doing that at sufficient intensity 6 sets minimum per body part per week
to maintain not just
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
Of course getting morning sunlight all of those things combined to have a
huge
outsized 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
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 your board certified physician. Thank you for joining for the beginning of this ask me anything
episode to hear the full episode and to hear future
episodes of these ask me anything sessions plus to receive
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