Resveratrol: dosage and effect on cardiovascular health | David Sinclair

Resveratrol: dosage and effect on cardiovascular health | David Sinclair

– [Dr. Patrick]: You know, the resveratrol
field, when I first was following it back in, I guess, the early 2000s, you know, I
was very skeptical that there would be any effect in humans taking resveratrol because,
certainly not from drinking a glass of wine. But from supplementing, just because it seemed
as though, like, the doses required to get some really beneficial effects, at least in
some of the rodent studies seemed sort of, you know, high and it didn’t seem very attainable. But as you know, there was a really sort of
compelling primate study in rhesus monkeys. I forgot when that was published. It was like mid-2000s, or 2011, or something
like that. – [Dr. Sinclair]: Right. Rafa de Cabo’s group with NIH. – [Dr. Patrick]: Yes, that’s right. They gave these rhesus monkeys resveratrol,
and I think they started out with a lower dose, like 80 milligrams per kilogram and
they went up to, like, 480. Any reason? Do you know why they start with… I’ve seen more than one study do that. – [Dr. Sinclair]: Yeah. So just anecdotally, what Rafa told me, I
think, is that they started at the low dose and didn’t see a change in pulse wave velocity
in the blood vessels, so they upped it and then that’s where they saw the benefit. – [Dr. Patrick]: Oh, okay. Well, this study was… You know, the doses were very doable on humans
when you, you know, convert and basically, you know, feeding these monkeys, they’re feeding
them, like, this terrible high sucrose diet, high sucrose and high fat, and they, like,
it caused them to have, like, 40% increased aortic stiffness, but the resveratrol completely
ameliorated it, like… So I was like, “Holy crap, that’s pretty cool.” I think that was the one study that sort of
changed my view and then I started to sort of get into the literature and read ones that
there was, you know, there’s been a variety of clinical studies, as you know, and… – [Dr. Sinclair]: Yeah. Well, I’m glad somebody is reading the literature. Because there was a “hate me” club with resveratrol
because it got so much attention. And anything that gets a lot of attention
gets the “hate me” club in reverse. But resveratrol, I still take resveratrol,
probably a gram or so every morning. – [Dr. Patrick]: A gram? Really? – [Dr. Sinclair]: Yeah. In my yogurt. I don’t measure it out, I just shake it in. So it might be half a gram to a gram. – [Dr. Patrick]: Is this from your own, like,
stash or is it like a… – [Dr. Sinclair]: It’s a stash in the basement. I’ve had it for years. – [Dr. Patrick]: It’s a private stash? – [Dr. Sinclair]: It is. I’m not a drug dealer. – [Dr. Patrick]: Because I don’t usually find
doses of resveratrol above 250 milligrams, I think. – [Dr. Sinclair]: Yeah. Right. You made a good point, which is it’s a really
insoluble molecule and that’s one of the… Well, there are two problems with resveratrol,
one is it’s really insoluble. So if you just give it as a dry powder to
an animal or a human, it’s less likely to get absorbed. We know that as a fact. Include it with a bit of fat, it’ll go up
five to tenfold in the bloodstream. – [Dr. Patrick]: Really? – [Dr. Sinclair]: It’s like a big effect we’ve
seen in mice and monkeys, it was with a bit of fat in the diet as well. And then the second problem with resveratrol
is that it’s light sensitive. And so those people who…researchers who
put it in a plate with worms or didn’t treat the molecule with respect, it goes brown. It goes off. It’s one of the reasons it’s very hard to
put in a cosmetic because your cosmetic will turn brown. If you use brown resveratrol, it won’t work. So you’ve got to keep it in the dark, in the
cold, and it’ll be fine. – [Dr. Patrick]: Okay. So… – [Dr. Sinclair]: Or in a basement. – [Dr. Patrick]: …cold, dark, and also I
think there’s various forms like trans-resveratrol. – [Dr. Sinclair]: I’d go for the trans because
when we gave the cis form to the sirtuin enzyme, it didn’t activate it, but the trans worked
brilliantly. Yeah. Rafa de Cabo, actually, he’s been a good friend
over the years. A great colleague. He did the study with us on the mouse, resveratrol
study that showed that on a high-fat diet, those mice were extremely healthy and longer
lived and their organs, when they opened up the mice, they were pristine. So the mice were still obese, so we didn’t
give them a lot of resveratrol, it was pretty low dose, but their organs were so beautiful. Their arteries, when you stain them for oil
or fat, it was night and day. The ones on resveratrol or the ones without
resveratrol were stained with fatty lumps. resveratrol, clean. And that alone makes me say, you know, resveratrol’s
probably not going to hurt me and it may very well help my cardiovascular system. – [Dr. Patrick]: It seems to be really important
for a cardiovascular system, like… And I’m just kind of, do you know why, why
is it…? – [Dr. Sinclair]: We have a number of ideas. And resveratrol is a dirty molecule, so there’s
not just one way it works. Sirtuins definitely are involved. We now have a mouse that’s mutant for the
resveratrol activation of SIRT1, so we now see that some aspects, like endurance, of
resveratrol seem to be through SIRT1. So one of the effects is through SIRT1’s anti-inflammatory
actions in the lining of the blood vessels, the endothelial cells. – [Dr. Patrick]: Oh. Okay. – [Dr. Sinclair]: Yeah. That seems to be important. And there’s other aspects also in DNA repair
as well. infiltration of macrophages in there seems
to be dampened. And we also looked at oxidative stress in
those arteries of those mice treated and it was way down in the resveratrol mice. – [Dr. Patrick]: Yeah. With the rhesus monkeys, with the, you know,
basically like, you know, completely reversing that 40% aortic stiffness, that’s like pretty,
it’s a pretty dramatic effect. So I was… – [Dr. Sinclair]: It is. And so, yeah, I think resveratrol, it’s… People are, you know, “Oh, is it true, is
it not?” “60 Minutes” did a story and then there was
an argument about how it was working. And so people are confused about the molecule,
and I still stand by it because the results, like you say, in animals. And there are clinical studies now that are
really positive in humans. Not all of them, sometimes it has no effect. There was one study where it interfered with
endurance exercise. Don’t understand that. – [Dr. Patrick]: Metformin was kind of shown
to do something similar where it prevented mitochondrial adaptations in [crosstalk 00:47:47]
but who knows? – [Dr. Sinclair]: I mean, maybe… Rhonda, what’s maybe happening is that if
you’re dampening free radicals too much, you’re actually losing that benefit. – [Dr. Patrick]: Hormetic effect. – [Dr. Sinclair]: Exactly. The mitohormesis. But I haven’t seen any downside. You know, I’m a N-of-one, as you would say,
in a clinical trial. I’ve had my heart checked out with a 3D movie
MRI. My heart looks like it’s 20, it’s got no sign
of aging. So, it doesn’t seem to be doing myself and
my dad any harm. So… – [Dr. Patrick]: How long have you been taking
it? – [Dr. Sinclair]: Oh, geez. Since 2003. – [Dr. Patrick]: Wow. And you take about a gram [inaudible 00:48:22]
or so a day. Yeah.

5 Replies to “Resveratrol: dosage and effect on cardiovascular health | David Sinclair”

  1. Watch the full episode:

    FoundMyFitness episode page:

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  2. "I haven't seen any downside" He said.
    Resveratrol: A Double-Edged Sword in Health Benefits.
    [4. Negative Effects of Resveratrol: Some studies have documented that it may behave as a pro-oxidizing agent [112]; thus, paradoxically, it may also have implication in pathology of several diseases].
    Research by Sinclair and others helped spark interest in resveratrol for its potential anti-aging properties. In 2004, Sinclair co-founded a company, Sirtris, to test resveratrol’s potential benefits and declared in an interview with the journal Science it was “as close to a miraculous molecule as you can find.” GlaxoSmithKline bought the company in 2008 for $720 million. By the time Glaxo halted the research in 2010 because of underwhelming results with possible side effects, Sinclair had already received $8 million from the sale, according to Securities and Exchange Commission documents. He also had earned $297,000 a year in consulting fees from the company, according to The Wall Street Journal. Sinclair is involved either as a founder, an investor, an equity holder, a consultant or a board member with 28 companies, according to a list of his financial interests. At least 18 are involved in anti-aging in some way, including studying or commercializing NAD boosters. The interests range from longevity research startups aimed at humans and even pets to developing a product for a French skin care company,, to advising a longevity investment fund.

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