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About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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October 8, 2010

Does Resveratrol Really Work? And Does SRT1720?

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Posted by Derek

You'll recall that we recently had the flap over two GSK/Sirtris executives running their own sideline business selling resveratrol as a dietary supplement. There's a lot of it out there, understandably, since the publicity around the compound has been intense for several years now. But even if it works, how likely is it that a person could take enough of it to show an effect?

A new paper goes back to the C. elegans nematode model to try to answer that question. The original life-extending results in this organism were done at 100 micromolar concentration, which is way more than any human being is going to be exposed to. Unless you're showering in the stuff, I suppose. The current study dials that back to levels that could be reached in human dosing.

What they saw was no effect on lifespan at 0.5 micromolar, which would be a realistic blood level for humans. When they turned up the concentration to 5 micromolar, there was a slight but apparently real effect of just under 4%. Now, 5 micromolar is a pretty heroic level of resveratrol - I think you could hit that as a peak concentration, but surely not hold it. The medicinal chemists in the audience will appreciate that some drug effects are driven by their Cmax, and others by their AUC, but this still seems to be a likely shortfall.

Oh, and there's another interesting part to this paper. The authors also looked at SRT1720, the resveratrol follow-up from Sirtris that has been the subject of all kinds of arguing in the recent literature. This compound is supposed to be several hundred times more potent than resveratrol itself at SIRT1, although if you've been following the story, you'll know that those numbers are widely believed to be artifacts of the assay conditions. And sure enough, the authors saw no effect on C. elegans lifespan when dosing with physiological concentrations of SRT1720. The authors finish, dryly, with:

Given the above-mentioned and conflicting findings for the efficiency of SRT1720 and the metabolic state in rodents, it is interesting to note that, as shown here, SRT1720 exerts no detectable effects on lifespan of an established model for the analysis of longevity. . .

Indeed it is. Given the recent follow-up work in this area, I can't say I'm surprised, but I am disappointed. And yes, in case anyone's wondering, I do actually hope that the Sirtris work (and other research on sirtuin compounds) leads to something good. It's just that the story is a lot messier than anyone would have liked, so far. All I have to do is look back on what I wrote just four years ago, and wonder if it really had to be this way. Did it?

Comments (75) + TrackBacks (0) | Category: Aging and Lifespan


COMMENTS

1. Anonymous on October 8, 2010 8:28 AM writes...

The lack of effect of resveratrol on lifespan in worms and flies was published 3 years ago.

Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans.

Mech Ageing Dev. 2007 Oct;128(10):546-52.

Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L.

The Sirtuin field seems to be one where even the negative results have to be published 3 or 4 times (which is a good thing, since many of the people in this field are reluctant to be influenced by data).

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2. anon on October 8, 2010 9:06 AM writes...

Why bother really discussing this issue (except in that it is extremely entertaining). There is no real science here - the entire field is about getting tenure at fancy institutions, getting rich, being on TV in a white lab coat with a charming australian accent, and publishing trash data in high profile journals. God I wish the outstanding, important, and understated high quality science published every day in society-level journals received 1% the attention of this resveratrol BS.

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3. Hap on October 8, 2010 9:06 AM writes...

I assume that there are at least 720 million reasons why people might not be influenced by negative data (not even getting to the people who want to live forever), particularly when it looks like the data implies that the positive results were an artifact of the methods used (something you might have figured out during due diligence, say).

Being convinced by data is so passe.

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4. anchor on October 8, 2010 9:26 AM writes...

Speaking of flogging a dead horse...why?

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5. Anonymous on October 8, 2010 9:47 AM writes...

here's why

http://www.sciencemag.org/cgi/content/full/329/5995/1012

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6. Fools on October 8, 2010 9:48 AM writes...

You people are fools. The study pointed out that resveratrol did extend life. Further, resveratrol has been shown to extend life in overweight mice and make normal mice much healthier. Further, don't confuse resveratrol with SRT1720. So many haters, so little time.

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7. darwin on October 8, 2010 10:04 AM writes...

The subject of future late night Kevin Trudeau infomercials

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8. anon on October 8, 2010 10:28 AM writes...

@#1

Just looked up that paper. Looks like a good one, done by real, critical scientists who aren't trying to get rich. Too bad it was published in an obscure journal - apparently that means that it doesn't count. The paper invalidates much of the field in one stroke.

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10. cancer_man on October 8, 2010 11:38 AM writes...

"But even if it works, how likely is it that a person could take enough of it to show an effect?"

Within the past year there have been five small human studies that have shown benefits of resveratrol in humans:
helps against pre-diabetes in 60 to 80 year olds (1000mg), anti inflamation (60mg and 100mg - two studies), boosts blood circulation to the brain, (250mg and 500mg), good for some heart valve function (200mg).


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11. anonamous 2 on October 8, 2010 11:40 AM writes...

I've mentioned it before, but it's worth mentioning that the life span extension caused by 100 micromolar resveratrol requires AMP kinase, but not sir-2.1: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680339/

And they haven't published it yet, but David Gems and Linda Partridge have been giving talks that directly refute previous data that showed sirtuin expression extending life span in worms and flies.

Though it's also worth mentioning that worm experimenters are feeding 100 (or 5 or 0.5) micromolar resveratrol. That doesn't mean that the internal concentration of resveratrol in the worm is anywhere near the media concentration. Any drug you give to the worm can be metabolized by the live e. coli which is used as a food source. The drugs also have to be absorbed by the worm's intestine, etc. C. elegans can be quite impervious to many drugs -- they're certainly not like permeable cells that indiscriminately absorb everything you put in the media.

As far as I know, pharmacokinetics is pretty much ignored by worm researchers. My institutional access won't let me read this latest paper, but I doubt they did anything to determine resveratrol levels within the worms.

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12. cancer_man on October 8, 2010 11:55 AM writes...

Here is a 45 minute interview with David Gems on the aging field, etc:

http://thesciencenetwork.org/programs/the-new-science-of-ageing/david-gems

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13. Hap on October 8, 2010 11:59 AM writes...

so many haters, so little time...

And so little data, well, data that says what you want anyway. Good luck with your investment portfolio.

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14. Derek Lowe on October 8, 2010 12:18 PM writes...

Anon 2, you'll be glad to hear that the authors address this problem, mentioning that the cuticle of the nematodes is a pretty strong barrier. They say that they have some unpublished work done with fluorescent tags that suggests that small molecules are largely taken in with the E. coli used for feeding, and that transport (active or passive) across the cuticle is nonexistent.

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15. TLGJR on October 8, 2010 1:12 PM writes...

I'm not a scientist but I do read research papers and I am very much involved in the subject of aging and longevity. It is known by some in this field that resveratrol works best in a matrix that is a mixture of other molecules. I have seen anecdotal evidence of this. And there is research to substantiate this. My mother who is 87 has been taking a low dose 200 mgs of resveratrol matrix (Longevinex) for almost 6 years now and has noticed benefits that are profound to her. As has a friend who is now 89 and been taking this same matrix for almost 6 years. In my mothers case she has a family history of heart disease and cancer. Her mother died of heart disease at the age of 57, her father died of heart disease at the age of 70 and her brother died of heart disease after a life long battle and a 5 way bypass at the age of 77. Many of her cousins died young of cancer. Needless to say my mother is happy to be alive and healthy at 87. I take this matrix myself as does my daughter. Hatred and disdain should have no place in mans quest to understand and benefit from a legitimate search for better health and longer life. Perfection is just a word and has no bearing on the fact that some effective answers exist now and will only get better with more time. I'm not letting petty politics stop me from seeing what's in front of me. T

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16. anon on October 8, 2010 2:23 PM writes...

@TLGJR

Boy, I am convinced. I am shocked you haven't published that compelling data about your mother, her friend, you, and your daughter. And, the people in the field who know that "resveratrol works best in a matrix that is a mixture of other molecules" are so lucky to have that inside information, which I am certain has been subjected to the most rigorous review and statistical analysis.

I agree with you, there is too much hatred, disdain, and demand for actual controlled and repeatable data in this "scientific" forum.

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17. Bill Sardi on October 8, 2010 3:13 PM writes...

The ups and downs of longevity science...three steps forward, four steps back (ugh). We all want to believe that at this juncture in history man can reach for what only was drempt of a short while ago. We like to believe the science is there. Unfortunately, we cannot prove longevity until years pass. The laboratory mice on a normal-calorie diet given resveratrol were profoundly healthier but experienced a slightly shortened lifespan. This molecule can be tricky to evaluate. Dosage appears to be important. Somehow red wine appears to produce profound longevity, at least in the French, but so far red wine resveratrol pills disappoint. But red wine is not just resveratrol. It appears a cocktail of molecules, like those provided in red wine, may prove to be a more promising direction. Studies point to synergistic effects with small molecule combos. One of the drawbacks of current science is to first to develop a theory of aging to then test in scientific studies. Aging cannot solely be defined as a sluggish Sirtuin1 gene. Humans age at different rates. There are three different speeds of human aging. As measured by accumulation of cellular debris (lipofuscin), human aging is virtually static during childhood growth, accelerates progressively thereafter, and slows in late life. Genetic analysis can be distracting. Genes only indicate a response, not necessarily a cause. What causes genes to be expressed or silenced as humans age?

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18. DT on October 8, 2010 3:24 PM writes...

TLGJR: Your mother started taking this pill at 81. Her mother died at 57, her father at 70, and her brother at 77. You really want to attribute this to the pill when she decided to take it so late relative to her family history? She was already in better health...outlier?

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19. Anon3 on October 8, 2010 3:53 PM writes...

Regardless of its efficacy or lack there of, resveratrol has done a remarkable job of underscoring the (often overlooked) limitations of animal models:
1) It is difficult to infer human dosing from the levels of compound needed to see an effect in model organisms. For example, you need the same amount of methotrexate (in mg) to see an immunomodulatory effect in a mouse as you do for a human >2500 times that size. Thus, the fact that it would be difficult for humans to achieve the plasma levels of reveratrol needed to see an effect in mouse models does not, by itself, argue against a real effect in humans.
2) Animal models of human disease are almost always acute and aggresive models. Injecting 1 million tumor cells (an NCI60 line, no less!) into a mouse may be the easiest way to model cancer, but it skips many key steps in human tumorigenesis, and poses a much more severe tumor burden than most human cancers. Similarly, inflammatory mouse models typical recapitulate a human disease that takes years of constant, low-level assault from an inflammatory stimulus to develop by using a few large doses, allowing the disease to develop in days. Thus, it is not unreasonable for a compound like reveratrol to require acute, high-level dosing in a mouse model, but to still be efficacious in humans exposed chronically at much lower levels.
Neither of these two points are meant to argue one way or another as to resveratrol's efficacy. Rather, they are meant to point out that one should be very careful making claims about the potency, or lack there of, of a compound based solely on animal models. It is fair to criticize the popular press for extrapolating from animal models and making wild claims about resvaratrol's potency, but scientists must remember not do the same thing in reverse. It is likely that the resveratrol stroy will take countless more experiments, and years to decades, before a final answer can be obtained.

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20. TLGJR on October 8, 2010 3:57 PM writes...

Anon, I don't want to convince you of anything and I couldn't care less what you think you know. Go on and ridicule and spread disdain and veiled hatred if it makes you feel powerful. I'm just glad I have my mom around to create more memories regardless of why people like you think she's still alive. And DT I merely wanted to let people know that 6 years of taking this supplement hasn't killed her and in fact she was failing very noticeably at 81 and is much better now. Attribute this to what makes you feel smart I don't care what others want to believe I have my mom around. T

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21. SP on October 8, 2010 4:03 PM writes...

Apparently now the singular of anecdote is data.

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22. Pearl on October 9, 2010 11:09 AM writes...

@ Cancer Man,
Thanks for informing this board of these studies - regardless of the actual mechanism, resveratrol does benefit humans at manageable doses.

"But even if it works, how likely is it that a person could take enough of it to show an effect?"

Within the past year there have been five small human studies that have shown benefits of resveratrol in humans:
helps against pre-diabetes in 60 to 80 year olds (1000mg), anti inflamation (60mg and 100mg - two studies), boosts blood circulation to the brain, (250mg and 500mg), good for some heart valve function (200mg).

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23. ronathan richardson on October 9, 2010 6:18 PM writes...

I would like to see a direct comparison of resveratrol with metformin in all of these studies. It seem quite clear that one thing resveratrol does is activate AMPK. We have a good drug that does that already--and yes resveratrol may show some positive effects, but it might just be a dirtier and crappier version of metformin.

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24. pearl on October 10, 2010 1:45 AM writes...

OK, so why isn't every American taking metformin?
Why don't you lead that charge ranathan richardson.

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25. cancer_man on October 10, 2010 6:04 AM writes...

@Pearl

This isn't a dig at Derek, but he's a biochemist who has posted about resveratrol and GSK at least 6 times in the past couple of years. Yet he asked if resveratrol was effective at all for humans despite five studies showing effectiveness in pre diabetes, heart valve function, anti inflamation and blood flow to the brain.

If Derek isn't serious about following resveratrol effectiveness in humans, we can't expect others to be at this point.

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26. Thumperska on October 10, 2010 8:06 AM writes...

@ T
I think you may be confusing skepticism with hate. Most of what people have said here falls into the former category. All we scientists want to know is if the effects you are experiencing are something beyond a placebo effect. Anecdotes won't cut it there, only controlled properly powered studies.

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27. Jose on October 10, 2010 8:22 AM writes...

Superstition with an N of Three! It's the new science!
By the by, the phrase "resveratrol works best in a matrix that is a mixture of other molecules" makes as much sense as supercaifragilisticexpealidocious.... we're not hating, we just believe in something called "data." That's not to say science is always right, or mistakes are never made, but there is a tedious, and orderly, path to establishing something as close as possible to "the truth."

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28. pearl on October 10, 2010 12:10 PM writes...

@ Cancer Man:
I think the sceptacism of resveratrol stems from several factors:
1)the science is not settled on how it works
2)at least one of Sirtris' NCEs does not work
3)the resveratrol media frenzy attracted many scam artists
4)the thought of a miracle pill seems a bit outlandish
5)the whole not 'FDA approved' line from big pharma, the herd like media, and way overly cautious physicians hurts - even though the FDA approves a lot of dangerous drugs - we read about them every day

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29. Anonymous on October 10, 2010 12:30 PM writes...

@ Cancer Man

No one here is going to be convinced by a handful of "small human studies" that claim to show benefits for "pre-diabetes" and "inflammation". You can find that kind of data for basically any herbal supplement using PubMed. As #23 said, let's see resveratrol head-to-head against the standard of care in a large, well-controlled clinical trial. Then let's talk.

The reason for hostility towards resveratrol is that we wouldn't be having this debate -- you wouldn't even *know* what resveratrol was -- if it wasn't for a mountain of lies about Sirtuins, aging, the french paradox, etc... that made some people rich and defrauded the scientific community. Now that all that preface has been debunked, you're shifting the goalposts, and arguing that even if the science was wrong, the compound is still useful. Except that resveratrol is nothing special -- there are dozens of garbage nutraceuticals for which you can show small effects in small human studies. None of them are better than the standard of care, and without knowledge of the target/mechanism, they don't even help us learn anything useful about physiology that advances the science. This is a dead-end.

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30. TLGJR on October 10, 2010 1:17 PM writes...

Anonymous, Wrong.... I AM convinced as are many others hence the large number of sales of these supplements. The mountain you refer to is not all lies. We all think that doing something is better than doing nothing , nothing being the "standard of care" you refer to. The standard of care doesn't work and here's where you're wrong again, the debate about resveratrol the hostile and the believer is a direct result of the fact that the standard of care does not work if it did we would be enjoying better lives and not looking for an answer. Maybe your end is dead but my eyes are wide open. I'm one year older than my father was when he died at 61 after 30 years of suffering chest pains and the physical limitations that went with them. I can do any physical activity I care to and enjoy this greatly. T

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31. Anonymous on October 10, 2010 1:25 PM writes...

#30

You're saying that the standard of care for diabetes and inflammation is "nothing".

Hmmm...

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32. Pearl on October 10, 2010 7:25 PM writes...

@ Anon,
You are making some serious allegations against the Sirtris founders.
The only lie the Sirtris founders told is that you have to take large doses of resveratrol to experience health benefits. Science is proving that false - despite the serious lack of funding for a nonpatentable molecule.

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33. cancer_man on October 10, 2010 8:12 PM writes...

It's easy to charge fraud against people anonymously. I don't know if the Sirtris compounds will work or not. The difference between me and several who post here about them is that I don't pretend to know.

I'm also not shifting goalposts by simply pointing out that there have been at least five studies in the past year showing that resveratrol has been effective against pre diabetes and inflamation while improving heart function. While statistically significant, I don't know to what degree resveratrol has been effective in those cases because I don't know much about heart valve function and pre diabetes levels.

By the way, is the video of a fat mouse on resveratrol running twice as far as a fat mouse without also fraud? Maybe so, but it would be nice to have evidence than just saying "all lies."
Could that mouse do the same thing with the dozens of other garbage nutraceuticals?

And yes, of course resveratrol and the Sirtris drugs could be effective even if the science isn't well understood.


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34. anon on October 10, 2010 8:34 PM writes...

I think the fundamental problem here is that it is difficult/impossible to prove that something DOESN'T work, and there are lots of people on this board with a great desire to believe that it DOES work. So, they pull out really questionable, anecdotal claims and statements to lend some credibility to their desire that this stuff works.

It really is too bad, actually. It would be great if this was a forum where we could have a smart, high level discussion about the actual published data and the extend to which it does (or does not) support the claims made. But, it is not to be, because of all the cr.p arguments and claims made by people who so desperately want this to be true, for person or financial or reasons, or just to have some hope.

The reality, as most of us serious bench medical scientists know, is that it is INCREDIBLY hard to get stuff like this to actually work. New potential drugs work WAY too infrequently to satisfy the desire for hope from the lay public (egged on, often in intentionally misleading ways, by the investing public). Thus arguments like this one.

It is NOT the responsibility of skeptics to convince t believers of a negative - that reveratrol DOES NOT work. Anyway, that is impossible. PLEASE, true believers, convince us skeptics that it DOES work with more than just anecdotes and conjecture. Point to the positive data, and when we come back with caveats/counter data, tell us why we are wrong by invoking more than your mother or children, or a clinical trial or study that "will be published soon."

How bout lets be scientists here, rather than high priests or other forms of believers.

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35. anon on October 10, 2010 8:45 PM writes...

@cancerman

"And yes, of course resveratrol and the Sirtris drugs could be effective even if the science isn't well understood."

Can you please cut it out with this kind of garbage. We all know this. The fundamental question WHETHER they work. Early on in this thread #1 cited a high quality paper which, if you believe it (and I do), completely disproved the idea that resveratrol leads to an increase in lifespan in flies and worms. Basically suggesting that several of Sinclairs papers are wrong. The paper implies that Sinclair made sure to do the experiment just enough times to get the positive result he wanted, and no more. Also implies there was substantial data picking. Given the incredible $$$ he was hoping to make on this stuff via his company and his desire for tenure at Harvard, he certainly had an incentive to fudge.

Given this, why do you believe this stuff works? What published are are you pointing to in your head that makes u a tentative believer?

Permalink to Comment

36. anon on October 10, 2010 8:58 PM writes...

I am interested to know why pearl and cancerman seem to strongly believe in resveratrol. What high quality, repeated, published science has convinced you of its efficacy (for example, please give the references for the five recent human studies you have mentioned). Lets read them and subject them to critical review. Lets look at the controls, etc. and see if we buy it or not. Would be interesting/fun. Lets be scientists.

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37. cancer_man on October 10, 2010 10:08 PM writes...

anan, what strong belief? Several posting here think resveratrol is worthless, a.k.a. snakeoil. I saw a fat mouse on reversatrol greatly out distance a fat mouse without. Sinclair published that fat mice on resveratrol were much healthier and lived 20 percent longer than control fat mice. Is one of those or both fraud and/or poorly conducted research? Was the SRT 501 (a resveratrol blend) study that showed significantly lower glucose levels when diabetics took it more fraud or poorly conducted research? What about the studies showing resveratrol stopped the spread of liver cancer in 75% of the monkeys on resveratrol versus the 5% in the control group? A conspiracy of resveratrol researchers? It doesn't mean resveratrol works well in humans, but it is an interesting substance. Asprin sure doesn't do any of the above.

And now there are the five small human studies. I'll post those even though they haven't been duplicated several times in large populations or take into account the potential effects on left handed agnostic tap dancers...

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38. Anonymous on October 10, 2010 10:13 PM writes...

My assessment is that a number of individuals seem to have packed back some serious cash on this blunder/unknown entity. Sad, but perhaps true. My intuition tells me that this was a sales pitch to the world. Just that ..nothing else. Hey, sirtis seemed to do well until the exposure. Could be just another fluffy situation proping them up until the realization. i hope things in our industry change soon for the better. We don't need schlep's that over sell a company or tech. just to boost their cause. These characters need to go away...cease

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39. Anonymous on October 10, 2010 10:17 PM writes...

Remamber, anyone can polish a turd. LOL. Try not to laugh!!!

http://www.youtube.com/watch?v=hBj6PonX14A

Permalink to Comment

40. Anonymous on October 10, 2010 11:13 PM writes...

Cancer_man: "What about the studies showing resveratrol stopped the spread of liver cancer in 75% of the monkeys on resveratrol versus the 5% in the control group?"

Cancer_man, could you provide a reference for this? It is basically unprecedented to use monkeys to show pre-clinical efficacy of a cancer drug, both for cost and ethical reasons. I'd like to see how they did it (and how they got it approved by their institutional board.) Something about this does not sound right.


Permalink to Comment

41. cancer_man on October 11, 2010 12:02 AM writes...

The monkey cancer experiment was conducted in China in remote village near Tibet...

Or, perhaps this is what I meant:

NEW STUDY: Colon cancer study, Oct 27: 3.7% control mice vs 68.7% resveratrol-treated mice free of metastasis. Oral resv at 30 mg/kg.

I accidently switched animals:

Cancer conference report, Madrid - Resveratrol amazing results in monkeys for cardioprotection and diabetes @ 480mg per day

(sorry about the error)

Permalink to Comment

42. Jose on October 11, 2010 7:34 AM writes...

Cancer_man, I think you are confusing the words "gibberish" and "reference." Units like 480 mg per day generally have a another unit in there somewhere.... Madrid! Amazing! Bolus!

"Cancer_man," as in the X-Files? (slaps forehead).
Lies, damn lies and statistics --------->
Trolls, uber-trolls, and meta-meme-trolls.

Permalink to Comment

43. cancer_man on October 11, 2010 7:52 AM writes...

Jose,

It was a tweet, you twat.

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44. cancer_man on October 11, 2010 8:01 AM writes...

The fact remains that Derek, who is a biochemist and has posted sevearl times on resveratrol hasn't felt the need to be bothered if it has efficacy in humans.

Next post, the 5 studies, for those too lazy to Google....

Permalink to Comment

45. ex GSK on October 11, 2010 10:20 AM writes...

To Cancer man,

It is good that you believe in the healing powers of resveratrol, but like most things really believing it to be true will not make it so, fairy stories told by Witty and chumbs should be taken with a large pinch of salt.
Otherwise like many others before you will be believing this will save your GSK job until you are out of the door.
As to your post 37, is there anything indications this stuff does not work well on, its amazing.

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46. TLGJR on October 11, 2010 12:49 PM writes...

Jose, I guess you don't like Mary Poppins. But as far as supercaifragilisticexpealidocious ( and I cut and pasted that word so it's your spelling) Red wine is a resveratrol matrix and I think it's been around almost as long as statin drugs, or avandia both of which have become just as controversial as resveratrol. T

Permalink to Comment

47. VedPathak on October 11, 2010 1:07 PM writes...

I published my medchem prospective on resveratrol in a letter in C&E News in 22nd March 2010 issue. If you missed it, here is the link

http://pubs.acs.org/cen/letters/88/8812letters.html#1

Permalink to Comment

48. hibob on October 11, 2010 2:19 PM writes...

#41 Cancer_man #40 anonymous #42 Jose:
The cite:

Mol Nutr Food Res. 2010 Feb;54(2):259-67.
Oral administration of resveratrol in suppression of pulmonary metastasis of BALB/c mice challenged with CT26 colorectal adenocarcinoma cells.

from the abstract:
"3.7% of the control mice (n=27) and 68.7% of the resveratrol-treated mice (n=26) exhibited free of metastasis."

So they found that 17.86 out of 26 mice were free of metastasis?? That's some nice work with the microtome.

#30. TLGJR: And the difference between this and religion is?

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49. Anonymous on October 11, 2010 2:29 PM writes...

VedPathak wrote in his letter, "There is no reason to get excited about resveratrol just yet."

But he also wrote, "I agree with Matt R. Kaeberlein's summary: "There's a lot of interesting stuff going on with resveratrol and a lot of interesting stuff going on with the sirtuins. How it fits together is the big question." "

And this is what Matr R. Kaeberlin wrote this past March:

"Compounds such as these ((resveratrol and rapamycin)), identified from longevity studies in model organisms, hold great promise as therapies to target multiple age-related diseases by modulating the molecular causes of aging."

"nothing to get excited about just yet" ... "hold great promise to target multiple age-related diseases..."

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50. TLGJR on October 11, 2010 3:20 PM writes...

Hi hibob, Bottom line, I take a few pills of a resveratrol matrix, I notice a difference in the way I feel and so do the others in my circle of family and friends who take the pills. I read all the research I can find and some of it is good and some is not, just like the research on most all the drugs that have FDA approval. I know people who have taken well researched and approved drugs and have experienced negative reactions and stopped taking them. I also know people who are taking drugs and find that they help. I don't get your comment about the difference between my observations and religion. I merely shared some observations and would be willing to share the research which prompted me to start and continue to take the pills. It's no big deal as the ultimate destination of all life is death. I just enjoy my family, my level of health and all the activities that are a part of life and desire to keep it going as long as I can. The verbal sparring and oneupmanship notwithstanding I just want to help and be helped. T

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51. anon on October 11, 2010 3:55 PM writes...

Just looked at that paper where resveratrol reduces the extent of lung metastases in a mouse model of cancer. Looks pretty neat and the science looks high quality. This was obviously only in one experimental system, so tough to know how generalizable it is. But, I think it looks really interesting. I'd be interested in knowing if, assuming we all agree that this is high quality science, what the potential confounders could be to make this less interesting than appears on first glance. Couldn't immediately think of any.

So, based on this cite I think it looks like there may really be some anticancer effect, though could be secondary to influence on the mouse physiology (still counts though, since anticancer is anticancer). This is obviously not aging, but anticancer would be super!

Anybody got any similarly surprising cites to counter the Partridge paper mentioned in the first comment on this thread? I'd be interested in considering the possibility that the claimed anti-aging effect might not be BS. But, only based on data. I don't care how resveratrol "makes you feel."

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52. cancer_mana on October 11, 2010 6:06 PM writes...

As requested:

1) PREDIABETES

'In a very small and preliminary study, older patients with impaired fasting glucose taking a resveratrol supplement appeared to have improvements in postprandial glucose and insulin resistance, according to Jill P. Crandall, MD, of Albert Einstein College of Medicine in Bronx, N.Y., and colleagues....'She and colleagues found that after four weeks of resveratrol supplements, fasting plasma glucose was unchanged, but both peak post-meal glucose and three-hour glucose area under the curve declined (185 mg/dL versus 166 mg/dL, and 469 versus 428, respectively, P=0.001).'

http://www.medpagetoday.com/MeetingCoverage/ADA/20967?blg=mmt1

2) HEART

"The study published in Nutrition, Metabolism & Cardiovascular Diseases, is the first research to evaluate the acute effects of resveratrol supplementation on circulatory function, revealing that resveratrol improves flow-mediated dilatation (FMD) - a marker of cardiovascular function. (19 obese people)

http://www.nutraingredients-usa.com/Research/Resveratrol-shows-metabolic-benefits-for-obese-Study

3) BRAIN BLOODFLOW

"A single dose of 250 or 500 milligrams of
resveratrol was found to boost blood flow in the brain but did not affect cognitive performance, according to new findings published in the American Journal of Clinical Nutrition.

“The results of the current study provide the first indication in humans that resveratrol may be able to modulate cerebral blood flow variables,” wrote the researchers, led by David Kennedy from the Brain, Performance and Nutrition Research Centre at Northumbria University."
http://www.nutraingredients.com/Research/Resveratrol-may-boost-blood-flow-in-the-brain-Study

3) ANTI-INFLAMMATION (40MG BLEND)

"A report published online on June 9, 2010 in The Journal of Clinical Endocrinology & Metabolism reveals the finding of a trial conducted at Kaleida Health's Diabetes-Endocrinology Center of Western New York of an anti-inflammatory benefit for resveratrol.... Twenty healthy participants were randomized to receive Polygonum cuspidatum extract containing 40 milligrams resveratrol per day or a placebo for 6 weeks. Blood samples collected at the beginning at the trial and at 1, 3 and 6 weeks were analyzed for indices of oxidative and inflammatory stress in addition to other factors.

http://www.lef.org/newsletter/2010/0803_Resveratrol-Suppresses-Inflammation-in-Human-Trial.htm

5)ANTI-INFLAMMATION, LOWERS INSULIN (100MG BLEND)

Inhibits loss of "flow mediated dilation"
Lowered insulin and insulin resistance.

http://www.longevinex.com/articles/longevinex-obliterates-first-sign-of-blood-vessel-aging-marker-of-inflammation-in-humans/

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53. RealityCHK on October 11, 2010 7:01 PM writes...

Post #49

What he (VedPathak)meant, though interesting stuff going on with resveratrol and sirtuins, it might take a while to fix PK and other stuff, probably in the analogues, or in the minor components, those yet to be discovered. Interesting off course, GSK bought it..where are we now after few years..?

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54. Jerry Yang on October 11, 2010 9:32 PM writes...

The resveratrol analogue, pterostilbene, has alot of potential. Plenty more bioavailable than res. Not sure if it activates SIRT1 however.

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55. Spiny Norman on October 12, 2010 1:04 AM writes...

Haha. @49 -- there is an important difference between resveretrol and rapamycin. Namely: rapamycin has been shown to substantially extend lifespan in a carefully-controlled, double-blind, multi-site study using multiple mouse strains.

Resveretrol has not been shown to do this. But we'll know soon enough.

The same consortium that published the multisite rapamycin study has a similarly well-controlled study running on resveretrol. And it will have enough statistical power to detect even small diffferences, if they occur.

I'm betting that they won't.

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56. Otis on October 12, 2010 1:22 AM writes...

From hearing Sinclair hype his Pfizer rebuttal , I'm disappointed in what was published. It's not looking to promising, and life extension is a lofty goal. Nematodes life spans are variable through many genes, and can't recall any publications where they translate.

Even caloric restriction studies are specific to certain strains of mice. With a new strain, they don't translate. It just takes 8-12 years to complete a longevity study.

Everyone's tired of resveratrol and it's a shame that the FDA allow's it to be sold as a supplement. If you want to work with resveratrol, you're almost forced to be a suppliment salesman. It is, at least, a decent tool to study pathways in yeast, etc.

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57. in writing please on October 12, 2010 3:30 AM writes...

Has anyone *asked* the worms what they *feel*?

"I squirm, therefore I am"?
"Why does somebody keep giving me this stuff that makes me feel like a rattlesnake on speed"?

Just to extract the maximum amount of melodrama, from all points of view, you will understand.

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58. Pearl on October 12, 2010 5:22 PM writes...

@ Otis,
who pontificates:
Everyone's tired of resveratrol and it's a shame that the FDA allow's it to be sold as a supplement.

I'll bet Otis works for big pharma - which is somewhat of a joke with regards to impressive results as of the last decade. The last big breakthroughs of big pharma, antibiotics and the antiviral AIDS cocktails.

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59. CharlesWT on October 13, 2010 10:35 PM writes...

After taking resveratrol for a few months, my graying hair turned dark brown. Except for the completely gray hair. It's still completely gray :( Looks odd.

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60. Cynthia on October 15, 2010 4:10 PM writes...

Everyone wants to take a magic pill to activate AMP Kinase and thereby improve glucose metabolism and insulin sensitivity (and all the resulting health benefits). Glycogen depletion is perhaps the most significant signal for activating AMP kinase. While a pill might be helpful in addition for people who are disabled or too sick, why not just reduce carbohydrates in the diet (and/or get some exercise)? Most people will find their health greatly improved just by skipping the bread and pasta etc and keeping the veggies and meats. I'm all for developing new and effective drugs, but shouldn't we approach problems first by easier and natural means? Cynthia Kenyon showed life extension in nematodes by cutting the glucose in their medium (no resveratrol required) and was persuaded to cut it in her own diet, with very positive health effects.

One anecdote for those persuaded by their personal experience that resveratrol is great- my husband's pre-diabetes and overweight was reversed simply by cutting carbs. Why take an expensive supplement if you don't have to?

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61. nevin on October 16, 2010 1:29 AM writes...

Maybe I do not want to cut my carbs.
And with the western diet moving into the rest of the world cutting carbs is not going to happen - thanks Ronald McDonald. Lets get reals here Cynthia

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62. nevin on October 16, 2010 1:30 AM writes...

Maybe I do not want to cut my carbs.
And with the western diet moving into the rest of the world cutting carbs is not going to happen - thanks Ronald McDonald. Lets get reals here Cynthia

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63. Jose on October 16, 2010 7:40 AM writes...

I only have the patience to slog through one piece of scientific doggerel, but cancer-man, your first cited study is a total joke.

"For their study, the researchers recruited 10 patients ages 60 to 80 who had impaired glucose tolerance. Over four weeks, patients took one of three doses of resveratrol (1g, 1.5g, or 2g) with a standard meal that included 110 grams of carbohydrates, 20 grams of protein, and 20 grams of fat."

No control group, not even a comparison group? They saw no dose-response, and there N was 10? The PI does say it is preliminary, but any scientist worthy of the title wouldn't even report such schlock.

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64. Anonymous on October 16, 2010 3:00 PM writes...

Jose, I looked through the rest of cancer-man's citations. They're equally ridiculous.

#2 links to an article about an in vitro study of adipocytes, not a clinical trial.

#3 "brain bloodflow" is a negative result. the authors were looking for cognitive improvement due to resveratrol and didn't find any.

#5 is a press release from a company that sells resveratrol. its not even a published study.

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65. cancer_man on October 18, 2010 4:16 PM writes...

With respect to the studies:

#2) I accidently posted the wrong link as is obvious by what I excerpted. Read through this and then snicker:
http://www.drpressman.com/resveratrol-supplements-could-improve-heart-health-study/

#1) It's an encouraging preliminary result on 10 people. How is it schlock?

#3) "brain bloodflow" is only partly negative. There was a notable increase in brain bloodflow. (positive) but increase in cognitive function (negative) yet those in the study were around 20 years old, an age unlikely to show cognitive gains.

#4) Any problem with the 40mg resveratrol blend on inflamation study?

#5) The 100mg study used a resveratrol blend and was supported by the vendor. The brain flow study also used a specific popular resveratrol brand.
The summary says that the results of the study will be presented at an upcoming meeting of the Japanese Circulation Society.

All 5 studies are junk science?

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66. Anonymous on October 18, 2010 9:31 PM writes...

"All 5 studies are junk science?"

Yes.

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67. cancer_man on October 19, 2010 7:53 AM writes...

Thanks anon for elaborating.

As China hoards rare earths and The Spice -- I mean resveratrol -- we won't let you and your ilk have any when you come crawling.

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68. Anonymous on October 20, 2010 8:41 PM writes...

cancer_man,

you should read this article

http://www.theatlantic.com/magazine/print/2010/11/lies-damned-lies-and-medical-science/8269

it explains why we are sceptical of the clinical studies you cite.

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69. cancer_man on October 23, 2010 10:26 PM writes...

I understand those issues, but the article is esstentially stating we can never really know how a supplement or drug affects people since even large randomized studies have later shown to be wrong.

I'd also give less weight to studies that used a specific resveratrol brand as in #5, although some brand needs to be used as a non 98% pure brand was used in the pre diabetes and brain bloodflow studies.


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70. Layman on November 9, 2010 10:02 AM writes...

As a layman, I can tell you that reading through this email string has been a little like listening to first graders argue about who has the nicest mom.

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71. Martin on November 18, 2010 5:39 PM writes...

errgh,

this stuff is still being peddled by a newspaper that I usually respect:
http://www.smh.com.au/lifestyle/wellbeing/forget-the-fountain-of-youth-x2026-pop-a-pill-for-a-long-and-healthy-life-20101117-17xpr.html

Bad taste in my mouth and no, it's not grapeskins...

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72. daniel drummond on November 28, 2010 5:21 AM writes...

I wish you would give your opinion on Metformin.
See
http://www.impactaging.com/papers/v2/n11/pdf/100230.pdf

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73. Summer on May 20, 2011 1:10 AM writes...

Let's just all have a glass of red wine tonight and hope we live to see tomorrow. Lol. This is a great thread!! Loved reading every bit of it.

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74. Lissa Immel on January 7, 2013 4:21 PM writes...

You could definitely see your expertise in the paintings you write. The world hopes for more passionate writers such as you who are not afraid to say how they believe. At all times go after your heart. "We are near waking when we dream we are dreaming." by Friedrich von Hardenberg Novalis.

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75. kaneka qh on February 14, 2014 10:10 PM writes...

Truly when someone doesn't understand after that its up to other visitors that they will help, so here it occurs.

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