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Two New Studies Cast Doubt on Resveratrol

doubts about resveratrol

To drink or not to drink...unfortunately that's still the question.

New work produced by Pfizer and Amgen cast doubt on the manner in which health supplement resveratrol is said to work. Resveratrol is a substance found in moderate quantities in red wine, and is believed to help prevent the negative side effects of aging. As we discussed in our previous article about resveratrol, prominent researchers supposed that it worked by activating a certain gene, SIRT1. This activation is thought to produce the benefits of a caloric restriction diet even among those with high fat and high caloric intake. In the October 2009 volume of Chemical Biology and Drug Design, Amgen offered experimental results that indicate resveratrol does not, in fact, activate SIRT1. Pfizer, in the January 2010 volume of the Journal of Biological Chemistry, offers similar results, showing that resveratrol (and related substances such as SRT1720) do not active SIRT1 and did not reduce blood sugar in mice fed a high fat diet. This last effect (or lack thereof) is in direct contradiction to previous resveratrol research published by David Sinclair of Harvard University in Nature. To simplify: Pfizer and Amgen are saying that resveratrol doesn’t work in the way people thought, and may, in fact, not work at all.

Considering the complexity of this research, there isn’t much to be said by us non-scientists at this time. As I mentioned in our previous resveratrol installment, it’s going to take years of more research, and many rounds of conflicting results, before anyone is likely to conclusively know if and resveratrol works on mice…let alone humans. Those proponents of the substance should take heart in the fact that SIRT1 activation is just one possible mechanism by which resveratrol could induce the benefits of a caloric restriction (CR) diet. Opponents should point out that Pfizer’s mice didn’t show any benefits of CR, so that no matter what mechanism resveratrol is supposed to be using, it didn’t seem to work. Pfizer also points out that resveratrol (and especially related substance SRT1720) did not improve mitochondrial capacity, and had many other effects on cells, some of which could complicate its use in humans.

Cynics, like myself, are happy to call attention to a potential conflict of interest. Pfizer and Amgen are competitors with GSK, one of the companies spending millions of dollars in clinical trials to see how resveratrol works. One would think that Pfizer and Amgen had something to gain by proving that GSK’s potential products wouldn’t work. That being said, they would have even more to gain if they found that resveratrol does work and if they could determine a way to market a SIRT1 activator themselves.

Again, I find myself advocating a “wait and see” policy to resveratrol. There are very few health supplements with undeniable scientific support. Even Vitamin D and Fish Oil are having to jump through hoops at the moment. Resveratrol, and the entire SIRT1 activation posse, are in need of more research and a resolution to conflicting results. Eventually there will be supplements, genetic treatments, and nanotechnology to preserve your body. In the meantime, those looking to live forever may find benefits from regular exercise, eating right, and staying stress free.

[photo credit Wiki Commons, Zereshk]

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29 comments

  • Ted Highsmith says:

    Who cares how resveratrol works. Numerous studies (both human and animal) show that it does.

  • Nosybody says:

    I'm not surprise at these studies. I been waiting for few years now to hear some drug companies sponsored studies to try to discredit any natural treatment or prevention that can hurt their markets.

  • Bill Sardi says:

    The glitter that surrounds resveratrol has not been tarnished. But the positive human epidmiologic data that supports resveratrol, in the form of wine intake, is when it is combined with other molecules in relatively low dose. There is now a growing body of scientific evidence that red wine molecules (resveratrol, quercetin, catechin, ferulic acid, malvidin, gallic acid, kaempferol) produce more than additive effects — their biological effect is synergistic, that is, multiplied many times. This was demonstrated in a mouse study where an array of 3 molecules (quercetin, resveratrol, rice bran IP6) exerted 9-fold greater influence over the mouse genome (1711 genses) versus plain resveratrol (225 genes) or a calorie restricted diet (198 genes). What the drug companies did here was to tell the public to wait for mega-Sirtuin1 gene activators which were purportedly 1000-fold activators of Sirtuin1. The problem is that this back-fired. Not only did these patentable Sirtuin1 activators not work (they didn't stimulate the Sirtuin1 gene nor did they reduce blood sugar), but there is other corroborative data which shows over-stimulation of this gene is not beneficial. Then a human study was conducted using plain resveratrol (emulsified, stabilized, micronized) in a very high dose, 2500 and 5000 milligrams, which produced very modest and transient benefits in humans regarding blood sugar control. However, these are doses known to induce selective cell death (apoptosis) and would only be appropriate for treatment of active cancer. So it appears the drug companies were intentionally attempting to strip the luster off of resveratrol and set the stage for their new chemical entities — the mega-Sirtuin1 activators. This effort to steer the public away from resveratrol appears to have backfired. Pharma companies have also spread misinformation that resveratrol is not biologically available, another untruth. This is because resveratrol poses a considerable threat to pharmaceutical dominance. This single molecule, resveratrol, could replace all anti-inflammatory, anti-cholesterol, anti-bacterial, anti-viral, anti-fungal, anti-depressant, anti-cancer drugs. Relatively low-dose resveratrol (more than what is provided in the diet) should be employed today in place of aspirin for heart attack, in place of anti-inflammatories for brain trauma (concussion), and a host of other conditions. But this means doctors prescribing nutriceuticals, not pharmaceuticals. A great discovery has been made, but the public seeks confirmation from their doctors. This may never occur.

  • John says:

    I am not aware of any study which has shown resveratrol to increase the life-span of mice, let alone any other mammal. David Sinclair's studies on mice have shown health benefits but no increase in life-span. This suggests that resveratrol does not mimic the effects of a caloric restricted diet.
    Sinclair did show that resveratrol reduced the damaging effects of a high-fat diet on mice, giving them the same life-span as healthy mice, but no life-extension.
    So it's very annoying that people still claim there are studies proving resveratrol mimics CR in mice. I'd be delighted if anyone could give me the details of any such studies.

  • John says:

    Can you give details or a reference to one human study please?

  • Allan Fielding says:

    The quality of science journalism has reached an all time low. I read the original papers by Pfizer and Amgen and neither address the issue of Resveratrol's ability to up regulate sirtuins. Both discuss the molecule being developed by Glaxo, which is not similar to resveratrol at all. Furthermore many of the animal studies on Resveratrol, particularily Transmax, the lab grade material used in many of such studies, have been replicated multiple times by researchers at different institutions. It is infuriating to see articles such as this one that take such liberties with the data and make completely unwarranted conclusions which are then redistributed and often embellished in the process.

    • Otis says:

      Agreed, I’ve reread the Pfizer paper and you can see the summary in Figure 8. They did not study Resveratrol in vivo with mice.

      The author needs to read the primary literature, or find someone who can.

      • Otis says:

        Agreed about the liberties taken by the journalist.

        One point with you…

        No lab uses TransMax. This makes your comment SPAM.

        • A Fielding says:

          I beg to differ. Among the labs using Transmax are:
          University of Ferrara Thallab, Yasheva University Medical Center Lab, University of Northumbria Cognitive Sciences Lab, Ottawa Hospital (part of Health Canada) research lab. I can list another 20 if you like. Please do not be so anxious to accuse someone of spam without first ascertaining the truth.

  • Susanne at Stanford says:

    Although resveratrol's epigenetic effects do seem to be enhanced by combination with various polyphenols, such as curcumin, pomegranate extract and alpha lipoic acid, the combination of Quercetin and resveratrol has the opposite effect, that is a down regulation of sirtuin activation and interference with the critical metabolites of resveratrol. Quercetin should not be used in combination with Resveratrol for these reasons. In fact, in Bill Sardi's own study it was shown that sirtuins were down regulated by a factor of almost 3 times by the addition of Quercetin to resveratrol.

  • Roger Anderson says:

    The Pfizer study was done in vitro and therefore did not measure the effects of the critical metabolites of resveratrol. Sirtuin activation is more likely a result of the pathways and enzymes modulated by trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate
    than it is of free resveratrol. I strongly suspect that the in vivo effects of resveratrol are tied to these metabolites. In fact, in some animal studies in which beneficial effects were observed there was no detectable amount of free resveratrol in the blood plasma however the liver and epithelial tissues of the intestine did show significant amounts of the metabolites.

  • Andre Chinati says:

    Leonard Guarente, now at Glaxo would appear to agree that the in vivo examination by the Pfizer researchers is of little significance and that, in fact, “ignores any possibility of direct activation of SIRT1 that may occur in a cellular environment that is not reproduced in vitro”. Often pharmaceuticals, although targeted at specific pathways, actually affect up to several thousand other off-target pathways and processes. These often unidentified effects clearly, in many cases, play a strategic part in the pharmaceutical's efficacy.

  • Nigel says:

    John, billions of people in the world eat a western style (high fat) diet. They would (and will) benefit from resveratrol – just like the mice on a high fat diet benefited. Further, Sirtris has tested resveratrol on humans and has seen the health benefits and the upregulation of sirtuins.

  • James Betz says:

    Pfizer's conclusion, essentially that the Glaxo analog only works on fluorophore-conjugated peptides is strange to say the least. I would like to see their data and know upon what basis they posit this contention. If this were the case than thousands of studies in which fluorophore-conjugated peptides were used would also be suspect. This would represent a huge setback for the research community.

  • Tony says:

    At least this time those drug companies didn't try to hide the fact that they paid for the studies. Normally they use front groups to conceal where the money comes from.

  • nosybody says:

    I'm not sure if this is really Mr Sardi or not, but if it is then I'm very glad to hear his comments because he is very knowledeable in this field. I have a personal testimony using his 3rd generation product that I give credit to that brought my father back to health and vitality fromm his stroke. He had a minor stroke back in July 14 2007 and wasn't the same since. Then I started giving him that 3rd generation stuff on a monday and notice he was back to normal and doing thinks around the house the following saturday when I didn't have to work. The improvement was within days after starting him their resveratrol mixture. I can't prove to my friends and relatives of that but I know what I saw on that day.

  • nosybody says:

    I forgot to add that his speech was slurred, he was very weak and got no strength to walk and move the right side of his body. His was very forgetful and would repeat saying same things within minutes of saying it before. He was this way from July to February, that's 7 months being the same condition from the stroke. Only until February 2008 that he was back to normal within days of taking those supplement.

  • nosybody says:

    I've read that the fat mice did lived longer with resveratrol compare with control group that didn't. It was the nother studies with regular healthy non fat mice that resveratrol didn't show any significate longer live but was heart healthier. As it turns out later finding that all those nonfat mice from the studies had died from retrovirus which reveratrol has no benefit for. You would think that would be listed as the causes of dealth and not age related melabolic causes of dealth.

  • no fat lady says:

    Sitris tested 2.5 grams of SRT 501 on diabetics, and the results looked promising two years ago. SRT 501 wasn't a compound tested by Pfizer, but it is a resveratrol blend and believed to be 3 -4 times more potent than resveratrol alone.

    A liver/colon cancer trial at Sirtris has ended or is about to end where 10 patients received 5 grams of SRT 501 periodically. (A mouse liver cancer study showed those taking regular resveratrol did not have the cancer spread in 70% as opposed to 5% in the non-reesveratrol control group.

    It will be interesting to see the latest cancer results as well as efficacy of SRT 2041. This isn't over yet.

    • Inspector says:

      I know of a human trial with hyper dosages by GSK- Sirtris that was recently halted, apparently due to high liver toxicity levels caused by those dosages. However, I believe it was conducted on cancer patients.

  • Interesting says:

    Dang. We have conflicting studies, both from eminent sources, both sources having at least an indirect interest in the outcome of the study.
    We also have a finding that the SIRT2 is not the mechanism of operation of resveratrol, which may or may not mean that it does not prevent aging, or perhaps in a different way than caloric restriction.
    But I believe it is still worth taking for now. Resveratrol costs all of about $20 per month to take if bought at a pharmacy and, being made from rice husks or grape skins, no adverse side effects have been shown or seem likely. So in five years I will either be $1,000 poorer or several years younger than I would have been otherwise.

  • Interesting says:

    (That is, in five years when they have the answer about the effectiveness of resveratrol.)

  • Interesting says:

    Human trials are only underway but there are some, mostly about resveratrol and cancer, see
    http://clinicaltrials.gov/ct2/results?term=resv
    and the references in the Wikipedia article

  • Otis says:

    Agreed, I’ve reread the Pfizer paper and you can see the summary in Figure 8. They did not study Resveratrol in vivo with mice.

    The author needs to read the primary literature, or find someone who can.

    • Otis says:

      Agreed about the liberties taken by the journalist.

      One point with you…

      No lab uses TransMax. This makes your comment SPAM.

      • A Fielding says:

        I beg to differ. Among the labs using Transmax are:
        University of Ferrara Thallab, Yasheva University Medical Center Lab, University of Northumbria Cognitive Sciences Lab, Ottawa Hospital (part of Health Canada) research lab. I can list another 20 if you like. Please do not be so anxious to accuse someone of spam without first ascertaining the truth.

  • Inspector says:

    I know of a human trial with hyper dosages by GSK- Sirtris that was recently halted, apparently due to high liver toxicity levels caused by those dosages. However, I believe it was conducted on cancer patients.

  • Resveratrol says:

    I believe Resveratrol has a good components to fight cancer and recent study tells that it also a drug for preventing Alzheimer disease what else is the neurodegeneration disease which is a fatal case. If there’s a bad thing about this Resveratrol, why there is a lot of product promoting resveratrol, their best component to fight cancer, heart disease, anti-oxidant and anti-stress?

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