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September 5, 2014: by Bill Sardi
The editor of the journal Pharmacological Research is calling it the “resveratrol fiasco.” [Pharmacological Research Aug 30, 2014] Researchers in Hong Kong are calling resveratrol “a hopeless illusion.” [Pharmacological Research Aug 22, 2013]
Decrying the lack of human research studies, claiming the promised hope of resveratrol has been hiding behind “non-human research as a cover” for back-door marketing of resveratrol dietary supplements, these investigators say resveratrol, the much heralded red wine molecule that is believed to be partly responsible for the French Paradox, “may indeed turn out to be nothing more than a sleight of hand.”
However, there was no outcry of scientific deception as long as resveratrol was bottled in a concentrated polyphenolic mixture in red wine and wasn’t threatening Big Pharma’s prescription elixirs. The U-shaped mortality risk curve for modest (3-5 glasses/day) wine consumption is well established. [Annals New York Academy Science May 2002]
A seemingly valid critique is that resveratrol in wine could not possibly be responsible for the French Paradox, the fact that the wine-drinking French exhibit far lower mortality rates from coronary artery disease than non-wine drinkers. However, Professor Roger Corder of the William Harvey Research Institute, author of The Red Wine Diet, has documented it is the total polyphenols in red wine, not resveratrol alone, that exerts the beneficial health effects of red wine. [Nature Nov 2006]
Since the beneficial health effects of red wine have been demonstrated in a multi-polyphenol mix found in red wine rather than resveratrol by itself, resveratrol dietary supplements should include other polyphenolic molecules in an attempt to replicate its known synergistic effects with other molecules.
Researchers mistakenly claim resveratrol has become a popular dietary supplement that is supported a lack of human studies. Actually resveratrol isn’t even in the top 100-selling herbal supplements.
Just when the public’s interest is piqued by some remarkable science, a scientific paper makes news headlines that resveratrol could cause cancer [Molecular Carcinogenesis Aug 2010], doesn’t prolong life in laboratory mice fed a normal-calorie diet [NIH Newsroom Aug 29, 2012], is not biologically available [Journal Translational Medicine June 3, 2014], and is potentially toxic and resulted in kidney failure. [British Journal Hematology March 2013]
Even more disconcerting, the leading cardiac resveratrol researcher was falsely accused of scientific fraud even though two other research groups had validated his findings in duplicate experiments. [Journal Cardiovascular Pharmacology Feb 2000; Canadian Journal Physiology & Pharmacology May 1, 2012; Free Radical Biology Medicine July 1999; ResveratrolNews.com Sept 25, 2013]
Researchers have conclusively demonstrated that resveratrol, as a biological stressor, activates protective endogenous enzymatic antioxidants (catalase, glutathione, SOD, heme oxygenase) to “cardio-protect” the heart prior to a heart attack, which is deemed the best form of heart protection. [American Journal Physiology Heart Circulatory Physiology May 2007]
Pre-treated animals undergoing an experimentally-induced heart attack experience far less heart muscle damage (area of scarring or fibrosis). [American Journal Physiology Heart Circulatory Physiology June 2002] The dose was critical in producing this effect with mega-doses of resveratrol actually increasing the area of damage (except for a commercially available resveratrol-based combo of natural molecules that did not increase heart muscle damage even in high-dose concentrations). [Experimental Clinical Cardiology 2010]
The problem here is that for ethical reasons such an experiment cannot be conducted among humans. Nor can a human study be designed that would allow half of high-risk heart patients to take an inactive placebo and the other half a resveratrol pill as such a study may result in needless loss of life. At the very least resveratrol should be tested among high-risk heart patients against existing therapy.
The overly skeptical investigators in Hong Kong argue over which genes are being activated by resveratrol when that does not need to be pre-determined before human resveratrol studies ensue. Patients may be dying needlessly of mortal heart attacks while researchers argue over which gene targets are put into play by resveratrol.
These investigators argue there is no good evidence to show resveratrol “acts as a calorie restriction mimic by extending life in any species under ‘normal’ conditions.” The chart below counters that claim.
While these disbelievers claim “there is little or no evidence to date that demonstrates any significant resveratrol-mediated cardio-protective advantage in humans,” they fail to take the research community to task for not having put resveratrol to the test. You can’t beg for studies the research community fail to conduct.
Dr. Frank Sellke, a leading cardiac researcher, calls one of the animal studies conducted by the falsely accused resveratrol researcher is of “major importance” [PLoS One Dec 23, 2010] and goes on to say “extensive research in the past several decades has identified multiple mechanisms by which resveratrol modifies the cardiovascular risk factors that lead to coronary artery disease, yet translation to the clinical arena has been unexpectedly slow.” [Current Atherosclerosis Reports Dec 2011]
While the resveratrol cynics claim the safety of resveratrol in human applications has yet to be thoroughly investigated, a decade of relatively safe use without serious side effect by tens of thousands of consumers among 432 available brands provided in various doses validates its relative safety. This doesn’t mean there aren’t side effects, particularly when taken in high doses and with other polyphenols, resveratrol appears to be safer than aspirin and in fact can replace aspirin, even overcome aspirin resistance. [Journal Cardiovascular Pharmacology Aug 2006]
Researchers noted a study where resveratrol induced diarrhea in human subjects. This problem likely emanates from a less concentrated extraction of resveratrol from Giant Knotweed (Polygonum cuspidatum) that contains emodin, known to induce loose stool. [Journal Agriculture Food Chemistry June 2014] Botanical extracts exceeding 85% resveratrol should virtually eliminated this occurrence.
The reported 5000 mg dose used among multiple myeloma patients that induce rapid kidney failure was a pro-oxidant dose and should have been expected to result in kidney failure given that resveratrol is pools in the kidneys. [British Journal Hematology March 2013]
In an answer to the alleged kidney toxicity posed by mega-dose resveratrol, a commercially available resveratrol-based dietary supplement has undergone animal and human toxicity testing [Food Chemistry & Toxicology Sept 2013] and has been shown, unlike plain resveratrol, to avert a potentially harmful pro-oxidant effect even in mega-dose concentration in rodent hearts. [Experimental Clinical Cardiology 2010]
The criticism that there are no long-term survival studies involving resveratrol is unfair. Resveratrol pills were popularized in 2003 when Harvard Professor David Sinclair linked resveratrol to the effects produced by a limited calorie diet. A conclusive long-term longevity study may be impractical and impossibly expensive. Such a study would require many decades, though possibly a shorter study among 80+ year olds could reveal a positive longevity effect in a short time period.
These unduly critical researchers suggest more studies among large mammals such as swine to evaluate biological mechanisms involved. However, a research team at Brown University Medical School led by Frank Sellke MD has already conducted 7 different studies in swine using resveratrol. [PubMed.gov; Annals New York Academy Science July 2013]
It appears the $720 million that Glaxo Smith Kline paid for the experimental drug company that was developing a resveratrol-based drug was a pay-off to keep the drug off the market. Even the developmental drug company’s executives attempted to sell their resveratrol-based drug as a dietary supplement, what amounts to a tacit admission that resveratrol dietary supplements are equivalent to a three-quarters of a billion-dollar drug. [Xconomy.com August 13, 2010]
If you want to find out the real reason why cardiology fears resveratrol read about the New Jersey cardiologist who has recommended a resveratrol pill for his patients over the past ten years. A Medicare audit revealed none of the patients under his care have experienced a heart attack over that time. [ResveratrolNews.com Jan 30, 2012] ©Bill Sardi, ResveratrolNews.com
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