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Controversy over resveratrol supplementation and correlation of mouse trials to human trials

faridaro profile image
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Resveratrol Supplements Are Finally Put to the Test

Written By Michael Greger M.D. FACLM on May 24th, 2018

“If one searches the Internet for anti-aging interventions, a vast array of techniques are offered, from starvation regimes to dietary supplements and growth hormones. All are for sale, but none so far have been proven as the magic bullet, despite exorbitant claims on many of the websites.” Resveratrol is one supplement you’ll likely come across, a component of red wine that gained notoriety as a possible explanation for the so-called French Paradox, which turned out to be not so paradoxical after all.

As I discuss in my video Resveratrol Impairs Exercise Benefits, it turns out that “countries with high wine consumption are those in which saturated fat consumption used to be low but increased in recent years.” So, the low mortality from ischemic heart disease may just reflect the earlier, lower levels of saturated fat consumption, and the wine may just be a confounding factor. It did, however, help spark interest in resveratrol, the purported active ingredient of red wine about which scientific papers are now published every day.

More than a hundred of those papers on resveratrol have been called into question though, as one of the leading researchers in the field was found guilty of taking millions in taxpayer money only to fabricate and falsify his data.

Hundreds of studies still remain, though. Does this mean pills can now replace a healthy diet? Even a group of resveratrol scientists don’t think resveratrol is worth supplementing: “In contrast to the lacking data on resveratrol in humans, the animal data are promising and indicate the need for further human clinical trials.” In rodents, resveratrol supplementation decreased cardiovascular risk factors, improved cardiovascular function and physical capacity, and decreased inflammation, leading to improved vascular function. But, when it was put to the test in people, almost the exact opposite was found.

Specifically, combining resveratrol with athletic training abolished the reduction in blood pressure, cholesterol, and triglycerides normally associated with training; had a more arterial-constricting effect than a dilating effect; “and led to a significantly lower increase in the training-induced increase in maximal oxygen uptake.”

Rodents on resveratrol get enhanced exercise performance, but, in people, the resveratrol induced a 45 percent lower increase in maximum aerobic capacity compared with those taking a sugar pill. The human subjects were working out like crazy, and the resveratrol undercut their efforts.

This raises a larger issue. Mouse models are a cornerstone of modern biomedical research, and yet systematic studies as to their usefulness are rarely done. Consider this: nearly 150 human clinical trials testing anti-inflammatory drugs have failed—without exception—after those same drugs had shown promise in trials on mice. In analyzing the carry-over from the mouse trials to the human trials, researchers determined that “the result was surprising, almost shocking: the correlation was not only poor, it was virtually absent for the main study areas: burns, trauma, endotoxemia.” It turns out, for example, that mice may be up to a million times less sensitive to inflammatory endotoxins than humans.

The takeaway is that the negative effects they found add to the growing body of evidence questioning the positive effects of resveratrol supplementation in humans. Maybe the problem, though, was resveratrol supplementation—that is, giving people capsules containing 50 times the resveratrol they would normally get from eating grapes, berries, peanuts, or chocolate. Was it just too much of a good thing? To see if the amount one gets from drinking red wine would be beneficial, we can look to the Chianti region of Tuscany to determine whether resveratrol levels achieved with diet help protect against inflammation, cancer, cardiovascular disease, and death. The answer? None of the above. Despite the fact that U.S. annual sales of resveratrol supplements have reached $30 million, there are limited and conflicting human clinical data demonstrating any human benefits, and there are no data concerning its long-term safety.

The exercise study was supported in part by a manufacturer of resveratrol supplements. To their credit, however, the researchers responded to an angry letter by a supplement company consultant that “it is our opinion that we, as scientists, have a responsibility to report what we find, and not to twist our findings to fit the commercial interests.”

The benefits of red wine over white do not appear to be due to the resveratrol, but to the estrogen synthase blockers

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faridaro
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park_bear profile image
park_bear

Thanks for this. Important take away here is animal studies really must be confirmed by human studies.

MBAnderson profile image
MBAnderson

Thank you faridaro.

Rats. Double rats. I just bought a $34 bottle from Life Extension. It may well be true (although there weren't references in the article,) i.e., what's good for mice may not mean anything for us, but if it is, how do you explain that billions of dollars are still being spent on trials in rodents? Are all those scientists wrong?

I'm really beginning to question the value of a lot of supplements. I'm probably going to stop buying half of what I use now. I need to raise my standards, significantly, for what passes as compelling evidence.

Look at what Life Extension says about resveratrol.

"Resveratrol is a plant compound that supports the healthy expression of genes associated with slowing down aspects of the aging process — as well as overall health. Optimized Resveratrol also contains synergistic phytonutrients like quercetin, trans-pterostilbene, fisetin, plus a red grape and wild blueberry fruit blend for additional polyphenols, anthocyanins, and more.

Benefits at a Glance

Promotes “youthful gene expression” similar to calorie restricted diets

Encourages healthy insulin sensitivity and mitochondrial function

Supports a healthy inflammatory response

Contains a red grape and wild blueberry fruit extract blend

Augmented with synergistic trans-pterostilbene, quercetin, and fisetin

Read More About Resveratrol

Studies show that calorie-restriction diets can activate youthful gene expression, a process that slows down certain aspects of aging. But resveratrol triggers many of the same favorable gene expression changes as calorie restriction, without the difficult diet to adhere to.

Resveratrol’s health benefits

Found in red grapes, resveratrol may be the most effective compound for maintaining optimal health and promoting longevity1 — the most active form of which is trans-resveratrol.

In higher doses, resveratrol promotes healthy insulin sensitivity, encourages enhanced mitochondrial function, promotes a healthy inflammatory response, and protects against the effects of a high-fat diet.2-16 And our Optimized Resveratrol formula includes a red grape and wild blueberry blend for additional polyphenols, anthocyanins, and more.

Augmenting Resveratrol

Combining trans-pterostilbene with resveratrol confers even greater health benefits. Laboratory tests show that pterostilbene (a compound from the same chemical family as resveratrol) encourages cardiovascular health, supports glucose levels already within the normal range, and promotes cognitive health.17-25 It also encourages healthy mitochondrial and metabolic function,26,27 promotes antioxidant activity,19,23 and supports a healthy inflammatory response.19,23,28

Also contains Fisetin and Quercetin

The flavonol compound fisetin can "switch on" the cell-signaling molecules for youthful gene expression, DNA protection, healthy cellular function,29 and even supports vulnerable neurons against the presence of oxidative stress.28,30-34 And research indicates that fisetin synergistically enhances resveratrol, stabilizing it and shielding it from metabolic breakdown.35

Quercetin is a bioflavonoid that promotes cardiovascular health,36-39 supports healthy cholesterol levels already within normal range,40 helps reduce oxidative stress, promotes a healthy inflammatory response in blood vessel walls as a result of healthy gene expression,41 and supports healthy blood glucose levels already within normal range.42-48

Ratings based on results of the 2018 ConsumerLab.com Survey of Supplement Users.

consumerlab.com/survey2018."

faridaro profile image
faridaro in reply toMBAnderson

Can relate to your frustration - just this week I came across some negative information on expensive probiotic (have couple of pkgs) in which one of the strains is enterococcus faecalis which according to the article has potential to become opportunistic and cause serious health issues. It seems like the more you know the more you realize how much you don't know.

Regarding resveratrol - last year I've heard an interview with Jay Davidson, ND who briefly stated that bad news about resveratrol are rocking naturopathic world. However, when I searched online - couldn't find any information. Don't have time to do any research right now as we are moving to another area after living in the same house for 31 years - lots of work!

park_bear profile image
park_bear in reply tofaridaro

Oooooh - enterococcus faecalis is definitely a bad actor, a known pathogen causing chronic prostatitis. No good reason to put that in a supplement AFAIK.

There is also the matter of folate being carcinogenic, see my writing here:

dailykos.com/stories/2018/5...

park_bear profile image
park_bear in reply toMBAnderson

>"how do you explain that billions of dollars are still being spent on trials in rodents? Are all those scientists wrong?"

Not wrong, because mice are much cheaper to work with and there are things you can do to mice you cannot do to humans, BUT, animal trial results are preliminary and carry much lower evidentary weight until being confirmed in humans.

Gioc profile image
Gioc in reply topark_bear

It seems to me that the search for success depends a lot on the researcher, the intention, attention, genius, a lot of work and a bit of luck never hurts.

I tried high dose resveratrol just to see if I could notice any potential health benefits over a 3 month period with no apparent benefit. High dose resveratrol is expensive . I think melatonin may offer more in terms of life extension, value, neuroprotection and antioxidant potential!

Art

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