Does Resveratrol Make You Live Longer?

Resveratrol, known as the red wine molecule, became a household word in 1991 when a scientist from Bordeaux University appeared on the popular TV show “60 Minutes” and attributed the so-called French Paradox to the French habit of drinking red wine. The term “French Paradox” itself was coined in the newsletter of the International Organization of Vine and Wine to explain a curious finding.

If you chart death from heart attack versus the amount of saturated fat and cholesterol consumed in different countries, there appears to be a straight line. The more animal-based foods populations eat, the higher their death rates appear to be. However, two countries didn’t fall in line with that straight line. Finland seemed to be doing worse than expected, and France appeared to be doing better than expected. Hence, the paradox. How could France have saturated fat and cholesterol intake similar to Finland, but five times fewer fatal heart attacks?

Everyone had their pet theories to explain the paradox. Was it the wining? Was it the dining? Yes, animal foods are associated with coronary heart disease mortality, but plant foods appear to be protective. So, might the fact that the French were eating four times as many vegetables help account for their lower death rates? It turns out, however, that there may be no paradox at all.

According to an investigation by the World Health Organization, French physicians were just under-reporting heart disease deaths on the death certificates by as much as 20 percent. So, if you correct for that, France basically comes right back in line with the death versus animal fat and death versus cholesterol lines, with about four times the fatal heart attack rates as Japan and about four times the animal fat consumption. By the time of the correction, however, resveratrol research had already taken root, culminating in more than 17,000 scientific publications to date.

But only about 1 to 2 percent of the published reports were human clinical trials, and after many millions of dollars spent and many years of disappointing results, the scientific tide started to turn. Reviews began to ask whether resveratrol was a molecule whose time had come and gone: “Should we now consign resveratrol to our intellectual garbage cans and move on to better things?” Of course, it didn’t help matters when a leading resveratrol researcher was found guilty of 145 counts of fabrication and falsification of data, throwing the whole field into turmoil.

But in 2013, resveratrol was primed to make a comeback with the apparent confirmation that it was a STAC, a sirtuin-activating compound, that is, a compound that purportedly activates a longevity enzyme. This has been called into question, though. Commentaries with titles like “Is resveratrol an imposter?” “Promising therapeutic, or hopeless illusion?” and “The resveratrol fiasco” were published, suggesting that the seeming sirtuin activity was probably the result of experimental artifacts. “In summary,” a recent review concluded, “the jury is out.” The proof is in the pudding, though. Does resveratrol enhance longevity or not?

Yeast is the big success story, with resveratrol extending the lifespan of brewer’s yeast by up to 70 percent. Resveratrol also helped microscopic roundworms live longer, but it failed fruit flies, mosquitoes, and water fleas. Anything bigger than a unicellular fungus or a microscopic worm? Yes, resveratrol can extend the lives of honeybees and, most excitingly, two vertebrates, short-lived fish: Gunther’s and turquoise killifish. Unfortunately, most studies on mammals (mostly mice) failed to show a lifespan benefit.

Resveratrol is said to extend the lives of so-called model organisms by mimicking caloric restriction, but flies and mice show robust life-extension responses to dietary restriction, yet don’t seem responsive to resveratrol. That may just be true of healthy animals, though. Give resveratrol to mice in extremis, whether bombarded by radiation, poisoned with endotoxins, or having their intestines punctured to cause sepsis-induced kidney failure, and they do survive longer with resveratrol than they otherwise would under those conditions. Resveratrol can also help mediate the life-shortening effects of high-fat diets in mice.

The lifespans of heathy mice and rats fed normal diets are not affected by resveratrol, but the compound partially prevented the premature deaths of mice fed high-fat diets.

The authors of a meta-analysis of the effect of resveratrol on longevity across species concluded that, based on the fact that most mouse studies failed to show a benefit, it’s “inappropriate for resveratrol to be marketed as a life-extending health supplement.” True, no study has demonstrated resveratrol lifespan extension in healthy rodents, only in “metabolically compromised mammals,” but isn’t that a pretty accurate description of most of the U.S. population these days?

Studies on monkeys fed diets high in butterfat and sugar found that resveratrol decreased artery and abdominal fat inflammation. Combined with the shift towards normalizing the lifespans of mice on high-fat diets, pharmacology journal commentaries were published with titles like “Resveratrol—Pills to replace a healthy diet?” speculating whether “resveratrol is the compound that will allow us to be more and more inactive while eating too much in general and too much fat and sugar in particular.”

Yes, a nutrition journal editorial entitled “Dodging physical activity and a healthy diet” conceded, exercise and dietary modification are the “most potent, cheapest, and easiest ways to prevent lifestyle-related chronic diseases,” but might resveratrol on its own “take the edge off the consequences of your lifestyle?” No wonder annual sales of resveratrol supplements reached $30 million in the U.S. alone. Approaching the peak in interest around the time Oprah Winfrey mentioned it in 2009, it was estimated that two-thirds of people in the United States taking multiple daily dietary supplement regimens included resveratrol. But what do the human data show? I’ll cover that, next.