Web edition: June 23, 2010
Resveratrol, a constituent of grapes, peanuts and certain other plants, can fight the proliferation of fat cells and improve the uptake of sugar from the blood, a pair of new studies show. Their findings suggest mechanisms to explain why grape products, including wine, have developed a reputation as heart healthy, obesity-fighting and beneficial for people developing diabetes.
The French Paradox — why France’s fatty cuisine has not saddled its population with rampant heart disease — has mystified nutrition researchers for decades. The French penchant for drinking lots of wine has suggested one explanation. And a number of studies have indicated that alcohol of all types can, in moderation, fight heart disease, diabetes and more.
However, resveratrol has been gaining renown as a potentially pivotal player in the French Paradox. This compound, which some plants make as a natural antibiotic to fight pathogenic bacteria and fungi, has a number of different but equally beneficial actions in human cells. Diets rich in the chemical seem to protect the heart, slow weight gain, boost the rate at which the body burns fat (at least in studies with mice) and even extend lifespan (again, in mice).
But a nagging question has been how resveratrol achieves such benefits. And that’s what the two new studies homed in on.
Ariel Roguin of the Rappaport Faculty of Medicine at the Technion–Israel Institute of Technology, in Haifa, and his colleagues focused on the heart. Many age-related features of cardiovascular disease trace to the body’s waning ability to rehab parts of vessels that have sustained disease or injury. Contributing to this problem is an age-related decrease in endothelial progenitor cells, or EPCs — essentially blood-vessel repair squads that the bone marrow makes to patch up the endothelium, or interior surface, of damaged blood conduits.
Indeed, the Israeli team notes, “the decreased ability of older people to repair the vascular endothelium has been attributed partially to an age-associated decline in EPC number and function.” In the July American Journal of Clinical Nutrition, Roguin’s team offers data indicating that among 30-year-olds who previously had consumed no more than two drinks a week, upping their intake to a glass of red wine daily improved both vascular function and the quality of their EPCs.
Fifteen men and women took part, drinking 250 milliliters (8 fluid ounces) of red wine daily for three weeks. To gauge how well their vessels worked — how responsive they were to changing conditions — the researchers tightened a blood-pressure cuff on each volunteer’s forearm for 5 minutes to reduce blood flow. Afterward, they measured how quickly vessels dilated and returned blood flow to normal. Sick vessels don’t dilate quickly.
These recruits weren’t elderly, didn’t have heart disease and never smoked — hardly ideal models of senior citizens. Still, their vessels dilated more — restoring blood flow more quickly — after they had been drinking wine daily.
The researchers also collected EPCs from the volunteers’ blood before and immediately following the trial and subjected them to a battery of tests. Those experiments showed that EPCs extracted at the end of the trial reproduced more rapidly than those from before the wine-drinking experiment and proved better able to migrate — something they’d have to do to repair damaged vessels.
Moreover, when EPCs were exposed to short pulses of blood glucose — to simulate the blood’s sugar-rich environment after a high-carbohydrate meal — EPC migration rates dropped. Red wine completely prevented this drop.
The blood-sugar challenge also reduced the EPCs’ production of nitric oxide, the chemical that vessels use to dilate. However, ”this decreased nitric oxide production was partly restored by red wine,” the Israeli team showed.
In the second study, Pamela Fischer-Posovszky and her colleagues at the University of Ulm, Germany, worked with test-tube colonies of human adipocytes — aka fat cells — and fat-precursor cells. Adding resveratrol to their growth medium inhibited the transformation of precursors into bone fide fat cells, they report in the same issue of the American Journal of Clinical Nutrition.
In mature fat cells, resveratrol also boosted the uptake of glucose (a good thing, since resistance to uptake is a hallmark of type-2 diabetes) and diminished the fat cells’ secretion of various inflammation-boosting compounds. Such fat-derived pro-inflammatory agents have been implicated in heart disease and tissue damage associated with diabetes.
Many of resveratrol’s benefits appeared to rely on Sirt1, an enzyme that orchestrates a number of intracellular activities. For instance, when the Ulm scientists added resveratrol to fat cells lacking the gene to make Sirt1, the cells proliferated at a far higher rate than when Sirt1 was present. And in mouse cells, resveratrol inhibited the transformation of fat-precursor cells into mature fat cells — unless those cells were unable to make Sirt1. However, some biochemical benefits of resveratrol persisted even in the absence of Sirt1, Fischer-Posovszky's group showed.
“Both studies provide new insights into the mechanisms underlying the potential benefits of resveratrol in metabolic disease,” write Evi Mercken and Rafael de Cabo of the National Institute on Aging, in an accompanying editorial. Based on these new findings, they say, “it is clear that resveratrol acts both indirectly (through adipose tissue) and directly (through endothelial cells) to prevent cardiovascular disease.”
Indeed, so promising are the emerging data on resveratrol that its potential to prevent disease and treat metabolic disease "cannot be overlooked," Mercken and de Cabo say. Still, the data fall far short of a slam dunk in proving wine, grapes and reserveratrol supplements warrant medicinal status. What these and a host of related studies really do signal is that it’s time “to conduct well-controlled, long-term clinical studies to determine the potential use of this molecule in preventive and therapeutic interventions for metabolic disorders,” they argue.
Wine is a good source of resveratrol. So are grapes and grape juice. But we should all observe some caveats, starting with: If a little is good, a lot may not be. So, the byword remains moderation. Moreover, resveratrol's benefits may not extend to nixing existing disease. For instance, it may inhibit formation of new fat cells, but do nothing to diminish the number, size or vascular risks of fat cells already planted in depots around the body.
So the disappointing take-home here is that from middle-age onward, adding resveratrol-rich foods to the diet probably will not obviate our need to still watch calories, exercise regularly and moderate intakes of sugar and fats.
Fischer-Posovszky, P., et al. 2010. Resveratrol Regulates Human Adipocyte Number and Function in a Sirt1-Dependent Manner. American Journal of Clinical Nutrition 92(July):5.
Hamed, S., et al. 2010. Red Wine Consumption Improves in vitro Migration of Endothelial Progenitor Cells in Young, Healthy Individuals. American Journal of Clinical Nutrition 92(July):161.
Mercken, E.M. and R. de Cabo. 2010. A Toast to Your Health, One Drink at a Time. American Journal of Clinical Nutrition 92(July):1.
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