Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults

Semba RD, Ferrucci L, Bartali B et al.
JAMA Intern Med. 2014 May 12. doi: 10.1001/jamainternmed.2014.1582

Background

Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenol found in grapes, red wine, peanuts, chocolate and certain berries and Asiatic plant roots. It has anti-inflammatory effects in vitro and in animal models [1,2] and was shown to increase lifespan and health in mice fed a high-calorie diet [3-6].
It has been postulated that the cardioprotective effects of red wine could be attributed to resveratrol [7] and also the ‘French paradox’, in which a low incidence of coronary heart disease is seen despite a high dietary intake of cholesterol and saturated fat, has been attributed to resveratrol and other polyphenols in wine [8].
Preliminary evidence suggests that resveratrol may also have anti-inflammatory effects in humans. There is, however, little epidemiological data that supports a link between physiologic levels of resveratrol achieved with diet alone, and health in humans.
This study measured urinary metabolites of resveratrol in a population-based cohort, to correlate these levels to all-cause mortality, inflammation and prevalence and incidence of CV disease and cancer. Study participants were at least 65 years of age, who participated in the ‘Invecchiare in Chianti’ (Aging in Chianti Area: InCHIANTI) study [9]. Participants were evaluated at a 3-year (n=926), 6-year (n=844) and a 9-year (n=768) follow-up visit.

Main results

• During 9 years of follow-up, 268 (34.2%) participants passed away. There were no significant differences in the proportion of participants who died across quartiles of total urinary resveratrol metabolite concentrations.
• No differences were seen in alcohol intake, current smoking, gut resveratrol metabolites, microbial resveratrol metabolites, total urinary resveratrol metabolites, IL-1β, triglycerides, coronary artery disease, or cancer, between participants who died and those who did not.
• In multivariable models adjusting for age, sex, BMI, serum levels of lipids, chronic diseases, and other variables, no significant association between total urinary resveratrol metabolites and all-cause mortality was found. This did not change in models that also included markers of inflammation.
• No significant associations were seen between urinary resveratrol metabolites and all-cause mortality in sensitivity analyses that excluded participants who died in the first year (possibly due to other existing illnesses) or participants who consumed more than 4 drinks per day, to exclude potential effects of excessive alcohol consumption.
• In multivariable models, no statistically significant increased hazards were found for dietary resveratrol intake and all-cause mortality, when comparing resveratrol intake quartiles with the highest quartile.
• 174 of 639 (27.2%) participants who were free of CV disease at enrollment developed CV disease. The proportions of participants with incident CV disease were 22.3%, 29.6%, 28.4% and 28.0% respectively for increasing resveratrol quartiles (P=0.44).

Conclusion

Contrary to all hypotheses, these data show that urinary resveratrol metabolites do not predict longevity in older community-dwelling adults, and that they are not associated with markers of inflammation, and prevalent or incident CV disease. Resveratrol levels achieved via the diet are not associated with protection against disease and markers of disease. Urinary resveratrol levels were significantly correlated with alcohol intake, which can likely be attributed to wine intake, considering that the study was conducted in the Italian Chianti wine region.

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