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To the Editor Potential disease-preventive effects of the red grape constituent resveratrol are a subject of intense biomedical research and attract a lot of media interest. Recently, Semba et al1 poured cold water over the idea that resveratrol as a dietary constituent prevents heart disease or cancer or prolongs life. The study suggests that the intake of red wine by elderly persons, as judged by urinary levels of resveratrol metabolites, did not affect overall mortality, incidence of cardiovascular disease or cancer, or biomarkers of incipient inflammation. This publication elicited considerable negative resonances in the international lay press (eg, “Red wine health benefits ‘overhyped’”).2 We submit that several aspects render the study unsuitable to warrant such negative resonance. Participants were classified into quartiles based on their urinary resveratrol metabolite levels measured once at the start of the study. We seriously doubt that this single value can accurately reflect lifetime exposure because the impact of resveratrol on health is likely to have been heavily influenced by consumption patterns prior to the investigation. The dose-response relationships that govern the efficacy of resveratrol are unclear and may display hormetic properties with opposing effects observed at small and large doses.3 In the study by Semba et al,1 the first quartile of urine levels contained values from participants who refrained from resveratrol consumption and those whose resveratrol intake was low, militating against the ability to tease out potential differences between resveratrol-naive participants and those with a low intake. Nutritional status of study participants is one of the many variables that affect disease prevention outcomes. Resveratrol is likely to engage its effects via subtle disturbances of abnormal cell metabolic processes associated with high fat intake typical of the Western diet.4 This means that resveratrol may cause its preventive efficacy only in individuals who have consistently ingested high amounts of fat and/or have the metabolic syndrome, but not in healthy ones.5 The article by Semba et al1 does not give any indication as to the amount of fat consumption by the participants. A quarter to a third of them were prediabetic or diabetic; assessment of study end points vs resveratrol consumption in this subgroup vis à vis the metabolically uncompromised participants might have been revealing.
Brown K, Rufini A, Gescher A. Do Not Throw Out the Resveratrol With the Bath Water. JAMA Intern Med. 2015;175(1):140–141. doi:10.1001/jamainternmed.2014.7000