Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men

Key points In rodents, resveratrol has been shown to enhance training‐induced changes in cardiovascular function, exercise performance and the retardation of atherosclerosis. We examined the effect of 8 weeks of exercise training with and without concomitant resveratrol supplementation in aged men. Exercise training potently improved blood pressure, blood cholesterol, maximal oxygen uptake and the plasma lipid profile. Resveratrol supplementation reduced the positive effect of exercise training on blood pressure, blood cholesterol and maximal oxygen uptake and did not affect the retardation of atherosclerosis. Whereas exercise training improved formation of the vasodilator prostacyclin, concomitant resveratrol supplementation caused a shift in vasoactive systems favouring vasoconstriction. The present study is the first to demonstrate negative effects of resveratrol on training‐induced improvements in cardiovascular health parameters in humans and adds to the growing body of evidence questioning the positive effects of resveratrol supplementation in humans. Abstract Ageing is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which in animal studies has been shown to decrease atherosclerosis, and improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training‐induced improvements in cardiovascular health parameters in aged men. Twenty‐seven healthy physically inactive aged men (age: 65 ± 1 years; body mass index: 25.4 ± 0.7 kg m −2 ; mean arterial pressure (MAP): 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O 2 min −1 ) were randomized into 8 weeks of either daily intake of either 250 mg trans‐ resveratrol ( n = 14) or of placebo ( n = 13) concomitant with high‐intensity exercise training. Exercise training led to a 45% greater ( P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (−4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 vs. 1174 ± 121 pg ml −1 ; P < 0.02) and muscle thromboxane synthase was higher in the resveratrol group after training ( P < 0.05). Resveratrol administration also abolished the positive effects of exercise on low‐density lipoprotein, total cholesterol/high‐density lipoprotein ratio and triglyceride concentrations in blood ( P < 0.05). Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 (VCAM‐1). Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation can blunt these effects.