Context: Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications.

Objective: To investigate effects of long-term RSV treatment on inflammation and MetS.

Setting and design: A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital.

Participants: Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm.

Intervention: Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks.

Main outcome measures: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition.

Results: RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo.

Conclusion: RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.