High-Dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men

OBJECTIVE: Overproduction of hepatic apolipoprotein B (apoB)-100 containing very low-density lipoprotein particles and intestinal apoB-48 containing chylomicrons contributes to hypertriglyceridemia seen in conditions such as obesity and insulin resistance. Some, but not all, preclinical and clinical studies have demonstrated that the polyphenol resveratrol ameliorates insulin resistance and hypertriglyceridemia. Here, we assessed intestinal and hepatic lipoprotein turnover, in humans, after 2 weeks of treatment with resveratrol (1000 mg daily for week 1 followed by 2000 mg daily for week 2) or placebo. APPROACH AND RESULTS: Eight overweight or obese individuals with mild hypertriglyceridemia were studied on 2 occasions, 4 to 6 weeks apart, after treatment with resveratrol or placebo in a randomized, double-blinded, crossover study. Steady-state lipoprotein kinetics was assessed in a constant fed state with a primed, constant infusion of deuterated leucine. Resveratrol treatment did not significantly affect insulin sensitivity (homeostasis model of assessment of insulin resistance), fasting or fed plasma triglyceride concentration. Resveratrol reduced apoB-48 production rate by 22% (P=0.007) with no significant effect on fractional catabolic rate. Resveratrol reduced apoB-100 production rate by 27% (P=0.02) and fractional catabolic rate by 26% (P=0.04). CONCLUSIONS: These results indicate that 2 weeks of high-dose resveratrol reduces intestinal and hepatic lipoprotein particle production. Long-term studies are needed to evaluate the potential clinical benefits of resveratrol in patients with hypertriglyceridemia, who have increased concentrations of triglyceride-rich lipoprotein apoB-100 and apoB-48. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT01451918.