Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial

OBJECTIVE: Insulin resistance is associated with increased lipolysis and elevated concentrations of free fatty acids, which in turn contribute to impaired vascular function. We hypothesized that lowering free fatty acids with acipimox, a nicotinic acid derivative that impairs free fatty acid efflux, would improve endothelial function, measured by flow-mediated dilation, in individuals with metabolic syndrome. METHODS: Eighteen subjects with metabolic syndrome and 17 healthy controls were enrolled and treated with acipimox 250 mg orally every 6 hours, or placebo, for 7 days in a randomized, double-blind, crossover trial. RESULTS: Acipimox reduced free fatty acid concentrations among individuals with metabolic syndrome to near normal levels (P=0.01), but there was no change among healthy controls (P=0.17). Acipimox did not improve endothelial-dependent flow-mediated dilation in either group (metabolic syndrome: P=0.42, and healthy controls: P=0.16), although endothelial-independent nitroglycerin-mediated dilation among those with metabolic syndrome tended to increase (20.3%, P=0.06). There were no changes in blood lipids or markers of inflammation following therapy. There was minimal correlation between change in flow-mediated dilation and baseline measures of body-mass index (ρ=−.09) or waist circumference (ρ=−0.15). CONCLUSIONS: In groups with normal or elevated baseline free fatty acids, short-term reductions do not improve endothelial function assessed by flow-mediated dilation.