Bezafibrate Mildly Stimulates Ketogenesis and Fatty Acid Metabolism in Hypertriglyceridemic Subjects

Our objective was to determine whether bezafibrate, a hypotriglyceridemic drug and peroxisome proliferator-activated receptor (PPAR)-α agonist, is ketogenic and increases fatty acid oxidation in humans. We measured fatty acid metabolism and ketone levels in 13 mildly hypertriglycemic adults (67 ± 11 years old) during 2 metabolic study days lasting 6 h, 1 day before and 1 day after bezafibrate (400 mg of bezafibrate per day for 12 weeks). β-Hydroxybutyrate, triglycerides, free fatty acids, fatty acid profiles, insulin, and glucose were measured in plasma, and fatty acid β-oxidation was measured in breath after an oral 50-mg dose of the fatty acid tracer [U-13C]linoleic acid. As expected, 12 weeks on bezafibrate decreased plasma triglycerides by 35%. Bezafibrate tended to raise postprandial β-hydroxybutyrate, an effect that was significant after normalization to the fasting baseline values ( p = 0.03). β-Oxidation of [U-13C]linoleic acid increased by 30% ( p = 0.03) after treatment. On the metabolic study day after bezafibrate treatment, postprandial insulin decreased by 26% ( p = 0.01), and glucose concentrations were lower 2 to 5 h postprandially. Thus, in hypertriglyceridemic individuals, bezafibrate is mildly ketogenic and significantly changes fatty acid metabolism, effects that may be linked to PPARα stimulation and to moderately improved glucose metabolism.