Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects

Background and aimsTo compare the effects of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), with those of fenofibrate, on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects.Methods and resultsTwenty overweight and obese subjects participated in a randomized, double-blind, placebo-controlled intervention trial and received 3.7 g/d n-3 fatty acids (providing 1.7 g/d EPA and 1.2 g/d DHA), 200 mg fenofibrate or placebo treatment for 6 weeks separated by a 2 weeks wash-out period. Fish oil and fenofibrate treatment reduced triglyceride (−0.61 ± 0.81 mmol/L, P < 0.001, and −0.34 ± 0.85 mmol/L, P = 0.048, respectively) and increased HDL cholesterol concentrations (0.13 ± 0.21 mmol/L, P = 0.013, and 0.10 ± 0.18 mmol/L, P = 0.076), as reflected by a decrease of large very VLDL particles and increases of large HDL particles and medium size HDL particles. Fish oil increased serum LDL cholesterol concentrations (0.34 ± 0.59 mmol/L, P = 0.013). Fenofibrate reduced concentrations of soluble endothelial selectin (sE-selectin) (−4.1 ± 7.5 ng/mL, P = 0.032), but increased those of macrophage chemoattractant protein 1 (MCP1) (28 ± 55 ng/mL, P = 0.034). Fish oil had no effects on these markers.ConclusionAlthough n-3 LCPUFA and fenofibrate can both activate PPARα, they have differential effects on cardiovascular risk markers. In overweight and obese subjects fenofibrate (200 mg/d) or n-3 LCPUFA (3.7 g/d) treatment for 6 weeks did not improve markers for low-grade systemic inflammation, while fenofibrate had more profound effects on plasma lipids and markers for vascular activity compared to fish oil.Registration number clinical trials EudraCT 2006-005743-28.