Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health

Abstract

Oxidation of low-density lipoprotein (LDL) and hyperhomocysteinemia are believed to play a role in therogenesis. Whether n-3 polyunsaturated fatty acids increase LDL susceptibility to oxidation or influence homocysteine (Hcy) metabolism has long been a subject of controversy. In this study, we evaluated the effect of 8 weeks of dietary supplementation with 6 g/day of fish oil (FO; 3 g of n-3 fatty acids) on plasma lipoproteins, in vitro LDL peroxidation, antioxidant status, and plasma Hcy concentrations in 16 normolipidemic subjects. FO rapidly and significantly (P <.01) decreased plasma total and very low density lipoprotein triglyceride concentrations and had no effect on LDL or high-density-lipoprotein cholesterol. The mean lag time before onset of Cu2+-induced LDL oxidation, as well as plasma and LDL α-tocopherol and β-carotene concentrations, was unchanged. However, changes in plasma aminothiol concentrations occurred during the study. Specifically, a progressive and significant increase in total Hcy plasma concentrations was observed (13.4% and 20% after 4 and 8 weeks, respectively; P <.01). Total glutathione concentrations were significantly higher after 8 weeks (P <.05). The tHcy increase was not associated with changes in plasma folate or vitamin B12 concentrations. However, concentrations of plasma nitric oxide metabolites (NOx = NO2 + NO3) were significantly higher than at baseline after 8 weeks of FO intake (74%; P <.01). Further, the changes in total Hcy and NOx plasma concentrations observed after 8 weeks of FO were found to be significantly correlated (r =.78, P <.001). With this study, we report for the first time the apparent interaction of n-3 fatty acids and nitric oxide on Hcy metabolism. (J Lab Clin Med 2003;141:41-9)