HIGHLY PURIFIED EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID IN HUMANS HAVE SIMILAR TRIACYLGLYCEROL-LOWERING EFFECTS BUT DIVERGENT EFFECTS ON SERUM FATTY-ACIDS

To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum li pids, apolipoproteins, and serum phospholipid fatty acids in humans, w e conducted a double-blind, placebo-controlled, parallel design interv ention study. Healthy nonsmoking men (n = 234) aged 36-56 y were rando mly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decrea sed 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the D KA group across all quartiles of baseline triacylglycerol concentratio ns. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L ( P = 0.0002) in the DHA group. In the EPA group, serum total cholestero l decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0. 04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increase d by 69% and EPA increased by 29%, indicating retroconversion of DHA t o EPA. In the EPA group, serum phospholipid EPA increased by 297% wher eas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids incr eased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the D HA group. We conclude that both DHA and EPA decrease serum triacylglyc erols, but have differential effects on lipoprotein and fatty acid met abolism in humans.