Dose-response effects of fish-oil supplementation in healthy volunteers

We performed a randomized, controlled study on the dose-response effects of daily supplementation of 1.5, 3, and 6 g of the marine fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) as their ethyl esters for 12 wk in 45 healthy normotriglyceridemic male volunteers. Significant dose-related increases of the n-3 fatty acids 20:5, 22:5, and 22:6 in plasma phospholipids (p less than 0.0001) were found, corresponding roughly to decreases of the n-6 fatty acids 18:2 and 20:4 (p less than 0.001). Serum triglycerides and HDL3-cholesterol concentrations showed a dose-dependent reduction (p less than 0.05) and HDL2 cholesterol increased (p less than 0.05). Results for 3 and 6 g n-3 fatty acids were similar. No dose-dependent effects were observed in the VLDL-, LDL-, and total HDL-cholesterol subfractions; blood pressure; bleeding time; erythrocyte deformability; or capacity of polymorphonuclear leukocytes to kill Staphylococcus aureus. This study indicates that 3 g n-3 ethyl ester fatty acids appears to be the appropriate supplementation dose in humans, at least regarding lipid-profile changes and the ability to incorporate such fatty acids in the plasma phospholipids.