BACKGROUND:Vegetarians are generally deficient in long-chain n-3 fatty acids. Long-chain n-3 fatty acids have a beneficial effect on plasma lipid levels, and some studies showed that they had breast cancer suppression effect. One of the biomarkers of breast cancer risk is the ratio of urinary 2-hydroxyestrone (2-OHE(1)) to 16alpha-hydroxyestrone (16alpha-OHE(1)). OBJECTIVE:To investigate the effect of docosahexaenoic acid (DHA, 22:6n-3) supplementation on blood lipids, estrogen metabolism and oxidative stress in vegetarians. DESIGN:Single-blind, randomized, placebo-controlled trial. INTERVENTIONS:Twenty-seven postmenopausal vegetarian women were recruited. After a 2-week run-in period with 6 g placebo corn oil, the subjects were subsequently randomized to receive either 6 g corn oil (n=13) or 6 g DHA-rich algae oil (2.14 g of DHA/day) (n=14) for 6 weeks. Two subjects in corn oil group withdrew before completion. MAIN OUTCOME MEASURES:Plasma lipids, urinary 2-OHE(1) and 16alpha-OHE(1), urinary F(2)-isoprostanes and plasma alpha-tocopherol. RESULTS:Plasma LDL-DHA and EPA level increased significantly by DHA supplementation. DHA decreased plasma cholesterol (C) levels (P=0.04), but did not influence the levels of plasma TG, LDL-C and HDL-C, alpha-tocopherol, urinary F(2)-isoprostanes, 2-OHE(1), 16alpha-OHE(1) and ratio of 2-OHE(1) to 16alpha-OHE(1) as compared to corn oil. CONCLUSION:DHA supplementation at a dose of 2.14 g/day for 42 days decreases plasma cholesterol but neither does it show beneficial effects on estrogen metabolism, nor does it induce deleterious effects on the observed in vivo antioxidant or oxidative stress marker in postmenopausal vegetarian women. SPONSORSHIP:A grant (# DOH89-TD-1062) from Department of Health, Executive Yuan, Taiwan.