Effects of fish oil supplementation on biomarkers of vascular endothelial function in middle-aged and older adults: a randomized controlled trial

Abstract

Objective: This trial evaluated marine-derived omega-3 supplementation for primary cardiovascular prevention in middle-aged and elderly adults, focusing on endothelial activation markers and vasodilation. Methods: 240 participants were randomized to four groups receiving 0 g, 1 g, 2 g, or 4 g daily of fish oil (containing 129 mg DHA and 182 mg EPA per gram) for 12 weeks. Fasting blood samples were analyzed for fatty acids and endothelial function biomarkers (NO, ET-1, ICAM-1, MCP-1, Ox-LDL) at baseline and post-intervention. Results: Baseline characteristics and dietary intake did not differ significantly among groups (P > 0.05). Post-intervention analysis revealed a significant increase (P < 0.05) in serum EPA and DHA in all fish oil groups except the control group. The key between-group result was a significantly greater reduction in ICAM-1 (−24.21% vs. −10.90%; P = 0.026) and MCP-1 (−27.38% vs. −14.92%; P = 0.024) in the 1 g d⁻¹ group compared to control, with higher doses (2 g d⁻¹ and 4 g d⁻¹) not showing incremental benefit. No other biomarkers (NO, ET-1, Ox-LDL) showed significant between-group differences. Notably, within-group changes included increased NO in the 2 g d⁻¹ group and decreased ET-1 in the 1 g d⁻¹ and 4 g d⁻¹ groups from baseline. Conclusions: This study found that low-dose fish oil significantly reduced endothelial inflammatory markers (ICAM-1, MCP-1) with a U-shaped dose–response in a community-based middle-aged/elderly population, suggesting optimal anti-inflammatory effects at modest intake. No effects were seen on vasodilatory or oxidative lipid markers.