Omega-3 Fatty Acid Supplementation and Vascular Health Biomarkers – A Systematic Review and Meta-Analysis

BACKGROUND: Cardiovascular diseases (CVDs) remain the leading global cause of death, partly due to vascular dysfunction. Dietary supplements, including omega-3 fatty acids, are suggested to support vascular health, but their therapeutic effectiveness and optimal dosing are still uncertain. OBJECTIVES: This systematic review and meta-analysis study assessed the efficacy and dose-response effects of omega-3 fatty acids on vascular health biomarkers in individuals with CVDs. DATA SOURCES: A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted through May 2025. STUDY SELECTION: Eligible randomized controlled trials (RCTs) with a minimum intervention duration of four weeks. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study quality. Data were synthesized as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane tool, and the certainty of the evidence (CoE) was appraised using the GRADE framework. MAIN OUTCOME(S) AND MEASURE(S): The pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilation (FMD). RESULTS: Twenty RCTs involving 1,208 participants were included, with 80% judged at low risk of bias. Omega-3 supplementation (0.3-4.7 g/day) showed no significant effect on PWV, including in subgroups with hypertension or established CVDs. In contrast, omega-3s improved AIx. FMD elevations were greater for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than for alpha-linolenic acid. These findings were consistent across sensitivity analyses and supported by dose-response relationships, indicating that achieving approximately 1,650 mg EPA and 750 mg DHA may be important for optimizing vascular outcomes. The CoE ranged from moderate to low. CONCLUSIONS: Omega-3 fatty acids may enhance endothelial function and reduce arterial wave reflection. Future trials with refined methods are needed to maximize clinical benefit. SYSTEMATIC REVIEW REGISTRATION: Systematic review registered with PROSPERO, registration number CRD420251065121.