Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Lower Extremity Arterial Disease

Background: Omega-3 polyunsaturated fatty acid (PUFA) supplements are used to treat lower extremity arterial disease (LEAD), but their effects on patient outcomes remain controversial. Objective: We aimed to investigate the effect of omega-3 PUFA supplements on outcomes in LEAD patients. Design: We systematically searched for randomized controlled trials (RCTs) published before February 2020 in PubMed, the Cochrane Library, EMBASE, Medline, and ClinicalTrials.gov. Three researchers extracted the study design, sample size, omega-3 PUFA dosage, and patient characteristics. A random-effects model was used. The primary outcomes were the mean change in the ankle-brachial index (ABI) and pain-free and maximal walking distance. The secondary outcomes were the mean changes in triglycerides and other lipid profiles, high-sensitivity C-reactive protein level, blood pressure, flow-mediated vasodilatation, and incidence of cardiovascular events. Results: Sixteen RCTs and 1,852 patients were analyzed. Most of the included RCTs had a low risk of bias. The grade quality was moderate in ABI, C-reactive protein, and cardiovascular events; very low in triglyceride; and low in the other outcomes. The use of omega-3 PUFAs was not significantly associated with the primary outcomes, but it was significantly associated with a reduced triglyceride level, with a moderate effect size (Hedges' g=-0.34, 95% CI [-0.55-0.13], p < 0.01, I²=32.5%). This significant association was only found for marine-based omega-3 PUFAs. Omega-3 PUFAs and eicosapentaenoic acid dosages >2 g per day were associated with reduced levels of triglycerides. Meta-regression also showed that the use of eicosapentaenoic acid was significantly negatively associated with the triglyceride level in a dosage-dependent manner. No significant association was found in the other secondary outcomes. Conclusion: This meta-analysis showed that the use of marine-based omega-3 PUFAs was significantly associated with a reduced level of triglycerides. The strength of the association depended on the dosage of eicosapentaenoic acid. (CRD42020168416 at PROSPERO.).