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

Abstract

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.)