Impact of Omega-3 supplementation on homocysteine levels in humans: A systematic review and meta-regression analysis of randomized controlled trials

Aims: Although some evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) supplementation influences enzymes involved in forming homocysteine (Hcy) and improving hyperhomocysteinemia, these findings are still contradictory in humans. The aim of this systematic and meta-analysis study was to investigate the effects of omega-3 supplementation on Hcy using existing randomized controlled trials (RCTs). Data synthesis: Available databases, including PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, and Embase, were searched to find relevant RCTs up to June 2021. The effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Conclusion: A total of 20 RCT studies with 2676 participants were included in this article. Our analyses have shown that omega-3 supplementation significantly reduced plasma Hcy levels (WMD: 1.34 μmol/L; 95% CI: 1.97 to −0.72; P < 0.001) compared to the control group. The results of subgroup analysis showed that omega-3 supplementation during the intervention <12 weeks and with a dose ≥3 gr per day causes a more significant decrease in Hcy levels than the intervention ≥12 weeks and at a dose <3 gr. In addition, omega-3 supplements appear to have more beneficial effects in individuals with high levels of normal Hcy. This meta-analysis showed that omega-3 supplementation significantly improved Hcy. However, further studies are needed to confirm the findings.