Effects of omega-3 polyunsaturated fatty acids supplementation for patients with cardiovascular disease risks: a dose-response meta-analysis.

BACKGROUND Previous studies assessing the impact of omega-3 polyunsaturated fatty acids (ω-3 PUFA) have shown conflicting results in regard to the cardiovascular mortality. It is likely that higher dose of ω-3 PUFA would have a greater effect on the major adverse cardiovascular events (MACEs). Therefore, we performed a dose-response meta-analysis to explore the potential protective effect of ω-3 PUFA, with the increase of daily intake and extension of the intervention period, on patients with cardiovascular disease risks. Outcomes included major adverse cardiovascular events, cardiovascular and all-cause mortality. METHODS A systematic literature search of PubMed, Embase and the Cochrane Library from inception to September 31, 2019 was conducted to identify the randomized controlled trails (RCTs) of ω-3 PUFA supplementation, which reported cardiovascular events or deaths and recruited no less than 500 participants. We evaluated the effect of ω-3 PUFA through the pooled relative risks (RR) and 95% confidence intervals (95% CI), and further carried out subgroup analysis and dose-response meta-analysis. RESULTS Fourteen trials including 87718 individuals were reviewed. By conventional statistical significance, there was no apparent difference between the two groups on major adverse cardiovascular effects (RR 0.94, 95% CI 0.84-1.04) and all-cause mortality (RR 0.96, 95% CI 0.91-1.00), but there was an effect on the cardiovascular mortality (RR 0.93, 95% CI 0.88-0.99). However, with the dose increased and intervention period prolonged (daily dose × intervention period > 8 grams/day × years), subgroup analyses showed a more obvious reduction of MACEs (RR 0.79, 95% CI 0.65-0.95) and all-cause mortality (RR 0.93, 95% CI 0.85-1.03). Furthermore, the dose-response meta-analysis presented a 13.05% reduction of MACEs and 8.99% reduction of all-cause mortality with 10 grams/day × years increments. CONCLUSIONS Updated with the newly published RCTs, this meta-analysis indicated that large dose and long period of interventions with ω-3 PUFA supplementation produce a close association with MACEs and cardiovascular or all-cause mortality. A dose-response beneficial effect was preliminarily established.