The effect of omega-3 fatty acids and its combination with statins on lipid profile in patients with hypertriglyceridemia: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background/aim: Omega-3 fatty acids (OM3-FA), a promising treatment for high triglycerides, have gradually attracted public attention. However, some studies showed that their application presented tricky problems, like increasing low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to systematically evaluate the effect of OM3-FA or their combination with statins on the lipid profile in patients with hypertriglyceridemia.

Materials and methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) guidelines. PubMed, Embase, Web of science, and Cochrane library were searched up to May 15, 2022. The random-effects model was applied to calculate the mean difference (MD) and associated 95% confidence intervals (CI).

Results: This meta-analysis included 32 studies with 15,903 subjects. When OM3-FA was used as monotherapy compared with placebo, it significantly decreased TG (MD: -39.81, 95% CI: -54.94 to -24.69; p < 0.001), TC (MD: -2.98, 95% CI: -5.72 to -0.25, p = 0.03), very low-density lipoprotein cholesterol (VLDL-C) (MD: -25.12, 95% CI: -37.09 to -13.14; p < 0.001), and non-high-density lipoprotein cholesterol (non-HDL-C) levels (MD: -5.42, 95% CI: -8.06 to-2.78; p < 0.001), and greatly increased LDL-C (MD: 9.10, 95% CI: 4.27 to 13.94; p < 0.001) and HDL levels (MD: 1.60, 95% CI: 0.06 to 3.15; p = 0.04). Regarding apolipoprotein B (Apo-B) and apolipoprotein AI (Apo-AI), no significant effect was identified. When OM3-FA was combined with statins, significant reductions were observed in the concentrations of TG (MD: -29.63, 95% CI: -36.24 to -23.02; p < 0.001), TC (MD: -6.87, 95% CI: -9.30 to -4.45, p < 0.001), VLDL-C (-20.13, 95% CI: -24.76 to -15.50; p < 0.001), non-HDL-C (MD: -8.71, 95% CI: -11.45 to -5.98; p < 0.001), Apo-B (MD: -3.50, 95% CI: -5.37 to -1.64; p < 0.001), and Apo-AI (MD: -2.01, 95% CI: -3.07 to -0.95; p < 0.001). However, the combined therapy did not exert significant changes on the levels of high-density lipoprotein cholesterol (HDL-C) and LDL-C compared to control group.

Conclusion: The use of OM3-FA either as monotherapy or in combination with statins may potentially reduce the levels of TG, TC, VLDL-C, non-HDL-C, Apo-B, and Apo-AI while increasing the levels of LDL-C and HDL-C. Nevertheless, the effects of OM3-FA observed in this review should be interpreted with caution due to the high heterogeneity between the included studies.

Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022329552].

Keywords: Omega-3 fatty acids; hypertriglyceridemia; low-density lipoprotein cholesterol; meta-analysis; statins; triglyceride.