Does omega-3 PUFAs supplementation improve metabolic syndrome and related cardiovascular diseases? A systematic review and meta-analysis of randomized controlled trials

Literature is inconsistent regarding the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) supplementation on patients with metabolic syndrome (MetS) and related cardiovascular diseases (CVDs). Therefore, the aim of this systematic review and meta-analysis is to summarize data from available randomized controlled trials (RCTs) on the effect of omega-3 PUFAs on lipid profiles, blood pressure, and inflammatory markers. We systematically searched PubMed, Embase, and Cochrane Library databases to identify the relevant RCTs until 1 November 2022. Weighed mean difference (WMD) was combined using a random-effects model. Standard methods were applied to assess publication bias, sensitivity analysis, and heterogeneity among included studies. A total of 48 RCTs involving 8,489 subjects met the inclusion criteria. The meta-analysis demonstrated that omega-3 PUFAs supplementation significantly reduced triglyceride (TG) (WMD: -18.18 mg/dl; 95% CI: -25.41, -10.95; p < 0.001), total cholesterol (TC) (WMD: -3.38 mg/dl; 95% CI: -5.97, -0.79; p = 0.01), systolic blood pressure (SBP) (WMD: -3.52 mmHg; 95% CI: -5.69, -1.35; p = 0.001), diastolic blood pressure (DBP) (WMD: -1.70 mmHg; 95% CI: -2.88, -0.51; p = 0.005), interleukin-6 (IL-6) (WMD: -0.64 pg/ml; 95% CI: -1.04, -0.25; p = 0.001), tumor necrosis factor-alpha (TNF-alpha) (WMD: -0.58 pg/ml; 95% CI: -0.96, -0.19; p = 0.004), C-reactive protein (CRP) (WMD: -0.32 mg/l; 95% CI: -0.50, -0.14; p < 0.001), and interleukin-1 (IL-1) (WMD: -242.95 pg/ml; 95% CI: -299.40, -186.50; p < 0.001), and significantly increased in high-density lipoprotein (HDL) (WMD: 0.99 mg/dl; 95% CI: 0.18, 1.80; p = 0.02). However, low-density lipoprotein (LDL), monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1 (ICAM-1), and soluble endothelial selectin (sE-selectin) were not affected. In subgroup analyses, a more beneficial effect on overall health was observed when the dose was <= 2 g/day; Omega-3 PUFAs had a stronger anti-inflammatory effect in patients with CVDs, particularly heart failure; Supplementation with omega-3 PUFAs was more effective in improving blood pressure in MetS patients and blood lipids in CVDs patients, respectively. Meta-regression analysis showed a linear relationship between the duration of omega-3 PUFAs and changes in TG (p = 0.023), IL-6 (p = 0.008), TNF-alpha (p = 0.005), and CRP (p = 0.025). Supplementation of omega-3 PUFAs had a favorable effect on improving TG, TC, HDL, SBP, DBP, IL-6, TNF-alpha, CRP, and IL-1 levels, yet did not affect LDL, MCP-1, ICAM-1, and sE-selectin among patients with MetS and related CVDs.