Marine-Based Omega-3 Fatty Acids and Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized...

Metabolic syndrome (MetS) is a set of cardiometabolic abnormalities, including central obesity, dyslipidemia, hypertension, and hyperglycemia, that substantially increases the risk of cardiovascular disease and type 2 diabetes. Marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve MetS components through triglyceride-lowering, anti-inflammatory, and insulin-sensitizing effects; however, randomized controlled trial (RCT) results remain inconsistent, and the influence of dose and intervention duration is unclear.

Following PRISMA guidelines, PubMed, Embase, Scopus, and Web of Science were searched to June 2024 for RCTs in adults with MetS or its components. Eligible trials assessed marine-derived omega-3 supplementation (EPA/DHA) versus placebo or control and reported at least one MetS diagnostic criterion (triglycerides, HDL cholesterol, fasting plasma glucose, blood pressure, or waist circumference) or related parameter (LDL cholesterol, HOMA-IR, or HbA1c). Data were extracted in duplicate and quality assessed using the Cochrane Risk-of-Bias Tool. Trials were categorized by dose-low (<1000 mg/day), medium (1000-2000 mg/day), and high (>2000 mg/day)-and duration: short-term (ST; ≤8 weeks), medium-term (MT; >8-12 weeks), and long-term (LT; >12 weeks). Meta-regression using ordinary least squares estimated dose-duration effects. Publication bias was assessed with funnel plots and Egger's test for outcomes with ≥3 studies.

Twenty-one RCTs (n ≈ 1950) were included. For triglycerides, the largest reductions occurred in the high-dose LT (-56.78 mg/dL ± 3.44) and ST (-50.873 mg/dL ± 3.04) groups, and MT duration (-41.536 mg/dL ± 4.12), showing that in high doses of omega-3, the beneficial effect of reducing TGs was more prominent in long-term and short-term treatment other than with medium-term duration of treatment. In comparison, the result for medium-dose with MT duration was (-24.93 mg/dL ± 0.464) and for LT duration was (-31.843 mg/dL ± 0.46), all p < 0.001. In LDL cholesterol, an increase in the low-dose ST group (+7.04 mg/dL ± 4, p < 0.001) and low-dose LT group (+35.525 mg/dL ± 4.33, p < 0.001) was observed. In other subgroups, either there were no data available or the number of studies was limited and could not be considered as statistically significant in meta-analysis due to low power. As for HDL cholesterol, FBS, SBP, DBP, waist circumference, BMI, and HOMA-IR, the data extracted from the included studies were not sufficient to be eligible for the meta-analysis.

Marine-derived omega-3 supplementation produces substantial triglyceride reductions, especially at doses >2000 mg/day for ≥8 weeks. HDL cholesterol and blood pressure benefits are not consistent, fasting glycemia is largely unaffected, and LDL cholesterol may increase, especially in low doses. High-dose marine omega-3s can be considered as part of dietary strategies for MetS management, with monitoring for LDL changes. Standardized intervention protocols and long-term RCTs are needed to clarify dose and duration-response relationships.