The effect of n-3 supplementation on clinical outcomes in patients with sepsis: an umbrella review of systematic reviews and meta-analysis.

Sepsis affects 50 million people globally, contributing to 20 % of all deaths and significantly increasing healthcare costs due to intensive care needs. Although the role of n-3 fatty acids in reducing sepsis mortality remains debated, recent studies suggest their potential in modulating immune responses and improving outcomes. This umbrella review aims to clarify the benefits of n-3 supplementation on mortality rate, length of intensive care unit (ICU) stays and days on mechanical ventilation in patients with sepsis. Following Cochrane and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodologies, a systematic search was conducted across multiple databases up to February 2025. After independent screening, data extraction and critical appraisal, meta-analyses were reassessed using the DerSimonian and Laird model. Evidence was graded using the GRADE approach, categorising outcomes based on strength and quality. A comprehensive search identified 934 records, of which thirty-four randomised controlled trials (RCT) from twenty-one systematic reviews and meta-analyses focused on n-3 supplementation in sepsis patients. n-3 significantly reduced mortality (risk ratio: 0·79, 95 % CI 0·69, 0·90), length of ICU stays (mean difference (MD): -3·6 d, 95 % CI -4·39, -2·81) and ventilation days (MD: -2·86 d, 95 % CI -4·46, -1·26). Parenteral nutrition showed slightly better outcomes than enteral nutrition, and EPA and DHA provided superior results compared with mixed oils. These findings suggest n-3 supplementation could improve mortality, ICU stays and ventilator dependency in patients with sepsis. However, the certainty of the evidence ranges from low to very low, emphasising the need for further high-quality RCT to validate these benefits. Also, clinicians should prescribe n-3 supplements cautiously in this regard.