The Role of Omega-3 Polyunsaturated Fatty Acid Supplementation in Postoperative Recovery of Colorectal Cancer: Systematic Review and Meta-Analysis

Background: China is currently developing standards for Food for Special Medical Purposes (FSMP) targeting for oncology patients. However, substantial challenges remain in defining optimal fortification levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Accumulating evidence suggests that ω-3 PUFA intake improves postoperative prognosis by modulating oncological parameters in colorectal cancer (CRC) patients. This meta-analysis aimed to evaluate the therapeutic efficacy of ω-3 PUFA supplementation in enhancing postoperative safety and recovery stability following CRC surgery, to address critical gaps in nutritional interventions for optimizing clinical outcomes. These findings are expected to FSMP standard development, clinical nutrition protocols and product innovation. Methods: A systematic literature search was conducted, in accordance with PRISMA guidelines, across major databases until June 16, 2025. Data were analyzed using RevMan v5.4 (Cochrane Collaboration). Results: Thirty-four randomized controlled trials (RCTs) (n = 2889) were included. Compared to controls, the ω-3 PUFAs group showed significantly increased levels of nutritional markers: total protein (p < 0.00001), albumin (p = 0.001); immunological parameters: CD3+/CD4+/CD8+ T-cells, CD4+/CD8+ ratio (all p < 0.0001); Karnofsky Performance Status (KPS) scores (p = 0.04); and serum ω-3 PUFA concentrations (p = 0.0004). Significant reductions were observed in inflammatory markers, such as procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) (p = 0.004 to < 0.00001); and clinical outcomes, such as hospitalization duration (p < 0.00001), infectious complications (p < 0.00001), anastomotic leakage (p = 0.0005), surgical site infections (p = 0.03). No significant intergroup differences were detected for white blood cells, transcription factor activity, mortality, or crypt cell proliferation indices (p = 0.06–0.55). Conclusions: Overall, ω-3 PUFA supplementation significantly attenuates postoperative inflammation, enhances immune function, shortens hospitalization, and improves the quality of life in CRC patients, though without mortality benefit. Notably, post hoc dose–response analysis identified a supplementation range of 0.16–0.30 g/kg/day as a potentially optimal supplementation range for Chinese CRC populations, providing foundational evidence for clinical practice and FSMP standardization.