Comparative effects of different EPA/DHA supplementation regimens on nutritional and inflammatory outcomes in patients with lung cancer: an exploratory systematic review and network meta-analysis

Background Lung cancer is often accompanied by malnutrition and systemic inflammation. The effects of ω-3 (n-3) polyunsaturated fatty acids (PUFAs) regimens with different doses and EPA/DHA compositions remain uncertain. Objective This network meta-analysis (NMA) aims to compare the nutritional and inflammatory outcomes of different n-3 PUFA supplementation regimens in patients with lung cancer. Methods This systematic review followed the PRISMA guidance. We searched eight databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, CBM, Wanfang, and VIP, with the search cut-off date set as November 5, 2025, and a supplementary search was carried out on March 25, 2026. Supplementation regimens were classified according to total daily n-3 PUFA dose and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) composition. The primary outcomes were change from baseline in body weight and post-intervention mid-upper arm circumference (MUAC). Secondary outcomes were post-intervention TNF-α, IL-6, and C-reactive protein (CRP) levels. All-cause attrition was analyzed separately from adverse events. Primary network meta-analyses were restricted to randomized controlled trials (RCTs), while non-randomized comparative studies were retained as supplementary evidence. Random-effects models were used, and certainty of evidence was assessed using the GRADE approach. Results Twelve reports from 11 independent studies involving 728 participants were included (seven RCTs and four non-randomized comparative studies). Six RCTs contributed to the analysis of body-weight change; no regimen differed significantly from control. Findings for MUAC were limited and inconsistent. Medium-dose EPA-dominant n-3 PUFA was associated with lower TNF-α levels, while medium-dose EPA-dominant n-3 PUFA and medium-dose pure EPA were associated with lower CRP levels. No significant differences were found for IL-6 or all-cause attrition. Certainty of evidence ranged from very low to high, with very low certainty for body-weight estimates. Conclusion The available evidence does not show a consistent improvement in body weight or MUAC with n-3 PUFA supplementation. Some EPA-containing regimens were associated with lower TNF-α or CRP levels, but these estimates came from sparse networks with few direct comparisons. The evidence is insufficient to identify an optimal dose or EPA/DHA composition. Larger RCTs directly comparing supplementation regimens are needed. Systematic review registration Identifier, CRD420251171789. PROSPERO website: www.crd.york.ac.uk/PROSPERO/home