Immunonutrition for Modifying Inflammatory Markers and Improving Clinical Outcomes Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis Publisher Pubmed



Hajimohammadebrahimketabforoush M ; Meybodi TE ; Mehmandoost M ; Fallah M ; Bahri A ; Hajimirzaei SM ; Sharifi H ; Zare A ; Oveisi S ; Zali A ; Shojaei S ; Herfedoustbiazar B ; Fahim F
Source: BMC Neurology Published:2026

Abstract

Background: Traumatic brain injury (TBI) induces a severe hypermetabolic state with elevated energy expenditure and progressive systemic inflammation. Nutritional optimization in this setting is challenging, particularly in severe TBI (Glasgow Coma Scale [GCS] = 3–8). Its clinical role in these hospitalized TBI patients remains unclear. This systematic review and meta-analysis aimed to evaluate the impact of immunonutrition on neuroinflammation and neurosurgical outcomes in TBI patients, with a focus on omega-3 fatty acids, arginine, and glutamine. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically reviewed the available evidence from PubMed, Scopus, and Web of Science. The inclusion criteria focused on severely hospitalized TBI patients with a GCS score of 3 to 8 who were receiving immunonutrition components. The quality and certainty of the evidence were assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, respectively. Results: A total of 12 studies were eligible and included in our comprehensive full-text review. However, only 5 articles were included in the meta-analysis. Systematic review findings indicated that immunonutrition was associated with reductions in inflammatory markers, decreased rates of nosocomial infections, and improvements in CO₂ reactivity, blood–brain barrier integrity, and cerebral edema. The meta-analysis results showed non-significant trends toward a lower mortality rate (p = 0.06), shorter hospital length of stay (LOS) (p = 0.09), and reduced ICU LOS (p = 0.12). Considerable heterogeneity was observed across some outcomes; however, due to the limited number of studies, formal meta-regression was not statistically justified. Instead, leave-one-out sensitivity analyses were performed to confirm the stability and robustness of the pooled estimates, alongside efforts to reduce heterogeneity. Conclusions: Despite heterogeneity and a limited number of studies, consistent trends support the beneficial role of immunonutrition in severe TBI. These findings highlight the physiological plausibility and clinical safety of such interventions, warranting larger, standardized trials to confirm these effects. © The Author(s) 2025.