The Role of Nutritional Supplementation in Preventing Postoperative Complications. A Systematic Review and Meta-Analysis

Marina Sartini^1,2*Filippo Del Puente³Alessio Carbone^1,4Martino Oliva¹Sara Pessano^5,6Marcello Feasi³Carolina Piccinini¹Elisa Schinca^1,2Gianluca Ottria¹MARIA LUISA CRISTINA^1,2

• ¹Dept. Health Sciences - Univeristy of Genoa, GENOVA, Italy
• ²Operating Unit Hospital Hygiene - Galliera Hospital, GENOVA, Italy
• ³Dept. Infectious Diseases - Galliera Hospital, GENOVA, Italy
• ⁴Dept. Medicine and Division of Medical Oncology - Galliera Hospital, GENOVA, Italy
• ⁵Dept. Public Health, Experimental and Forensic Medicine, Unit Biostatistics and Clinical Epidemiology, Medical Statistics and Biometry Post-graduate Schoool - University of Pavia, Pavia, Italy
• ⁶Scientific Direction, Clinical Epidemiology Unit - IRCCS Giannina Gaslini, GENOVA, Italy

IIntroduction: Hospital-acquired infections represent an increasingly urgent issue, particularly in intensive care and surgical settings, also in light of growing concerns about antibiotic resistance. Concurrently, nutrition—due to its immunomodulatory effects—is gaining attention as a key factor across multiple medical disciplines. The aim of this study was to assess perioperative nutritional interventions—immunonutrition, probiotics, synbiotics, and protein integration—in reducing Surgical Site infections (SSIs), healthcare-associated infections (HAIs) and hospital length of stay (LOS) in surgical patients. Methods: A comprehensive search on principal databases was performed on December 2024. As effect measures, was calculated the Odds Ratios (OR). The assessment of potential bias and the evaluation of study quality was conducted. Thirty-nine publications were selected for inclusion in the meta-analysis. Results: Immunonutrition was associated with a reduction in infectious complications (OR = 0.36) and showed a probable reduction in SSIs (OR = 0.35). Some benefits may also be obtained with the administration of probiotics (OR = 0.61). Bloodstream infections (BSIs) appeared to be substantially reduced with probiotics (OR = 0.42), although the certainty of evidence was low. Analytical studies showed weaker effects than RCTs of immunonutrition on SSI reduction compared with randomized control trials (RCTs), underscoring the importance of RCT evidence for clinical recommendations. Discussion: Based on RCT evidence, immunonutrition demonstrates robust efficacy in preventing SSIs with moderate certainty evidence, and appears ready for clinical implementation in high-risk surgical setting. Probiotics showed moderate effects on selected infectious outcomes, supported by low-certainty evidence, and may be considered as complementary interventions. Protein supplementation demonstrated statistical significance; however, the very low certainty of evidence precludes firm recommendations. Clinical implementation should prioritize interventions supported by RCT evidence within multimodal prevention strategies. Future research should address heterogeneity in nutritional formulations, standardize outcome definitions, and evaluate real-world effectiveness.