Perioperative Immunonutrition for Elective Surgery: Review of Mechanisms, Summary of Evidence, and Future Directions

Surgical trauma triggers a complex metabolic and inflammatory response that can profoundly affect patient recovery and clinical outcomes. The magnitude of this stress response correlates with surgical complexity, patient comorbidities, and baseline nutritional status. Immunonutrition refers to the strategic use of specific nutrients, including arginine, glutamine, omega-3 polyunsaturated fatty acids, and nucleotides, to modulate immune and inflammatory responses beyond their basic nutritional value. These pharmaconutrients possess distinct immunomodulatory properties that may attenuate surgical stress responses, enhance immune function, and improve clinical outcomes. While numerous randomized controlled trials and meta-analyses have been conducted over the past several decades, significant methodological heterogeneity, variable product compositions, inconsistent administration protocols, and divergent patient populations complicate the interpretation of findings. Recent well-designed investigator-initiated trials without industry funding have failed to demonstrate benefits, raising questions about the validity of earlier positive findings and challenging current guideline recommendations. The evidence base reveals promising signals of benefit in selected populations combined with substantial limitations. Available evidence suggests that immunonutrition may be most beneficial in severely malnourished patients undergoing major gastrointestinal surgery, particularly when administered perioperatively or postoperatively, though the certainty of this evidence remains moderate at best, given the methodological limitations in the existing literature. From an economic perspective, immunonutrition may represent a dominant intervention in appropriate patient populations, though cost-effectiveness estimates derive primarily from older studies with methodological limitations. However, focus on specialized immunonutrition should not distract from fundamental perioperative nutritional care, including systematic risk screening, optimization when feasible, early postoperative feeding, and achievement of adequate protein and calorie targets. Only through methodologically rigorous research addressing fundamental questions can the promise of perioperative immunonutrition be fully realized.