Preoperative oral whey protein supplementation improves postoperative inflammatory and nutritional biomarkers: a systematic review and meta-analysis
Abstract
Surgical stress triggers catabolic processes and insulin resistance, leading to impaired recovery. Preoperative nutritional support, particularly with high-quality proteins like whey, is hypothesized to mitigate these effects. This meta-analysis evaluates the impact of preoperative oral whey protein supplementation on postoperative metabolic and inflammatory biomarkers. A systematic search of PubMed, Web of Science, Scopus, and Cochrane databases (2000–2024) identified randomized controlled trials (RCTs) comparing preoperative whey protein with standard care/placebo. Primary outcomes included C-reactive protein (CRP), serum albumin, blood glucose, and insulin resistance (HOMA-IR). Meta-analysis was performed using a random-effects model. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Seven RCTs involving surgical patients were included. Pooled results demonstrated that preoperative whey protein significantly reduced postoperative CRP levels (SMD = -0.92; 95% CI: -1.80 to -0.04; p = 0.04) and increased serum albumin levels (SMD = 0.93; 95% CI: 0.13 to 1.73; p = 0.02). Effects on blood glucose and insulin resistance were inconsistent across trials. Subgroup analysis revealed that the anti-inflammatory and nutritional benefits were more pronounced in major surgeries and when whey was combined with carbohydrates. Meta-regression suggested that the timing of outcome assessment and intervention composition are key moderators of effect stability. Preoperative oral whey protein supplementation is a promising intervention to attenuate the surgical stress response by modulating inflammatory markers and supporting nutritional status. Despite high heterogeneity, the evidence supports its integration into perioperative care protocols, though standardized dosages and larger-scale trials are warranted to confirm clinical outcomes.