Optimal delivery of enteral protein in the critically ill: A systematic review and meta-analysis of randomised controlled trials

BACKGROUND AND AIM: Critically ill patients experience acute muscle wasting, associated with impaired clinical outcomes. It has been suggested that greater dietary protein delivery may attenuate muscle wasting and improve outcomes, but the optimal dose is unknown. The aim of this systematic review and meta-analysis was to evaluate the effect of enteral protein delivered to achieve doses recommended within international guidelines (1.2-2.0 g/kg bodyweight/day) compared to enteral protein delivered below international guidelines (<1.2 g/kg/day) on mortality and clinical, patient-centred, and muscle outcomes. METHODS: A systematic review of databases MEDLINE, EMBASE, CINAHL, and CENTRAL was performed from database inception through to 2 July 2025. Randomised controlled trials (RCTs) of adult critically ill patients comparing 'greater protein' delivery (1.2-2.0 g/kg/day) versus 'lesser protein' delivery (<1.2 g/kg/day) predominantly via enteral nutrition (EN), with similar energy delivery, were identified. Risk ratios were pooled for binary outcomes and mean differences or standardised mean differences for continuous outcomes using random-effects models. Subgroup analyses investigated the effect of exclusive EN; acute kidney injury (AKI) as defined within individual trials; and higher severity of illness (Sequential Organ Failure Assessment score ≥9) for the primary outcome (mortality). RESULTS: = 0.00; 3 RCTs, n = 755: greater protein n = 390; lesser protein n = 365), with ICEMAN evaluation suggesting that the evidence for effect modification was of moderate credibility. CONCLUSIONS: Greater protein delivery does not reduce mortality or improve any clinical outcomes compared with lesser protein, and may be associated with increased mortality in patients with AKI, though subgroup definitions varied across trials. SYSTEMATIC REVIEW REGISTRATION: CRD42025547923.