Tabriz University of Medical Sciences Health Promotion Perspectives 2228-6497 15 2 2025 07 15 Protein intake and clinical outcomes in critically ill patients: A dose–response and pairwise meta-analysis of randomized controlled trials 98 109 10.34172/hpp.025.43894 EN Mohaddeseh Badpeyma https://orcid.org/0000-0001-8150-8997 Faezeh Ghalichi Roghayeh Molani-Gol Hamed Valizadeh Yousef Javadzadeh Ahmadreza Rasouli Mohammad Alizadeh https://orcid.org/0000-0002-7408-8573 Sorayya Kheirouri https://orcid.org/0000-0001-6249-4462 Journal Article 10.34172/hpp.025.43894 2024 12 08 2025 02 04 Background: The optimal protein intake for critically ill patients remains uncertain. This systematic review and dose–response meta-analysis aimed to evaluate the effect of high-protein nutritional support on clinical outcomes in intensive care unit (ICU) patients. Methods: Randomized controlled trials (RCTs) comparing high- versus low-protein nutrition in critically ill adults with similar energy intake were identified through PubMed, Web of Science, and Scopus (up to June 2023). A random-effects model was used to pool risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Linear and non-linear trends were assessed using the one-stage cubic spline regression model. Results: Twenty-three RCTs were included. The summary RR was 0.83 (95% CI: 0.64–1.08; I2=63.6%; n=17) for mortality and 1.05 (95% CI: 0.88–1.25; I2=0%; n=7) for infections. The summary MD was -0.23% (-0.76 to 0.29, I2=5.6%, n=14) for mechanical ventilation days, -0.40 (-1.11 to 0.32, I2=0%, n=17) for ICU days, 0.73 (-1.11 to 2.58, I2=6%, n=10) for hospital days, and -3.44 (-4.99 to -1.90; I2=16.4%; n=5) for muscle atrophy. There was no evidence of linear or nonlinear trends. Conclusion: Although higher protein intake had no significant effect on mortality or length of stay, it was associated with reduced muscle wasting. This suggests a potential role in preserving lean mass and supporting long-term functional recovery. Systematic Review Registration: PROSPERO CRD42024480303.