Protein nutritional support in critically ill adults shows heterogeneous mortality benefits and potential harm from very high early doses.

This narrative review assesses protein nutritional support and supplementation strategies for critically ill adults, specifically addressing populations with sepsis, severe burns, and general critical illness. The review highlights that evidence regarding specific protein sources, functional amino acids, and metabolic modulators remains heterogeneous. Randomized trials and meta-analyses do not show a uniform mortality benefit from higher protein provision, indicating that the clinical picture is complex and not fully resolved.

The primary outcomes examined include mortality, functional impairment, negative nitrogen balance, skeletal muscle breakdown, wound healing, metabolic tolerance, and acute kidney injury. Results indicate that mortality benefit from higher protein provision is not uniform across studies. Conversely, there is a potential for harm associated with very high early doses, which may be detrimental in specific patient subgroups.

Safety and tolerability profiles vary; while serious adverse events were not explicitly reported in the summary data, poor metabolic tolerance was noted in selected patients. The review cautions that very high early doses may be harmful. Key limitations include the heterogeneity of evidence and the lack of uniform mortality benefits observed in rigorous trials.

Practice relevance suggests that current guidelines generally support progressive enteral-first protein delivery after hemodynamic stabilization, targeting at least 1.2–1.3 g/kg/day. Higher targets are more consistently justified in severe burns. Clinicians should interpret findings conservatively, recognizing that evidence remains heterogeneous and that causality is not definitively established for mortality benefits.