Proteins in artificial nutrition: toward an individualized and phase-specific prescription

Protein is a central component of artificial nutrition, yet its optimal dose and timing remain controversial. Provision of both insufficient and excessive protein is associated with adverse outcomes. Inadequate intake promotes negative nitrogen balance, muscle wasting, impaired tissue healing and repair, and increased risk of infection, whereas excessive protein may exceed metabolic capacity, causing azotemia, hepatic or renal strain, and reduced metabolic flexibility - particularly in patients with renal dysfunction. Emerging evidence indicates that the optimal protein dose is strongly influenced by patient-specific characteristics and evolves throughout the course of illness, supporting an individualized, phase-adapted strategy for protein provision rather than a fixed universal target. During early critical illness, catabolism predominates and high protein doses may not be effectively utilized. In contrast, during recovery and stabilization, higher protein targets appear beneficial for restoring lean body mass and functional capacity. This dynamic trajectory underscores the need to abandon universal recommendations in favor of personalized prescriptions. Although instruments such as nitrogen balance, body composition analysis, and indirect calorimetry can provide information about protein dosage, their routine use in clinical practice is limited and interpretation in acute illnesses remains difficult. Pragmatic, bedside strategies and the phenotyping of patients using biomarkers are, therefore, needed to tailor protein provision according to disease stage, organ function, and anabolic capacity. This opinion paper explores mechanistic insights, evidence from clinical trials, and guidelines on protein supplementation, explores biomarker-driven personalization, and highlights ongoing challenges and future research priorities in nutritional therapy.