Protein First: Whey Protein Administration Strategy in Critically ill Patients

Abstract

Patients in critical condition treated in the ICU often experienced hypercatabolism, which accelerated muscle mass loss while simultaneously impairing immune function. The current nutritional paradigm shifted from merely meeting energy requirements to a "Protein First" strategy, emphasizing the early provision of adequate protein ranging from approximately 1.2 to 2.0 grams per kilogram of body weight per day, and even up to 2.5 g/kg/day in cases of severe catabolism  or  in  patients  undergoing  renal  replacement therapy (RRT). Whey protein was chosen primarily due to its high  biological  value,  rapid  absorption,  and  richness  in leucine, which activated the mTORC1 pathway to stimulate muscle protein synthesis. Various narrative evidences and clinical trial results demonstrated that enteral formulas with a high   protein-to-energy   ratio   based   on   whey   facilitated achieving protein targets without the risk of overfeeding. Administration of this formula type also improved nitrogen balance, correlated with reductions in inflammatory markers, and shortened ventilator duration in some patients. Mechanistically, the leucine content of approximately 10–12% in whey activated the mTORC1 pathway while suppressing proteolysis. Intermittent or bolus protein administration was suggested  to  produce  higher  anabolic  amino  acid concentration peaks compared to continuous delivery. Protein doses  were  adjusted  individually  by  monitoring gastrointestinal tolerance and organ function, especially in patients  with  acute  kidney  injury  (AKI)  or  liver  disease. Enteral routes were prioritized, while parenteral nutrition was only considered when enteral intake was insufficient. The "Protein First" strategy, prioritizing early and measured whey protein administration, represented a logical and effective approach to suppress catabolism, preserve muscle mass, and improve metabolic outcomes in critically ill patients.