Biological Responses During High-dose Protein Nutrition

Reduced protein intake is associated with adverse outcomes in critically ill patients. Paradoxically, large scale randomized clinical trials have failed to demonstrate a beneficial effect of protein supplementation, perhaps because biological mechanisms associated with individual patient responses to nutrition, are poorly understood. The objective of this study was to determine the effect of exogenous protein dose on whole body protein balance (WBPB) and associated blood transcriptomic markers of metabolic response. We conducted a randomized controlled trial to determine the effect of high dose (2.5 g/kg/d by parenteral amino acid infusion for 48 h) versus usual (0.8 g/kg/d) or moderate (1.75 g/kg/d) doses on metabolic response as measured by whole body protein balance (WBPB). As a comprehensive and well annotated method to achieve untargeted biomarker identification, the blood transcriptome was interrogated by RNA sequencing every 12 h to identify molecular signatures that reflect the propensity to experience an anabolic response during protein supplementation.