BACKGROUND & AIM: Polytrauma patients are characterized by a negative nitrogen balance and muscle wasting. Standard nutrition is relatively inefficient to improve muscle protein turnover. The aim of this study was to investigate the effect of enteral nutrition (EN) supplemented with specific amino acids on protein metabolism in polytrauma patients. METHODS: In a double blind study, 12 polytrauma patients were randomized to receive EN supplemented with either a mixture of cysteine, threonine, serine and aspartate (AA patients) or alanine at isonitrogenous levels (Ala patients). An intravenous infusion of l-[1-(13)C]-leucine was performed in the fed state between day 9 and 12 post-injury (Df) in patients and in a group of healthy volunteers (n=8) (EN+Ala) to measure whole body leucine kinetics, plasma and muscle protein synthesis rates. Nitrogen balance, 3-methyl histidine excretion were measured from day 3 to Df. RESULTS: The contribution of total plasma proteins to whole body protein synthesis was greatly increased, from 11% in healthy volunteers to about 25% in polytrauma patients. AA supplementation had no effect on nitrogen balance, leucine kinetics or plasma protein synthesis in patients. In contrast, the urinary excretion of 3-methyl histidine tended to decrease along the study in the AA supplemented group compared to an increase in the Ala group. Muscle protein synthesis tended to be higher in the AA group than in the Ala group (46%, P=0.065). CONCLUSION: During injury, an increased supply of cysteine, threonine, serine and aspartate could be able to better cover the specific amino requirements, thus resulting in improved muscle protein synthesis without impairment of acute phase protein synthesis.