Overnight branched-chain amino acid infusion causes sustained suppression of muscle proteolysis

Short-term (3 to 4 hours) infusion of branched-chain amino acids (BCAA) has been shown to suppress muscle protein breakdown. Whether these effects are sustained with chronic elevations of BCAA is not known. In the present study, we examined the effect of an overnight (16-hour) systemic BCAA infusion on whole-body and skeletal muscle amino acid metabolism, as assessed by simultaneously measured ³H-phenylalanine and ¹⁴C-leucine kinetics in eight normal volunteers; 10 overnight-fasted subjects studied during a 4-hour saline infusion served as controls. Overnight BCAA infusion increased plasma BCAA concentrations by fivefold to eightfold, and this was associated with a 20% to 60% decline in arterial concentrations of other amino acids. For Phe, this decline was mediated by a reduction in the systemic rate of appearance ([R_a] 0.38 ± 0.03 v 0.60 ± 0.01 μmol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu R_a, calculated more indirectly as the difference between the total Leu R_a and the unlabeled Leu infusion rate, did not differ between groups. In the forearm, overnight BCAA infusion resulted in a diminished net release of Phe (-3 ± 2 v -18 ± 4 [saline] nmol/min/100 mL, P < .02), and BCAA balance became markedly positive (751 ± 93 v -75 ± 30, P < .001). The diminished net forearm Phe release was accounted for by a decrease in local Phe R_a (P < .02). As with the systemic endogenous Leu R_a, forearm Leu R_a was not reproducibly affected by infused BCAA. These findings suggest a need for caution in the application of amino acid tracer kinetic methods when tracer and unlabeled tracee are infused simultaneously. In conclusion, overnight BCAA infusion caused a sustained decline in most plasma amino acids and in net forearm release of Phe, effects attributable to a sustained suppression of whole-body and muscle proteolysis.