Determination of the tolerable upper intake level of leucine in acute dietary studies in young men

Background: Leucine has been suggested to improve athletic performance. Therefore, the branched-chain amino acids (BCAAs), especially leucine, are popular as dietary supplements in strength-training athletes; however, the intake of leucine in excess of requirements raises concerns regarding adverse effects. Currently, the tolerable upper intake level (UL) for leucine is unknown. Objective: The objective of the current study was to determine the UL for leucine in adult men under acute dietary conditions. Design: Five healthy adults (20-35 y) each received graded step-wise increases in leucine intakes of 50, 150, 250, 500, 750, 1000, and 1250 mg . kg(-1) . d(-1), which corresponded to the Estimated Average Requirement (EAR) and the EAR x3, x5, x10, x15, x20, and x25 in a total of 29 studies. The UL of leucine was identified by the measurement of plasma and urinary biochemical variables and changes in leucine oxidation by using L-[1-C-13]-leucine. Results: A significant increase in blood ammonia concentrations above normal values, plasma leucine concentrations, and urinary leucine excretion were observed with leucine intakes >500 mg . kg(-1) . d(-1). The oxidation of L-[1-C-13]-leucine expressed as label tracer oxidation in breath ((FCO2)-C-13), leucine oxidation, and a-ketoisocaproic acid (KIC) oxidation led to different results: a plateau in (FCO2)-C-13 observed after 500 mg . kg(-1) . d(-1), no clear plateau observed in leucine oxidation, and KIC oxidation appearing to plateau after 750 mg . kg(-1) . d(-1). Conclusion: On the basis of plasma and urinary variables, the UL for leucine in healthy adult men can be suggested at 500 mg . kg(-1) . d(-1) or similar to 35 g/d as a cautious estimate under acute dietary conditions. This trial was registered at clinicaltrials.gov as NCT00972582. Am J Clin Nutr 2012;96:759-67.