Tolerability of Leucine in Humans

Abstract

Use of dietary supplements, especially among athletes is increasing. Among the amino acids, the branched-chain amino acids (BCAA-leucine, valine and isoleucine) are popular as dietary supplements especially among strength training athletes. In particular, leucine as a supplement is widely consumed because it has been implicated to be the key amino acid involved in stimulating muscle protein synthesis. This chapter will present current dietary leucine intakes, define the concept of safe upper limits (UL) and summarize a recent study in humans conducted to address leucine tolerability. In the 2005 Dietary References Intake (DRI) report, men 51 through 70 years of age had the highest intakes, at the 99th percentile for leucine, at 14,100 mg·d-1 (~ 201 mg·kg·d-1). In order to directly explore leucine tolerability in humans we proposed a novel model. We hypothesized that with increasing intakes of leucine above the estimated average requirement (EAR of 50 mg·kg-1·d-1) in adult men, the oxidation of leucine will increase and will reach a maximum, after which the leucine oxidation will achieve a plateau. This ‘metabolic limit’ to oxidize leucine may be used as a marker of an intake after which increasing intakes may result in increasing risk of adverse effects. Five healthy young men participated in the study. Each subject participated in a dose-escalation study design, where graded stepwise increases in leucine intake (150, 250, 500, 750, 1000 and 1250 mg·kg-1·d-1 corresponding to the EAR, EARx3, x5, x10, x15, x20 and x25) were provided on each study day. Oxidation of L-[1-13C]leucine to 13CO2 in breath (F13CO2) was measured on each study day. With increasing intakes of leucine, a dose-response in leucine oxidative capacity was observed, with a breakpoint estimated at 550 mg·kg-1·d-1 or 39 g·d-1. Simultaneous and significant increases in blood ammonia concentrations, plasma leucine concentrations and urinary leucine excretion were observed with leucine intakes higher than 500 mg·kg-1·d-1. These results taken together with the recent animal data suggest that under acute dietary conditions, as a cautious estimate, intakes greater than 500 mg leucine·kg-1·d-1 may potentially increase the risk of adverse events, and could be proposed as the UL for leucine in healthy adults.