Determination of the safety of leucine supplementation in healthy elderly men

Abstract

Leucine, a branched-chain amino acid (BCAA), has been shown to stimulate muscle protein synthesis, and thus has been proposed to prevent age-related muscle atrophy (sarcopenia). Therefore, leucine supplementation may have potential benefits in elderly populations to preserve muscle mass. The tolerable upper intake level (UL) for leucine intake in young men has recently been determined to be 500 mg kg(-1) day(-1), and increases in blood ammonia concentrations were seen at intake levels above 500 mg kg(-1) day(-1); the UL for leucine in elderly is unknown. The objective of the current study was to determine the safety of leucine supplementation in healthy elderly men. Six healthy elderly men (72.2 ± 3.5 years) received graded stepwise increases in leucine intakes ranging from 50 to 750 mg kg(-1) day(-1), on eight separate study days. Plasma and urinary biochemical variables, including blood ammonia, and an oral primed-continuous protocol of L-1-(13)C-Leucine was performed. Blood ammonia concentrations above normal values (35 µmol/L) were observed at leucine intakes >550 mg kg(-1) day(-1). Leucine oxidation measured as a F(13)CO2 (rate of label tracer oxidation) increased with increasing leucine intakes and started to plateau after 450 mg kg(-1) day(-1). Two-phased linear regression analysis of the F(13)CO2 data revealed a breakpoint of 431 mg kg(-1) day(-1) (R (2) = 0.73), suggesting that the upper limit to oxidize leucine was reached at that point. Taking the data together the upper limit for leucine intake in healthy elderly could be set similar to young men at 500 mg kg(-1) day(-1) or ~35 g/day for an individual weighing 70 kg.

BCAA Metabolism and Insulin Sensitivity – Dysregulated by Metabolic Status?

“…In humans (estimated to have roughly 10% the energy and protein requirements of rats), healthy adult male subjects given 10 times the estimated average requirement of leucine showed no adverse events . Similar observations have been made in elderly male subjects . These observations have led to the proposed Tolerable Upper Limit (UL) for leucine (approximately 500 mg/kg/day) .…”

“…[116] Similar observations have been made in elderly male subjects. [117] These observations have led to the proposed Tolerable Upper Limit (UL) for leucine (approximately 500 mg/kg/day). [116,117] Lastly, extremely high protein intakes have been evaluated for safety during short periods and have shown no harmful effects (the details of which are reviewed elsewhere [111] ), suggesting protein/BCAA consumption is unlikely to independently cause insulin resistance.…”

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults

“…The WP-MND supplement contributed to an additional 6 g leucine per day, representing 0.086 g/kg BW/day based on a median bodyweight of 70 kg. In total, leucine intake in the WP-MND group was 0.171 g/kg BW/day in 75% of subjects, which is well below the TUL for leucine of 0.5 g/kg BW/ day [28][29][30].…”

Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view

“…The tolerable upper intake level of leucine, in both healthy young (20–35 years) and elderly (72.2 ± 3.5 years) subjects, has been shown to be similar at a dose of 500 mg kg −1 day −1 or ~35 g day −1 for an individual weighing 70 kg (Elango et al, ; Rasmussen et al, ). In a dose‐ranging study in normal volunteers, ingestion of 60 g BCAAs was well‐ tolerated and markedly raised the BCAA plasma concentration 300 min after administration (leucine went up to about 2000 nmol mL −1 ).…”