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

Am J Clin Nutr. 2012 Oct;96(4):759-67. doi: 10.3945/ajcn.111.024471. Epub 2012 Sep 5.


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 stepwise 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 ×3, ×5, ×10, ×15, ×20, and ×25 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-[1-¹³C]-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-[1-¹³C]-leucine expressed as label tracer oxidation in breath (F¹³CO₂), leucine oxidation, and α-ketoisocaproic acid (KIC) oxidation led to different results: a plateau in F¹³CO₂ 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 ~35 g/d as a cautious estimate under acute dietary conditions.

Trial registration: NCT00972582.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ammonia / blood
  • Biomarkers / blood
  • Biomarkers / chemistry
  • Biomarkers / metabolism
  • Breath Tests
  • Carbon Isotopes
  • Dietary Supplements / adverse effects
  • Guidelines as Topic*
  • Humans
  • Keto Acids / metabolism
  • Kinetics
  • Leucine / administration & dosage
  • Leucine / adverse effects*
  • Leucine / metabolism
  • Male
  • Models, Biological
  • Nutrition Policy*
  • Oxidation-Reduction
  • Performance-Enhancing Substances / administration & dosage
  • Performance-Enhancing Substances / adverse effects
  • Performance-Enhancing Substances / metabolism
  • Young Adult


  • Biomarkers
  • Carbon Isotopes
  • Keto Acids
  • Performance-Enhancing Substances
  • Ammonia
  • alpha-ketoisocaproic acid
  • Leucine

Associated data