title: Determination of the tolerable upper intake level of leucine in acute dietary studies in young men.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Rajavel
authors.initials: R
authors.lastname: Elango
authors.forename: Karen
authors.initials: K
authors.lastname: Chapman
authors.forename: Mahroukh
authors.initials: M
authors.lastname: Rafii
authors.forename: Ronald O
authors.initials: RO
authors.lastname: Ball
authors.forename: Paul B
authors.initials: PB
authors.lastname: Pencharz
mesh_terms: D000328:Adult; D000641:Ammonia / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D001944:Breath Tests; D002247:Carbon Isotopes; D019587:Dietary Supplements / Q000009:adverse effects; D017408:Guidelines as Topic; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D018673:Nutrition Policy; D010084:Oxidation-Reduction; D058573:Performance-Enhancing Substances / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002247:Carbon Isotopes; D007651:Keto Acids; D058573:Performance-Enhancing Substances; D000641:Ammonia; C013082:alpha-ketoisocaproic acid; D007930:Leucine