Clinical trial NCT00972582: Upper Limit of Leucine Intake in Adults
Official title: Determination of the Tolerable Upper Limit of Leucine Intake in Adult Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: leucine intake
tolerable upper limit
adults
amino acid supplements
Excessive Leucine Intake
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2009-09-07
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: When dietary amino acid supplements are consumed by humans they are normally in addition to their normal daily requirements. The investigators' laboratory played a leading role in defining the estimated average requirement (EAR) and the recommended dietary intake for the "essential" amino acids (Dietary Reference Intakes 2005). The other important but less well studied component of Dietary Reference Intakes (DRI) is - What is a safe upper limit of intake? The investigators now propose to determine the safe upper limits of the dietary essential amino acids. The recently published DRI (2005) defines the Tolerable Upper Intake Level (UL) as 'the highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population.' As intake increases above the UL, the potential risk of adverse effects may increase'. In this proposal, the investigators define a novel method to define the safe upper limit where the 'maximum oxidative potential' of an amino acid identifies the 'metabolic limit' to dispose the amino acid. Intakes of amino acid above this level will increase the potential for adverse effects to appear.

Detailed description: The objective of the study will be to determine the 'metabolic limit' of leucine oxidation in healthy young men by:

A) Measuring leucine oxidation in response to short term (8 hr) graded excess leucine intake B) Correlating changes in leucine oxidation with changes in plasma concentrations of keto-isocaproic acid (KIC, the first breakdown product of leucine metabolism), other essential amino acids, ammonia, urea, creatinine, glucose, insulin, and electrolytes (sodium, potassium, chloride) to identify potential biomarkers C) Correlating changes in leucine oxidation with changes in urinary excretion of leucine and ketoisocaproic acid (KIC), urea and creatinine to identify potential biomarkers

Eligibility criteria: Inclusion Criteria:

* Male
* 18-35 years old

Exclusion Criteria:

* Report a recent history of sudden weight loss
* Have unusual dietary habits such as chronic consumption of caffeinated beverages or alcohol
* Have any endocrine disorders
* Are currently using any prescribed medications

Primary outcomes:
measure: Breath carbon dioxide production
timeFrame: Study Visits 1-7 (-45min,-30min,-15min, +2.5hrs, +3hrs, +3.5Hrs +4hrs)
Secondary outcomes:
measure: Plasma
timeFrame: Study Visits 1-7 (Hourly)
measure: Urine
timeFrame: Study Visits 1-7 (8hr timepoint)
measure: VCO2
timeFrame: Study Visits 1-7 (after 5hr meal)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto, Canada
name: Paul B Pencharz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB. 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.