Upper Limit of Leucine Intake in Adults

Study Overview
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Brief Summary
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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
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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

Official Title
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Determination of the Tolerable Upper Limit of Leucine Intake in Adult Humans

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Leucine Increase


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leucine<br> | Dietary Supplement: Leucine Increase<br>* Graded stepwise increases in leucine intakes (50, 250, 500, 750, 1000, 1250 and 1500mg/kg/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breath carbon dioxide production |  | Study Visits 1-7 (-45min,-30min,-15min, +2.5hrs, +3hrs, +3.5Hrs +4hrs) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma |  | Study Visits 1-7 (Hourly) | 
| Urine |  | Study Visits 1-7 (8hr timepoint) | 
| VCO2 |  | Study Visits 1-7 (after 5hr meal) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leucine intake, tolerable upper limit, adults, amino acid supplements, Excessive Leucine Intake