Effect of Branched Chain Amino Acids on Muscle
Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Branchamin 4% (Drug)
Phase: N/A
Status: Completed
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s): K. Sreekumaran Nair, M.D., Principal Investigator, Affiliation: Mayo Clinic
Summary
With aging, there is a decrease in muscle mass and function especially in the energy
storehouses of cells called mitochondria. Amino acids, the building blocks of protein, and
insulin have been shown to increase muscle mitochondrial protein synthesis and thereby
function. Branched chain amino acids which can only be provided in the diet seem to be key
in this process. Therefore in our study, our aim is to study the effect of branched chain
amino acids on muscle mitochondrial protein synthesis in both the young and elderly. By
doing so, we can then elucidate if branched chain amino acid supplementation has future
potential in improving quality of life and performance in the elderly. The study will
involve blood sampling and needle muscle biopsy.
Clinical Details
Official title: Branched Chain Amino Acids as Stimulant of Muscle Mitochondrial Function in Elderly People
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Does branched chain amino acids stimulate muscle mitochondrial ATP production in young and elderly?
Secondary outcome: Does branched chain amino acids increase abundance of mRNA of genes encoding mitochondrial proteins and transcription factors equally in young and old?Does branched chain amino acids increase levels of phosphorylated signaling proteins through the mTOR pathways equally in the young and old? Does branched chain amino acids increase fractional synthesis rates of specific mitochondrial proteins, mitochondrial protein concentrations and mitochondrial enzyme activities equally in the young and old?
Detailed description:
Skeletal muscle mito ATP production in young people are stimulated by insulin when infused
with a mixture of amino acids while clamping blood glucose at the basal level. Our
preliminary results indicate that this effect on mito ATP production is directly related to
amino acid levels. Recent publications indicated that infusion of insulin with amino acids
specifically stimulate muscle mitochondrial protein synthesis with no effect on synthesis or
contractile proteins or sarcoplasmic proteins. The recent publications also indicated that
intracellular amino acid anabolic sensors are stimulated by amino acids. It appears that
BCAA, especially leucine has a specific effect in stimulating intracellular signaling or
translation of mRNA to protein synthesis. It has been shown that amino acids, especially
leucine, stimulate protein synthesis by activation of the mTOR pathway in mTOR
phosphorylates p70S6 kinase which in turn phosphorylates the ribosomal S6 protein, resulting
in increased activity of the protein synthesis complex. Activated mTOR also phosphorylates
eIF4E-BP1 and activates the protein synthesis initiation complex. It is the abundance of
specific mRNAase that determines synthesis of which specific proteins are promoted. Our
preliminary data supports that amino acids selectively promotes muscle mitochondrial protein
synthesis by enhancing the abundance of transcripts of genes that encode mitochondrial
proteins. Administration of an amino acid mixture, specifically BCAA, is proposed as a
stimulant of muscle mitochondrial ATP production. Secondary measurements will be performed
to understand the underlying mechanism of enhanced muscle ATP production. These results are
likely to contribute to our understanding of the basic mechanisms of the regulation of
mitochondrial biogenesis in humans which will have potential future application.
This is a cross-sectional study between young and old. The study will use the new proteomic
techniques established in our laboratory to profile and quantify mitochondrial protein
synthesis in the participants. The combination of metabolic labeling with stable isotope
and measuring synthesis rates of specific mito proteins by tandem mass spectrometry will
determine whether actual stimulation by BCAA occurs differentially in young and elderly.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Young (age 18-30) or old (age 65-80) Body mass index <30
Locations and Contacts
Mayo Clinic, Rochester, Minnesota 55905, United States
Additional Information
Starting date: September 2005
Last updated: March 14, 2011
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