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Effect of Branched Chain Amino Acids on Muscle

This study has been completed.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00170144
First received: September 13, 2005
Last updated: March 14, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention
Healthy
Drug: Branchamin 4%

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Branched Chain Amino Acids as Stimulant of Muscle Mitochondrial Function in Elderly People

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Does branched chain amino acids stimulate muscle mitochondrial ATP production in young and elderly?

Secondary Outcome Measures:
  • 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?

Estimated Enrollment: 40
Study Start Date: September 2005
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Young (age 18-30) or old (age 65-80) Body mass index <30

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00170144

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: K. Sreekumaran Nair, M.D. Mayo Clinic
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00170144     History of Changes
Other Study ID Numbers: 05-004000
Study First Received: September 13, 2005
Last Updated: March 14, 2011
Health Authority: United States: Institutional Review Board

ClinicalTrials.gov processed this record on November 25, 2014