Accepted for/Published in: JMIR Research Protocols
Date Submitted: Aug 25, 2023
Date Accepted: Aug 27, 2023
Influence of Branched Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism following Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Control Trial
ABSTRACT
Background:
Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched chain amino acids (BCAAs) have shown to have advantageous effects of on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA with exercise may synergize the effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism towards enhanced synthesis of kynurenic acid, thereby reducing fatigue.
Objective:
The objective of this randomized, double blind, placebo-controlled trial is to compare the effects of acute (~45 minutes) and chronic (8 week) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesize outcomes are modulated by changes in kynurenine metabolism in 24 (12/group) older adults.
Methods:
Older adults (60-80 years of age) who do not exercise more than 2 days per week and self-report fatigue ( 3 on a scale of 1-10) will be recruited. Participants will be randomized to either exercise + BCAA group or to exercise + placebo group. Participants will engage in high-volume, moderate-intensity whole body exercise training (aerobic and resistance exercise) either in-person or web-based sessions 3x per week for eight weeks. Participants also will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 ml of calorie free, flavor enhanced water. Muscle biopsies will be collected pre and post intervention following a 12 hour fast to examine changes in biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and physical fatigue and metabolism after 8-week exercise training between the two groups. Mental and physical fatigue will be measured pre and post intervention. Mental fatigue will be subjectively assessed through the completion of validated questionnaires. Physical fatigue will be measure by isometric handgrip, 1-repetition maximum, chair rise, 400-meter walk, and cardiopulmonary exercise tests.
Results:
The study was funded in March 2022, with an anticipated projected data collection period of January 2023 through December 2023.
Conclusions:
The discovery that kynurenine concentrations are associated with fatigue and are responsive to BCAA supplementation during exercise training could have important implications for the development of future interventions, both lifestyle and pharmacologic, to treat fatigue in older adults. Clinical Trial: ClinicalTrials.gov NCT05484661; https://clinicaltrials.gov/ct2/show/NCT05484661
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