Branched-Chain Amino Acids and Central Fatigue
Open accessAbstract
An account of the tryptophan (Trp)-5-hydroxytryptamine (5-HT)-central fatigue theory is provided and an explanation of how oral administration of BCAAs can decrease fatigue on the basis of this theory is given. The rate-limiting step in the synthesis of 5-HT is the transport of Trp across the blood-brain barrier. This transport is influenced by the fraction of Trp available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs, which are transported via the same carrier system. During endurance exercise, there is an uptake of Trp by the brain, suggesting that this may increase the synthesis and release of 5-HT in the brain. Oral intake of BCAAs may reduce this uptake and also brain 5-HT synthesis and release, thereby delaying fatigue. Other hypotheses for the effect of BCAAs on central fatigue are included.
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The three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine are unique among the EAAs for their roles in protein metabolism, neural function, and blood glucose and insulin regulation.
“The three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine are unique among the EAAs for their roles in protein metabolism [150], neural function [151–153], and blood glucose and insulin regulation [154].”
From International Society of Sports Nutrition Position Stand: protein and exercise (2017) · cites this paper as [153]
BCAAs do not enhance exercise performance, but they may reduce central fatigue and attenuate muscle damage during prolonged exercise.
“While there is strong evidence showing that BCAAs do not enhance exercise performance [192, 193], they may reduce central fatigue [194] and attenuate muscle damage during prolonged exercise [195].”
From The athletic gut microbiota (2020) · cites this paper as [194]
Tryptophan (the 5-HT precursor) competes with BCAAs to cross the blood-brain barrier.
“Critically, tryptophan (the 5-HT precursor) competes with BCAAs to cross the blood-brain barrier [109]”
From International Society of Sports Nutrition Position Stand: nutritional considerations for single-stage ultra-marathon training and racing (2019) · cites this paper as [109]
When consumed during prolonged exercise, BCAAs increase the BCAAs:tryptophan ratio, confirming the central fatigue hypothesis.
“When consuming during prolonged exercise, BCAAs showed an increase in the BCAAs:tryptophan ratio, confirming the central fatigue hypothesis [49].”
From Oral Branched-Chain Amino Acids Supplementation in Athletes: A Systematic Review (2022) · cites this paper as [49]
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- Authors
- Newsholme, E. A., & Blomstrand, E.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Blomstrand, Eva
- ORCID
- Blomstrand, Eva
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 136
- Issue
- 1
- Pages
- 274S-276S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2104638114
- Cited by
- 150
- References
- 22
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 8
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- branched-chain amino acids, central fatigue, tryptophan, serotonin, blood-brain barrier transport, endurance exercise, large neutral amino acids, amino acid competition
- MeSH terms
- Amino Acids, Branched-Chain, Brain, Fatigue, Humans, Serotonin, Tryptophan
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