Meeusen · International journal of sport nutrition and exercise metabolism 2007 · narrative review · n=?

Amino acids and the brain: do they play a role in "central fatigue"?

Cited 59 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic rationale and human trial findings without systematic review methodology.

PubMed 18577773 · doi:10.1123/ijsnem.17.s1.s37 · record verified 2026-08-26

What was done

This narrative review evaluated approximately 20 years of research on the central fatigue hypothesis in prolonged exercise. It examined the physiological roles of brain neurotransmitters—specifically serotonin (5-HT), dopamine (DA), and noradrenaline (NA)—and assessed whether nutritional supplementation with precursor amino acids (tryptophan, tyrosine, and branched-chain amino acids [BCAAs]) alters central fatigue, perceived exertion, and exercise performance.

What was found

The abstract reports no quantitative values. Mechanistic studies show 5-HT increases during exercise in running rats and remains elevated at exhaustion, whereas DA release rises during exercise but drops at fatigue. Plasma ratios of tryptophan, tyrosine, and BCAAs regulate their competitive entry across the blood-brain barrier for neurotransmitter synthesis. While BCAA supplementation (to suppress 5-HT synthesis) and tyrosine ingestion (to support DA/NA synthesis) can modify perceived exertion and selected cognitive measures, well-controlled laboratory trials have failed to show a consistent positive effect on actual exercise capacity or physical performance.

Why it matters

This review clarifies the gap between neurochemical theory and practical sports nutrition, showing that targeting central neurotransmitter synthesis via oral amino acid supplementation does not reliably translate into enhanced endurance performance.

Limits

The abstract provides no statistical metrics, sample sizes, or search parameters typical of a systematic review. Much of the direct mechanistic evidence linking neurotransmitter dynamics to fatigue relies on animal models, and human data show inconsistent functional outcomes.

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