# Effects of Leucine Supplementation on Athletic Performance, Central Fatigue, and Serum Metabolism in Endurance Athletes: A Randomized Controlled Trial and Targeted Metabolomics Study

**Authors:** Tieying Li, Wei Xu, Jun Chen, Zhaobo Kan, Xuemei Sui, Zhiguang Zhao, Qirong Wang

PMC · DOI: 10.3390/metabo16020094 · 2026-01-27

## TL;DR

This study found that leucine supplementation improved muscle strength and aerobic capacity in endurance athletes, possibly by reducing the breakdown of branched-chain amino acids.

## Contribution

The study provides new evidence that leucine supplementation can enhance athletic performance and reduce central fatigue in endurance athletes.

## Key findings

- Leucine supplementation increased ankle muscle strength and VO2max in endurance athletes.
- Leucine reduced the catabolism of branched-chain amino acids, as indicated by increased α-ketoisovaleric acid levels.
- Differential metabolites were enriched in BCAA biosynthesis and degradation pathways.

## Abstract

Objectives: We aimed to investigate the effects of 6 weeks of leucine supplementation on athletic performance, central fatigue, and serum metabolome in endurance athletes, and to provide valuable insights into nutritional strategies for endurance athletes. Methods: Twenty cross-country skiers were recruited and randomized into 2 groups: the placebo (PLA) group and the leucine (LEU) group. Subjects were given leucine (8.5 g) + sucrose (14 g) or only sucrose (14 g) supplements twice each day from Monday to Saturday for 6 weeks. Test parameters include body composition, aerobic capacity, isokinetic muscle strength, blood biochemistry, and targeted metabolomics. Results: After intervention, compared to the PLA group (1) the ankle muscle strength (p = 0.01), VO2max (p = 0.01) and valine in serum (p = 0.03) were increased in the LEU group. (2) Targeted metabolomics results showed that the differential metabolites were enriched in the branched chain amino acids (BCAAs) biosynthesis and degradation. (3) The LEU group had a significant increase in α-ketoisovaleric acid (p = 0.03), which can reduce the continuous decomposition of BCAAs. Conclusions: In conclusion, a six-week intervention of leucine supplementation significantly enhanced ankle muscle strength in endurance athletes, likely through a reduction in BCAA catabolism. Additionally, this combined supplementation strategy demonstrated potential benefits in improving aerobic endurance and may contribute to the attenuation of exercise-induced central fatigue.

## Linked entities

- **Chemicals:** leucine (PubChem CID 857), valine (PubChem CID 1182), α-ketoisovaleric acid (PubChem CID 49), sucrose (PubChem CID 5988)

## Full-text entities

- **Genes:** CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}
- **Diseases:** muscle soreness (MESH:D063806), cardiovascular diseases (MESH:D002318), infection (MESH:D007239), gastrointestinal disorders (MESH:D005767), cerebrovascular diseases (MESH:D002561), hypertension (MESH:D006973), dairy allergies (MESH:D007787), metabolic disorders (MESH:D008659), weight gain or loss (MESH:D015430), Fatigue (MESH:D005221), liver/kidney dysfunction (MESH:D051437), diabetes (MESH:D003920), muscle damage (MESH:D009133), injury (MESH:D014947), fracture (MESH:D050723), muscle (MESH:D019042)
- **Chemicals:** Cr (MESH:D003404), beta-alanine (MESH:D015091), GSH (MESH:D005978), sucrose (MESH:D013395), Lipid (MESH:D008055), Desaminotyrosine (MESH:C008869), Amino Acid (MESH:D000596), Propanoate (MESH:D011422), CoA (MESH:D003065), carbohydrate (MESH:D002241), fatty acid (MESH:D005227), MDA (MESH:D008315), Blood lactate (-), bile acid (MESH:D001647), BCAA (MESH:D000597), isopropanol (MESH:D019840), Cholesterol (MESH:D002784), CHO (MESH:C034482), LA (MESH:D007811), water (MESH:D014867), LEU (MESH:D007930), Valine (MESH:D014633), Testosterone (MESH:D013739), glycogen (MESH:D006003), beta-(m-Hydroxyphenyl) hydracrylic acid (MESH:C041797), Bilirubin (MESH:D001663), Lactate (MESH:D019344), Isoleucine (MESH:D007532), nitrogen (MESH:D009584), Cortisol (MESH:D006854), EDTA (MESH:D004492), UA (MESH:D014527), acetonitrile (MESH:C032159), TG (MESH:D014280), alanine (MESH:D000409), C (MESH:D002244), fat (MESH:D005223), pyruvate (MESH:D019289), T (MESH:D014316), Glycylleucine (MESH:C015905), ammonium formate (MESH:C030544), alpha-ketoisovaleric acid (MESH:C001505), TC (MESH:D013667), ammonia (MESH:D000641), Oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942045/full.md

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Source: https://tomesphere.com/paper/PMC12942045