Disclaimer: This interpretation is strictly based on public data from the original literature. Conclusions reflect only findings in mouse models and do not constitute medical or product efficacy claims. The safety of GABA as a dietary ingredient is supported by multiple studies; its application as a sports supplement requires consideration of individual differences and professional guidance.

As a novel food resource, γ-aminobutyric acid (GABA) has gained increasing attention in the sports and health field in recent years. A study by Sakashita et al., published in Biochemical and Biophysical Research Communications, used multi-level cell–animal experiments to investigate the effects and molecular mechanisms of combining dietary GABA supplementation with exercise training on endurance. This research provides scientific evidence for GABA as a dietary nutrient for endurance training.

1.Cell Experiment: GABA Activates PGC-1α Expression in Myocytes

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α) is a key transcriptional coactivator regulating mitochondrial biogenesis, oxidative metabolism and glycogen storage, and its expression level is positively correlated with muscular aerobic capacity. To explore the regulatory effect of GABA on PGC-1α in myocytes, researchers differentiated C2C12 myoblasts into myotubes (to mimic mature myocytes), treated them with gradient concentrations of GABA (0.005–5 mg/mL) for 24 hours, and detected PGC-1α mRNA expression via qRT-PCR (with GAPDH as the internal reference).

The results showed that PGC-1α expression increased in a concentration-dependent manner at GABA concentrations ≥ 0.1 mg/mL. The 0.5, 1 and 5 mg/mL groups exhibited significantly higher expression than the control group (p<0.05), confirming that GABA upregulates PGC-1α transcription in myocytes.

2.In Vivo Uptake Assay: Orally Administered GABA Is Effectively Absorbed by Skeletal Muscle

To verify whether dietary GABA can enter muscle tissue, 7-week-old male C57BL/6J mice were randomly divided into a GABA group (intragastric administration of 200 mg/kg body weight GABA) and a control group (intragastric administration of normal saline). Thirty minutes later, skeletal muscle was collected, and metabolites were analyzed using LC-MS (ion-pair + PFPP dual methods).

The metabolic profiles were highly similar between the two groups (138 metabolites in the GABA group, 140 in the control group). Muscle GABA levels were significantly elevated in the GABA group, confirming that orally administered GABA

can be effectively taken up and accumulated in skeletal muscle.

3. Animal Experiment: “GABA + Training” Synergistically Enhances Endurance and Activates the PGC-1α Pathway

A treadmill exhaustion test was used to evaluate endurance in mice under four dietary and training regimens for 4 weeks, with simultaneous measurement of skeletal muscle molecular and metabolic indicators. The groups were designed as follows:

l Control group: standard diet, no training

l GABA group: standard diet + 0.025% GABA supplementation (human equivalent dose ≈ 100 mg/day), no training

l Training group: standard diet + treadmill training

l GABA + Training group: standard diet + 0.025% GABA supplementation + treadmill training

The results showed no significant difference in treadmill exhaustion time between the untrained control and GABA groups. In contrast, mice that received treadmill training had significantly longer exhaustion times at Week 2 and Week 4 than the untrained control group. Notably, the GABA + Training group had significantly longer exhaustion times than the Training group at both Week 2 and Week 4.

Conclusion

This study confirms a synergistic effect between dietary GABA supplementation and endurance training in mouse models, providing scientific support for GABA as a dietary nutrient for endurance training and offering a new perspective for optimizing exercise capacity through “nutrition–exercise” synergistic interventions. Further research is needed to verify its efficacy in humans and clarify its underlying molecular mechanisms.