Exercise Modalities, Training Dose, and the MSTN–FST Axis in Adults: A Systematic Review and Multilevel Meta-Analysis

Background/Objectives: Structured exercise may modulate the myostatin–follistatin (MSTN–FST) axis, but evidence across exercise modalities and doses remains uncertain. Methods: We systematically searched seven bibliographic databases for controlled exercise interventions lasting at least four weeks in adults (PROSPERO CRD420261492548). Multilevel random-effects models with study-clustered CR2 correction accounted for dependent effect sizes; sensitivity, exercise-modality subgroup, and linear duration analyses were exploratory. Results: Thirty-seven independent studies were included. Structured exercise was associated with lower circulating MSTN (16 effects from 10 studies; Hedges’ g = 1.79, 95% confidence interval [CI] 0.62–2.96) and higher circulating FST (12 effects from 7 studies; g = 1.62, 95% CI 0.18–3.06). Heterogeneity was high and both prediction intervals crossed the null. Effect directions generally persisted across assumed within-study correlations and after excluding HIFT/CrossFit-type interventions, although excluding extreme effects attenuated the estimates. Exploratory analyses showed no clear difference between resistance-based and non-resistance-based exercise, and program duration was not linearly associated with either outcome. GRADE certainty was moderate for both outcomes. Conclusions: Structured exercise may favorably alter circulating MSTN and FST, but sparse modality- and dose-specific evidence precludes identifying a superior modality, optimal dose, confirmed intracellular mechanism, or validated clinical surrogate endpoint.