Exercise Modalities, Training Dose, and Circulating Myostatin and Follistatin in Adults: A Systematic Review and Multilevel Meta-Analysis

Exercise-associated changes in circulating myostatin (MSTN) and follistatin (FST) across training modalities remain uncertain. Seven bibliographic databases were searched for controlled exercise interventions lasting at least four weeks in adults (PROSPERO CRD420261492548). Multilevel random-effects models used study-clustered CR2 inference. Renewed retrieval enabled assessment of 203 of 220 reports. The review included 79 reports from 78 study families; 39 studies contributed primary effects. Exercise was associated with lower MSTN (57 effects; 33 studies; Hedges’ g = 1.25, 95% CI 0.68–1.82) and higher FST (42 effects; 23 studies; g = 1.58, 95% CI 0.92–2.23). Heterogeneity remained high and reference-model prediction intervals crossed zero. Excluding extreme effects attenuated the pooled magnitudes. Graph-exclusion and leave-one-study-out analyses retained positive average-effect intervals. Exploratory modality and dose analyses did not establish superiority or an optimal prescription. GRADE certainty was low for both outcomes. Exercise may alter circulating MSTN and FST, but assay differences, retrieval restrictions and heterogeneous protocols limit interpretation. These findings do not establish a confirmed intracellular mechanism or validated clinical surrogate endpoint.