Acute cardiovascular exercise and circulating neurotrophic factors in humans: A systematic review and meta-analysis of mechanisms and methodological moderators

Acute cardiovascular exercise is widely proposed to modulate neurotrophic factors implicated in brain plasticity, yet empirical findings remain inconsistent and difficult to interpret. This systematic review and meta-analysis synthesized evidence on the acute effects of a single bout of cardiovascular exercise on circulating neurotrophic factors in healthy adults and identified methodological sources of variability. We searched PubMed, Web of Science, Scopus, Embase, PsycINFO, ScienceDirect, and SPORTDiscus, supplemented by gray literature sources. Eligible studies included healthy adults undergoing a single exercise bout with peripheral neurotrophic outcomes. Study selection, data extraction, and risk of bias assessment were conducted by two reviewers. Findings were synthesized narratively, and a focused random-effects meta-analysis was conducted for the subset of studies reporting extractable pre- and post-exercise BDNF data. Twenty-two studies (N = 628) were included, assessing brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1). Acute exercise was consistently associated with transient increases in BDNF, particularly following moderate-to-vigorous intensities and immediate post-exercise sampling. The meta-analysis confirmed a moderate, statistically significant increase in circulating BDNF (pooled Hedges' g = 0.48, 95 % CI [0.29, 0.68], p < 0.001), with directionally larger effects following higher-intensity exercise and in younger adults. In contrast, evidence for VEGF and IGF-1 was limited and inconsistent, and too sparse to pool. Exercise intensity, biological sample type, and sampling timing emerged as key moderators. Overall confidence in the evidence appears moderate for BDNF and low for VEGF and IGF-1, reflecting differences in study volume, consistency, and methodological variability.