Dose-Response Effects of Exercise Training on Circulating Brain-Derived Neurotrophic Factor (BDNF): A Systematic Review and Meta-analysis of Randomised Controlled Trials.
Gang Huang, Liang Tan, Lianghao Zhu et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and meta-analysis pooled randomised controlled trials comparing chronic exercise with non-exercising controls to assess circulating brain-derived neurotrophic factor (BDNF). Across 48 trials, 56 comparisons and 2361 participants, exercise was associated with a mean increase in circulating BDNF (Hedges’ g = 0.41, 95% CI 0.25 to 0.57; p < 0.001). Results varied substantially across studies, and analyses did not establish a relationship between prescribed exercise dose and the BDNF effect. The authors caution that circulating BDNF is not a validated surrogate for brain BDNF.
Key findings
- Exercise was associated with higher circulating BDNF overall (g = 0.41, 95% CI 0.25 to 0.57; p < 0.001), with substantial heterogeneity (I 2 = 67.0%).
- The pooled effect was g = 0.27 (95% CI 0.10 to 0.44) for serum and g = 0.69 (0.37 to 1.00) for plasma comparisons; the matrix moderator was not significant under trial-cluster robust inference (p = 0.065).
- Neither total prescribed exercise volume (β = 0.037 per 1000 min, p = 0.614) nor vigorous versus moderate intensity (β = - 0.190, p = 0.361) was associated with the BDNF effect in the joint dose model.
- The overall effect remained positive when sampling occurred approximately ≥ 24 h after exercise (g = 0.35, 95% CI 0.12 to 0.58); Egger's test indicated small-study effects (p = 0.011).
Why it matters
The findings suggest that chronic exercise can be accompanied by an increase in circulating BDNF, but the substantial variability and very low certainty limit confidence in the size and consistency of that effect. Because circulating BDNF is not a validated proxy for brain BDNF, the biomarker change should not be interpreted as evidence of increased central BDNF or neuroplasticity.
What to keep in mind
The evidence was rated very low certainty, with substantial heterogeneity and small-study effects. Moderator and dose-response findings were uncertain, and circulating BDNF is not a validated surrogate for brain BDNF.