Effects of Regular Exercise on Peripheral Brain-Derived Neurotrophic Factor in Neurological and Non-Neurological Populations: A Meta-Analysis with Meta-Regression.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41594760 · doi:10.3390/brainsci16010039
What was done
Researchers conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) across five databases (PubMed, Web of Science, ScienceDirect, Scopus, Cochrane) through October 2025. They evaluated the effects of exercise interventions on peripheral brain-derived neurotrophic factor (BDNF) in populations with neurological conditions (e.g., multiple sclerosis, cognitive impairment, depression, schizophrenia) and non-neurological conditions (e.g., obesity, type 2 diabetes, cancer). Quality of trials was evaluated using the PEDro scale and certainty was graded using GRADE. Random-effects meta-analyses, subgroup comparisons (disease category, exercise modality, assay type), and meta-regressions (exercise duration, frequency, volume, age, baseline BDNF) were performed.
What was found
Across 19 RCTs comprising 850 participants, exercise significantly elevated peripheral BDNF compared to controls (SMD = 1.03, 95% CI: 0.56 to 1.49, p < 0.0001). Effects were similar between neurological (SMD = 0.91, 95% CI: 0.31 to 1.50) and non-neurological groups (SMD = 1.23, 95% CI: 0.47 to 1.99; between-group p = 0.51). Subgroup analysis showed significant effects for resistance training (SMD = 1.57, 95% CI: 0.91 to 2.23), aerobic exercise (SMD = 1.44, 95% CI: 0.36 to 2.52), and combined training (SMD = 0.55, 95% CI: 0.21 to 0.89). Meta-regression showed no significant moderation by intervention duration (p = 0.834), weekly frequency (p = 0.648), session length (p = 0.233), or total weekly minutes (p = 0.919), but age (β = 0.0348, p = 0.020) and baseline BDNF (β = -0.035, p = 0.0258) were significant moderators.
Why it matters
This review shows that regular exercise, particularly resistance and aerobic training, consistently increases peripheral BDNF across diverse clinical disorders, supporting its role as a neuroplasticity-promoting intervention regardless of primary disease category.
Limits
The overall certainty of evidence was rated as low under GRADE. Individual trials had small sample sizes (averaging under 45 participants per trial) and frequently lacked blinding of participants and outcome assessors. Substantial clinical and methodological heterogeneity existed across patient diagnoses, exercise prescriptions, and BDNF laboratory assay techniques.
Cited by
- supports Exercise has been shown to increase BDNF (brain-derived neurotrophic factor) levels and improve cognition.