Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials

Background: Exercise training may affect the blood levels of brain-derived neurotrophic factor (BDNF), but meta-analyses have not yet been performed comparing pre- and post-intervention BDNF concentrations in patients with multiple sclerosis (PwMS). Objective: To perform a meta-analysis to study the influence of exercise on BDNF levels and define components that modulate them across clinical trials of exercise training in adults living with multiple sclerosis (MS). Method: Five databases (PubMed, EMBASE, Cochrane Library, PEDro database, CINAHL) were searched up to June 2021. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 13 articles in the meta-analysis, including 271 subjects. To investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. We performed the meta-analysis to compare pre- and post-exercise peripheral levels of BDNF in PwMS. Results: Post-exercise concentrations of serum BDNF were significantly higher than pre-intervention levels (Standardized Mean Difference (SMD): 0.33, 95% CI: [0.04; 0.61], p-value = 0.02). Meta-regression indicated that the quality of the included studies based on the PEDro assessment tool might be a source of heterogeneity, while no significant effect was found for chronological age and disease severity according to the expanded disability status scale. Conclusion: This systematic review and meta-analysis shows that physical activity increases peripheral levels of BDNF in PwMS. More research on the effect of different modes of exercise on BDNF levels in PwMS is warranted.