Is resistance training effective to increase BDNF in multiple sclerosis? An updated systematic review and...

Brain-derived neurotrophic factor (BDNF) is a key mediator of neuroplasticity and has been associated with disease progression in multiple sclerosis (MS). While aerobic exercise is consistently linked to BDNF modulation, the specific contribution of isolated resistance training (RT) remains unclear, as previous reviews have largely combined multimodal exercise interventions.

To systematically review and meta-analyze the effects of isolated RT on peripheral BDNF levels in individuals with MS (PROSPERO: CRD420251141069).

Searches were conducted in PubMed, Web of Science, Scielo, Scopus, PEDro and Cochrane up to January 10, 2026, using PICOT criteria. Controlled experimental studies investigating isolated RT and BDNF outcomes were included. Risk of bias was assessed using RoB 2.0 and ROBINS-I, and certainty of evidence was evaluated using GRADE. Due to methodological heterogeneity, a random-effects model was applied to estimate pooled effects.

Four studies (three RCTs and one controlled non-randomized trial), totaling 126 participants with MS, were included. Interventions lasted 8-24 weeks, with training frequencies of 2-3 sessions per week. Meta-analytic synthesis revealed positive pooled effects (SMD = 0.49; 95%CI: 0.15 to 0.83; Z = 2.80; p < 0.005; I2  = 0%; Q = 1.681) with wide confidence intervals without crossing zero. With the Hartung-Knapp adjustment, due to the reduced number of studies, the analysis continued to show a positive intervention effect: (SMD = 0.49; 95%CI: 0.42 to 0.56; t = 3.716; p = 0.0339). Two studies using low-to-moderate intensity protocols (Pilates-based RT and low-load RT with bands/weights) showed significant increases in serum BDNF after 8 weeks. In contrast, studies employing higher loads (≈80% of one-repetition maximum: 1RM) demonstrated no significant BDNF changes despite functional gains. Overall certainty of evidence was rated as low due to risk of bias, inconsistency, and imprecision.

Isolated RT may increase peripheral BDNF levels in individuals with MS, but this effect is supported by limited and low-certainty evidence. Furthermore, given that only four studies were included in the meta-analysis, we suggest interpreting the results with some caution.