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Peer-reviewedCC BY 4.0PLOS One

Is resistance training effective to increase BDNF in multiple sclerosis? An updated systematic review and meta-analysis of isolated interventions

  • William Riciere Pedon1
  • Gustavo De Conti Teixeira Costa2
  • Lorenzo de Ávila Rodrigues Cortizo Vidal1
  • Pedro Augusto Inacio1
  • Marcelo Magalhães Sales3,4
  • Ivanéria Mendonça Martins3
  • James Oluwagbamigbe Fajemiroye4,5
  • Sergio Machado6
  • Vicente Aprigliano7
  • Gabriela Ribeiro Inacio5
  • Adolfo Mundombe Cameia1,8
  • Gaspar R. Chiappa9
2 more authors
  • Eduardo da Matta Mello Portugal10
  • Alberto Souza Sá Filho1,4,10
10 affiliations
  1. 1Graduate Program in Human Movement and Rehabilitation, Evangelical University of Goiás (UniEVANGÉLICA), Anápolis, Goiás, Brazil
  2. 2Faculdade de Educação Física e Dança – FEFD, Universidade Federal de Goiás (UFG – Campus Samambaia), Goiânia, Goiás, Brazil
  3. 3Graduate Program in Environmental and Society of State University of Goiás (UEG), Academic institute of health and biological sciences. Southwest Campus, Quirinópolis, Goiás, Brazil
  4. 4Graduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás (UniEVANGÉLICA), Anápolis, Goiás, Brazil
  5. 5Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, Brazil
  6. 6Graduate Program in Mental Health and Psychiatry; Federal University of Rio de Janeiro, UFRJ-IPUB, Rio de Janeiro, Brazil
  7. 7Escuela de Ingeniería de Construcción y Transporte, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
  8. 8Departamento de Pediatria da Universidade Rainha Njinga a Mbande (URNM), Malanje, Angola
  9. 9Faculty of Health Sciences, Universidad Autónoma de Chile, Providencia, Chile
  10. 10Graduate Program in Physical Education at Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil
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Abstract

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

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Cite

BibTeXRIS
BibTeX
@article{pedon2026resistance,
  title = {{Is resistance training effective to increase BDNF in multiple sclerosis? An updated systematic review and meta-analysis of isolated interventions}},
  author = {William Riciere Pedon and Gustavo De Conti Teixeira Costa and Lorenzo de Ávila Rodrigues Cortizo Vidal and Pedro Augusto Inacio and Marcelo Magalhães Sales and Ivanéria Mendonça Martins and James Oluwagbamigbe Fajemiroye and Sergio Machado and Vicente Aprigliano and Gabriela Ribeiro Inacio and Adolfo Mundombe Cameia and Gaspar R. Chiappa and Eduardo da Matta Mello Portugal and Alberto Souza Sá Filho},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0359019},
  url = {https://doi.org/10.1371/journal.pone.0359019},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Is resistance training effective to increase BDNF in multiple sclerosis? An updated systematic review and meta-analysis of isolated interventions
AU  - William Riciere Pedon
AU  - Gustavo De Conti Teixeira Costa
AU  - Lorenzo de Ávila Rodrigues Cortizo Vidal
AU  - Pedro Augusto Inacio
AU  - Marcelo Magalhães Sales
AU  - Ivanéria Mendonça Martins
AU  - James Oluwagbamigbe Fajemiroye
AU  - Sergio Machado
AU  - Vicente Aprigliano
AU  - Gabriela Ribeiro Inacio
AU  - Adolfo Mundombe Cameia
AU  - Gaspar R. Chiappa
AU  - Eduardo da Matta Mello Portugal
AU  - Alberto Souza Sá Filho
PY  - 2026
DA  - 2026/10/27
JO  - PLOS One
DO  - 10.1371/journal.pone.0359019
UR  - https://doi.org/10.1371/journal.pone.0359019
AB  - Background: 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. Objective: To systematically review and meta-analyze the effects of isolated RT on peripheral BDNF levels in individuals with MS (PROSPERO: CRD420251141069). Methods: 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. Results: 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. Conclusion: 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.
SN  - 1932-6203
ER  -