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Folate Supplementation for Peripheral Neuropathy: A Systematic Review.

  • 2025-10-20
  • Nutrients 17(20)
    • Ana Carolina Alves Maues
    • Mònica Gemma Moren Abat
    • María Benlloch
    • Gonzalo Mariscal

Study Design

Type
Systematic Review
Sample size
n = 1,367
Methods
Up to July 2025, a comprehensive search of four electronic databases, encompassing PubMed, Scopus, Web of Science, and Cochrane Library, was executed, collecting studies evaluating the folate in managing PN.
  • Rigorous Journal

Background

Peripheral neuropathy (PN) represents a considerable and rapidly growing global health burden, with diabetic PN alone impacting nearly half of diabetic patients. Evidence from experimental studies highlighted that folate supplementation may protect nerve health by supporting myelin maintenance, minimizing oxidative stress, and enhancing neurotrophic factors. Nevertheless, its clinical efficacy and safety in managing PN have not yet been established. This study seeks to evaluate the role of folate in managing PN regarding the efficacy and safety endpoints.

Methods

Up to July 2025, a comprehensive search of four electronic databases, encompassing PubMed, Scopus, Web of Science, and Cochrane Library, was executed, collecting studies evaluating the folate in managing PN. Outcomes included pain scores, symptom improvement endpoints, Neuropathy Total Symptom Score (NTSS) scores, epidermal nerve fiber density (ENFD), biomarkers, and side effects.

Results

The narrative synthesis demonstrated consistent symptomatic benefits with pain reductions reaching 3 points, with symptom resolution rates of 87.5% and NTSS-6 score enhancements varying from 0.9 to 1.5 points. Notably, objective structural improvements in ENFD were observed, with increases reaching 97%. Furthermore, folate showed an excellent safety and tolerability profile with only one adverse event reported among 1367 individuals. Folate significantly decreased homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels.

Conclusions

Folate showed promising symptomatic benefits for peripheral neuropathy, with objective structural improvements (ENFD) and favourable biomarker changes (homocysteine, hs-CRP reduction), with an excellent safety profile.

Research Insights

Adverse Events Reported

  • Vitamin B9→Overall tolerability

    folate showed an excellent safety and tolerability profile with only one adverse event reported among 1367 individuals.

    Finding
    Reported
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