Folate Supplementation for Peripheral Neuropathy: A Systematic Review

source extracted confidence: high 2026-04-09
#humans #folic-acid #dietary-supplements #peripheral-nervous-system-diseases #treatment-outcome

Folate Supplementation for Peripheral Neuropathy: A Systematic Review

Alves et al., 2025 | Nutrients | Systematic Review

Citation

Alves Maues Ana Carolina, Moren Abat Mònica Gemma, ... Mariscal Gonzalo. Folate Supplementation for Peripheral Neuropathy: A Systematic Review. Nutrients. 2025-Oct-20;17(20). doi:10.3390/nu17203299

Abstract

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.

Key Findings

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-sensitivi

Outcomes Measured

  • C-reactive protein

Population

Field Value
Population See abstract
Sample Size 1367
Age Range See abstract
Condition stress

MeSH Terms

  • Humans
  • Folic Acid
  • Dietary Supplements
  • Peripheral Nervous System Diseases
  • Treatment Outcome
  • Diabetic Neuropathies
  • Female
  • Biomarkers
  • Male
  • Homocysteine

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09