# Folate Supplementation for Peripheral Neuropathy: A Systematic Review

## TL;DR

This study reviews evidence that folate supplementation may help reduce pain and improve nerve health in peripheral neuropathy patients, with few side effects.

## Contribution

This is the first systematic review to evaluate the clinical efficacy and safety of folate in managing peripheral neuropathy.

## Key findings

- Folate reduced pain scores by up to 3 points and improved symptom resolution rates to 87.5%.
- Folate increased epidermal nerve fiber density by up to 97% and lowered homocysteine and hs-CRP levels.
- Folate showed an excellent safety profile with only one adverse event reported among 1367 individuals.

## 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.