Folate Supplementation for Peripheral Neuropathy: A Systematic Review

Area of Science:

• Neurology
• Nutritional Science
• Clinical Research

Background:

• Peripheral neuropathy (PN) is a growing global health issue, particularly diabetic PN.
• Experimental data suggest folate may protect nerves via myelin support, reduced oxidative stress, and enhanced neurotrophic factors.
• Clinical evidence for folate's efficacy and safety in PN management is lacking.

Purpose of the Study:

• To evaluate the efficacy and safety of folate in managing peripheral neuropathy.
• To assess folate's impact on pain, symptoms, nerve structure, and biomarkers in PN patients.

Main Methods:

• A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library up to July 2025.
• Studies evaluating folate for PN management were collected.
• Outcomes included pain scores, symptom resolution, NTSS, ENFD, biomarkers, and adverse events.

Main Results:

• Folate supplementation led to significant pain reduction (3 points) and high symptom resolution rates (87.5%).
• Objective improvements in epidermal nerve fiber density (ENFD) were observed (up to 97% increase).
• Folate demonstrated an excellent safety profile with minimal adverse events and reduced homocysteine and hs-CRP levels.

Conclusions:

• Folate shows promising symptomatic and structural benefits for peripheral neuropathy.
• Folate supplementation positively impacts key biomarkers and exhibits a favorable safety profile.
• Further clinical evaluation supports folate as a potential therapeutic agent for PN.