Folic Acid Supplementation for Autoimmune Rheumatic Diseases—Approaches and Opportunities for Research

Jozélio Freire de Carvalho; Theresa Lynn May; Allain Amador Bueno

doi:10.53941/jmai.2025.100011

Abstract

Introduction: Folate, in its supplemental form as folic acid, plays a crucial role in cellular metabolism, DNA synthesis, and cell division. Folate deficiency can lead to elevated homocysteine (HHcy) levels, which contribute to endothelial dysfunction, atherosclerosis, and cardiovascular disease (CVD). Since CVD is a leading cause of mortality in patients with autoimmune rheumatic diseases (ARDs), investigating folate’s potential role in modulating disease progression and inflammatory processes is of clinical relevance. Objective: To review the current evidence on the impact of folate supplementation in patients with ARDs. Methods: A comprehensive literature search was conducted in PubMed, SciELO, and LILACS databases from 1965 to May 2023, using MeSH terms related to folic acid, folate, and various ARDs. The reference lists of selected articles were also screened to identify additional relevant studies. Results: Among all retrieved articles, only one randomized controlled trial met the inclusion criteria. The study included 26 patients, primarily women, with autoimmune hand osteoarthritis (AHO). Participants received either folate alone (6400 mg), folate plus cobalamin (6400 mg + 20 mcg), or a lactose placebo for two months. The combination of folate and cobalamin significantly improved handgrip strength compared with the other groups, achieving outcomes similar to nonsteroidal anti-inflammatory drug (NSAID) therapy but with fewer tender joints and no reported side effects. Conclusion: Current evidence on folate supplementation in ARDs remains extremely limited. The available trial suggests potential benefits of folate, particularly when combined with cobalamin, in symptom management for AHO. Given its low cost and favorable safety profile, further randomized, double-blind, placebo-controlled studies are warranted to investigate the efficacy of folate in managing pain and slowing disease progression in ARDs.

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