Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#humans #folic-acid #nitric-oxide #vitamin-b-12 #vitamin-b-6

Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis

Mangoni et al., 2024 | Eur J Clin Invest | Meta Analysis

Citation

Mangoni Arduino A, Zinellu Angelo. Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis. Eur J Clin Invest. 2024-Apr;54(4):e14158. doi:10.1111/eci.14158

Abstract

BACKGROUND: Metabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative stress in rheumatoid arthritis (RA). METHODS: We conducted a systematic review and meta-analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6 , and vitamin B12 ) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE. RESULTS: In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54-0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57-1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = -6.62, 95% CI -9.65 to -3.60, p < 0.001; low certainty). By contrast, there were non-significant between-group differences in vitamin B12 and folic acid. In meta-regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C-reactive protein, triglycerides, and analytical method) and folic acid (biological matrix). CONCLUSIONS: The results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081).

Key Findings

In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54-0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57-1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = -6.62, 95% CI -9.65 to -3.60, p < 0.001; low certainty). By contrast, there were non-significant between-group differences in vitamin B12 and folic acid. In meta-regress

Outcomes Measured

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Population

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

MeSH Terms

  • Humans
  • Folic Acid
  • Nitric Oxide
  • Vitamin B 12
  • Vitamin B 6
  • Methionine
  • Vitamins
  • Arthritis, Rheumatoid
  • Biomarkers
  • Homocysteine

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Meta-Analysis, Systematic Review, Journal Article
  • Vertical: vitamin-b6

Provenance

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