• Arduino A Mangoni and Angelo Zinellu.
• Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
• Eur. J. Clin. Invest. 2024 Apr 1; 54 (4): e14158e14158.

BackgroundMetabolomic 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).MethodsWe 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.ResultsIn 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).ConclusionsThe 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).© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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