Serum Homocysteine, Folate, and Vitamin B₁₂ Levels in Patients with Systemic Lupus Erythematosus: A Meta-Analysis and Meta-Regression

Background: Patients with systemic lupus erythematosus (SLE) have elevated cardiovascular risk. Hyperhomocysteinemia may be one of the contributing factors to this phenomenon. This study therefore aimed to compare the serum homocysteine levels and the levels of folate and vitamin B12, cofactors for homocysteine metabolism, between individuals with and without SLE. Methods: A literature search was performed in PubMed, Embase, and the Cochrane library (from inception to March 31, 2019). Studies comparing serum homocysteine, folate or vitamin B12 levels between individuals with and without SLE were selected. Of the 1040 screened studies, 50 studies met the inclusion criteria. Results: A total of 50 studies involving 4396 patients with SLE were included. Patients with SLE had a significantly higher serum level of homocysteine (standardized mean difference [SMD], 1.134; 95% CI, 0.795–1.474) and lower level of vitamin B12 (SMD, −0.359; 95% CI, −0.638 to −0.080) than controls. The folate level didn’t differ markedly between SLE patients and the control group (SMD, −0.276; 95% CI, −0.674–0.123). Subgroup analysis showed consistent results in adult SLE patients. A random effects meta-regression analysis revealed a significantly inverse correlation between the SMD of homocysteine levels and C3 levels (coefficient, −0.0356, 95% CI, −0.054 to −0.0171; P <.001) and C4 levels (coefficient, −0.0876, 95% CI, −0.1407 to −0.0345; P =.0012). Conclusions: Serum homocysteine levels were higher and vitamin B12 levels were lower among individuals with SLE than those without SLE. Physicians are encouraged to monitor these parameters and offer timely interventions for patients with SLE.