Combined B-vitamin supplementation on homocysteine and vascular outcomes in coronary heart disease: a meta-analysis

Hyperhomocysteinemia (Hcy) independently predicts coronary heart disease (CHD) and adverse cardiovascular events. Although folic acid plays a key role in Hcy metabolism, the effect of combined B-vitamin supplementation (folic acid, VB6, and VB12) on clinical outcomes in CHD remains uncertain. A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception through April 2025 using MeSH terms including “folic acid,” “vitamin B6,” “vitamin B12,” “coronary heart disease,” and “homocysteine.” A random-effects model was used for meta-analysis. Thirteen studies involving 14,539 participants were included in the meta-analysis (7,338 patients treated with folic acid combined with vitamin B complex and 7,301 controls). Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: −2.36; 95% confidence interval (CI): (−3.09 to −1.62); p p p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85–1.07; p = 0.44). Combined B-vitamin supplementation effectively lowers serum Hcy levels and the incidence of vascular restenosis in patients with CHD. However, its impact on cardiovascular events and mortality remains inconclusive. Meta-analysis of 13 RCTs (n = 14,539): combined B vitamins lower serum Hcy Combined B-vitamin supplementation lowers vascular restenosis in CHD patients Exerts no significant impact on major CV events or mortality Hcy-lowering appears CHD-specific; broader CV benefits remain unproven