Folic acid supplementation with and without vitamin B6 and revascularization risk: a meta-analysis of randomized controlled trials

Abstract

Background & aims: There is a growing amount of data and a continuing controversy over the effect of folic acid supplementation with and without vitamin B6 on revascularization risk.

Methods: We conducted a meta-analysis based on up-to-date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of revascularization using a random-effects model. Total revascularization was defined as any arterial revascularization. Restenosis was defined as stenosis of more than 50 percent of the luminal diameter.

Results: Overall, folic acid supplementation had no significant effect on coronary revascularization (9 trials, n = 27,418, RR = 0.99; 95%CI:0.88-1.11, P = 0.88), coronary artery bypass grafting (CABG) (5 trials, n = 10,703, 0.90; 0.79-1.03, P = 0.11), percutaneous coronary intervention (PCI) (5 trials, n = 10,703, 1.05; 0.89-1.23, P = 0.59), coronary restenosis (3 trials, n = 926, 1.05; 0.89-1.23, P = 0.59) or total revascularization (7 trials, n = 29,314, 1.06; 95%CI: 0.99-1.13, P = 0.10). However, a greater beneficial effect was observed for coronary revascularization among those trials with a moderate dose of vitamin B6 (5-10 mg/d; RR: 0.47; 95%CI: 0.28-0.80, P = 0.005), but not in trials without vitamin B6 or with a high dose of vitamin B6. And a non-significant greater total revascularization risk was observed in trials with a higher folic acid dose (>2 mg/d, RR = 1.11; 95%CI: 0.98-1.25, P = 0.09; ≥5 mg/d, RR = 1.98; 95%CI: 0.93-4.20, P = 0.08).

Conclusions: Our analyses indicate that folic acid supplementation has no significant effect on coronary revascularization, CABG, PCI, coronary restenosis or total revascularization. However, a combination of folic acid and moderate vitamin B6 may be beneficial in reducing coronary revascularization risk.

Keywords: Folic acid supplementation; Meta-analysis; Randomized controlled trials; Revascularization risk.