Efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in coronary artery disease: A meta-analysis of randomized controlled trials

Abstract

The aim of the present study was to conduct an updated meta-analysis of relevant randomized controlled trials (RCTs) in order to estimate the effect of folic acid supplementation on endothelial function and the concentration of plasma homocysteine in patients with coronary artery disease (CAD). An extensive search of PubMed was conducted to identify RCTs that compared folic acid with placebo therapy. The mean difference (MD) and 95% confidence interval (CI) were used as a measure of the correlation between folic acid supplementation and endothelial function/plasma homocysteine concentration. Of the 377 patients included in this analysis, 191 patients underwent folic acid supplementation and 186 individuals underwent placebo treatment. Compared with the use of a placebo, folic acid supplementation alone exhibited significant efficacy on increasing flow-mediated dilation (FMD; MD, 57.72 μm; 95% CI, 50.14-65.31; P<0.05) and lowering the concentration of plasma homocysteine (MD, -3.66 μmol/l; 95% CI, -5.44--1.87; P<0.05; I², 87%). There was no significant change in the response to end diastolic diameter, glyceryl-trinitrate diameter, heart rate, baseline and peak hyperemic flow and systolic and diastolic blood pressure between the folic acid and placebo groups (P>0.05). Therefore, the meta-analysis indicated that 5 mg folic acid daily supplementation for >4 weeks significantly improved FMD and lowered the concentration of plasma homocysteine in patients with CAD. However, more RCTs are required in order to confirm these observations.

Keywords: coronary artery disease; endothelial function; folic acid; homocysteine; meta-analysis.

Figure 1

Search process for inclusion in this meta-analysis comparing the efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in patients with CAD. CAD, coronary artery disease.

Figure 2

Risk of bias graph. Light grey squares indicate an unclear risk of bias, dark grey squares indicate high risk of bias and medium grey squares indicate low risk of bias.

Figure 3

Risk of bias summary. ‘?’ Indicates unclear risk of bias, ‘−’ indicates high risk of bias and ‘+’ indicates a low risk of bias.

Figure 4

MD with 95% CI estimates for FMD, EDD, GTN diameter change, heart rate, baseline and peak hyperemic flow, systolic and diastolic BP (folic acid vs. placebo), by summarizing different results of included trials in this study. MD, mean difference; CI, confidence interval; FMD, flow-mediated dilation; EDD, end diastolic diameter; GTN, glyceryl-trinitrate; BP, blood pressure.

Figure 5

Funnel plot of FMD, EDD, GTN diameter change, heart rate, baseline and peak hyperemic flow, systolic and diastolic BP (folic acid vs. placebo), by summarizing different results of included trials in this study. FMD, flow-mediated dilation; EDD, end diastolic diameter; GTN, glyceryl-trinitrate; BP, blood pressure.

Figure 6

MD with 95% CI estimates for plasma homocysteine concentration (folic acid vs. placebo), by summarizing different results of included trials in this study. MD, mean difference; CI, confidence interval.