Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials.
OBJECTIVE
We conducted a meta-analysis of relevant randomized trials to assess whether folic acid supplementation reduces the progression of atherosclerosis as measured by carotid intima-media thickness (CIMT).


METHODS
This analysis included 2052 subjects from ten folic acid randomized trials with the change in CIMT reported as one of the end points. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effect models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity.


RESULTS
Our analysis showed that folic acid supplementation significantly reduces the progression of CIMT (WMD: -0.04 mm; 95%CI: -0.07, -0.02; P<0.001), particularly in subjects with chronic kidney disease (CKD) (WMD: -0.16 mm; 95%CI: -0.26, -0.07; P=0.0006) or high cardiovascular disease (CVD) risk (WMD: -0.05 mm; 95%CI: -0.11, 0.00; P=0.06) but not in subjects who were generally healthy with only elevated homocysteine concentrations (WMD:0.00 mm; 95%CI: -0.01, 0.01; P=0.35). Furthermore, meta-regression analysis of the data showed that the baseline CIMT levels (P=0.011) and the percent reduction of homocysteine (P<0.001) were positively related to the effect size. Consistently, a greater beneficial effect was seen in those trials with baseline CIMT levels ≥0.8 mm (WMD: -0.14 mm; 95%CI: -0.19, -0.08; P<0.0001), and a reduction in the homocysteine concentration ≥30% (WMD: -0.22 mm; 95%CI: -0.38, -0.06; P=0.009). In the corresponding comparison groups, the effect sizes were attenuated and insignificant.


CONCLUSIONS
Our findings indicate that folic acid supplementation is effective in reducing the progression of CIMT, particularly in subjects with CKD or high CVD risk and among trials with higher baseline CIMT levels or a larger homocysteine reduction.
Institute of Biomedicine, Anhui Medical University, Hefei, China.
Xianhui
X
Qin
Minrui
M
Xu
Yan
Y
Zhang
Jianping
J
Li
Xin
X
Xu
Xiaobin
X
Wang
Xiping
X
Xu
Yong
Y
Huo
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D019317:Evidence-Based Medicine; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*
D015415:Biomarkers; D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid