Meta-analyses Folic acid supplementation with and without vitamin B6 and revascularization risk: A meta-analysis of randomized controlled trials Xianhui Qin a, b , Fangfang Fan c , Yimin Cui d , Fang Chen e , Yundai Chen f , Xiaoshu Cheng g , Yuming Li h , Binyan Wang a , Xin Xu i , Xiping Xu i , Yong Huo c, * , Xiaobin Wang j, ** a Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China b Institute of Biomedicine, Anhui Medical University, Hefei, China c Department of Cardiology, Peking University First Hospital, Beijing, China d Department of Pharmacy, Peking University First Hospital, Beijing, China e Department of Cardiology, Capital Medical University Affiliated with Beijing Anzhen Hospital, Beijing, China f Department of Cardiology, People’s Liberation Army General Hospital, Beijing, China g Department of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, China h Institute of Cardiovascular Disease and Heart Center, Pinjing Hospital Logistics University of the Chinese People’s Armed Police Forces, Tianjin, China i Guangdong Institute of Nephrology, Southern Medical University, Guangzhou, China j Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA article info Article history: Received 27 September 2013 Accepted 5 January 2014 Keywords: Folic acid supplementation Revascularization risk Randomized controlled trials Meta-analysis summary 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 ¼ 27,418, RR ¼ 0.99; 95%CI:0.88e1.11, P ¼ 0.88), coronary artery bypass grafting (CABG) (5 trials, n ¼ 10,703, 0.90; 0.79e1.03, P ¼ 0.11), percutaneous coronary intervention (PCI) (5 trials, n ¼ 10,703, 1.05; 0.89e1.23, P ¼ 0.59), coronary restenosis (3 trials, n ¼ 926, 1.05; 0.89e1.23, P ¼ 0.59) or total revascularization (7 trials, n ¼ 29,314, 1.06; 95%CI: 0.99e1.13, P ¼ 0.10). However, a greater beneficial effect was observed for coronary revascularization among those trials with a moderate dose of vitamin B6 (5e10 mg/d; RR: 0.47; 95%CI: 0.28e0.80, P ¼ 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 ¼ 1.11; 95%CI: 0.98e1.25, P ¼ 0.09; 5 mg/d, RR ¼ 1.98; 95%CI: 0.93e4.20, P ¼ 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. Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. 1. Introduction Our previous meta-analysis of randomized controlled trials (RCTs) showed that folic acid supplementation could significantly reduce the risk of stroke, 1,2 the risk of cardiovascular disease in patients with chronic kidney disease, 3,4 and the progression of carotid intima-media thickness. 5 Furthermore, folic acid supple- mentation was found to have no significant effect on total cancer incidence or total cancer mortality. 6 An earlier study Abbreviations: CABG, coronary artery bypass grafting; PCI, Percutaneous coro- nary intervention; RCTs, randomized controlled trials. * Corresponding author. Tel.: þ86 10 66551122 2704; fax: þ86 10 66530556. ** Corresponding author. Johns Hopkins University Bloomberg School of Public Health, Department of Population, Family and Reproductive Health, 615 N. Wolfe Street, E4132, Baltimore, MD 21205-2179, USA. Tel.: þ1 410 955 5824; fax: þ1 410 502 5831. E-mail addresses: huoyong@263.net.cn (Y. Huo), xiwang@jhsph.edu, xiaobinwang18@gmail.com (X. Wang). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu 0261-5614/$ e see front matter Ó 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. http://dx.doi.org/10.1016/j.clnu.2014.01.006 Clinical Nutrition xxx (2014) 1e10 Please cite this article in press as: Qin X, et al., Folic acid supplementation with and without vitamin B6 and revascularization risk: A meta- analysis of randomized controlled trials, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.01.006