Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background and aim: Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP). Methods and results: We performed a systematic search of all available RCTs conducted up to October 2018 in the following databases: PubMed, Scopus, and Cochrane. RCTs that investigated the effect of folate on CRP were included in the present study. Data were combined with the use of generic inverse-variance random-effects models. Statistical heterogeneity between studies was evaluated using Cochran's Q-test. Ten RCTs (1179 subjects) were included in the present meta-analysis. Pooled analysis results showed that folate supplementation significantly lowered the serum CRP level (weighted mean difference (WMD): �0.685 mg/l, 95 CI: �1.053, �0.318, p < 0.001). However, heterogeneity was significant (I 2 = 96.7, p = 0.000). Stratified analyses indicated that sex, intervention period, and type of study population were sources of heterogeneity. Following analysis, results revealed that the greatest impact was observed in women (WMD: �0.967 mg/l, 95 CI: �1.101, �0.833, p = 0.000), patients with type 2 diabetes mellitus (WMD: �1.764 mg/l, 95 CI: �2.002, �1.526, p = 0.000), and intervention period less than 12 weeks (WMD: �0.742 mg/l, 95 CI: �0.834, �0.650, p = 0.000). Conclusion: This meta-analysis suggested that folic acid supplementation could significantly lower the serum CRP level. Folic acid leads to greater CRP lowering effect in women, patients with T2DM, and those with less than 12-week intervention. © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II Universit