Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy A systematic review and meta-analysis (PRISMA-compliant article)

Background: To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy. Methods: Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model. Results: A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = -3.51, 95% CI: -4.20 to -2.83, P < .001) and vitamin B12 (WMD = -62.23, 95% CI: -83.27 to -41.19, P < .001) were decreased significantly compared with the control group. Conclusions: Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.