What is the Effect of Folic Acid Supplementation on the Incidence or Reduction of Phenytoin-Induced Gingival Overgrowth? A Systematic Review

Background: Several published studies have reported both positive and negative effects regarding the administration of folic acid (FA) on either prevention, or reduction of phenytoin (PHT)-induced gingival overgrowth (PIGO). Several other published studies have evaluated the effect of FA supplementation upon gingival health. Objective: The primary objective is a systematic assessment review of studies evaluating the efficacy of FA therapy for the prevention or reduction of PIGO. Secondary objectives entail evaluation of the FA and seizure control, on the mechanism of Drug-IGO, and on FA supplementation and gingival health. Materials and methods: Electronic databases (a Medline via PubMed database, and Cochrane Central Register of Controlled Trials) search was conducted; other sources were searched such as Google Scholar and clinicaltrials.gov. Reference lists of retrieved articles were searched. Randomized placebo-controlled trials (RCTs) assessing the effect of topical or systemic administration of folic acid on gingival enlargement in phenytoin patients were included. Two reviewers (HH, RB) performed the study search, data extraction, and risk of bias assessment. The literature was reviewed regarding PHT-FA interaction, and FA supplementation to promote gingival health. Results: The main research was through Pubmed search, and done on February, 15, 2015. It resulted in eight items. Only five items were considered for screening. The other three items were not interventional. One extra title was found on Google Scholar website. The total RCTs included for the systematic review were six trials. Studies regarding FA and gingival health were also evaluated which produced another four items. Conclusion: FA supplementation may improve the gingival health status, and may delay the onset of PICO, as there are only at present a limited number of studies with a limited number of subjects, further studies are necessary to confirm or deny the positive effects of FA therapy. In PHT-treated epileptic patients properly managed, FA supplementation has a very limited risk in interfering with seizure control. Due to very limited toxicity and the potential for promoting gingival health, future FA supplementation therapy studies should be considered.