Folic Acid as an Adjunct to Methylphenidate in Pediatric Attention Deficit Hyperactivity Disorder: A Systematic Review

A bstract Background: The potential link between serum folic acid levels and attention deficit hyperactivity disorder (ADHD) has prompted investigation into folate supplementation as a therapeutic strategy. However, current evidence regarding its clinical utility remains inconsistent. Aim: This systematic review specifically evaluates whether adjunctive folic acid, when added to standard methylphenidate therapy, provides additional benefit in improving core ADHD symptoms or treatment-related adverse effects in pediatric patients. Materials and Methods: A systematic literature search was conducted on Scopus, Proquest, Cochrane, Epistemonikos, Google Scholar, and PubMed up to June 22, 2024. Studies were selected based on population, intervention, comparison, outcomes and study design (PICOS) framework, focusing on children with ADHD treated with folic acid alongside standard care compared to control groups (placebo or alternative). Outcomes of interest included ADHD symptom severity, anthropometric measures, and appetite-related side effects. Results: Out of 17,522 initial records, three studies met the inclusion criteria, comprising a total of 135 participants (68 intervention and 67 control). All included trials had an intervention duration of approximately 60 days. The synthesis revealed no statistically significant differences between the folic acid and control groups regarding core ADHD symptoms, including hyperactivity, inattention, aggression, and social or emotional functioning. Similarly, folic acid supplementation did not significantly alter anthropometric parameters such as weight, height, or body mass index. Regarding side effects, while scores for nausea showed no significant change, a statistically significant difference was observed in anorexia scores ( P < 0.01) in one study. Conclusion: The current limited evidence suggests that folic acid supplementation does not significantly improve core behavioral symptoms in children with ADHD. While there appears to be a statistical difference in appetite-related outcomes (anorexia), these findings should be interpreted with caution. Further research utilizing larger cohorts and rigorous randomized controlled designs is necessary to draw definitive clinical recommendations.