Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the benefits and harms of vitamin D supplementation for attention-deficit/hyperactivity disorder (ADHD) patients. Methods: We followed the standard methodological procedures of the Cochrane Handbook for Systematic Reviews of Intervention. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Science and Conference Proceedings Citation Index-Social Science and Humanities (Web of Science), ClincalTrials.gov, and World Health Organization's International Clinical Trials Registry Platform were searched for RCTs in January 2019. Independently, two authors (J.G., T.X.) extracted data, assessed the risk of bias, combined the data, and graded evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation approach. Our primary outcomes were assessed through rating scales of ADHD severity. Secondary outcomes measured were the possible adverse effects of vitamin D supplementation and vitamin D status after supplementation for ADHD. Results: We included four RCTs with 256 children addressing vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms. Vitamin D supplementation demonstrated a small but statistically significant improvement in ADHD total scores, inattention scores, hyperactivity scores, and behavior scores. The improvement was likely limited due to the low to very low quality of evidence in the literature. There was no statistically significant improvement in oppositional scores. Reported adverse events in the vitamin D group were mild and not significantly different from the control group. Vitamin D supplementation increased serum vitamin D levels and the ratio of patients with sufficient vitamin D levels. Conclusions: Vitamin D supplementation as adjunctive therapy to methylphenidate appeared to reduce ADHD symptoms without serious adverse events, associated with improved vitamin D status. However, considering the generally low strength of evidence, well-designed RCTs are needed to determine the efficacy and safety of vitamin D supplementation for both children and adults with ADHD, especially in the setting of a combination of vitamin D and other ADHD treatments.
Keywords: attention-deficit/hyperactivity disorder; effect; meta-analysis; supplementation; vitamin D.