The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and meta-analysis of randomized controlled trials

Systematic review and meta-analysis of randomized controlled trials in children younger than 18 years with autism spectrum disorder. The included trials enrolled children with ASD from New Zealand, Ireland, Egypt, and Iran, with both sexes represented in most studies; overall, 5 RCTs and 349 participants were included, and 3 RCTs with 104 participants contributed to the hyperactivity analysis.

Active treatment was oral cholecalciferol (vitamin D3). Four randomized trials used 2,000 IU/day, and one trial used 300 IU/kg/day with a maximum of 5,000 IU/day. Treatment duration ranged from 3 to 12 months, with two trials lasting 12 months.

Vitamin D supplementation did not improve core autism spectrum disorder symptoms, but it showed a beneficial effect for hyperactivity. Pooled effects were not significant for social interaction (MD -1.54, 95% CI -4.09 to 1.01; p = 0.24), communication (MD -0.05, 95% CI -1.79 to 1.69; p = 0.96), or repetitive and restricted behaviors (MD 0.85, 95% CI -0.33 to 2.02; p = 0.16). Hyperactivity improved modestly (MD -3.20, 95% CI -6.06 to -0.34; p = 0.03). All trials reported vitamin D as well tolerated, with adverse effects that were not serious and were comparable between groups.

Evidence was limited by a small number of randomized trials and a modest total sample size. Outcomes were measured with different ASD rating scales, and some analyses showed heterogeneity. At least one sensitivity analysis suggested that results changed when studies using vitamin D plus DHA were excluded, and the review does not provide strong support for vitamin D as a treatment for core ASD symptoms, especially without low baseline vitamin D levels.