Dear Editor:
Prior studies have demonstrated that vitamin D levels are significantly lower in individuals with autism spectrum disorder (ASD),
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and an increased risk of autism has been reported in studies where individuals are exposed to less sunlight or produce less vitamin D.
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Open-label clinical trials in Egypt and China found that vitamin D3 supplementation in children with ASD led to significant reductions in total Aberrant Behavior Checklist (ABC) and Childhood Autism Rating Scale scores.
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However, these studies were limited by a high dropout rate, lack of a social responsiveness measure, and limited reporting of side effects. We conducted an open-label trial of moderate doses of vitamin D3 supplementation in children with ASD to examine treatment tolerability and changes in behavior using the Social Responsiveness Scale (SRS), ABC, and Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) assessments.
All procedures were approved by the Committee on Human Research at the University of California, San Francisco (UCSF), and registered on Clinicaltrials.gov. Children with ASD between 3 and 8 years of age and with a low serum level of 25(OH)D (<30 ng/mL) were recruited from the autism clinic at UCSF. Oil-based vitamin D3 drops were administered daily for 3 months (6000 IU/day for the first 10 days followed by 300 IU/kg/day). Six of ten screened participants met eligibility criteria (all female; M
age = 5.5 ± 1.6 years). Two participants (twins) discontinued vitamin D treatment after 8 weeks due to the parental belief that the treatment was ineffective. An additional participant was lost to follow-up, and hence three children completed the 3-month study. No adverse reactions or side effects were reported, and urine calcium levels remained within the normal range in the two subjects who provided samples. Serum vitamin D levels increased from a mean of 28 ng/mL (SD 2) at baseline to 82 (SD 50) at 3 months. The initial CGI ratings were 4 (moderately ill) for two subjects and 5 (markedly ill) for one subject. The improvements (CGI-I) were rated 3 (minimally improved) for two subjects and 2 (much improved) for one subject. The mean total ABC score improved from 63 to 39 (decrease of 24, SD 26, p = 0.25), and the mean total SRS score improved from 113 to 83 (decrease of 31, SD 5, p = 0.01). In exit interviews, parents reported that their children became more engaged and social while taking the supplement, which is consistent with the clinical observations. The results of this small, open-label trial provide additional evidence that moderate dose vitamin D3 supplementation is likely to be safe over a 3-month period.
This study has a number of important limitations, primarily the small sample size and the lack of a control group. Recruitment of subjects was difficult because many children were already taking vitamin D supplements while other interested parents declined the study and decided to supplement their child's diet with vitamin D on their own.
Vitamin D is well-tolerated, inexpensive, easy to administer, and readily available. There are now several open-label trials in children with ASD with similar findings of clinically important improvements in behavior, and the current open-label study also documents improvements in social responsiveness. After the current study was conducted and this letter was submitted, a randomized, placebo-controlled trial of vitamin D supplementation (300 IU/kg/day) in 109 children was published, and statistically significant improvements were found in several scales. including the total ABC and SRS, providing additional strong evidence that vitamin D may be a safe and effective treatment option.
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Vitamin D has numerous actions that provide a plausible mechanism of action for improving symptoms. We believe there is now a compelling need to conduct a large, randomized, double-blind, placebo-controlled trial to validate further the results of the recently published randomized controlled trial and definitively determine whether vitamin D supplementation produces beneficial effects in children with ASD.
