by Ashley Jordan Ferira, PhD, RDN
Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with significant social, communication and behavioral deficits and challenges.1 No cure exists for ASD, although early interventions (birth to 3 years) can yield developmental improvements.1 ASD impacts approximately 1 in 68 children in the US and is 4.5 times more common in boys (1 in 42) than girls (1 in 189).2
Vitamin D’s extraskeletal roles are numerous, including its role as a neurosteroid, impacting both brain development and connectivity, and likely synaptic plasticity as well.3 Vitamin D is also one of the most common micronutrient deficiencies. Previous research has revealed associations between gestational and early childhood vitamin D insufficiency and ASD.4 This suggests that hypovitaminosis D represents a modifiable risk factor for ASD.4 Furthermore, preliminary evidence demonstrates that gene variants related to vitamin D metabolism play a role in the pathophysiology of ASD.5 Robustly designed intervention trials have been scant.
The first double-blind randomized controlled trial (RCT) utilizing vitamin D3 supplementation in children with ASD was published in The Journal of Child Psychology and Psychiatry in 2018.6 The study included 109 Egyptian children (85 boys; 24 girls) 3-10 years of age with confirmed ASD diagnosis. The children were randomized to receive vitamin D3 drops (300 IU D3/kg/day; not to exceed 5,000 IU/day) or matching placebo drops daily for 4 months.6 Serum 25-hydroxyvitamin D (25[OH]D) levels were measured at baseline and 4-months. For ethical reasons, children who were identified to have vitamin D deficiency (25[OH]D <20ng/mL) were excluded from the study and administered vitamin D supplementation by the study authors.6 Autism symptoms were assessed using validated measures completed by two different psychologists and a senior psychiatrist.6
Four months of daily vitamin D3 supplementation at 300 IU/kg/day:6
- Significantly increased average 25(OH)D levels, from 26.3 ng/mL at baseline to 45.9 ng/mL at 4 months
- Was well-tolerated, with no observed aberrations in pertinent biochemical markers (e.g. calcium, liver enzymes, creatinine, BUN, etc.)
Following 4 months of vitamin D3 supplementation, improvements (all p <0.05, most p <0.01; as compared to placebo) were demonstrated in many core manifestations of ASD, including:6
- Total Childhood Autism Rating Scale (CARS) score
- Aberrant Behavior Checklist (ABC): irritability, hyperactivity, lethargy/social withdrawal, inappropriate speech, stereotypic behavior
- Autism Treatment Evaluation Checklist (ATEC): sociability, cognitive awareness, behavior
- Social Responsiveness Scale (SRS): total & social awareness, social cognition and autistic mannerism
This rigorously designed RCT is the first of its kind to demonstrate safety and efficacy of vitamin D3 supplementation in children with ASD.6 Two previous open-label vitamin D3 supplementation studies also demonstrated improvements in ASD symptoms.7-8 Wide-scale studies are warranted to continue to critically ascertain the effects of vitamin D on ASD.
Why is this Clinically Relevant?
- ASD prevalence has risen over the past few decades, and no cure exists2
- Vitamin D insufficiency is common in pediatric and adult patients
- Associational and intervention trials demonstrate that vitamin D plays a role in ASD
- Clinicians should help women of childbearing age, pregnant and lactating mothers, and children (from birth onward) achieve vitamin D sufficiency through daily vitamin D3 supplementation, as this important micronutrient potentially represents “low-hanging fruit” in the fight against ASD incidence and development
- CDC. Autism Spectrum Disorder. Facts about ASD. https://www.cdc.gov/ncbddd/autism/facts.html. Accessed April 13, 2018.
- CDC. Autism Spectrum Disorder. Data & Statistics. https://www.cdc.gov/ncbddd/autism/data.html. Accessed April 13, 2018.
- Cannell JJ. Vitamin D and autism, what’s new? Rev Endocr Metab Disord. 2017;18(2):183-193.
- Wang T et al. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2016;25(4):341-350.
- Schmidt RJ et al. Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. Early Hum Dev. 2015;91(8):483-489.
- Saad K et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry. 2018;59(1):20-29.
- Saad K et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci. 2016;19(8):346-351.
- Feng J et al. Clinical improvement following vitamin D3 supplementation in autism spectrum disorder. Nutr Neurosci. 2017;20(5):284-290.