Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: a study protocol for a factorial randomised, double-blind, placebo-controlled trial

There is strong mechanistic evidence to suggest that vitamin D and omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs), specifically docosahexaenoic acid (DHA), have the potential to significantly improve the symptoms of autism spectrum disorder (ASD). However, there are no trials that have measured the effect of both vitamin D and n-3 LCPUFA supplementation on autism severity symptoms. The objective of this 2 × 2 factorial trial is to investigate the effect of vitamin D, n-3 LCPUFAs or a combination of both on core symptoms of ASD.Children with ASD living in New Zealand (n = 168 children) will be randomised to one of four treatments daily: vitamin D (2000 IU), n-3 LCPUFAs (722 mg DHA), vitamin D (2000 IU) + n-3 LCPUFAs (722 mg DHA) or placebo for 12 months. All researchers, participants and their caregivers will be blinded until the data analysis is completed, and randomisation of the active/placebo capsules and allocation will be fully concealed from all mentioned parties. The primary outcome measures are the change in social-communicative functioning, sensory processing issues and problem behaviours between baseline and 12 months. A secondary outcome measure is the effect on gastrointestinal symptoms. Baseline data will be used to assess and correct basic nutritional deficiencies prior to treatment allocation. For safety measures, serum 25-hydroxyvitamin D 25(OH)D and calcium will be monitored at baseline, 6 and 12 months, and weekly compliance and gastrointestinal symptom diaries will be completed by caregivers throughout the study period.To our knowledge there are no randomised controlled trials assessing the effects of both vitamin D and DHA supplementation on core symptoms of ASD. If it is shown that either vitamin D, DHA or both are effective, the trial would reveal a non-invasive approach to managing ASD symptoms.Australian New Zealand Clinical Trial Registry, ACTRN12615000144516 . Registered on 16 February 2015.