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

Abstract

Background: 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.

Methods/design: 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.

Discussion: 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.

Trial registration: Australian New Zealand Clinical Trial Registry, ACTRN12615000144516 . Registered on 16 February 2015.

Keywords: ASD; Autism; Omega-3 fatty acids; Supplements; Vitamin D.

Fig. 1

Schematic diagram of study design. ¹Blood biomarkers: 25-hydroxyvitamin D (25(OH)D), red blood cell (RBC) fatty acids, calcium, albumin, iron studies, vitamin B₁₂, folate, full blood count and vitamin A. Questionnaires: sociodemographics, medical history, eating/mealtime behaviours and food diary. ²Questionnaires: sociocommunicative functioning, sensory problems and aberrant behaviours (primary outcomes); gastrointestinal symptoms (secondary outcome), sun exposure and skin colour. Anthropometry: weight and height. ³Blood biomarkers: 25(OH)D, RBC fatty acids, calcium and albumin. Questionnaires: sociocommunicative functioning, sensory problems, aberrant behaviours (primary outcomes) and eating/mealtime behaviours and diet quality. Anthropometry: weight and height. ⁴Blood biomarkers: 25(OH)D, calcium and albumin. *Gastrointestinal symptoms (secondary outcome) and medication/supplement use/incidence of adverse events/supplement compliance will be monitored throughout the study period