Inflammation (IL-1β) Modifies the Effect of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids on Core Symptoms of Autism Spectrum Disorder-An Exploratory Pilot Study‡.

Carlos A. Camargo,Marlena C. Kruger,Hajar Mazahery,Welma Stonehouse,Cathryn A. Conlon,Barbara J. Meyer,Bobby Tsang,Kathryn L. Beck,Pamela R. von Hurst,Owen Mugridge

doi:10.3390/nu12030661

Abstract

Background: The role of vitamin D and omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA) in improving core symptoms of autism spectrum disorder (ASD) in children has been investigated by a few randomised controlled trials and the results are mixed and inconclusive. The response to treatment with these nutrients is heterogenous and may be influenced by inflammatory state. As an exploratory analysis, we investigated whether inflammatory state would modulate the effect of these nutrients on core symptoms of ASD. Methods: Seventy-three New Zealand children with ASD (2.5–8.0 years) completed a 12-month randomised, double-blind, placebo-controlled trial of vitamin D (VID, 2000 IU/day), omega-3 LCPUFA; (OM, 722 mg/day docosahexaenoic acid), or both (VIDOM). Non-fasting baseline plasma interleukin-1β (IL-1β) was available for 67 children (VID = 15, OM = 21, VIDOM = 15, placebo = 16). Children were categorised as having undetectable/normal IL-1β (<3.2 pg/ml, n = 15) or elevated IL-1β (≥3.2 pg/mL, n = 52). The Social Responsiveness Scale (SRS) questionnaire was used to assess core symptoms of ASD (baseline, 12-month). Mixed model repeated measure analyses (including all children or only children with elevated IL-1β) were used. Results: We found evidence for an interaction between baseline IL-1β and treatment response for SRS-total, SRS-social communicative functioning, SRS-awareness and SRS-communication (all Pinteraction < 0.10). When all children were included in the analysis, two outcome comparisons (treatments vs. placebo) showed greater improvements: VID, no effect (all P > 0.10); OM and VIDOM (P = 0.01) for SRS-awareness. When only children with elevated IL-1β were included, five outcomes showed greater improvements: OM (P = 0.01) for SRS-total; OM (P = 0.03) for SRS-social communicative functioning; VID (P = 0.01), OM (P = 0.003) and VIDOM (P = 0.01) for SRS-awareness. Conclusion: Inflammatory state may have modulated responses to vitamin D and omega-3 LCPUFA intervention in children with ASD, suggesting children with elevated inflammation may benefit more from daily vitamin D and omega-3 LCPUFA supplementation.

Highlights

Autism spectrum disorder (ASD) is a complex neurodevelopment disorder with heterogeneous clinical presentation and aetiology
There were no significant differences in baseline characteristics between children with and without inflammation (Table 2) or between treatment groups at baseline
We investigated whether pre-treatment blood IL-1β concentrations predicted vitamin D or omega-3 long chain polyunsaturated fatty acids (LCPUFA) treatment response

Summary

Introduction

Autism spectrum disorder (ASD) is a complex neurodevelopment disorder with heterogeneous clinical presentation and aetiology. Peripheral and central IL-1β administration reduces neurogenesis and induces impaired social interaction, anxiety and stress which are symptoms associated with ASD [13,14,15]. The role of vitamin D and omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA) in improving core symptoms of autism spectrum disorder (ASD) in children has been investigated by a few randomised controlled trials and the results are mixed and inconclusive. We investigated whether inflammatory state would modulate the effect of these nutrients on core symptoms of ASD. Methods: Seventy-three New Zealand children with ASD (2.5–8.0 years) completed a 12-month randomised, double-blind, placebo-controlled trial of vitamin D (VID, 2000 IU/day), omega-3 LCPUFA; (OM, 722 mg/day docosahexaenoic acid), or both (VIDOM).

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Discussion

Conclusion