Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review

Eur J Nutr. 2018 Oct;57(7):2571-2582. doi: 10.1007/s00394-017-1528-6. Epub 2017 Sep 7.


Purpose: Nutritional supplements have been used for correction of deficiencies that may occur in patient with autism spectrum disorder (ASD) and to improve core symptoms. We aim to provide current best evidence about supplements for nutritional deficiencies and core symptoms in children with ASD and to evaluate the effectiveness and safety.

Methods: A systematic literature search of scientific databases was performed to retrieve relevant randomized controlled trials. Risk of bias was assessed for each study.

Results: 18 randomized controlled trials of five supplements were included. B6/Mg was not helpful for improving ASD symptoms (seven RCTs). Two RCTs of methyl B12 reported some improvement in ASD severity but the effects on the correction of deficiencies were inconclusive. Two RCTs of vitamin D3 both reported increased levels of mean 25(OH)D in serum but inconsistent results in behavioral outcomes. Omega-3 fatty acid supplementation did not affect ASD behaviors but may correct deficiencies (six RCTs). One RCT of folinic acid reported positive results in improving ASD symptoms measured by various behavioral scales.

Conclusions: Current evidence for the use of supplements for correcting nutritional deficiencies in children with ASD and to improve the symptoms is little. More studies are needed.

Keywords: Autism spectrum disorder; Core symptoms; Nutritional deficiency; Supplements.

Publication types

  • Systematic Review

MeSH terms

  • Autism Spectrum Disorder / diet therapy*
  • Child
  • Cholecalciferol / administration & dosage
  • Databases, Factual
  • Dietary Supplements
  • Humans
  • Malnutrition / diet therapy*
  • Randomized Controlled Trials as Topic


  • Cholecalciferol