Folic acid and autism: What do we know?

Nutr Neurosci. 2016 Sep;19(7):310-7. doi: 10.1179/1476830514Y.0000000142. Epub 2016 Mar 1.


Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was κ = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed.

Keywords: Autistic disorder; Folic acid; Vitamins.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adolescent Nutritional Physiological Phenomena
  • Autism Spectrum Disorder / blood
  • Autism Spectrum Disorder / epidemiology
  • Autism Spectrum Disorder / etiology*
  • Autism Spectrum Disorder / prevention & control
  • Child
  • Child Nutritional Physiological Phenomena
  • Diet / adverse effects
  • Dietary Supplements / adverse effects*
  • Evidence-Based Medicine*
  • Female
  • Fetal Development*
  • Folic Acid / adverse effects*
  • Folic Acid / blood
  • Folic Acid / therapeutic use
  • Folic Acid Deficiency / blood
  • Folic Acid Deficiency / diet therapy
  • Folic Acid Deficiency / physiopathology
  • Folic Acid Deficiency / prevention & control
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / etiology
  • Hyperhomocysteinemia / physiopathology
  • Hyperhomocysteinemia / prevention & control
  • Incidence
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Pregnancy
  • Reproducibility of Results
  • Risk Factors


  • Homocysteine
  • Folic Acid