Folate and methionine metabolism in autism: A systematic review

Penelope A.E. Main, Manya T. Angley, Philip Thomas, Catherine E. O'Doherty, Michael Fenech

Research output: Contribution to journalReview articlepeer-review

69 Citations (Scopus)


Background: Autism is a complex neurodevelopmental disorder that is increasingly being recognized as a public health issue. Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folatemethionine cycle may play a key role in the etiology of autism. Objective: The objective was to conduct a systematic review to examine the evidence for the involvement of alterations in folatemethionine metabolism in the etiology of autism. Design: A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folatemethionine pathway in autism. Eighteen studies met the inclusion criteria, 17 of which provided data on metabolites, 5 on interventions, and 6 on genes and their related polymorphisms. Results: The findings of the review were conflicting. The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used. Most genetic studies were inadequately powered to provide more than an indication of likely genetic relations. Conclusions: The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism. There is also a need to determine whether functional benefits occur when correcting apparent deficits in folate-methionine metabolism in children with autism.

Original languageEnglish
Pages (from-to)1598-1620
Number of pages23
JournalAmerican Journal of Clinical Nutrition
Issue number6
Publication statusPublished or Issued - 1 Jun 2010
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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