The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the γ-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders.Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity.The review found evidence for the involvement of the γ-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the γ-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the γ-glutamyl cycle and the interaction of genotype in relation to these factors.Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions comprising autistic disorder which is characterised by impairments in reciprocal social interaction and communication and the presence of stereotyped behaviours, Asperger's Syndrome which is distinguished by no significant delay in early language acquisition or cognitive abilities, and pervasive developmental disorder - not otherwise stated (PDD-NOS) in which individuals do not fully meet the criteria for autistic disorder or Asperger's syndrome. Over the last 30 years the number of diagnosed cases has increased from 0.4-0.5 to 4.0 per 1000 for autistic disorder and from 2 to 7.7-9.9 per 1000 for autism spectrum disorders [1-3] which is largely attributable to bro