Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses

Alessandra Frustaci, Monica Neri, Alfredo Cesario, James B. Adams, Enrico Domenici, Bernardo Dalla Bernardina, Stefano Bonassi

Research output: Contribution to journalArticlepeer-review


Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

Original languageEnglish
Pages (from-to)2128-2141
Number of pages14
JournalFree Radical Biology and Medicine
Issue number10
Publication statusPublished - May 15 2012


  • Amino acids
  • Antioxidants
  • Autistic disorder
  • Biological markers
  • Case-control studies
  • Free radicals
  • Genetic polymorphisms
  • Glutathione
  • Oxidative stress
  • Oxidoreductases
  • Vitamins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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