Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
Open accessAbstract
Background Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism.Objective The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism.Design Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children.Results Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children.Conclusions An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.
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Children with ASD have higher levels of oxidised glutathione and F2-isoprostane than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [153]
Children with ASD have reduced capacity for methylation than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [153]
Children with ASD have lower levels of total glutathione and glutathione peroxidase than typically developing children.
“Recent evidence shows that children with ASD have lower levels of total glutathion and glutathione peroxidase (an enzyme involved in antioxidant defense and detoxification), higher levels of oxidised glutathione and F2—isoprostane (a marker of oxidative stress and lipid peroxidation) and reduced capacity for methylation than typically developing children [16,153].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [153]
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- Authors
- James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A.
- Affiliations
- Arkansas Children's Hospital (US)
- Corresponding author
- James, S Jill
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 80
- Issue
- 6
- Pages
- 1611-1617
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2112109116
- Cited by
- 955
- References
- 65
- Citations by year
- 2026: 26 · 2025: 25 · 2024: 25 · 2023: 28 · 2022: 32 · 2021: 42 · 2020: 64 · 2019: 43 · 2018: 47 · 2017: 50 · 2016: 46 · 2015: 64 · 2014: 71 · 2013: 54 · 2012: 57
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- autism spectrum disorder, oxidative stress, methionine metabolism, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine, glutathione, plasma metabolites, leucovorin, betaine, methylcobalamin, dietary intervention, children
- MeSH terms
- Adenosine, Autistic Disorder, Betaine, Child, Chromatography, High Pressure Liquid, Leucovorin, Cystathionine, Cysteine, Female, Glutathione, Homocysteine, Humans, Male, Methionine, Methylation, S-Adenosylhomocysteine, S-Adenosylmethionine, Vitamin B 12, Biomarkers, Case-Control Studies, Oxidative Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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