Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109)

Chen, Lei; Xiao, Shi; Liu, Hua; Mao, Xiao Ou; Gui, Lue-Ning; Wang, Hua; Cheng, Yong

doi:10.1038/s41398-020-01135-3

Cited by 112 publications

(94 citation statements)

References 45 publications

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“…The lower SAM/SAH ratio is indicative of impaired methylation capacity and a lower GSH with elevated GSSG represents impaired redox capacity [8]. These initial findings have been confirmed in several other prospective, controlled studies in blood [9][10][11][12] and brain samples [13][14][15], and a meta-analysis has confirmed the consistency of these findings across multiple studies and multiple laboratories [5]. A meta-analysis of 22 studies confirmed a consistent finding of impaired DNA methylation in ASD [16] and impaired DNA methylation has been associated with mitochondrial dysfunction in ASD [17].…”

Section: Introductionmentioning

confidence: 60%

“…Lastly, some individuals with ASD have lower intake and blood levels of B12 compared to controls. For example, a meta-analysis of 29 studies reported children with ASD had a significantly lower dietary intake of B12 compared to controls [ 64 ], while another meta-analysis of 16 studies found plasma B12 concentrations significantly lower in ASD compared to controls, although evidence of potential publication bias was found [ 5 ]. These finding may be due to feeding difficulties, which are common in individuals with ASD [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although ASD is currently classified as a psychiatric disorder, a number of medical comorbidities and biochemical abnormalities are associated with ASD and may contribute to symptoms. These include immune disorders [ 2 ], mitochondrial dysfunction [ 3 , 4 ], oxidative stress [ 5 ], seizures [ 6 ], gastrointestinal problems [ 7 ], and impaired methylation capacity [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, homocysteine is also the precursor to cysteine, which is the rate-limiting substrate for the production of GSH. ASD is associated with lowered concentrations of GSH in blood [ 8 , 9 , 24 ], mitochondria [ 25 ], lymphoblasts [ 25 ], and brain tissue [ 15 , 26 ], and a recent meta-analysis found consistent depletion of GSH in ASD across 14 studies [ 5 ]. Since GSH is produced from homocysteine (and cysteine), GSH depletion may lead to the depletion of homocysteine by consuming it as a precursor.…”

Section: Introductionmentioning

confidence: 99%

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The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5–75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.

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Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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“…the evidence for markers of oxidative stress associated with glutathione metabolism, lipid peroxidation, protein oxidation, DNA oxidation and antioxidant enzyme activity has been comprehensively reviewed in recent years [45,[98][99][100][101][102][103]. In the context of neurodevelopment, this has significant implications for the redox regulation of neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

Mahony¹,

O’Ryan²

2021

Preprint

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with extensive genetic and aetiological heterogeneity. While the underlying molecular mechanisms involved remain unclear, significant progress has been facilitated by recent advances in high-throughput transcriptomic, epigenomic and proteomic technologies. Here, we review recently published ASD proteomic data and compare proteomic func-tional enrichment signatures to those of transcriptomic and epigenomic data. We iden-tify canonical pathways that are consistently implicated in ASD molecular data and find an enrichment of pathways involved in mitochondrial metabolism and neurogenesis. We identify a subset of differentially expressed proteins that are supported by ASD tran-scriptomic and DNA methylation data. Furthermore, these differentially expressed proteins are enriched for disease phenotype pathways associated with ASD aetiology. These proteins converge on protein-protein interaction networks that regulate cell pro-liferation and differentiation, metabolism and inflammation which demonstrates a link between canonical pathways, biological processes and the ASD phenotype. This review highlights how proteomics can uncover potential molecular mechanisms to explain a link between mitochondrial dysfunction and neurodevelopmental pathology.

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The effect of nutritional interventions reducing oxidative stress on behavioural and gastrointestinal problems in autism spectrum disorder

Çolak

Sarıyer

Noğay

2023

Intl J of Devlp Neuroscience

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Background and aims: Although the exact cause of autism spectrum disorder (ASD), which is a neurodevelopmental disorder, is not known, it is thought that environmental factors are also effective in addition to genetic risk factors. Studies are showing an increase in oxidative stress markers and a decrease in some antioxidant enzymes in individuals with autism. This study aims to try to explain the effect of nutritional interventions that reduce oxidative stress on behavioural and gastrointestinal problems in ASD based on a literature review.Methods: All relevant studies from 2000 to 2021 were identified through a systematic search in the PubMed and Web of Science databases by using key search terms. A systematic search of the electronic databases resulted in a total of 3235 potential articles, and data were extracted from 24 studies.Results: There were 9 clinical trials and 15 animal studies. Most studies find statistically significant results for nutritional supplementation compared with placebo ASD symptoms. Conclusion:Most studies on the interventions of nutritional supplements that reduce oxidative stress in individuals with ASD have found improving effects on ASD symptoms, and no serious side effects have been observed. However, more interventional studies are needed to determine the precise effects of oxidative stress-reducing nutritional supplementation.

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Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109)

Cited by 112 publications

References 45 publications

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

The effect of nutritional interventions reducing oxidative stress on behavioural and gastrointestinal problems in autism spectrum disorder

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