Who are the delightful authors, what is the title of the study, and what year was it published?
Authors: Yusra A Al-Yafee, Laila Y Al- Ayadhi, Samina H Haq, and Afaf K El-Ansary
Title: Novel metabolic biomarkers related to sulfurdependent detoxification pathways in autistic patients of Saudi Arabia. BMC Neurology 2011, 11:139
Year: 2011
What is the study about?
A study conducted in Saudi Arabia investigated novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic children and compared them to control subjects to better understand how oxidative stress could contribute to autism in this population. The study aimed to shed light on the relationship between xenobiotics, neurotoxins that can harm a child’s health, and an inefficient detoxification system, which can lead to oxidative stress, gut dysbiosis, and immune dysfunction.
According to physicians who use a biomedical approach to treat autism, those on the spectrum often suffer from oxidative stress and immune problems. This study aims to investigate the role of detoxification in the etiology of autism by analyzing selected parameters related to sulfur-dependent detoxification mechanisms in plasma samples from autistic children in Saudi Arabia and comparing them to samples from control subjects.
What previous research is referenced by the authors that supports the need for this study?
There is evidence of altered oxidative stress in individuals with autism, as indicated by several findings. First, reduced enzymatic activities of glutathione peroxidase (GPX) [studies in 1978, 2002, & 2003], superoxide dismutase (SOD) [the 1978 study, and same 2003 study], and catalase [another 2002 study, and a 2004 study], as well as reduced levels of total glutathione (GSH), GSH/GSSG, and cysteine [a 2009 study] have been reported, suggesting reduced endogenous antioxidant capacity. Additionally, exogenous antioxidant levels, including vitamin C, vitamin E, vitamin A in plasma, and zinc and selenium in erythrocytes, have been reported to be reduced in autism [a 2004 study].
Second, evidence of impaired energy metabolism has been observed in autism, with magnetic resonance spectroscopy studies showing reduced synthesis of ATP [a 1993 study], and higher levels of lactate [another 2009 study, another 1993 study, & a 1999 study] and pyruvate [a 1992 study] being reported.
Third, improvement in certain behaviors has been observed following antioxidant administration to individuals with autism. In double-blind, placebo-controlled trials, high-dose vitamin C [a third study in 1993] or carnosine [a third 2002 study] improved autistic behavior over baseline observations. Similarly, supplementation with betaine and folinic acid increased blood levels of GSH and cysteine, as well as the GSH/GSSG ratio, in children with autism [the same previous 2009 study].
Fourth, increased excretion of oxidative stress biomarkers has been reported in children with autism, including the F2 isoprostane 8 isoprostaglandin F2a [a 2005 study], nitric oxide [the same 2003 study], thiobarbituric acid reactive substances, and xanthine oxidase activity in red cells [another 2003 study]. Consistent with these findings, children with autism were found to have increased body burdens of environmental toxins that generate oxidative stress [studies in 1998, 2000, 2010, & 2011].
Taken together, these lines of evidence suggest that at least some children with autism exhibit enhanced oxidative stress, which may contribute to the development or severity of autism symptoms. However, the exact mechanisms underlying how oxidative stress can lead to autism are not yet clear.
What methods were used?
Participants
This study enrolled 40 Saudi children aged between 3 and 16 years old, with half of them diagnosed with Autism Spectrum Disorder (ASD) and the other half without any developmental or psychiatric disorders serving as a control group. The ASD group consisted entirely of non-verbal males with an IQ below 80. The control group was recruited from a well-baby clinic at King Khaled University Hospital and were age-matched with the participating ASD children. Participants were recruited through the Autistic Research and Treatment Center (ART Center) clinic in Saudi Arabia
Dependent Variables
All of the dependent variables assessed in this study are metabolic biomarkers related to sulfur-dependent detoxification mechanisms, which are involved in the detoxification of neurotoxins and oxidative stress.
The levels of reduced glutathione, total glutathione, GSH/GSSG ratio, glutathione reductase, and glutathione-s-transferase were measured to determine the antioxidant defense mechanism and oxidative stress in autistic children. The authors also measured the levels of thioredoxin, thioredoxin reductase, and peroxiredoxins, which are involved in cellular redox balance, further indicating the potential involvement of oxidative stress in the pathogenesis of autism.
The study used plasma samples from blood collected from autistic children and age-matching control children.
What were the findings?
T-tests
- Total glutathione: significantly lower levels in the autism group
- Oxidized Glutathione (GSSG): significantly higher in the autism group
- GSH/GSSG ratio: significantly lower levels in the autism group
- Glutathione reductase (GR) activity: no significant difference
- Glutathione-s-transferase (GST) activity: significantly lower levels in the autism gorup
- Thioredoxin (Trx) levels: significantly higher levels in the autism group
- Thioredoxin reductase (TrxR): significantly higher levels in the autism group
- Peroxiredoxins I: significantly higher levels in the autism group
- Peroxiredoxins III: significantly higher in the autism group
Correlations
The most significant correlations were observed between glutathione and thioredoxin-related parameters. Moreover, the study found that Thioredoxin reductase activity levels correlated negatively with the age of the participants in both groups. These findings suggest that Thioredoxin reductase activity levels decrease with age, which could increase the risk of oxidative stress and contribute to the pathogenesis of Autism Spectrum Disorder (ASD).
What are the implications of the findings?
This study underscores the significant role of oxidative stress in autism, linking it to factors such as mitochondrial dysfunction, leaky blood-brain barriers, increased cytokines, and autoimmune responses to brain antigens. The research highlights the importance of sulfur metabolism in maintaining cellular homeostasis and raises concerns about decreased plasma GSH levels in autistic individuals. The findings also suggest that oxidative stress contributes to the increased male-to-female ratio observed in autism and reveal higher GSSG levels, indicating increased intracellular oxidative stress.
Furthermore, the study connects reduced plasma glutathione-S-transferase in autistic patients to poor detoxification power and supports the hypothesis that oxidative stress contributes to autism’s etiology through overexpression of TrxR. The overexpression of Prx I, Prx III, and Prx3 in autistic patients demonstrates their role in autism’s pathology, with Prx3 specifically impacting mitochondrial membrane potential and H2O2 regulation. Finally, the raised levels of Trx, TrxR, and Prxs in autistic patients suggest a connection to H2O2 stress.
Early Intervention
Based on the study’s findings, the authors suggest that early intervention with safe and effective antioxidant supplementation such as omega-3, carnosine, and selenium may be helpful in children with Autism Spectrum Disorder (ASD) due to impaired antioxidant status. They propose that identifying children at risk for oxidative stress using diagnostic biomarkers, such as glutathione and thioredoxin, could facilitate early detection and intervention. Additionally, the authors propose that identifying novel biomarkers for monitoring oxidative stress in children with ASD could lead to potential therapeutic approaches using vitamins, minerals, and antioxidants. Thus, monitoring biomarkers such as glutathione and thioredoxin could improve cognitive function and overall quality of life for individuals with ASD.
What other studies within the library is this one related to?
The study by Wu et al. (2022) found selenium supplementation improved social and cognitive behavior, diminished repetitive stereotyped behavior, and restored the learning and memory abilities of the mice.
The study by Zhao et al. (2023) found that selenium levels were positively correlated with gross motor and total scores (TS). This means that lower selenium levels indicate lower gross motor and total scores, while higher selenium levels indicate higher scores.
The study by Singh et al. (2014) found that sulforaphane treatment improved autism symptoms such as social interaction, aberrant behavior, and verbal communication.
Acetaminophen (i.e., Tylenol, and other names) is implicated as a factor related to oxidative stress. The review by Parker et al. (2022) is of relevance concerning the self-delivery of the drug, the frequency of delivery, overdosage; the treatment of low fevers that may not necessitate the drug; and the approval of the drug based on on non-damage to the liver.
Can I read the study somewhere?
Mhmm. Right here.
The Causes of Autism 