Autism and Oxidative Stress Interventions: Impact on Autistic Behavior

Review Article

Austin J Pharmacol Ther. 2014; 2 (2).1015

Autism and Oxidative Stress Interventions: Impact on Autistic Behavior

*Ana Maria Castejon and Jordan Ashley Spaw

Department of Pharmaceutical Sciences, College of Pharmacy Nova Southeastern University, USA

*Corresponding author: : Ana Maria Castejon, Department of Pharmaceutical Sciences, College of Pharmacy Nova Southeastern University, 3200 S University Drive Fort Lauderdale, FL, USA

Received: February 03, 2014; Accepted: February 10, 2014; Published: February 13, 2014


Autism is an increasingly prevalent neurodevelopmental disorder in the United States, which relies on applied behavioral therapy as means of treatment. This disorder has been linked to increased levels of oxidative stress and lower anti–oxidant capacity. Metabolites in the interconnected transmethylation and transsulfuration pathways are significantly altered in autism, causing decreased glutathione synthesis. This review article was performed to support the role of oxidative stress in autism and its clinical symptoms. The use of the glutathione redox ratio as a biomarker for disease and treatment status was supported. Anti-oxidant supplementation, or ways to improve the altered metabolite levels in the interconnected pathways, has been associated with decreased autistic behaviors and severity. These interventions should be further studied in order to determine their effectiveness at improving metabolic imbalances in Autism Spectrum Disorder (ASD). Overall, oxidative stress related metabolites could have potential use as biomarkers and help determine treatments.


Autism was first noted in 1943 as a neurodevelopmental disorder [1] and now affects 1 out every 88 children in the United States [2]. This disorder is clinically characterized by deficits in social interactions, hyper–focused repetitive behaviors, and impaired verbal and non–verbal expressive speech [2,3]. The etiology of autism stems from genetic, neurological and environmental factors [3], which are also supported by other neurological diseases. Environmental insults, like oxidative stress, are known to play a role in some neurological conditions such as Parkinson’s Disease [4], Alzheimer’s Disease [5], schizophrenia [6] and bipolar disorder [7]. Excessive oxidative stress and it’s clinical implications in autism is now of particular interest.

Autism Spectrum Disorder (ASD) encompasses the wide range of clinical symptoms seen in those individuals whom have been diagnosed with some form of autism. Behavioral assessments often note inattention, aggression, impulsivity, hyperactivity, excessive compulsions, affective instability, and occasional psychosis in autistic children [8]. Most children are clinically diagnosed with autism by age 3 using a myriad of standardized behavioral examinations [9]. The heterogeneity of this disorder has made it very difficult to diagnose and treat using pharmacological therapy. Atypical antipsychotics, selective serotonin reuptake inhibitors and psychostimulants have all shown some clinical benefits in this disorder but they are often associated with significant side effects, showing the need for better and safer treatments [10]. Alternative pharmacological therapies, like nutritional interventions and vitamin⁄mineral supplements, cancorrect abnormal transmethylation and transsulfuration pathways, increase anti–oxidant capacity and possibly improve autistic behavior in a safer way with less side effects and better tolerability.


Metabolic abnormalities have been noted in autism and are related to the interconnected pathways of folate, methionine and glutathione metabolism [3,11]. Abnormal glutathione redox status stems from variations in these pathways; they are important for the regulation of normal redox homeostasis, cellular methylation potential and DNA synthesis [3,11]. Pathway imbalances most often lead to oxidative stress.

The transmethylation and transsulfuration pathways are shown in Figure 1. The methionine, or transmethylation pathway, describes the pathway where a methyl group is given to homocysteine by methylcobalamin via methionine synthase [11] Methylcobalamin obtains the methyl group needed for this methionine regeneration from methyltransferase activity and 5–methyltetrahydrofolic acid. Methionine can then produce increased amounts of S–adenosylmethionine (SAM), another methyl donor, and regenerate homocysteine. Homocysteine links the transmethylation and transsulfuration pathways; it can then either be used again in the transmethylation cycle or irreversibly removed by cystathione–B synthase (CBS) forming cysteine. The presence of cysteine is required for glutathione synthesis.