James, S. J., Melnyk, S., Fuchs, G., Reid, T., Jernigan, S., Pavliv, O. et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am. J. Clin. Nutr. 89, 425-430

Department of Pediatrics and Biostatistics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 01/2009; 89(1):425-30. DOI: 10.3945/ajcn.2008.26615
Source: PubMed


Metabolic abnormalities and targeted treatment trials have been reported for several neurobehavioral disorders but are relatively understudied in autism.
The objective of this study was to determine whether or not treatment with the metabolic precursors, methylcobalamin and folinic acid, would improve plasma concentrations of transmethylation/transsulfuration metabolites and glutathione redox status in autistic children.
In an open-label trial, 40 autistic children were treated with 75 microg/kg methylcobalamin (2 times/wk) and 400 microg folinic acid (2 times/d) for 3 mo. Metabolites in the transmethylation/transsulfuration pathway were measured before and after treatment and compared with values measured in age-matched control children.
The results indicated that pretreatment metabolite concentrations in autistic children were significantly different from values in the control children. The 3-mo intervention resulted in significant increases in cysteine, cysteinylglycine, and glutathione concentrations (P < 0.001). The oxidized disulfide form of glutathione was decreased and the glutathione redox ratio increased after treatment (P < 0.008). Although mean metabolite concentrations were improved significantly after intervention, they remained below those in unaffected control children.
The significant improvements observed in transmethylation metabolites and glutathione redox status after treatment suggest that targeted nutritional intervention with methylcobalamin and folinic acid may be of clinical benefit in some children who have autism. This trial was registered at ( as NCT00692315.

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    • "However, because the CNS is affected in ASD, examining physiological abnormalities in the brain may reveal more about what is abnormal than inspecting abnormalities in blood or urine samples. A number of studies have reported evidence of oxidative stress in individuals with ASD (Yorbik et al., 2002; James et al., 2004, 2006, 2009a,b; Ming et al., 2005; Chauhan and Chauhan, 2006; Yao et al., 2006; Al-Gadani et al., 2009; Melnyk et al., 2012; Rose et al., 2012a; Rossignol and Frye, 2012a) and their parents (James et al., 2008). Genetic variations in glutathione-related pathways have been observed in ASD (Boris et al., 2004; James et al., 2006; Bowers et al., 2011; Frustaci et al., 2012) and have been correlated in some studies with ASD behaviors (Goin-Kochel et al., 2009; Guo et al., 2012). "

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    • "Folic acid is an essential metabolite that plays a crucial role in methylation reactions throughout the body. It has been reported that some symptoms of autism may be improved and folate metabolism normalises with folic acid supplements (James et al., 2009; Ramaekers, Blau, Sequeira, Nassogne, & Quadros, 2007). Children born to women taking prenatal vitamin supplements also have lower scores of autistic behaviours compared to children with mothers who never or rarely took supplements (Braun et al., 2014). "
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    ABSTRACT: It has recently proposed that vitamin D and folate may be involved in the etiology of autism. We investigated the serum levels of vitamin D, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and folate in 54 young children, aged 3-8 years, with autism spectrum disorders (ASD) and in 54 age and gender matched normal controls. Vitamin D, Ca, P, ALP and folate levels in children with ASD were not different from control group. The correlational analysis in children with ASD revealed that Aberrant Behavior Checklist, Autism Behavior Checklist, and Childhood Autism Rating Scale scores and the level of cognitive development were not correlated with these laboratory findings. Our findings do not support the idea that serum levels of vitamin D and folate might be low in children with ASD. Nevertheless, it is possible that vitamin D and folate deficiency may be playing role in development of ASD at earlier ages or during prenatal period.
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    • "Thus, the use of KGD could be beneficial in ASD given that higher rates of mitochondrial ROS production and compromised cellular antioxidant status (69, 95, 96) have been reported in peripheral cells from children with ASD (44, 68, 69). "
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    ABSTRACT: The ketogenic diet (KGD) has been recognized as an effective treatment for individuals with glucose transporter 1 (GLUT1) and pyruvate dehydrogenase (PDH) deficiencies as well as with epilepsy. More recently, its use has been advocated in a number of neurological disorders prompting a newfound interest in its possible therapeutic use in autism spectrum disorders (ASD). One study and one case report indicated that children with ASD treated with a KGD showed decreased seizure frequencies and exhibited behavioral improvements (i.e., improved learning abilities and social skills). The KGD could benefit individuals with ASD affected with epileptic episodes as well as those with either PDH or mild respiratory chain (RC) complex deficiencies. Given that the mechanism of action of the KGD is not fully understood, caution should be exercised in ASD cases lacking a careful biochemical and metabolic characterization to avoid deleterious side effects or refractory outcomes.
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