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An open label trial was undertaken in 40 autistic children to determine whether treatment with metabolic precursors methylcobalamin and folinic acid would improve plasma biomarkers of oxidative stress and measures of core behavior using the Vineland Adaptive Behavior Scales (VABS). Metabolites involved in methionine and glutathione synthesis and VABS behavior scores were measured before and after a three month intervention period.
The results indicated that pre-treatment metabolites in autistic children were significantly different from values in age-matched control children. The three month intervention resulted in significant increases in cysteine, cysteinylglycine, and glutathione (GSH, p < 0.001). The oxidized disulfide form of glutathione (GSSG) was decreased (p < 0.008) and the glutathione redox ratio (GSH/GSSG) was increased after treatment (p < 0.001). Although significantly improved, these metabolites remained below control levels after intervention (p > 0.01). Similarly, increases in VABS composite score and sub-scores for Socialization, Communication, and Daily Living Skills increased after treatment (p < 0.007) but also remained below standard scores.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methyl B12 | Experimental | Subcutaneous injection of 75 micrograms/Kg |
|
| Folinic Acid | Experimental | 400 micrograms orally twice a day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylcobalamin (methylB12) | Drug | 75 ug/Kg methylB12 every 3 days by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glutathione redox status (GSH/GSSG) | HPLC analysis | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Vineland Adaptive Behavior Scales | Behavior measure | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| S. Jill James, PhD | University of Arkansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arkansas Children's Hospital Research Institute | Little Rock | Arkansas | 72202 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19056591 | Derived | James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009 Jan;89(1):425-30. doi: 10.3945/ajcn.2008.26615. Epub 2008 Dec 3. |
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| ID | Term |
|---|---|
| D001321 | Autistic Disorder |
| D001519 | Behavior |
| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C019476 | mecobalamin |
| D014805 | Vitamin B 12 |
| ID | Term |
|---|---|
| D045728 | Corrinoids |
| D045725 | Tetrapyrroles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 |
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| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |