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Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism^1,2,3

¹ From the Departments of Pediatrics (SJJ, SM, GF, TR, SJ, OP, and AH) and Biostatistics (DWG), University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR.

² Supported in part by funding from the National Institute of Child Health and Development (RO1 HD051873; to SJJ) and grants from the University of Arkansas for Medical Sciences Children's University Medical Group and the Arkansas Biosciences Institute (SJJ). Methylcobalamin was donated by Hopewell Compounding Pharmacy (Hopewell, NJ).

³ Reprints not available. Address correspondence to SJ James, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Slot 512-41B, Little Rock, AR 72202. E-mail: jamesjill{at}uams.edu.

Background: Metabolic abnormalities and targeted treatment trials have been reported for several neurobehavioral disorders but are relatively understudied in autism.

Objective: 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.

Design: In an open-label trial, 40 autistic children were treated with 75 µg/kg methylcobalamin (2 times/wk) and 400 µg 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.

Results: 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.

Conclusion: 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 clinicaltrials.gov as NCT00692315.

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				M. E. Geraghty, G. M. Depasquale, and A. E. Lane Nutritional Intake and Therapies in Autism: A Spectrum of What We Know: Part 1 ICAN: Infant, Child, & Adolescent Nutrition, February 1, 2010; 2(1): 62 - 69. [Abstract] [PDF]