Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism.
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.


METHODS
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.


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.


CONCLUSIONS
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.
James
S Jill
SJ
Department of Pediatrics and Biostatistics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA. jamesjill@uams.edu
Melnyk
Stepan
S
Fuchs
George
G
Reid
Tyra
T
Jernigan
Stefanie
S
Pavliv
Oleksandra
O
Hubanks
Amanda
A
Gaylor
David W
DW
D001321:Autistic Disorder / Q000097:blood / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006801:Humans; D002955:Leucovorin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008745:Methylation; D009752:Nutritional Status; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D014803:Vitamin B Complex / Q000097:blood / Q000494:pharmacology*
D014803:Vitamin B Complex; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C019476:mecobalamin; D005978:Glutathione; D014805:Vitamin B 12; D002955:Leucovorin