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

Abstract

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 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.

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.

Figures

FIGURE 1

Diagram of tetrahydrofolate (THF)-dependent pathway of methionine transmethylation to homocysteine and the transsulfuration pathway from homocysteine to GSH synthesis. MS, methionine synthase; SAH, S-adenosylhomocysteine; SAHH, SAH hydrolase; GSSG, oxidized glutathione disulfide; SAM, S-adenyosylmethionine; MTase, methyltransferase.

FIGURE 2

Study design and patient follow-up.

FIGURE 3

Scatterplots of individual data for plasma cysteine (A), GSH:GSSG ratios (B), and GSSG concentrations (C) from 40 autistic children before and after 3-mo treatment with methylcobalamin and folinic acid. GSH, glutathione; GSSG, oxidized disulfide form of glutathione.