Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism.
OBJECTIVE
The study objectives were to determine whether methyl B12 treatment improves behavioral measures in children with autism and whether improvement is associated with increased plasma concentrations of glutathione (GSH) and an increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), both of which have been previously identified to be low in children with autism.


METHODS
This was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methyl B12. Following this 12-week study, subjects were given the option of entering a 6-month open-label trial of methyl B12.


METHODS
All procedures took place at the UC Davis M.I.N.D. Institute.


METHODS
Subjects were 3 to 8 years old with autism.


METHODS
All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks.


METHODS
Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12.


RESULTS
Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. Nine (9) subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG.


CONCLUSIONS
Comparison of the overall means between groups suggests that methyl B12 is ineffective in treating behavioral symptoms of autism. However, detailed data analysis suggests that methyl B12 may alleviate symptoms of autism in a subgroup of children, possibly by reducing oxidative stress. An increase in glutathione redox status (GSH/GSSG) may provide a biomarker for treatment response to methyl B12. Additional research is needed to delineate a subgroup of potential responders and ascertain a biomarker for response to methyl B12.
Bertoglio
Kiah
K
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center, Sacramento, CA, USA.
Jill James
S
S
Deprey
Lesley
L
Brule
Norman
N
Hendren
Robert L
RL
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D015415:Biomarkers; D014815:Vitamins; D005978:Glutathione; D014805:Vitamin B 12