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Clinical and Laboratory Results From Randomized Controlled Trial of Methylcobalamin Injections for Children with Autism

Saturday, 4 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
F. Widjaja1, J. E. Choi1, S. Bent1, S. J. James2 and R. L. Hendren1, (1)University of California, San Francisco, San Francisco, CA, (2)University of Arkansas for Medical Sciences, Little Rock, AR

Methylcobalamin (MB12) injection may act as a superoxide free radical scavenger (antioxidant) to decrease homocysteine levels and chronic oxidative stress in children with autism.


To determine if methylcobalamin supplementation can improve behavioral measures in children with autism; if improvement is associated with biomarkers in methylation pathway; and if a predictor of positive behavioral response can be found in this pathway.


This is an 8-week, double-blind, randomized, placebo-controlled study of injectible methyl B12 in 50 children with autism, followed by an optional open-label extension study lasting eight to 16 weeks. Behavioral assessments and blood samples are obtained at baseline, weeks 8 and 16.

75 mcg/kg methylcobalamin or placebo subQ were administered by parents once every 3 days for 8 weeks. The primary outcome measure was the CGI-I (Clinical Global Impression-Improvement).  Secondary measures included the ABC (Aberrant Behavior Checklist), BASC (Behavior Assessment System for Children), CCC (Children’s Communication Checklist), SRS (Social Responsiveness Scale) and PDDBI (Pervasive Development Disorder Behavior Inventory).


Fifty subjects ( 40 males, 10 females; aged 2 year 11 months to 7 year 9 months) were randomized in the study. Forty four subjects have completed the study and six are currently ongoing.  Plasma B12 levels were not deficient at baseline but were in high normal range (~900 pg/ml). Methyl B12 injections were well tolerated. 19 responders (43%) were identified out of the 44 subject who completed the study. 13 of them were on active B12 and 6 were on placebo. Chi-square analysis of CGI-I responder status compared to baselinewas marginally significant (p=.06). Responders were defined as having CGI Improvement as very much improved (1) or much improved (2). Mean values of the CGI-I are significantly lower in active B12 group compared to the placebo group (t-test, p=.01).

Compared to the placebo group, the MB12 group demonstrated significant improvement after 8 weeks on the ABC irritability subscale (p=.01), the ABC hyperactivity subscale (p=.02), the BASC Externalizing subscale (p=.05), the BASC Behavioral Symptoms Index (p=.08), the CCC Syntax (p=.02) and the CCC Initiation subscale (p=.05).. Higher homocysteine & SAH predicts positive behavior response (p=.02). Lower SAM/SAH predicts positive behavior response (p=.03). Within the methylcobalamin group, homocysteine and SAH levels were significantly reduced from baseline after treatment. Homocysteine levels were positively correlated with SAH only at levels ≥9 μmol/L in the methylcobalamin treated group.


Methylcobalamin injections (75μg/Kg) three times weekly significantly lowered the mean CGI-I score, the ABC irritability and hyperactivity subscales and significantly reduced plasma homocysteine levels compared to placebo in children with autism. Data from this study support the potential usefulness of methyl B12 for treating irritability in children with autism. Predictors of positive behavioral response included Homocysteine, SAH and SAM/SAH ratio. Methylcobalamin may be acting as a free radical scavenger.

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