For the study, Richard Frye, M.D., Ph.D., of the Arkansas Children’s Hospital and colleagues randomly assigned 48 children (aged 3 to 14 years) diagnosed with ASD and language impairment to receive either daily folinic acid (2 mg/kg, capped at 50 mg) or placebo for 12 weeks. Researchers used the CELF-preschool-2, CELF-4, and the Preschool Language Scale-5 instruments to measure changes in verbal communication.
At the end of the 12-week period, the children taking folinic acid showed significantly greater improvements in verbal communication than placebo (an average of 5.7 standardized points better). Several secondary measures such as daily living skills, stereotypic behaviors, and internalizing problems also improved more in the folinic acid groups.
Frye and colleagues also screened the children for the presence of antibodies to the folate receptor alpha (FRAAs) in the blood, which would indicate a dysfunction in the transport of folate from the blood to the brain. They found that children with positive FRAA results showed a particularly strong improvements in verbal communication when given folinic acid (about 7.3 standardized test points).
“This study suggests that FRAAs predict response to high-dose folinic acid treatment,” the authors wrote. “[F]uture studies will be needed to define factors that predict response to treatment, investigate optimal dosing and help understand whether other compounds could work synergistically with folinic acid.”
While no serious adverse events were reported by children in the folinic acid group, the authors did caution that “[s]ince ASD is likely a lifelong disorder the long-term adverse effect of any treatment is a concern. As folinic acid may increasingly become used to treat ASD in the future, short-term and long-term adverse effects should be studied in more detail to ensure safety.”
For related information, see the Psychiatric News article “Program Teaches Social Skills to Adolescents With Autism” and the American Journal of Psychiatry article “Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior.”