The Efficacy of Folic Acid in Fragile X Syndrome and Other Developmental Disabilities

Folic acid is the parent compound of a family of molecules which are coenzymes for cellular DNA synthesis. Folate-deficient humans may show a variety of neuropsychiatric symptoms, and some reports suggest that folate administration in certain psychiatric populations may lead to beneficial changes. In the late 1970s, the in vitro expression of the fragile sites in human X chromosomes was demonstrated to be suppressed in culture media enriched with folic acid and thymidine. This in vitro phenomenon led to a series of 14 reports that used folic acid as a treatment for patients with fragile X syndrome and an additional case report of two mentally retarded children without fragile X syndrome. A reduction in the number of cells with fragile X sites was found during therapy. Although several uncontrolled case studies drew very optimistic conclusions about the therapeutic value of folic acid for psychiatric symptoms, the controlled investigations yielded more mixed findings. Evidence for a beneficial effect in postpubertal males was very limited, but four studies in prepubertal boys suggested a positive therapeutic effect. Studies employing doses higher than 10 mg/day did not show any therapeutic advantage. However, folic acid cannot be considered to have established efficacy for managing behavior problems or enhancing adaptive functioning in children or adolescents with fragile X syndrome. The possible use of folic acid in treating other developmental disorders is virtually unstudied.