Abstract: Objective To evaluate folic acid,homocysteine (Hcy),and glutathione (GSH) redox metabolism,and to evaluate the efficacy of folic acid supplementary on methylation cycles and oxidative stress in autistic children.Methods Fifty-three autistic children were enrolled in a case-control study.Folic acid,Hcy,and GSH metabolism in serum were measured by traditional methods and compared with fifty-three age-matched unaffected children.Eighty-three autistic children were enrolled in an open-label trial and participated in three months of structured teaching.Children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group),while the remaining received no supplementary (control group).Psychoeducational Profile-third edition (PEP-3) was measured at the beginning and end of the treatment.Folic acid,Hcy,and GSH metabolism in plasma were measured by high-pressure liquid chromatography before and after treatment and compared with 29 age-matched unaffected children.Results The results indicated significant differences in the serum concentrations of the folic acid,Hcy,GSH,oxidized glutathione disulfide (GSSG),and the ratio of GSH/GSSG between autistic children and matched healthy controls.The results illustrated folic acid intervention improved autism symptoms in cognitive verbal/preverbal,receptive language,and affective expression.Folic acid treatment improved the plasma concentrations of folic acid,Hcy,and GSH redox metabolism.The change of characteristic verbal behaviors scores in PEP-3 was negatively correlated with the change of Hcy(r =-0.411,P=0.027).Conclusion Autistic children have lower folic acid,higher Hcy and GSH/GSSG ratio than healthy controls.Folic acid supplementation could normalize methylation capability and oxidative stress status,moreover,folic acid supplementation may play a certain role in treatment response among autistic children.