title: Sulforaphane treatment of autism spectrum disorder (ASD).
abstract: Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.
authors.affiliation: Lurie Center for Autism, Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Lexington, MA 02421; Department of Pediatrics (Neurology), University of Massachusetts Medical School, Worcester, MA 01655;
authors.forename: Kanwaljit
authors.initials: K
authors.lastname: Singh
authors.affiliation: Lurie Center for Autism, Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Lexington, MA 02421;
authors.forename: Susan L
authors.initials: SL
authors.lastname: Connors
authors.affiliation: Department of Medicine, Massachusetts General Hospital Biostatistics Center and Harvard Medical School, Boston, MA 02114; and.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.affiliation: McKusick-Nathans Institute for Genetic Medicine and.
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Smith
authors.affiliation: Department of Pharmacology and Molecular Sciences, Lewis B. and Dorothy Cullman Chemoprotection Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Jed W
authors.initials: JW
authors.lastname: Fahey
authors.affiliation: Department of Pharmacology and Molecular Sciences, Lewis B. and Dorothy Cullman Chemoprotection Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 ptalalay@jhmi.edu Andrew.Zimmerman@umassmemorial.org.
authors.forename: Paul
authors.initials: P
authors.lastname: Talalay
authors.affiliation: Lurie Center for Autism, Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Lexington, MA 02421; Department of Pediatrics (Neurology), University of Massachusetts Medical School, Worcester, MA 01655; ptalalay@jhmi.edu Andrew.Zimmerman@umassmemorial.org.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Zimmerman
mesh_terms: D000293:Adolescent; D000328:Adult; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy*; D006801:Humans; D017879:Isothiocyanates / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D012919:Social Behavior; D013454:Sulfoxides; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017879:Isothiocyanates; D010919:Placebos; D013454:Sulfoxides; C016766:sulforaphane