Journal Article

Sulforaphane treatment of autism spectrum disorder (ASD)

Macklin, Eric A., Singh, Kanwaljit, Connors, Susan L., Talalay, Paul, Smith, Kirby D., Zimmerman, Andrew W., Fahey, Jed W.

2014

Overview

Significance Autism spectrum disorder (ASD), encompassing impaired communication and social interaction, and repetitive stereotypic behavior and language, affects 1–2% of predominantly male individuals and is an enormous medical and economic problem for which there is no documented, mechanism-based treatment. In a placebo-controlled, randomized, double-blind clinical trial, daily oral administration for 18 wk of the phytochemical sulforaphane (derived from broccoli sprouts) to 29 young men with ASD substantially (and reversibly) improved behavior compared with 15 placebo recipients. Behavior was quantified by both parents/caregivers and physicians by three widely accepted measures. Sulforaphane, which showed negligible toxicity, was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD. 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Acute stress disorders / Adolescent / Adult / Antioxidants / Atrial heart septal defects / Autism / Autistic disorder / Biological Sciences / Brassica / Broccoli / caregivers / Child Development Disorders, Pervasive - drug therapy / clinical trials / DNA damage / Fever / gene expression regulation / genes / Humans / inflammation / Isothiocyanates - adverse effects / Isothiocyanates - therapeutic use / Male / males / men / Mental health care / oral administration / Oxidative stress / parents / Peroxidation / Pervasive child development disorders / Phosphorylation / physicians / Placebos / Social Behavior / Social interaction / Sprouts / stereotyped behavior / Stereotypes / toxicity / Treatment Outcome / Young Adult