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.

Conflict of interest statement

Conflict of interest statement: U.S. patent applications have been filed by The Johns Hopkins University (inventors K.D.S., P.T., and A.W.Z.). P.T. and A.W.Z. have divested themselves from all potential financial benefits. The sulforaphane-rich broccoli sprout extract is not a commercial product. Broccoli sprouts and seeds rich in glucosinolates have been licensed by Johns Hopkins to Brassica Protection Products LLC (A. Talalay, son of P.T., is chief executive officer).

Figures

Fig. 1.

Schedule for study of the effects of sulforaphane in ASD.

Fig. 2.

Changes in total ABC and SRS scores. Forty male ASD participants who were treated daily with either placebo (initially n = 14) or sulforaphane (initially n = 26) for 4, 10, and 18 wk, followed by a terminal 4-wk untreated period (22 wk). Panels A (ABC) and D (SRS) show all observations. Means of changes in raw, unadjusted total scores (±SEM) at 4, 10, 18, and 22 wk are shown in B for ABC and E for SRS. Reductions in ABC score upon sulforaphane treatment were −20.2% (P = 0.035), −31.5% (P = 0.002), and −33.6% (P < 0.001), at 4, 10, and 18 wk, respectively. The corresponding changes in SRS were −12.2% (P = 0.29), −12.2% (P = 0.080), and −16.8% (P = 0.017). Panels C (ABC) and F (SRS) show the changes in total scores at all timepoints for placebo- and sulforaphane-treated participants. All changes were calculated from the initial values for each individual participant at time 0 (the means of the two values obtained at screening and at enrollment).

Fig. 3.

Changes in ABC subscores for irritability, lethargy, stereotypy, and hyperactivity. After 4, 10, and 18 wk of treatment with sulforaphane or placebo, and a 4-wk untreated recovery period (22 wk). Raw, unadjusted mean values of changes (±SEM) for sulforaphane- and placebo-treated participants are shown. Changes were significant at the 95% confidence level (*) for both irritability and lethargy at 10 and 18 wk of treatment.

Fig. 4.

Total scores for (A) ABC and (B) SRS of individual placebo- and sulforaphane-treated participants at baseline and after 18 wk. At 18 wk, total ABC scores were available for 35 (10 placebo and 25 sulforaphane) and total SRS scores for 37 (11 placebo and 26 sulforaphane). Only the differences for sulforaphane treatment were significant at 18 wk, thus a change in score of from 62.4 to 45.0 on the ABC scale (A) was significant (P < 0.001), and a change in score of from 121.5 to 105.2 on the SRS scale (B) was significant (P < 0.001). Means for the subjects shown, at 1 and 18 wk respectively, for placebo treatment, were 62.4 and 62.6 on the ABC scale, and 121.5 and 117.5 on the SRS scale.