A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Summer, 2021 | Number 3, Volume 35

Researchers explore effects of sulforaphane on behavior, biomarkers of children with ASD

While research indicates that sulforaphane—a molecule found in cruciferous vegetables such as broccoli—can improve the symptoms of individuals with autism spectrum disorders (ASD), a new study suggests that the benefits for children may be modest. However, it also indicates that sulforaphane can improve biomarkers of oxidative stress, inflammation, and mitochondrial function. 

In previous research, Andrew Zimmerman and colleagues found that administering sulforaphane to young men with ASD led to significant clinical benefits that persisted at a three-year followup. A separate open-label trial detected clinical improvements and changes in urinary metabolites in children and young adults after sulforaphane treatment. 

In the new study, Zimmerman and his team administered sulforaphane to 57 children with ASD between three and 12 years of age. In the first phase of the study, which was randomized and double-blind, participants took either sulforaphane or a placebo for 15 weeks. In the second open-label phase of the study, all participants took sulforaphane for another 15 weeks. (Forty children completed both phases.) The study concluded with a six-week “washout” period. 

The researchers report, “We found that sulforaphane was safe, but based upon the OACIS-1 [Ohio Autism Clinical Impressions Scale], our primary clinical outcome measure, its effects were not significant. Effect size estimates showed small improvements with sulforaphane, though not significant, for the general level of autism on the OACIS-I scale. There was significant improvement on one of the secondary measures (the Aberrant Behavior Checklist) but not on the Social Responsiveness Scale-2.” Larger beneficial effects were seen in a subsample of participants with non-severe ASD. 

Both groups of children improved during the open label trial, during which all of them were taking sulforaphane. “Notably,” the researchers say, “the social interaction severity subscale improved greatly among the (former) placebo group at week 22 when taking sulforaphane. 

While it may have been an ‘open-label’ effect, this finding coincides with the results from our previous trial of sulforaphane in young men.” While the improvements seen in children taking sulforaphane were small, the researchers say, “The clinical efficacy of sulforaphane in ASD in children in this trial and our previous trial in young men compares favorably to intranasal oxytocin and bumetanide in recent placebo-controlled clinical trials. Although outcome measures and statistical power differed between this study and the other two, sulforaphane appears to enhance socialization like oxytocin and improves other core features of ASD similar to bumetanide.” They add, “As a ‘natural’ dietary component, sulforaphane may have less potential for toxicity than either drug with long term use, although further studies of sulforaphane are needed in children with ASD, for both long-term safety and efficacy.” 

The researchers also report, “Biomarkers provided strong evidence for the biologic effects of sulforaphane, especially with respect to markers of glutathione redox status [a biomarker for oxidative stress], inflammatory cytokines, and mitochondrial function… These were promising findings that require further investigation of both the clinical effects and mechanisms of action of sulforaphane.” 

Side effects of sulforaphane treatment were mild, the researchers say, and included rare insomnia, irritability, and intolerance to sulforaphane’s taste and smell.


Citations

“Randomized controlled trial of sulforaphane and metabolite discovery in children with autism spectrum disorder,” Andrew W. Zimmerman, Kanwaljit Singh, Susan L. Connors, Hua Liu, Anita A. Panjwani, LiChing Lee, Eileen Diggins, Ann Foley, Stepan Melnyk, Indrapal N. Singh, S. Jill James, Richard E. Frye, and Jed W. Fahey, Molecular Autism, May 25, 2021 (free online). Address: Andrew Zimmerman, Department of Pediatrics, University of Massachusetts Medical School, 55 N. Lake Avenue, Worcester, MA 01655, [email protected]