Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder

BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on seve

Andrew W. Zimmerman, Kanwaljit Singh, Susan L. Connors, Hua Liu, Anita A. Panjwani, Li-Ching Lee, Eileen Diggins, Ann Foley, Stepan Melnyk, Indrapal N. Singh, S. Jill James, Richard E. Frye, Jed W. Fahey

Molecular Autism · 2021 · https://doi.org/10.1186/s13229-021-00447-5

Read the paper (22 pages)
Download the PDF (2.1 MB)

Abstract

BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen’s d 0.21; 95% CI – 0.46, 0.88 and 0.10; 95% CI – 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen’s d – 0.96; 95% CI – 1.73, – 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell. LIMITATIONS: The sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase. CONCLUSIONS: SF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers’ assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense.

Licence and reuse

LicenceCC-BY-4.0
May we host this PDF?Yes
May we publish a plain-language summary?Yes — this licence permits adaptations.
Commercial use permitted?Yes
Share-alike required?No

How to credit this work

Andrew W. Zimmerman; Kanwaljit Singh; Susan L. Connors; Hua Liu; Anita A. Panjwani; Li-Ching Lee; Eileen Diggins; Ann Foley; Stepan Melnyk; Indrapal N. Singh; S. Jill James; Richard E. Frye; Jed W. Fahey (2021). Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder. Molecular Autism. https://doi.org/10.1186/s13229-021-00447-5 Licensed under Creative Commons Attribution 4.0 (https://creativecommons.org/licenses/by/4.0/). Hosted by EVEC Athens (microgreens.org.gr). No changes were made to this article. Provided as-is, without warranties. EVEC Athens is not affiliated with, and this copy is not endorsed by, the authors or the publisher.

Explore this on our site

About this copy

This is a copy of the published article, hosted by EVEC Athens for free educational use under its open licence. The permanent scientific reference is the DOI above. We have not altered the file in any way. If you are an author or rights holder and want this copy removed, please use our notice and takedown procedure. We acknowledge every request within five working days, and act within ten.

Co-funded by the European Union.
This portal presents the microgreens methodology; the organisation behind it is EVEC Athens — the European Voluntary and Educational Center (evec.org.gr). Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the granting authority can be held responsible for them.

Open licence. Except where stated otherwise, the educational materials on this portal are licensed under CC BY 4.0 — free to use, adapt and share, including commercially, with credit. See the licence terms.

Accessibility. We aim for WCAG 2.1 AA and publish what does and does not yet meet it — see the accessibility statement. If anything here blocks you, tell us and we will send the material in a format that works for you.