Randomized controlled trial2018Open access

Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli

Bent S, Lawton B, Warren T, Widjaja F, Dang K, Fahey JW, Cornblatt B, Kinchen JM, Delucchi K, Hendren RL

Molecular autism · 92 citations

Review labels

Author industry ties

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design
Randomized controlled trial (indexed by PubMed)
Studied in
People
Main outcome
Health markers and function
Intake measured by
Not stated

Who paid for it

Funding
Possibly industry funded
Nonprofit
JS Foundation
Authors
At least one author declares a financial tie to industry

Based on 1 listed funder(s) and full-text disclosure statement.

Publication

Published
2018-05-29 · Mol Autism · vol. 9 · issue 1 · p. 35
Publisher
BioMed Central
Cited
113 citations · more than 96% of similar papers · 4.2× the field average
Impact
Top 10% most cited in its field
References
36 works
Access
Open access (journal) · CC-BY
Research areas
Genomics, phytochemicals, and oxidative stress · Sirtuins and Resveratrol in Medicine · Tryptophan and brain disorders
Keywords
Sulforaphane, Autism, Urinary system, Neuropsychology, Neurology, Medicine, Identification (biology), Autism spectrum disorder, Psychiatry, Internal medicine, Biology, Cognition, Botany
MeSH
humans, brassica, isothiocyanates, sulfoxides, antioxidants, social behavior, autistic disorder, adolescent, child, female, male, metabolome, young adult, biomarkers

10 authors

From US

  • Stephen Bent · correspondingSan Francisco VA Medical Center; University of California, San Francisco; University of California San Francisco Medical Center
  • Brittany LawtonUniversity of California, San Francisco
  • Tracy L. WarrenUniversity of California, San Francisco
  • Felicia WidjajaUniversity of California, San Francisco
  • Katherine DangUniversity of California, San Francisco
  • Jed W. FaheyJohns Hopkins University

Abstract

Background

Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action.

Methods

Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist-ABC) and social responsiveness (Social Responsiveness Scale-SRS) were measured at baseline and at the end of the study. Pearson's correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite.

Results

Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved - 7.1 points (95% CI - 17.4 to 3.2), and the SRS improved - 9.7 points (95% CI - 18.7 to - 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism.

Conclusions

Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD.

Trial registration

This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016.

Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).

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