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Mol Autism. 2018 May 30;9:35. doi: 10.1186/s13229-018-0218-4. eCollection 2018.

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

Author information

1
1Department of Psychiatry, University of California, San Francisco, 401 Parnassus, LP-119, San Francisco, CA 94143 USA.
2
2Department of Epidemiology and Biostatistics, University of California, San Francisco, 401 Parnassus, LP-119, San Francisco, CA 94143 USA.
3
Department of Medicine, UCSF, SFVAMC, 111-A1, 4150 Clement St, San Francisco, CA 94121 USA.
4
3Departments of Medicine, Pharmacology and Molecular Sciences, International Health, and Cullman Chemoprotection Center, Johns Hopkins University, 855 N. Wolfe St. Ste. 625, Baltimore, MD 21205 USA.
5
Nutramax Laboratories Consumer Care, Inc, 2208 Lakeside Blvd, Edgewood, MD 21040 USA.
6
5Metabolon, Inc, 617 Davis Dr. Suite 400, Durham, NC 27713 USA.

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.

KEYWORDS:

Antioxidant; Autism; Biomarker; Metabolomics

PMID:
29854372
PMCID:
PMC5975568
DOI:
10.1186/s13229-018-0218-4
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The study was approved by the Committee on Human Research at the University of California, San Francisco (UCSF) on November 5, 2015. Informed consent was obtained from the parent/caregiver of all study participants.RLH reports research grants from Curemark, BioMarin, Roche, Shire, Sunovion, Vitamin D Council and Advisory Boards for Curemark, BioMarin, Neuren, and Janssen. None of these grants or companies are directly involved in the subject of the current study. JWF was a co-author on the first randomized controlled trial examining the efficacy of sulforaphane and manufactured the product used in that study, which found a beneficial effect. BC is the Medical Director and Director of Consumer Product Support for Nutramax Laboratories Consumer Care, Inc., which supplied the sulforaphane supplement and matching placebo for this study at no cost. JMK is a senior scientist for Metabolon, which performed the metabolomic analyses for this study under a paid contract. All other authors declare that they have no conflict of interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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