Sulforaphane, a natural product derived from broccoli, shows promise in alleviating symptoms of autism
Sulforaphane treatment of autism spectrum disorder. Proceedings National Academy of Sciences: 2014-16940: K Singh, SL Connors, EA Macklin, KD Smith, JW Fahey, P Talalay, AW Zimmerman. From Johns Hopkins University School of Medicine; Massachusetts General Hospital, Harvard University; University of Massachusetts Medical School.
Fast / Facts Novelty
- Autism is a life-long, complex neurodevelopmental disorder, characterized by difficulties in communication and social interaction and by stereotypic, repetitive behavior.
- Its global prevalence is rising, and it afflicts 1-2% of children world-wide, predominantly males.
- There is currently no scientifically-accepted treatment that targets the core mechanisms of autism.
- In a randomized, placebo-controlled, double-blind clinical study, daily administration of sulforaphane to young male patients with moderate to severe autism (26 on sulforaphane, 14 on placebo) substantially (and reversibly) improved many aspects of behavior in the majority of those who received sulforaphane.
- Sulforaphane is a phytochemical derived from broccoli and other crucifers, and can be relatively easily administered in the diet.
- Sulforaphane protects against oxidative stress, depressed antioxidant capacity and glutathione synthesis, increased lipid peroxidation, enhanced neuroinflammation, and mitochondrial dysfunction. It can therefore counteract many of the same biochemical and molecular abnormalities that are characteristic features of autism.
- There were virtually no adverse effects of sulforaphane.
Background
The behavioral symptoms of autism, including poor social interaction and verbal communication, were first described 70 years ago by Leo Kanner, founder of pediatric psychiatry at Johns Hopkins.
In 1992, the Talalay research group isolated sulforaphane from broccoli based on its potent ability to stimulate the activities of genes that bolster the natural defenses of cells against oxidative stress, inflammation, and DNA-damaging chemical agents. The seemingly far-fetched idea of testing a dietary compound from broccoli, extensively studied for its ability to prevent cancer, to treat autism arose from the realization that similar biochemical abnormalities are also characteristic of autism.
The researchers report in the Proceedings of the National Academy of Sciences (Early publication after 3 p.m. Oct. 13, 2014) that those who received daily doses of sulforaphane (produced by broccoli and other cruciferous vegetables) experienced substantial improvements in their social interaction and verbal communication, as well as reduction in repetitive, ritualistic behaviors, compared to those who received placebo.
Despite extensive investigation into the causes of ASD and potential pharmaceutical interventions, there are currently few medical options other than efforts to ameliorate some of the most distressing symptoms. The authors believe that this study is one of few that attempts to correct the underlying cellular problems of ASD, and may thereby provide insight into fundamental causative mechanisms.
Many of these biochemical abnormalities of autism are related to metabolism at the cellular level, and studies show that the cells of those with ASD often have high levels of “oxidative stress,” which is the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.
Intriguingly, about half of parents report that their children’s autistic behavior improves substantially during episodes of febrile illness, and then reverts to baseline when the fever is gone. In 2007, Zimmerman, a principal in the current study, confirmed these anecdotal observations, though a mechanism for the fever effect was not identified. In an unusual and innovative approach, Zimmerman, Talalay, and Smith hypothesized that sulforaphane, which can mimic aspects of the fever processes at the cellular level, might improve symptoms of autism. The current study was designed to test the unusual idea that these two phenomena were related and whether improving cellular health could influence autism symptoms.
The patients’ parents/caregivers and physicians completed three widely-accepted standard behavioral assessments: Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Clinical Global Impressions-Improvement scale (CGI-I). These assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions, and other behaviors related to autism.
Twenty-six of the subjects were randomly selected to receive 50 to 150 micromoles (9 to 27 mg) of sulforaphane daily, based on their weight, or to receive placebo (n = 14). Behavioral assessments were again performed at 4, 10, and 18 weeks while treatment continued. A final assessment occurred for most of the participants 4 weeks after the end of treatment.
Most of those who responded to sulforaphane showed significant improvements by the first measurement after 4 weeks, and continued to improve during the rest of the treatment period. After 18 weeks, the average ABC and SRS scores of those who received sulforaphane had decreased 34 and 17 percent, respectively, with small to moderate improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation, and mannerisms.
Thus 13 of the 26 sulforaphane-treated subjects were observed to improve by family, friends and study staff: they were calmer, more socially interactive (on SRS and ABC, rated by parents) and autistic symptoms were “much or very much improved” on the Clinical Global Impressions scale (rated by study staff). Another 4 subjects improved by the rating scales but we did not predict that they were taking sulforaphane. All of these assessments and predictions were done during the study when both parents/caregivers and study staff were “blinded.” Remarkably, researchers reported that some treated subjects looked them in the eye and shook their hands, which they had not done before.
After 18 weeks of treatment, using the CGI-I scale, 46, 54, and 42 percent of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors, and verbal communication, respectively. The scores of those who took sulforaphane trended toward baseline values when sulforaphane was discontinued.
Zimmerman adds that the impressions of the clinical team (including parents), before they learned which subjects received sulforaphane or placebo, were that 13 of the participants dramatically improved. We found later that all 13 had been taking sulforaphane, which is half of the treatment group.
Conduct of Clinical Studies
Studies on the effects of sulforaphane on autism were designed at Johns Hopkins by Andrew W. Zimmerman in collaboration with Paul Talalay and Kirby D. Smith. Jed W. Fahey prepared the sulforaphane-rich broccoli sprout extract that was administered in capsules to the patients. The clinical studies were done at the Lurie Center (Lexington, MA) which is dedicated to the study of autism and is a satellite of the Department of Pediatrics of the Massachusetts General Hospital. Kanwaljit Singh, now a Research Associate at UMass Medical School, helped organize, conduct the study and performed statistical analyses. Other authors include Eric Macklin and Susan Connors, associated with Harvard Medical School.
Support
This work was supported by grants from the Nancy Lurie Marks Family Foundation, the Hussman Foundation, the Lewis B. and Dorothy Cullman Foundation, the Agnes Gund Foundation, the N of One Foundation, and the Brassica Foundation for Chemoprotection Research.
Conflict of Interests
U.S. patent applications have been filed by Johns Hopkins University (inventors A.W. Zimmerman, P. Talalay and K. D. Smith). Talalay and Zimmerman 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 University to Brassica Protection Products LLC (Antony Talalay, son of Paul Talalay, is the chief executive officer).The university owns stock in Brassica Protection Products.
Andrew W. Zimmerman, M.D.
Clinical Professor of Pediatrics (Neurology)
UMass Memorial Medical Center
University of Massachusetts Medical School
55 Lake Avenue, Worcester, MA, 01655
Tel: (508) 856-3279 | Fax: (508) 856-4287
Cell: (410)-935-0488
Email:Andrew.Zimmerman@umassmemorial.org
Paul Talalay, M.D
John Jacob Abel Distinguished Service Professor
Lewis B. and Dorothy Cullman Chemoprotection Center
Department of Pharmacology and Molecular Sciences
Johns Hopkins School of Medicine
725 N. Wolfe Street, Baltimore, MD 21205
Tel: (410) 955-3499 | Fax: 410-502-6818
Email: ptalalay@jhmi.edu
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