SUMMARY OF SCIENCE

A Promising New Treatment for Autism Syndrome Disorder

(ASD)
SULFORAPHANE, A NATURAL PRODUCT DERIVED FROM BROCCOLI,
SHOWS PROMISE IN ALLEVIATING SYMPTOMS OF AUTISM
KEY FACTS/NOVELTY
Autism is a life-long, complex neurodevelopmental disorder, characterized by
difficulties in communication and social interaction and by stereotypic, repetitive
behavior.
I ts 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.
I n 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. I t 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 I nterest. 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.