Summary

This small, randomized placebo-controlled trial found that sulforaphane, an extract of broccoli, given daily to males (ages 13-27) with autism spectrum disorder (ASD), showed significant improvement in autism symptoms from 4-18 weeks of treatment, compared with placebo. Significant improvements were seen in social interaction, abnormal behavior, and verbal communication. This effect did not persist 4 weeks after ending treatment. Symptoms were rated by both parents/caregivers as well as clinicians. Sulforaphane was selected for its low toxicity and its capacity to reverse biochemical abnormalities seen in ASD, including neuroinflammation.

Design

• Randomized controlled trial.
• N=44 male patients, ages 13-27, with moderate to severe ASD randomized (2:1) to receive 18 weeks of:
  • Sulforaphane (n=29)
  • Placebo (n=15)
• Sulforaphane is a phytochemical derived from broccoli, previously observed to induce transcriptional up-regulation of genes involved in protection of cells from oxidative stress, inflammation, and radiation.
• Anecdotal reports suggest a temporary improvement in ASD symptoms during febrile illness. Fever and sulforaphane both up-regulate heat-shock proteins, so this study was based on the premise that sulforaphane may cause a similar response in patients with ASD who are fever responders. Randomization was in two strata defined by history of improvement in ASD symptoms during febrile illness, as reported by parents.
• Sulforaphane or placebo were taken daily for 18 weeks. Dose of sulforaphane ranged from 50-150 micromoles, based on body weight.
• Setting: the Lurie Center for Autism of the Massachusetts General Hospital for Children, from 2011-2013.
• Primary outcomes, evaluated before, during, and after intervention:
  • Aberrant Behavior Checklist (ABC), completed by parents/caregivers.
  • Social Responsiveness Scale (SRS), completed by parents/caregivers.
  • Clinical Global Impression Severity (CGI-S) scale, completed by study physicians.
  • Clinical Global Impression Improvement (CGI-I) scale, completed by study physicians.

Results

• Sulforaphane group showed significant improvement compared with placebo group at 4, 10, and 18 weeks, based on parent/caregiver-based ABC scores. These effects were no longer seen 4 weeks after discontinuing treatment.
• At 18 weeks, the physician-derived CGI-I scale showed significant improvement in several ASD symptoms. Percent who were much or very-much improved, sulforaphane vs placebo:
  • Social interaction: 46% vs 0% (P=0.007)
  • Aberrant behavior: 54% vs 9% (P=0.014)
  • Verbal communication: 42% vs 0% (P=0.015)
• Blinded clinicians reported that 13 of the 40 participants who returned to the week 4 visit showed noticeable improvement in sociability and behavior, and all 13 were in the sulforaphane group.
• Before unblinding, families and caregivers reported gradual changes within the first 4 weeks of treatment in 18 of the 40 participants, and 17 of these were in the sulforaphane group.

Reference

Singh K, Connors SL, Macklin EA, et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci USA. 2014;111(43):15550-15555. doi:10.1073/pnas.1416940111.