Yes folks... broccoli chemical impacts on autism presentation

Please do not adjust your set. Broccoli, or least a chemical found in broccoli called sulforaphane has, under placebo-controlled, double-blind experimental conditions, been reported to impact on the presentation of autism according to the paper by Kanwaljit Singh and colleagues [1] (open-access).

Eat your greens @ Fir0002/Flagstaffotos

I had to do a bit of a double-take myself when I first read about these results (see here). Indeed, even the authors themselves seemed to be a little taken aback by their own findings if other media on this study is to be believed (see here). Still peer-reviewed science is peer-reviewed science and that goes just as much for this study as any other.

The paper is open-access but a few details might be useful:

• The study was previously registered in the US ClinicalTrials.gov database (see here). It involved comparing "capsules of sulforaphane-rich broccoli sprout extracts" with "indistinguishable placebo capsules" containing microcrystalline cellulose (wood pulp) in a small group of young men (aged 13-27 years) diagnosed with an autism spectrum disorder (ASD) administered daily over 18 weeks. As I mentioned, the study was also double-blind.
• Various measures - behavioural and physiological - were recorded at baseline (prior to study start) and at choice points during the 18 week study period. The results of the behavioural measures including the Aberrant Behaviour Checklist (ABC) and Social Responsiveness Scale (SRS) completed by parents/caregivers and the Clinical Global Impression Severity (CGI-S) and the Clinical Global Impression Improvement (CGI-I) scales completed by "study physicians" are included in the main paper results and conclusions.
• Results: well, first and foremost there were a few adverse events reported during the trial. The authors note that: "Sulforaphane treatment effectively improved core aberrant behaviors of ASD, and was safe and well-tolerated". But... "the sulforaphane group gained significantly more weight over the 18-wk period, compared with placebo" and there was mention of "single unprovoked seizures" occurring in two participants taking the active treatment. These seizures may well be unconnected to the sulforaphane capsules but one cannot rule out the possibility that they were connected.
• Forty participants completed the trial, or at least "part of the outcome measure evaluations" boiling down to "14 placebo and 26 sulforaphane". The statistical evaluation undertaken involved looking at "the differences between scores of individuals at 4, 10, 18, and 22 wk from their respective average pretreatment values". But the authors also undertook a separate intention-to-treat analysis that "included all 44 participants".
• The headlines: "many of the participants who were treated with sulforaphane in this study had statistically significant and clinically meaningful improvements during treatment with sulforaphane". With all due respect to parent/caregiver reports, I was particularly drawn to the fact that study physicians although blinded to who was on active treatment and who was taking a placebo were able to rate "13 of the 40 participants" as showing noticeable improvements in behaviour and sociability and "all were receiving sulforaphane". That's quite a feat by any study's standard.
• The authors conclude: "The substantial improvements of individual ASD patients’ trajectories were conspicuous and suggest that further investigation of sulforaphane in ASD is promising".

These are interesting results crying out for further independent [longer term] replication. The fact also that this was a trial of adolescents and adults with autism also fills a gap in the autism research market alluded to in previous posts on this blog (see here). 

Mechanism of effect? Well, there does seem to be quite a bit more to do in this area. The authors note that sulforaphane "was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD". Oxidative stress does indeed appear on the research radar when it comes to autism, at least some autism (see here) and sulforaphane fits the bill in terms of its potential 'protective' effects [2]. I've also talked about such mechanisms with another source of sulforaphane in mind (see here). That all being said, I don't doubt that there may be other biological processes at work.

So, in conclusion 'eat your greens' might very well be an important phrase for some on the autism spectrum. Whether eating the source material carries the same effect or will be equally well received as taking a daily pill is another matter...

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[1] Singh K. et al. Sulforaphane treatment of autism spectrum disorder (ASD). PNAS. 2014. October 13.

[2] Guerrero-Beltrán CE. et al. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol. 2012 Jul;64(5):503-8.

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Kanwaljit Singh, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, & Andrew W. Zimmerman (2014). Sulforaphane treatment of autism spectrum disorder (ASD) PNAS : 10.1073/pnas.1416940111