QuestioningAnswers: "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."
So said the findings reported by Stephen Bent and colleagues  continuing a theme in autism research circles examining the use of a compound called sulforaphane - "a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds" - in the context of [some] autism .
Once again, I'm sure that there may be people out there with brows
furrowing when it comes to talk of a 'broccoli chemical' potentially
impacting on the presentation of autism. But peer-reviewed science (placebo-controlled) is peer-reviewed science  and not just to be 'put to one side' because it doesn't follow the trends or [research] fashions of the day.
This latest work from Bent et al represents a not-so-methodologically strong attempt (i.e. not placebo-controlled) to bring the science of metabolomics into research proceedings to "examine
changes in physiological markers that may underlie beneficial treatment
effects from sulforaphane by analyzing changes in urinary metabolites."
Metabolomics by the way, as well as being music to my research ears, is
something that percolates through quite a lot of autism research these
days (see here and see here
for examples) as small molecules in urine, blood and other biofluids
are separated, detected and elucidated all in the name of science.
A small group of children participated in the Bent study; all had a "formal diagnosis of autism", all were reasonably happy to swallow a tablet containing sulforaphane ("weight-based dosing of sulforaphane")
and all were able to provide urine samples before the study started and
at the conclusion of the 12 week research period. Parents of
participants were also willing and able to complete a couple of
behavioural schedules: "the Aberrant Behavior Checklist (ABC) and... the Social Responsiveness Scale (SRS)" at "baseline, 4 weeks, and 12 weeks using an online and secure platform" about their children too.
Results: alongside looking at pre- and post-intervention behavioural scores, the authors also "examined the number of participants who had a clinical response."
This is a particularly important detail in the context of autism and
the continuing discussions about how the spectrum is well and truly
heterogeneous (the autisms?)
and so one shouldn't expect every single person diagnosed to somehow
have the same genetics and/or biochemistry; also affecting response to
any particular intervention. With that in mind, authors also reported
that (group) scores on one of their primary outcome measures - the SRS -
were significant, indicative of some positive change noted to behaviour
over the course of the intervention period. I say this bearing in mind
that this was an open-trial, where everyone took sulforaphane and
everyone knew that they were taking sulforaphane (including the parents
who did the scoring). As for those potential 'best-responders' to
sulforaphane use, we are told that: "Eight participants had a clinical response compared to seven who were classified as non-responders."
Then to those metabolomic results, and from a total of nearly 700
compounds identified in urine, approaching 80 of them seemed to show
some correlation with the behavioural symptom changes noted. They were
put into various categories depending on their biochemical form and/or
action, and correlations with behavioural scores (and significance) were
presented. Some of the best correlations that I could see were with
regards to sphingomyelin metabolism. The authors did seem a bit surprised by results in this area, but added: "It
is not clear how sulforaphane might alter sphingomyelin metabolism or
availability and whether this is related to clinical benefits, but if
this association is confirmed, it has important clinical and treatment
implications." I daresay that examination of sphingomyelin metabolism in other contexts (see here for example) might be revealing, particularly in the context of other behavioural/psychiatric labels  that could (and do) overlap with autism.
There is a further scheme of work to be followed when it comes to sulforaphane and autism on the basis of these and other scientific results
. I'd also suggest that the continued incorporation of the science
of metabolomics is a good thing, and adds a further tier of
investigation when it comes to studying intervention more generally in
the context of autism. It's also an important step in (eventually)
coming up with a 'test' for who might be a best-responder to the use of
sulforaphane and perhaps associated compounds...
 Bent S. et al. Identification of urinary metabolites that
correlate with clinical improvements in children with autism treated
with sulforaphane from broccoli. Molecular Autism. 2018; 9: 35.
 Singh K. et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5.
 Castillo RI. et al. From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism. Frontiers in Neuroscience. 2016;10:488.
 Sedlak TW. et al. Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Mol Neuropsychiatry. 2018 May;3(4):214-222.