Thursday, 5 May 2016

NAC for 'social impairment' in youth with autism... probably not

"The results of this trial indicate that NAC [N-acetylcysteine treatment was well tolerated, had the expected effect of boosting GSH [glutathione] production, but had no significant impact on social impairment in youth with ASD [autism spectrum disorder]."

So said the results reported by Logan Wink and colleagues [1] (open-access) who, continuing an autism research theme, looked at whether this important L-cysteine prodrug might have more to give when it comes to at least some facets of some autism. Their trial registration entry can be found here. Reporting results from "a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD" researchers followed some 30 children (aged 4-12 years) diagnosed with autism based on their use of NAC or a placebo. Alongside various biological measures including blood levels of "reduced and oxidized glutathione (GSH and GSSG)" and the big 'H' (homocysteine), the primary outcome was the effect on "the CGI-I scale anchored to study physician assessment of core social impairment considering the individuals’ overall level of cognitive, adaptive, and social functioning." I might add that other secondary behavioural outcomes were also included for study.

Bearing in mind the loss (dropping out) of some participants during the study period including details that "three withdrew due to irritability (NAC), diarrhea and encopresis (placebo), and defiant and self-injurious behavior (placebo), respectively" the authors report data on 25 study completers. Titrated doses of NAC depending on tolerance and body weight of participants did seem to do what they were supposed to in terms of an effect on levels of glutathione: "had the expected effect of boosting GSH production in peripheral blood" at 12 weeks.

But... on every other measure - biological and behavioural - there were no significant differences between the NAC and placebo groups leading the authors to conclude that their results "do not support the use of NAC for treatment of core social impairment of ASD." The research door does however remain open as they also comment that: "the health impact of the resultant increase on GSH remains unclear."

These are interesting results. NAC has seemingly found something of a research place in quite a few areas of psychiatry including 'some' autism (see here) and 'some' schizophrenia (see here). The focus has tended to be more on the 'irritability' side of things (see here) which makes it all the more surprising that one of the participants in the Wink trial receiving NAC actually withdrew 'due to irritability'. That being said, the very controlled nature of the Wink study cannot be readily ignored assuming no influence from the placebo [2].

I would like to see a little more on the whole NAC -- cysteine -- glutathione connection given previous discussions with autism in mind (see here). This includes the idea that blood levels of the various compounds involved might not be the same as 'brain levels' and taking into 'level of functioning' into account (see here). But in the context of the Wink data, one has to perhaps realise that NAC is not likely to be a panacea when it comes to autism...

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[1] Wink LK. et al. A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Molecular Autism. 2016; 7:26.

[2] Masi A. et al. Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis. Transl Psychiatry. 2015 Sep 22;5:e640.

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ResearchBlogging.org Wink, L., Adams, R., Wang, Z., Klaunig, J., Plawecki, M., Posey, D., McDougle, C., & Erickson, C. (2016). A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder Molecular Autism, 7 (1) DOI: 10.1186/s13229-016-0088-6