NAC is an interesting compound which has a variety of potential uses ranging from dealing with acetaminophen (paracetamol) overdose to applications based on its mucolytic action. A post last year over at Evolutionary Psychiatry had quite a nice summary of its various effects and links to potentially autism-relevant things like glutamate and also glutathione. My mind also wanders back to the sulphation issues in cases of autism which seem to have been forgotten in recent times.
I am sorry that I can't post a link to the full-text of the paper in this post, but please take my word that here is a summary of the paper in its entirety:
- This was a double-blind, randomised, placebo-controlled trial looking at 12 weeks supplementation with NAC with children (aged 3-10 years) diagnosed with autism. Doses were tied into 4 week blocks, starting at 900mg once daily for the first 4 weeks, then twice daily up to 8 weeks and three times daily for the last 4 week block. This schedule was based on published studies of NAC in other areas of health regarding tolerance.
- Data was acquired for 29 children (14 children on NAC and 15 on placebo) based on presented behaviour as measured using the Aberrant Behaviour Checklist (ABC), the Clinical Global Impression (CGI) scales, the Repetitive Behaviour Scale-Revised (RBS-R), and the Social Responsiveness Scale (SRS).
- Significant effects following NAC supplementation were noted on the primary outcome measure - the ABC - and in particular, the irritability subscale. That is NAC supplemented participants showed a group improvement on this measure, particularly at 4 weeks compared with baseline, although also continuing to improve up to the week 12 endpoint.
- Stereotypic/repetitive behaviours also saw some group improvement in the NAC supplemented arm of the trial, on both the ABC and RBS-R scales. Global clinical improvement based on the CGI for the NAC group was: n=5 much improved, n=6 minimally improved, n=2 no change and 1 child was judged much worse.
- Only few adverse effects were noted across the groups, mostly gastrointestinal (NAC = 11/14 with GI adverse effects vs. placebo = 7/15).
The first comments to make about this study is that (a) it was a pilot trial, (b) a short-term pilot trial and (c) completing participant numbers were low. That and the fact that behavioural outcomes were the sole purpose of this paper means that outside of what was overtly noted, no other conclusions based on biochemistry can be appropriately drawn from the results. I would however temper that last statement based on the trial registration entry for this research (here) which indicates some further investigation on levels of glutathione (GSH) and related metabolites in blood might be forthcoming.
All being said and done, every research area needs to start somewhere and as far as PubMed is concerned, this seems to be the first time that NAC has put in an appearance as an intervention option for autism spectrum conditions. The authors do speculate on two main modes of action for NAC based on glutamatergic modulation and/or antioxidation. I don't really think that I can offer too much more in the way of which hypothesis might be more relevant given that there is quite 'strong' evidence for both mechanisms potentially pertaining to cases of autism. Some evidence at least.
NAC has other medicinal uses also which one cannot at the moment rule out as being relevant to at least some cases of autism. I'm thinking about this fairly recent study on NAC inhibiting certain inflammatory cytokines under 'mild oxidative' conditions which could potentially be relevant given the links posited between autism and inflammation.
An interesting pilot trial opening up another area for further investigation.
* Hardan AY. et al. A randomized controlled pilot trial of oral N-Acetylcysteine in children with autism. Biological Psychiatry. February 2012.
Hi Paul Whiteley -ReplyDelete
NAC is some pretty amazing stuff, especially for rats. From the perspective of a potential mechanism to prevent autism, studies like these might be of interest eventually.
Many thanks for the comment and links pD - interesting indeed.ReplyDelete
The more I read about NAC, the more interesting it all becomes in terms of what it does and what it might tie into. The immune-cytokine connection is perhaps one of the more interesting areas; the trouble I can forsee if trying to get people to look at the immune side of things outside of the glutathione or glutamate connection.