Thursday, 19 September 2013

Autism and the GFCF diet: ScanBrit episode 2

"These preliminary observations on potential best responder characteristics to a gluten- and casein-free diet for children with autism require independent replication".

That sentence, taken from a recent (pre-print) publication I was very peripherally involved in writing, is probably the most important thing to take from the paper by Lennart Pedersen and colleagues* and certainly is a message that I would be very keen to promote.

Skandinavism @ Wikipedia 
ScanBrit, was/is a meeting of minds between the group I work with and other research groups based in Denmark and Norway, who wanted to experimentally examine the question of whether a diet devoid of foods containing gluten and casein might be able to impact on the presentation of autism in children.

Combined with a small but growing bank of research, the net outcome was that science should perhaps be looking at a possible dietary effect at least in relation to some cases of autism. One of the main issues being that the evidence base (including our own results**) was still limited in terms of the methodological quality of the investigations*** being undertaken (see here for a review). Oh and mechanism-wise, (i.e. how and why did diet 'work'?) we are still feeling around the edges, despite a few avenues of potential further inquiry (see here and here) including revisiting some older ideas.

In the most recent paper, (we) the ScanBrit collaboration were looking to further analyse the wealth of data which was generated over the course of the 2 years of experimental study and in particular, try and ascertain whether there were certain characteristics which might be markers for dietary response or not. As any person following the GFCF diet or their parents know, this is not an easy diet to follow and might, under certain circumstances, place a person at risk of nutritional deficiencies (see here) and/or other more socially-mediated issues (see here). Identifying markers of who might be a responder or non-responder would therefore save quite a lot of time, effort and expense.

Interestingly, as I've indicated in a previous post, some of the most significant and consistent behavioural changes which were noted in our original trial as correlating with the installation of a gluten- and casein-free (GFCF) diet were actually outside of the core symptoms of autism; instead potentially reflecting changes to attention and hyperactivity, more traditionally linked to the symptoms of attention-deficit (hyperactivity) disorder (ADHD). In other words, the effect of a GFCF diet might be more peripheral than anything else in cases of autism, in terms of targeting issues associated with ADHD which might also be present alongside the core autism symptoms (see my ESSENCE post and the very interesting paper by Sprenger and colleagues****).

Chronological age was identified as potentially being a factor influencing response to the GFCF diet, and in particular, those children aged between 7 and 9 years old as being potential best responders. I have to say that I am still mystified by this finding. Traditionally, I'd always assumed that there was a 'younger, the better' sentiment when applied to the possible effectiveness of dietary intervention on cases of autism, as per the rising tide of literature on other early interventions. Outside of the relatively small participant numbers we included for study, this could mean that there is some tie-in with the ADHD symptoms which seem to be targeted, bearing in mind my relative inexperience when talking about the manifestation of ADHD throughout childhood. In light of the recent case study from Dr Martha Herbert on a GFCF diet morphing into a ketogenic diet (see here), I do wonder if there might be other comorbidities also being affected which might also have some tie-in too. Who knows.

Again, without making too much of this variable at the current time, there was also a possibility for some involvement of one of the urinary compounds***** we focused on in the original ScanBrit trial as potentially being involved in response. I know biomarkers and autism is still a very complicated subject (see here) bearing in mind the heterogeneity of presentation and the potential influence of all that heightened risk of comorbidity. That all being said, trans-indolylacryloylglycine (IAG) whilst not being a biomarker for autism****** continues to garner interest with its possible connection to gastrointestinal (GI) comorbidity*******. More investigation needed here methinks.

I don't think we have made any startling discoveries with the publication of this paper. We were limited to the variables that we examined over the course of the study and so were unable to talk about whether other, more diet-relevant factors such as coeliac disease (CD) or related pathology - non-coeliac gluten sensitivity for example - might also be involved in response to diet. This was a major shortcoming of our original paper I'll freely admit.

That we found that inattention and hyperactivity might be key factors in dietary response however, is to my mind, potentially very important. That targeting such behavioural issues might also have a knock-on effect to more core autism presentation (as per our ADOS results on communication) is also an area requiring further investigation and perhaps reflects how autism (or should that be the autisms) is so very much more than just the formal clinical descriptions we give it. RDoC anyone?

Blogging about ones own peer-reviewed research is something that I've always been a little bit hesitant about doing. Aside from the possible charge of self-publicity and the natural tendency to think that yours is obviously an important paper (who wouldn't think that about their own work?), one might argue that important features such as the objectivity required for good science blogging, might to some degree be compromised. Sort of like marking your own homework as per one of my colleagues oft-cited phrases. I very much hope that I've not over-stepped the mark on good science blogging in this post on Lennart's paper. Indeed I'll end by reiterating part of the opening sentence to this post on the requirement for independent replication before anyone gets too excited about these results, as indeed the dietary research base as it presently stands is in need of more inquiry********.

And since we're on the topic of diet and autism, would that be one hump or two*********?


* Pedersen L. et al. Data mining the ScanBrit study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders: behavioural and psychometric measures of dietary response. Nutr Neurosci. 2013 (pre-print)

** Whiteley P. et al. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100.

*** Millward C. et al. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003498.

**** Sprenger L. et al. Impact of ADHD symptoms on autism spectrum disorder symptom severity. Res Dev Disabil. 2013 Aug 21;34(10):3545-3552.

***** Anderson RJ. et al. Identification of indolyl-3-acryloylglycine in the urine of people with autism. J Pharm Pharmacol. 2002 Feb;54(2):295-8.

****** Wright B. et al. Is the presence of urinary indolyl-3-acryloylglycine associated with autism spectrum disorder? Dev Med Child Neurol. 2005 Mar;47(3):190-2.

******* Wang L. et al. Is urinary indolyl-3-acryloylglycine a biomarker for autism with gastrointestinal symptoms? Biomarkers. 2009 Dec;14(8):596-603.

******** Winburn E. et al. Parents' and Child Health Professionals' Attitudes Towards Dietary Interventions for Children with Autism Spectrum Disorders. J Autism Dev Disord. 2013 Sep 1.

********* Al-Ayadhi LY. & Elyass Elamin N. Camel Milk as a Potential Therapy as an Antioxidant in Autism Spectrum Disorder (ASD). Evidence-Based Complementary and Alternative Medicine, 2013, Article ID 602834, 8 pages, 2013. doi:10.1155/2013/602834

---------- Lennart Pedersen, Sarah Parlar, Kajsa Kvist, Paul Whiteley, & Paul Shattock (2013). Data mining the ScanBrit study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders: Behavioural and psychometric measures of dietary response Nutritional Neuroscience