Parent power: autism and carnitine

For many years, science and the conducting of science, was seen as quite an exclusive club. Men and women in white laboratory coats holding up test tubes containing brightly coloured liquids to the light and inquiringly looking at each other as if to say 'yes, it's turned red/yellow/green' denoting some major experimental breakthrough. It always reminds me of comic Michael McIntyre and his 'wine at the restaurant' routine - 'yes, it's wine' (apologies for the mild swearing in the link). Nowadays with the onset of wider educational provision and a greater exposure to science via things like the web, the exclusivity of the science club has perhaps been reduced and science is gradually becoming a concept and field for all (as it should be).

I say all this because a few weeks back, the topic of parents of children with autism becoming involved in formally conducting scientific research on autism was raised on a external post I had some discussion about. Acknowledging that parents are perhaps the best scientists when it comes to their own children (observation, measuring, recording, the n=1, etc) the point being made was that quite a few areas of research in autism have, for one reasons or another, been driven forward by parents as a result of their combined professional qualifications and personal interest in autism. The example in that post was Lorna Wing and her pretty exceptional career in autism research perhaps partially as a result of her daughter.

There are quite a few other examples of parent power - too numerous for me to list here. My route into, and continued interest in autism research, was via another parent and retired Pharmacist, Paul Shattock OBE, and his desire to experimentally look at dietary intervention for some cases of autism (he is the Shattock P name that appears on nearly every paper I have been involved with). Another parent who has stepped up to the research mark is Prof. Jim Adams from Arizona State University and his impressive array of papers published on autism this year (2011). Jim is Presidents Professor of Engineering and Material Sciences but perhaps more relevant to this post, is a scientist with a daughter with autism.

Without turning into the Jim Adams appreciation society, his 2011 papers can be viewed here, here, here, here and here. I have already posted an entry about one of his papers on gastrointestinal bacteria and autism which made some interesting observations albeit with a few gaps. In this post, I want to discuss a recent paper by Jim and colleagues on a possible role for L-carnitine for autism (a copy of the full-text should be available here).

I first perhaps need to make a distinction between carnitine and a similar sounding compound, carnosine (the 'L-' bit takes us into the area of chirality which, although making me shudder, I am sure your friendly neighbourhood chemistry tutor can help explain). Carnitine is found in quite a few foodstuffs and can be biosynthesized, and is involved in energy production. Carnosine, a dipeptide of the amino acids beta-alanine and histidine, has a few potential effects, not least as an antioxidant.

Both compounds have shown up on the autism research radar. L-carnosine did pretty well in this small double-blind, placebo-controlled trial a few years back for example. Carnitine has however had the lion's share (get it, carnitine = Latin for 'flesh') in terms of research coverage starting at a link with mitochondrial problems and working onwards ever since. Indeed the study highlighted by Pauline Filipek and colleagues on carnitine deficiency in autism represents one of the very earliest studies suggestive of possible mitochondrial involvement in some cases of autism before the more recent interest.

Back to the Adams paper. I am not going to beat around the bush on this. I know some people might raise an eyebrow reading this paper when they see some of the authorship list and some quite high-profile recent media coverage. I'm not going to point to which authors and am not making any reference to, or judgement about this, because as far as this post (and blog) goes, it is all about the science (the journal Editors and peer-reviewers I assume have done their job for it to get through to publication and that's good enough for me). The basics then: a double-blind, placebo-controlled trial of 34 participants with ASD, aged between 3-10 years, mean ~ 6 years (notice the group were largely pre-pubescent) looking at the effects of L-carnitine vs. placebo over 3 months. Outcome measures were CARS, ATEC, and hand muscle testing among other things. A nice touch was that treatment adherence and side-effects data were also collected by parents of participants over the course of the trial. Various other lab exams were undertaken at baseline and study end (3 months).

The results. There were a few improvements noted on the various schedules included. Total CARS scores reduced, indicative of a group reduction of autistic symptoms (p=0.02). The ATEC domain of sensory/cognitive awareness also showed a significant group reduction (p=0.009). From the various lab exams, only levels of serum total and free carnitine were significantly different between the groups (as you would probably imagine given your experimental arm). Importantly also, adherence and side-effects were not significantly different between the groups, with only 'minor' side-effects reported. Additional correlations are reported between the various study instruments and outcomes but the correlation coefficients (r-squared values) were nothing too spectacular bearing in mind the small participant group numbers.

What can we surmise from all this? Well, L-carnitine was generally speaking well tolerated (first do no harm). More than that, it didn't seem to have any specific effects on the various blood chemistry examined during the study which is perhaps a good thing. Even more than that, it was associated with some clinical benefits, at least over the course of the 3-month study period. The authors list a number of strengths and limitations; strengths not least that this was a 'gold-standard' trial with that all important placebo arm (perhaps only lacking a cross-over period if I was to be a nit-picker). It was a small participant group but I don't tend to hold this against studies; one could argue that this is still a pilot study, being only the second study on this topic for autism that I have found. Generally speaking, finding a significant group effect is the first order of the day, followed by subsequent studies to look for those all-important best and non-responders.

What does it all mean? Good question and I wish I had a good answer for you. Carnitine is involved in fatty acid metabolism and ATP production. It enables fatty acid transport from the cytosol to the mitochondria, having a sort of backstage pass through the inner mitochondrial membrane. There is a suggestion (and it is indeed only a suggestion) that problems with either having enough available carnitine or with one or more of the carnitine acyltransferase enzymes might be linked to autism. The fact that there is a dearth of research in this area sadly means that I can offer no more information than this.

To end, I link to a video which gives us a real insight into the science of today.