Friday, 7 June 2013

Autism, the ketogenic diet and Dangermouse

I'm proud of my quite 'unusual' area of autism research interest focused primarily on whether diet might, in some way, shape or form, be linked to or impact on some cases of the autisms. It's not been a particularly popular area of research down the years it has to be said. Most of which I've put down to its links to areas far outside of the behavioural dyad (as its known these days). That and all the gastrointestinal (GI) baggage inevitably associated with diets like the gluten- and casein-free (GFCF) diet: leaky gut, gut bacteria, etc. which have been allied with other 'factors' leading to a sort of scientific death-by-association in some quarters.
Penfold  @Wikipedia  

Outside of the considerable politics, there is an evidence base to diet and autism. It's not a particularly strong scientific base it has to be said, but there are a few randomised controlled trials (RCTs) to be found, and in agreement with Tim Buie's latest take on gluten-free dietary intervention and autism* "There may be a subgroup of patients who might benefit from a gluten-free diet". Though we still don't know who.

Dr Buie, by the way, has also talked about things like lactose (the sugar in milk) intolerance and gut dysbiosis in cases of autism extending the potential of a dietary link. Assuming you adhere to the notion of the autisms - with all their heterogeneity and comorbidity - you might be inclined to also think that autism might not just be a condition of the grey-pink matter floating in the skull. Or maybe not....

Hopefully not being too 'me, me, me', I'm actually involved in writing a book about the area of diet and autism as we speak. It's been an interesting journey and allowed me to dig deep into the available science behind diet including some gems such as per this paper**. Outside of just GFCF diets, a variety of other food changes have also been on the research menu with autism in mind, including the ketogenic diet.

I've talked about the ketogenic diet before - what it is and how it is starting to enter mainstream medicine when it comes to managing certain types of epilepsy. Briefly, it's all about high fat (no, not that Hai Fat) and low carbohydrates and putting the body into a state known as ketosis. Indeed how this state seems to affect seizure patterns for some people. Yes, I know a similar sort of diet, sorry nutritional approach, has also been suggested as a weight loss measure but I'm not really that interested in that sort of thing on this blog.

With autism in mind and outside of any seizure-linked effect, there has been a suggestion, a small suggestion, that a ketogenic diet might also be able to affect certain behaviours linked to autism too as per the paper by Evangeliou and colleagues***. In a more case-study fashion, I'll also draw your attention to my fairly recent discussions on the paper by Martha Herbert and Julie Buckley (see here) on similar things. Other than that, we've got a bit of a scientific black hole when it comes to the question of whether such a very restrictive dietary intervention could 'help' where autism is present and who might be best responders.

The paper by David Ruskin and colleagues**** (open-access) which I'm finally getting to after quite a long-winded introduction, represents an addition to that autism-ketogenic diet literature and their observations of the BTBR 'Dangermouse' when on a ketogenic diet. OK I've exaggerated slightly. The BTBR mouse model of autism is not really Dangermouse; just a name I've assigned from my mis-spent youth watching far too much TV (see this post). But it is still quite a good mouse model of autism despite some recent criticism.

The Ruskin paper is open-access so I'm not going to go over the top with any description. It went something like: take several BTBR mice. House them with other mice (C57Bl/6). At 5 weeks of age, feed some of the mixed caged mice a ketogenic diet (KD) and others a control diet. Test mouse behaviour at 3-5 weeks of diet. Report results.

The results: well, the KD mice were certainly showing signs of ketosis as per some blood chemistry results including some much lower blood glucose levels (interesting!*****). There were also some interesting differences recorded to elements of mouse behaviour as a function of the use of the KD or not and mouse strain: "the KD did not affect behavior in C57Bl/6 mice". Importantly "the beneficial behavioral effects of the KD are not secondary to its well-known efficacy against epilepsy and seizure activity".

OK, it's another study of mouse behaviour and making the quite considerable leap from a proposed mouse model of autism to real-life autism. Mouse behaviour is not human behaviour (he says cleaning his whiskers). I'm no expert on how one goes about examining and testing mouse behaviour so I'll have to assume that the authors knew what they were doing and did it to the best of their abilities. I'm not necessarily expecting the Ruskin study to mark any substantial shift in opinion on how people view the research area of diet and autism it has to be said.

What this study does offer though, is another potentially fascinating glimpse into how diet might be related to some cases of autism. Indeed, whether the whole or facets of the intervention are worthy of much greater study. For example, I earlier mentioned Tim Buie's work on carbs and autism. The question is whether the lower carbohydrate load attached to a ketogenic diet might be the more important variable over and above fat, bearing in mind that there might be issues there too? Similarly, the authors ask whether the ketogenic diet might be something to consider where autism and certain types of epilepsy exist; as per another quote: "a KD could offer dual benefits in this difficult clinical population". Bear in mind however, I offer nothing like medical or clinical evidence by suggesting all this. Just speculating.

To close and paying homage to the era of Dangermouse (1980s), here's Neneh and Buffalo Stance.. ("know wot I mean?")


* Buie T. The relationship of autism and gluten. Clin Ther. 2013; 35: 578-583.

** Asperger H. Psychopathology of children with coeliac disease. Ann Paediatr. 1961; 197: 346-351.

*** Evangeliou A. et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003; 18: 113-118.

**** Ruskin DN. et al. Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS ONE. 2013; 8: e65021.

***** Yancy WS. et al. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition & Metabolism. 2005; 2: 34.

---------- Ruskin, D., Svedova, J., Cote, J., Sandau, U., Rho, J., Kawamura, M., Boison, D., & Masino, S. (2013). Ketogenic Diet Improves Core Symptoms of Autism in BTBR Mice PLoS ONE, 8 (6) DOI: 10.1371/journal.pone.0065021