Thursday, 3 March 2011

Forgotten research - sulphation and autism

There is a scene in the film Toy Story 2 where one of the main protagonists, Jessie (the yodelling cowgirl) sings about her unrequited love for her owner as she falls off and slips underneath her owner's bed and is quickly covered in dust and forgotten about. Her normally happy face turns to a sad frown.

Life is like that sometimes. Fashions come and go. Research is like that also; passing phases where concept A or compound B or intervention C wax and wane, wax and wane. Why do they wax and wane? Interest rises and falls; as does funding, as does expertise. For some things the evidence base, whilst initially promising, turns out not to be the heralded thing it was initially suggested to be. Others just fall underneath the bed and gather dust. One area that has gathered quite a bit of dust is the potential role of sulphate (sulfate) in autism spectrum conditions.

Quite a good description of the chemistry of sulphate can be found here. Many people may more readily know about sulphate in one of its more common uses, magnesium sulphate or Epsom salts, where for many thousands of years, people have bathed in Epsom salts in an attempt to 'cure' all kinds of ills.

In autism research, a possible role for sulphate has been discussed for many years. Those in the know will know that when you talk about sulphate and autism, one name comes up time after time: that of Dr Rosemary Waring, now retired, but previously of the University of Birmingham. Rosemary published extensively on a potential role for sulphate in autism (and other things) - some of her main works can be seen here, here and here. I had the previlige of working with her on a few occasions in connection to our creatinine work in autism.

The main findings on sulphate and autism suggested higher levels of urinary sulphate (and related metabolites) accompanied by increased protein excretion in autism compared to controls. Plasma levels of sulphate by contrast tended to be reduced. These issues seemed to be more relevant to those more severely affected by autism. Susan Owens has written a lot about this also.

What does this all mean? Well, our sulphation pathway is used for lots of different things. It helps us to get rid of various 'used' neurotransmitters, it helps maintain gut structural integrity via sulphated glycoproteins and it helps in the release of various digestive enzymes, to name but a few uses. In short, its pretty important. Sulphate is also pretty important when it comes to metabolising certain types of drugs.

Following a period of about 10 years where nothing further really happened with regards to sulphate research in autism, the recent paper by Yap and colleagues reignited some interest with their finding of increased urinary taurine (linked to alteration in cysteine metabolism - note this is not the same as cystine) which I posted about.

I was always struck by the significance and consistency of the original results obtained in the area of sulphate and autism. Adhering to my matra that science is about probability not absolutes, the significance (p) values obtained during some of the studies were impressive (p<0.001) and illustrated potentially how important this area of research could be.

On the basis of such issues with sulphate for some cases of autism, several people have explored the option of trying to replace potentially low plasma sulphate levels. Taking sulphate-complexes orally is not recommended; Epsom salts are quite a good laxative and other sulphate-complexes are used for things like tenderising meat. Given such issues, the use of Epsom salt baths have been suggested to offer an alterative for potentially increasing sulphate levels via transdermal passgae of sulphate across the skin (I am not recommending this by the way). As to the potential effects on the presentation of autism, I am yet to see any results from published clinical trials to corroborate the anecdotal reports of positive changes with some people with autism (of which there are quite a few).

So there we have it. Underneath the bed, a dusty little box of research on sulphate and autism. Going back to our Toy Story character Jessie, viewers of the film will know that at the end, like all good Disney productions, Jessie finds a new home with Woody, Buzz and the other toys complete with the name 'Andy' inscribed on the sole of her boot. Will the same happen to sulphate?