Glutathione and autism

I am going to be fairly brief with this topic on this occasion. Part of this is to ensure that I don't take up too much of my American readers' time on Thanksgiving Day and partly because this post is really more for me to get things straight in my mind about glutathione and its potential links with at least some cases of autism. If it helps you too, all the better.

USDA Agricultural Research Service

Glutathione (GSH) is fast becoming one of the elephants in the room compounds in relation to autism as it might also be in some other conditions. Quite a few people have been talking about it and its various chemical relations in connection to autism spectrum conditions for a while now. I have been following a few of those discussions down the years but always felt a little out of my depth when trying to piece together where it might fit into the heterogeneity that is autism.

A few things have changed of late which have made me take a little more interest in glutathione in general. First is a growing appreciation of the whole homocysteine-methionine cycle (the big 'H' in particular). Second is a little more understanding about oxidative stress and antioxidants (particularly the recycling of antioxidants). Finally a recent look back at just how important the work of Rosemary Waring on sulphation might actually be to some cases of autism.

A new paper has appeared on glutathione and autism from Yusra Al-Yafee and colleagues* (full-text) which has turned my head. Yes, it was another King Saud University publication to add to the many. For any UK-based academics watching, this is one research group who if were ever submitted, would not be fretting over the publications element to REF 2014.

Before I go on I should perhaps give a brief description of what glutathione is. So with a Twitter limit (140 characters or less): tri-peptide, antioxidant, xenobiotic metabolism, cofactor, DNA synthesis, nitric oxide, NAC, one-carbon metabolism. Out of this description, one of the most important functions for glutathione is its antioxidant capability and the link between low levels and oxidative stress. So, the reduced form of glutathione is basically the active, able to 'grab a free radical' version of glutathione and should be present in the greatest proportion when compared with the oxidised form, the 'I already have a free radical' form (glutathione disulfide), which is then recycled back to its reduced form to continue its scavenge. Ain't human bodies great things?

The current paper reported that levels of total glutathione were low in participants with autism, and when I say low, I mean low: 100% of participants were below the lowest level of total glutathione determined in the control group. For the second time in only a few days, the characters AUC and 1 has appeared on this blog, denoting that at least within this participant group, glutathione levels at a certain cut-off point seemed to distinguish 100% of autistic samples from control samples (and on more than one parameter, see table 3).  Of course the sample groups were small (n=20 apiece) so perhaps we should not read too much into this finding at the present time but it is interesting.

I probably will come back to glutathione in the near future to describe and discuss further. With all this talk of scavenging and mopping up, how about a bit of domestic routine courtesy of the late, great Freddie who passed away 20 years ago today.

* Al-Yaff A. et al. Novel metabolic biomarkers related to sulfur-dependent detoxification pathways
in autistic patients of Saudi Arabia. BMC Neurology. November 2011