Thursday, 29 November 2012

Metal measuring and autism

Now and again, two papers of a similar ilk are published temporally close together in the great autism research melting pot so as to cumulatively make for interesting reading.
Congratulations, it's a baby T-1000 @ Wikipedia  

In the case of this post, I am referring to the paper by Jim Adams and colleagues* and the paper by Yahya Al-Farsi and colleagues** which both examined the burden of metals present in cases of autism from the perspective of two very different geographical areas of the world. Both papers are published in the same journal too.

I should say that I've covered metals, heavy and toxic, before on this blog with reference to the background to this whole area (see here) and some research on that most controversial of areas, mercury and autism (see here). As with just about every other instance of autism research, the message is a messy one, with no 'one-size-fits-all' finding, which often wrongly gets translated as either 'it must be a universal effect' or 'there must be no effect' with seemingly no middle ground where the autisms are concerned.

Anyhow, a few details about the papers:

The Adams paper:

  • The hypotheses were: (a) "children with autism would have higher levels of some toxic metals in their blood and urine" (n=55) compared with asymptomatic controls (n=44), and (b) the severity of symptoms would be associated with the toxic metal burden.
  • This current study formed part of a wider body of work undertaken and published by the authors*** (open-access) looking at children aged 5-16 years. This follows other work in a similar vein**** (open-access).
  • Morning blood and urine samples were eventually analysed by an old favourite method (ICP mass spectrometry) and the severity of autistic symptoms assessed by various means including the ATEC.
  • Results: there were quite a few of them but most notably levels of lead in red blood cells (RBC) and urine were significantly elevated in the autism group compared with the control group, alongside urinary thallium, urinary tin and urinary tungsten.
  • In terms of the measured severity of autism correlating with the metals findings, a slightly complicated picture emerges which suggested that whole blood and RBC mercury concentrations showed "possibly" significant correlations with the three assessment instruments used.
  • The authors conclude that their results suggest that either there is increased exposure to these metals, increased absorption of these metals or decreased (fecal) excretion of these metals or some combination of these explanations. 

The Al-Farsi paper:

  • A very similar starting point by all means, testing the hypothesis that "children with ASD will show variations and deregulated levels of heavy metals and essential minerals when compared to non-ASD controls".
  • Based in the Sultanate of Oman, hair samples from children with DSM-IV autism (n=27) were analysed again by ICP-MS for the presence of various heavy metals and compared with results from age- and sex-matched asymptomatic controls (n=27).
  • Results: again, quite a few but generally speaking levels of heavy metals were elevated in the autism group compared to controls, and included cobalt, cadmium, chromium, aluminium and also our old friend lead.
  • When also looking at levels of essential minerals, a slightly more mixed picture emerges with lower levels of calcium and copper to be present but higher zinc, iron and sulphur (to name but a few).

OK, there are a few differences to point out between these studies outside of just the ethnicity of their autism cohorts and the possible differences in geographical exposure patterns. The Adams paper looked at blood and urine, the Al-Farsi paper looked at hair. The mean ages of the groups examined were also slightly different (Adams: autism = 5.3 years; Al-Farsi: autism = 10 years). So we are not able to directly transpose results one on top of another.

That being said, there were some similarities to these results not least about those findings related to lead. Indeed, I have quite an interest in all things lead for quite a few reasons, not least that even Superman had problems with lead so why wouldn't children exposed to the stuff, and those figures from last year (2011) which listed lead reduction as being one potential candidate among many as to why the US crime figures were falling. Exposure to lead is generally speaking not a great thing for developing or developed brains/bodies.

I'll admit to not being a great expert on how hair, blood and urine samples compare when looking at metals or any other kind of chemical/compound so I can't offer too much in the way of information about the functionality of these measures and the extent to which they reflect levels of these metals or indeed evidence of storage and any on-going physiological activity / effect. I am for some reason drawn back to the very recent CHARGE findings on air pollution and autism (bearing in mind that the reduction of lead in petrol we've seen over the past few decades) as an interesting variable potentially relevant to these results but will say no more than that at this time.

Accepting the issue of hair analysis, the Al-Farsi findings revealed some interesting trends with reference to the trace minerals examined. Higher zinc, higher iron and higher sulphur raise questions about what this means in light of other research indicating lower hair zinc (see this post) for example, and indeed that body of research on iron levels in autism (see this post and this post). The curse of messy heterogeneous autism research?

Interestingly both papers seem to wade back to similar biochemical pathways in terms of the potential significance of their findings. So glutathione pops up (see this post on where glutathione sits in the current autism research world) and how glutathione is a key component in both the processes of antioxidation-oxidative stress as well as being tied into the removal of things like metals. The feeling is that the consistently lower levels of glutathione (GSH) noted in cases of autism is probably not going to be a great thing for the biological processing of such toxic metals.

Both papers end with calls for further research into this complicated (and often controversial) area. I'd like to second that call given that this is a topic which seems to be cropping up more regularly in recent years. I know that when people start talking about toxic metals and autism, specific toxic metals, some conversations instantly move into areas which make some people a little uncomfortable. Irrespective of what causes such issues to become apparent, the questions must surely be (i) what effect, if any such burdens have contributing to the presentation of autism or indeed any of its potential comorbidities and (ii) whether there is something that can be done to ease any burden and what, if any, effects this might have on symptoms.

To close, how can I not make reference to some great music following a post about metal. Take it away AC/DC.

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* Adams JB. et al. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res. November 2012.

** Al-Farsi YM. et al. Levels of heavy metals and essential minerals in hair samples of children with autism in Oman: a case-control study. Biol Trace Elem Res. November 2012.

*** Adams JB. et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond). 2011; 8: 34.

**** Adams JB. et al. The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicology. 2009; Article ID 532640. doi:10.1155/2009/532640

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ResearchBlogging.org Adams, J., Audhya, T., McDonough-Means, S., Rubin, R., Quig, D., Geis, E., Gehn, E., Loresto, M., Mitchell, J., Atwood, S., Barnhouse, S., & Lee, W. (2012). Toxicological Status of Children with Autism vs. Neurotypical Children and the Association with Autism Severity Biological Trace Element Research DOI: 10.1007/s12011-012-9551-1

ResearchBlogging.org Al-Farsi, Y., Waly, M., Al-Sharbati, M., Al-Shafaee, M., Al-Farsi, O., Al-Khaduri, M., Gupta, I., Ouhtit, A., Al-Adawi, S., Al-Said, M., & Deth, R. (2012). Levels of Heavy Metals and Essential Minerals in Hair Samples of Children with Autism in Oman: a Case–Control Study Biological Trace Element Research DOI: 10.1007/s12011-012-9553-z