Questioning Answers: Metallomics analysis and autism

As an avid follower of several of the -omics, I was interested to read the report by Hiroshi Yasuda and colleagues* (open-access) on the application of a new -omics to me, metallomics - think metals affecting cellular functions - and in particular, the application of metallomics to autism.

This is not the first time that the work of Hiroshi Yasuda has appeared on this blog, as per my previous entry on 'the link with zinc' highlighting some interesting findings of zinc deficiency in quite a sizable proportion of their cohort diagnosed with an autism spectrum disorder (ASD).

Mick's home or 'ome Mick's? @ Wikipedia

The autism metallome?

Yasuda's latest paper - published in the same Nature family journal, Scientific Reports - extend their analysis of the metals outside of just zinc to include quite a few more and likewise report on what looks like the same cohort of participants as their previous paper.

A few details bearing in mind the paper is open-access:

Quite a big cohort (N=1967) of Japanese children diagnosed with an ASD were included for study.
Hair samples taken from as close to the scalp as possible (I assume denoting a more current metallomic profile) were analysed by everyone's favourite metal analysis technique, ICP-MS. I might add that not everyone is convinced that hair analysis is a great way of testing for metal status or anything else.
Results: well we know that zinc levels were already reported on the low side; indeed a zinc deficiency was present in over 40% of the 0-3 years age group (43%), getting a little better as the age ranges increased: 4-9 year olds (28%) and 10-15 year olds (3%) in males (who comprised most of the cohort). Females also showed a similar pattern across the age ranges (52%, 28%, 3% respectively).
Magnesium and calcium deficiency were also highlighted as being present among a proportion of their cohort; albeit not to the same extent of the rates of zinc deficiency.
A quote: "high toxic metal burden of aluminium, cadmium and lead of over their +2 S.D. level was observed in 339 (17.2%), 168 (8.5%) and 94 (4.8%) individuals".
A few examples are given showing the metallome of individual participants which seem to lead to an interesting suggestion that zinc deficiency (together with magnesium deficiency) might correlate somehow with a "high toxic metal burden".

Link with zinc

I'm not going to offer too much in the way of discussion about the zinc part of these results given my past reporting on the previous paper** by Yasuda et al alongside some background on zinc. A few additions perhaps are worthy of mention in light of the suggestion of an epigenetic role of zinc deficiency. Regular readers will already know that I'm getting quite enamoured with the whole 'your genome is not your destiny' revolution that seems to be occurring these days. I note for example the paper by Kurita and colleagues*** which in a mouse model at least, points to a possible epigenetic effect from zinc deficiency occurring in-utero. The assumption being that especially in that 0-3 age group where zinc deficiency was highest in the Yasuda study, gestational zinc deficiency might have preceded infantile deficiency? And then there's the whole inflammation side of things as per the paper by Wessels and colleagues**** bearing in mind what we call inflammation and also infection (see here).

Magnesium

The rates of magnesium deficiency were also quite striking in their Japanese cohort. I assume most people with some interest in autism will know all about the whole vitamin B6-magnesium connection stretching back some years now. Granted the evidence base looking for example, at supplementation with B6 and magnesium is still a little incomplete as per the Cochrane review from Nye and Brice***** but I would also draw your attention to some interesting studies in the decade of big hair and electro-pop (the 80's) by Lelord and colleagues******* (who are also credited with devising the rather nice Behaviour Summarised Evaluation Schedule). I might add that this is not the first time that magnesium deficiency has been reported in cases of autism, illustrated by the papers by Wecker and colleagues******** and Lakshmi and Geetha*********, although not universally so. The causes and effects of such deficiency? Well, lets just say that I have a few ideas outside of just faddy diets affecting intake but I'm not fooling myself that this process would be so simple and universal.

Calcium

As for the other findings, well, let's just say that I've done lead before (see here) so I'm not heading down that path again. Calcium deficiency is something that I am quite interested in as a result of the use of things like a casein-free diet as a possible intervention measure for some cases of autism. As discussed in other posts, calcium seems to have its own relationship to some cases of autism and especially the view that such dietary intervention might impact on calcium levels. Indeed calcium intake is known to often be a little lower in cases of autism*********. That being said, I'll also draw your attention to some other recent literature on the calcium-autism link (see here) and on whether or not the sunshine vitamin might also play some role in this complex relationship.

Yasuda and colleagues conclude their paper by talking about the possibility of "a critical term “infantile window” in neurodevelopment and for its therapy" in light of the deficiencies and elevations they found. I'm not sure that we are quite there yet so as to be able to suggest that supplementing with zinc or magnesium or calcium during the very earliest days is somehow able to mitigate the risk of autism onset. Certainly I'd be wary of seeing anyone make any general recommendations on such supplementation strategies during such early development without both confirmatory evidence of deficiency in specific cases (including whether seasonality might for example affect results**********) and some further safety work looking at optimal dosage and delivery. Oh, and a good explanation as to why the deficiency was there in the first place might also be a good idea...

To finish and to celebrate Rolf Harris continuing to wow audiences, a classic... Jake the Peg (with his extra leg).

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* Yasuda H. et al. Estimation of autistic children by metallomics analysis. Sci Rep. 2013; 3: 1199.

** Yasuda H. et al. Infantile zinc deficiency: association with autism spectrum disorders. Sci Rep. 2011; 1: 129.

*** Kurita H. et al. Prenatal zinc deficiency-dependent epigenetic alterations of mouse metallothionein-2 gene. J Nutr Biochem. 2013; 24: 256-266.

**** Wessels I. et al. Zinc deficiency induces production of the proinflammatory cytokines IL-1β and TNFα in promyeloid cells via epigenetic and redox-dependent mechanisms. J Nutr Biochem. 2013; 24: 289-297.

***** Nye C. & Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. 2005; 4: CD003497.

****** Lelord G. et al. Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Acta Vitaminol Enzymol. 1982; 4: 27-44.

******* Wecker L. et al. Trace element concentrations in hair from autistic children. J Ment Defic Res. 1985; 29: 15-22.

******** Lakshmi P. & Geetha A. Level of trace elements (copper, zinc, magnesium and selenium) and toxic elements (lead and mercury) in the hair and nail of children with autism. Biol Trace Elem Res. 2011; 142: 148-158.

********* Sharp WG. et al. Feeding problems and nutrient intake in children with autism spectrum disorders: a meta-analysis and comprehensive review of the literature. J Autism Dev Disord. February 2013.

********** Teresa M. et al. Trace element concentrations in blood and hair of young apprentices of a technical-professional school. Sci Total Environ. 1997; 205: 189-199.

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