Brief, Incomplete Note on Zinc

This is a good article that describes some of the basic aspects of zinc metabolism [Brown, 1998: (http://www.ajcn.org/cgi/reprint/68/2/425S.pdf) (http://www.ncbi.nlm.nih.gov/pubmed/9701156)], but the article doesn't address some of the fundamental problems that can occur, in my opinion, in the context of zinc supplementation. I've discussed some of the issues in previous postings [(http://hardcorephysiologyfun.blogspot.com/2009/01/copper-and-zinc-complexities-and.html); (http://hardcorephysiologyfun.blogspot.com/2008/12/zinc-toxicity-and-parp.html); (http://hardcorephysiologyfun.blogspot.com/2008/12/regulation-of-5-nucleotidase-activities.html)]. Levenson (2005) [Levenson, 2005: (http://www.ncbi.nlm.nih.gov/pubmed/15869126)] discusses, for example, some of the potential for neurotoxicity with excessive zinc supplementation. I don't even know where to start or what to say, because there are so many articles I've read in the context of neurodegenerative disorders or exercise physiology in relation to this. I can't cite things, partly because of the complexity, but there are probably 100 or 1,000 or more articles on every aspect of zinc metabolism one could imagine.

Brown (1998) discusses the fact that plasma zinc has usually been viewed as being maintained more or less independently of the "stores" of zinc in the body (in the liver and muscles, etc.). But Brown (1998) also mentions that severe reductions in the intake of zinc will lower plasma zinc. But I think this is unlikely to occur in most people. Exercise training does evidently reduce plasma zinc over time, if a person doesn't increase his or her intake of foods, such as meats, that are high in zinc. But I don't think exercise always decreases serum zinc, and it's not clear to me that a decrease in plasma zinc would always be a bad thing. One implication of the fact that the muscles, for example, can store some zinc is that maintaining some basic muscle mass could beneficially sequester zinc or exert a buffering effect on plasma zinc levels. This could conceivably help to prevent some of the potentially toxic effects of excessive zinc "fluxes," such as across the blood-brain barrier, etc. I just think that, to the extent that exercise does increase zinc "requirements," the increased requirement due to exercise could be compensated for by an increase in the intake of meat or other foods. That's just my opinion. One of the main problems with zinc supplementation, as I see it, is the fact that, in spite of the rapid turnover and transport of zinc in most parts of the body, metallothionein proteins tend to be upregulated by increases in the zinc intake. Metallothioneins can have some antioxidant effects, but one way of viewing the zinc-induced upregulation of the metallothionein protein concentrations, in any number of cell types, is as a cellular stress response. Metallothioneins can have antioxidant effects, but, fundamentally, their upregulation would seem to have the potential to lead to erroneous conclusions about "zinc status." In response to supplementation, there can be this extra zinc that is sequestered by metallothionein proteins in, for example, endothelial cells. When there is some oxidative stress or metabolic insult, this zinc could be released en masse. Moreover, the metallothioneins can sequester copper and iron, etc. This can make it seem as if the copper intake needs to be increased, when another, arguably safer, approach would be to stop supplementing with zinc and copper and let things return to a state that is characterized by as much "normalcy" as one could expect to see. That's just my opinion.