I searched PubMed and the Cochrane Library for publications from January, 1990, to February, 2011. I used the search terms “selenium”, “selenoprotein”, and the names of the individual selenoproteins in combination with the terms “polymorphism”, “Keshan disease”, “Kashin-Beck disease”, “mortality”, “immune function”, “immunity”, “regulatory T cells”, “Tregs”, “virus”, “antiviral-effect”, “HIV”, “brain”, “seizures”, Parkinson's disease”, “cognitive decline”, “dementia”, “Alzheimer's disease”,
ReviewSelenium and human health
Introduction
A decade ago, investigators believed that identification of optimal selenium status would benefit health. However, since then, excessive zeal for increasing selenium intake has at times had adverse consequences—a reminder that selenium was first known as a toxic element.1 This Review updates an earlier one2 and discusses present controversies, especially the effect of selenium on cancer and type-2 diabetes, with emphasis on clinically relevant studies. Appendix pp 1–4 provides additional relevant references.
Section snippets
Role of selenium: selenoproteins
In human beings, the nutritional functions of selenium are achieved by 25 selenoproteins that have selenocysteine at their active centre.3 The insertion of selenocysteine to form a selenoprotein is specified by the UGA codon in mRNA under specific conditions, but many other interacting factors are necessary.3, 4 In low selenium supply, the synthesis of some selenoproteins (eg, glutathione peroxidase, GPx4) is prioritised over that of others.4 Many selenoproteins are important enzymes and their
Selenium intake
In contrast to many other micronutrients, the intake of selenium varies hugely worldwide, ranging from deficient (associated with selenium-deficiency diseases; appendix p 5) to toxic concentrations that cause garlic breath, hair and nail loss, disorders of the nervous system and skin, poor dental health, and paralysis.22 Dietary selenium intake ranges from 7 μg per day to 4990 μg per day, with mean values of 40 μg per day in Europe and 93 μg per day (in women) to 134 μg per day (in men) in the
Mortality
In at least three prospective studies,32, 33, 34 high selenium status has been associated with low overall mortality. A non-linear association was noted between selenium status and all-cause and cancer mortality in 13 887 adult participants followed up for up to 12 years (until the end of 2000) in the US Third National Health and Nutrition Examination Survey.32 Figure 3 shows the updated follow-up of these participants to the end of 2006. Increasing serum selenium concentrations up to about 135
Type-2 diabetes
Evidence linking selenium to glucose metabolism is conflicting.119 High selenium status was associated with reduced diabetes prevalence in three case-control studies,120, 121, 122 while in the prospective EVA study,123 high plasma selenium correlated with a decreased risk of onset of hyperglycaemia during a 9-year follow-up period in male participants.
By contrast, high serum selenium concentration was associated with an increased prevalence of diabetes in the large US National Health and
Selenium status in relation to health effects
Selenium status varies widely in different parts of the world, in line with selenium intakes.1, 2 The distribution of plasma selenium in the UK132 and that in the USA133 (figure 4) shows the difference in status between Europe (represented by UK data) and North America (represented by US data). The dotted vertical line on figure 4 (at 122 μg/L) represents the concentration of baseline plasma selenium that marked a change from negative to positive in the risk of cancer, non-melanoma skin cancer,
Conclusions and suggestions for future research
The effects of selenium on human health are multiple and complex,1 necessitating further research to optimise the benefits and reduce the risks of this potent trace mineral. Trials should be undertaken only in populations of low or relatively low selenium status. Furthermore, since polymorphisms in selenoproteins affect both selenium status and disease risk or prognosis (table 1), future studies must genotype participants. Further work aimed at understanding the potential links between
Search strategy and selection criteria
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