Elsevier

The Lancet

Volume 379, Issue 9822, 31 March–6 April 2012, Pages 1256-1268
The Lancet

Review
Selenium and human health

https://doi.org/10.1016/S0140-6736(11)61452-9Get rights and content

Summary

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease-associated polymorphisms in selenoprotein genes has drawn attention to the relevance of selenoproteins to health. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type-2 diabetes. The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional selenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenium supplements.

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

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”,

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