ReviewThe importance of selenium to human health
Section snippets
Health conditions associated with selenium deficiency
Recognition of the important role of selenoproteins in metabolism helps to explain the adverse consequences of selenium deficiency in human and animal health. Selenium enters the food chain through plants, which take it up from the soil. Selenium deficiency has therefore been identified in parts of the world notable for their low soil content of selenium, such as volcanic regions.10 Acid soils and complexation, frequently with iron or aluminium, also reduce the uptake of selenium by plants, as
Health effects of less-overt selenium deficiency
There is evidence that less-overt selenium deficiency can have adverse consequences for disease susceptibility and the maintenance of optimal health. Low selenium status may contribute to the aetiology of the disease process but in some cases it may be an outcome of the condition itself and may exacerbate disease progression (eg, HIV infection). These difficulties are largely overcome in prospective epidemiological studies, particularly where the first few years of follow-up are excluded from
Immune function
Numerous studies suggest that deficiency of selenium is accompanied by loss of immunocompetence, probably not unconnected with the fact that selenium is normally found in significant amounts in immune tissues such as liver, spleen, and lymph nodes. Both cell-mediated immunity and B-cell function can be impaired.6
By way of contrast, supplementation with selenium, even in “selenium-replete” individuals, has marked immunostimulant effects, including an enhancement of proliferation of activated T
Viral infection
Selenium deficiency is linked to the occurrence, virulence, or disease progression of some viral infections.14
Beck and colleagues have shown that in a selenium-deficient host harmless viruses can become virulent,15 a situation that is likely to be relevant to the development of Keshan disease. When selenium-deficient mice were inoculated with a benign strain of the coxsackie virus (CVB3/0), mutations occurred in the genome to give a cardiovirulent form of the virus that caused myocarditis with
Reproduction
Selenium has long been recognised in animal husbandry as being essential for successful reproduction.27 Idiopathic miscarriage has been shown to be associated with selenium deficiency in veterinary practice,28 while in sheep,28 selenium supplements have been shown to prevent early pregnancy loss.29 Investigating whether this could also be relevant to human beings, Barrington and colleagues found significantly lower serum selenium in women who had had either first-trimester or recurrent
Mood
There are a number of indications that selenium is important to the brain: during selenium depletion the brain receives a priority supply;38 the turnover rate of some neurotransmitters is altered in selenium deficiency;39 supplementation with selenium reduced intractable epileptic seizures in children;40, 41 low plasma selenium concentrations in the elderly were significantly associated with senility and accelerated cognitive decline;38, 42 and brain selenium concentration in Alzheimer's
Thyroid function
Although deiodinase activity is relatively protected in conditions of marginal selenium availability,1 current European levels of selenium intake may nonetheless compromise thyroid-hormone metabolism. For example, plasma T3:T4 ratios in young Scottish people were as low as those normally found in elderly populations (J R Arthur, personal communication). Furthermore, selenium supplementation in a small group of elderly individuals decreased plasma thyroxine (T4) concentrations, consistent with
Cardiovascular disease
Selenium may be protective against cardiovascular disease.4 On theoretical grounds, this hypothesis is supported by the ability of GPx to combat the oxidative modification of lipids and to reduce platelet aggregation.4 GPx4 reduces hydroperoxides of phospholipids and cholesteryl esters associated with lipoproteins48 and may therefore reduce the accumulation of oxidised low-density lipoproteins in the artery wall. GPx is required for the metabolism of hydroperoxides produced in eicosanoid
Other oxidative-stress or inflammatory conditions
Selenium behaves both as an antioxidant and anti-inflammatory agent. This is because selenium in its antioxidant role, notably as GPx, can: reduce hydrogen peroxide, lipid and phospholipid hydroperoxides, thereby dampening the propagation of free radicals and reactive oxygen species; reduce hydroperoxide intermediates in the cyclo-oxygenase and lipoxygenase pathways diminishing the production of inflammatory prostaglandins and leukotrienes; and modulate the respiratory burst, by removal of
Cancer
Epidemiological studies since the 1970s have provided evidence of an inverse relation between selenium intake and cancer mortality. In a study by Schrauzer and colleagues,64 dietary intake of selenium in 27 countries was found to correlate inversely with total age-adjusted cancer mortality, while in an investigation of the relation between forage-crop selenium and county levels of cancer mortality in the USA, cancer mortality rates for the major cancer sites were found to be significantly
Current selenium intake and status in Europe
Selenium intakes in most parts of Europe are considerably lower than in the USA, soils being a poorer source of selenium.74 Selenium intake levels in some European countries are shown in table 3. When considering the adequacy or otherwise of these levels, we need to have appropriate standards against which to compare them. There is no consensus on this issue.
The UK Reference Nutrient Intake (NRI) of 75 μg per day for men and 60 μg per day for women has been determined as the intake believed to
Sources and bioavailability of selenium
With the exception of Brazil nuts (which are said to accumulate radioactive barium: R J P Williams, personal communication) and kidney, there are few good food sources of selenium in many European countries. Crab, liver, other shellfish, and fish are moderately good sources, although studies show marked differences in the ability of selenium from fish to increase selenium status.79, 82, 83 (The existence of different selenium compounds in fish, their dependence on fish species or source, or
Interaction with toxic metals in the food supply
Selenium seems to reduce the toxicity of several metals by forming inert metal selenide complexes. Mercury or methyl mercury in marine foods is found combined with selenium, which may protect against mercury toxicity.10 This binding may, incidentally, reduce the bioavailability of selenium from such foods.
Selenium research—the way ahead
The past 5 years have been an exciting time in selenium research. The previously-unsuspected role of host selenium status in the emergence of viral disease promises some new strategies for prevention and treatment.15, 19 Elucidation of the importance of novel viral selenoproteins may improve our understanding of HIV.14, 25 Baum's group is currently running two double-blind, placebo-controlled randomised trials on selenium supplementation of HIV-positive individuals: one in a cohort of 100
Conclusions
Recent evidence has reinforced the importance to health of adequate selenium status. Selenium intakes may be suboptimal with respect to disease risk, notably in populations of adults in the UK, parts of Europe and China, New Zealand, and even in the USA. Indications that this may be the case are strongest for cancer–where selenium intake at a much higher level than that required to saturate the selenoenzymes would appear to be beneficial—and HIV progression to AIDS. Further research is needed
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