Selenium is an essential trace element which has, however, a low threshold of toxicity commencing at approximately ten times the dietary requirement.
Current U.K. Reference Nutrient Intake. Children: 10-45 µg/d, depending on age; women: 60 µg/d; men: 75 µg/d. Maximum safe intake (all sources) for adult males: 450 µg/d. (Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy, 1993).

Selenium is present at the active site of two enzymes. Glutathione peroxidase, which is found as distinct intracellular and extracellular variants, catalyses in vitro the destruction of hydrogen peroxide and organic hydroperoxides. Within cells it forms, together with vitamin E and superoxide dismutase, part of cellular antioxidative capacity and may also, according to recent theory, serve as a selenium reservoir. The exact role of the extracellular (plasma) variant is not known, but it may function in the renal extra-cellular space. Type 1 iodo-thyronine 5′-deiodinase, present mainly in liver and kidney, mediates conversion of thyroxine (T4) to 3,3′-triiodothyronine (T3). An additional extracellular Se-containing protein, selenoprotein-P, accounts for approximately 50% of human plasma selenium; its function is unknown.
Deficiency is well documented in animal husbandry, causing serious problems which manifest as degenerative diseases (usually of muscle) and failure to thrive. Selenium supplementation will not only prevent these conditions, but usually remedy them in afflicted animals, and may not be required at all if vitamin E status is adequate. Two diseases (both endemic to parts of China) have been clearly linked to selenium deficiency in man. Keshan Syndrome is a cardiomyopathy prevalent amongst children and women, and Kashin-Beck Disease an osteoarthropathy afflicting children. With both conditions, large populations were at risk from a restricted and very selenium-deficient diet. Supplementation with selenium has virtually eradicated new cases of Keshan Syndrome, but only partially solved the problem of Kashin-Beck disease. Other factors may be necessary before selenium depletion is triggered into overt disease. For Keshan Syndrome, it has recently been postulated that infection with Coxsackie virus may have been such a factor; for Kashin-Beck Disease, the situation remains speculative.
Outside China, symptomatic selenium deficiency in humans appears to be restricted to patients on parenteral nutrition and children with inborn errors of metabolism who require very specialised diets. However, reports of this phenomenon are few, most subjects enduring even severe selenium depletion without apparent adverse clinical manifestations. That humans may be particularly tolerant of selenium depletion is suggested by the fact that the health of New Zealanders does not appear to be compromised despite having a selenium status that would be regarded as frankly deficient in other countries. The Chinese observations have stimulated much research into the involvement of selenium in the aetiology of many diseases, most recently focusing on the biochemical and molecular aspects of the element in relation to cancer and heart disease. Despite some significant progress in these fields, it has not, in general, been possible to clarify cause and effect in such investigations. Consequently, the role of selenium deficiency in relation to an increased disposition to various cancers remains controversial, as do recommendations for prophylaxis by supplementation with selenium at doses well in excess of recommended dietary amounts.
Given the current knowledge of selenium biochemistry, laboratory investigation of selenium deficiency should be restricted to the monitoring of patients receiving parenteral nutrition and other medically indicated diets, or the investigation of conditions arising from malnutrition or exotic dietary habits.

Selenium is used in the electronics industry and in the manufacture of shampoos, paints, dyes and glass. Smelting and refining processes may result in exposure to fumes of elemental selenium and selenium dioxide, in addition to hydrogen selenide. Acute symptoms described include intense irritation of eyes, nose, mouth and lungs, chronic exposure producing, in addition, “garlic breath”, nausea and anorexia.
Self-poisoning, accidental and deliberate, has occurred by ingestion of selenious acid alone, or more frequently, in combination with copper nitrate and nitric acid, as gun-blueing compound. This substance was implicated in the UK in an attempted criminal poisoning; the symptoms exhibited by the victim were consistent with chronic selenosis.
Following acute ingestion, symptoms described include gastrointestinal upset, abdominal pain, agitation, altered consciousness level and cardio-respiratory arrest. In such cases the contribution of the element alone to the poisoning is difficult to assess in view of the fact that solutions containing selenium may be quite strongly acidic.
Characteristic features of acute or chronic toxicity are well documented in livestock foraging on pasture rich in available selenium. Although humans resident in a number of ‘high selenium’ regions have been investigated, it is only in China that convincing symptoms of serious endemic selenosis have been observed; affected individuals suffered ‘garlic breath’, deformity and loss of hair and nails, skin lesions, gastrointestinal upset, and in some severe cases, serious neurological problems.
In the USA, some of these conditions also afflicted a number of people taking a supplement that had been incorrectly formulated and which contained 27 mg Se/tablet instead of 150 µg. In general however, use by healthy individuals of supplements of 100 – 150 µg/day does not appear to be detrimental. In the UK the requirement for, and the benefit of, extra-dietary selenium is currently under active consideration. Similar supplementation as an adjunct to therapy of diseases such as cystic fibrosis may be dangerous in view of the possibility of the illness lowering the threshold of toxicity for selenium.

Laboratory Indices of Selenium Status
There is currently considerable debate as to what is the most appropriate index of selenium status. In clinical practice selenium is usually measured in plasma (or serum), providing an index of recent intake of the element. However, plasma selenium has recently been shown to possibly be an acute-phase reactant, in which case the lowered concentration may be the result of tissue redistribution rather than a nutritional deficit. In this circumstance, an acute phase response should be confirmed by measurement of C-reactive protein. Normal plasma selenium concentrations are age-dependent. At birth, plasma values are 40-70% of maternal concentrations; depending on neonatal selenium status, and whether the infant is formula or breast fed, the plasma concentration may drop over the first four months of life. Thereafter it rises gradually, reaching adult values in the late teen years. Plasma selenium may drop during pregnancy by as much as 20%, but there is considerable variation in this and the mechanism is not understood.
Whole blood selenium concentrations are less responsive to fluctuations of intake, erythrocyte concentrations even less so, and it has been proposed that these matrices are more appropriate when undertaking population studies. However, they are more difficult to analyse than is plasma.
Functional deficiency, in so far as it is understood, may be assessed by monitoring the activity of glutathione peroxidase, the red cell enzyme providing a long-term record, the plasma variant sensitive to recent changes in Se intake. However, the lack of inter-laboratory analytical standardisation and problems of reproducibility, especially with the plasma enzyme, make this an impractical approach to first-line clinical monitoring. An immunoassay has been developed for selenoprotein-P, but its availability is limited and its usefulness to be confirmed. Measurement of urinary selenium is of no value in investigating deficiency.
In cases of known acute selenium poisoning, measurement of serum or plasma selenium concentration will confirm ingestion and degree of absorption, but may not provide a reliable indication of the severity of poisoning or a guide to prognosis. It is however, a good indicator of excessive chronic ingestion, but again may not reflect symptomatology.
In humans, the erythrocyte glutathione peroxidase activity plateaus before ‘normal’ plasma concentrations of selenium are exceeded. It is not, therefore, usually investigated in cases of toxicity, but may have some value in investigation of deficiency.
Renal excretion is the main means of selenium homeostasis in humans. With excessive ingestion, urinary concentrations rise, often dramatically. Urine selenium assay is a practical way of monitoring occupational exposure, and may be used to distinguish between chronic and acute exposure.
With excessive ingestion, pulmonary excretion of the metabolite dimethyl selenide occurs. This produces the characteristic ‘garlic breath’.

Thomas AG, Miller V, Shenkin A, Fell GS, Taylor. Selenium and glutathione peroxidase status in paediatric health and gastrointestinal disease. J Ped Gastroenterol Nutr 1994; 19: 213-9
Taylor A. Detection and monitoring for disorders of essential trace elements. Annals of Clinical Biochemistry 1996; 33: 486-510
Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL, Park K, Sanders BB, Smith CL, Taylor JR. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996; 276:1957-63
Rayman MP. Dietary selenium: time to act. BMJ 1997; 314: 387-8

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