SELENIUM

Functions and essentiality   Selenium (Se) is an integral part of the enzyme glutathione peroxidase (GSHPx), one of the mechanisms whereby intracellular structures are protected against oxidative damage (1). Selenium deficiency results both in a decrease in GSHPx activity and in GSHPx protein (2). GSHPx activity in blood and other tissues is linearly related to Se concentrations up to a level of 100 ng/ml in whole blood (3). Other selenoproteins have been isolated from mammalian tissues and of particular interest is the role of Se in the hepatic microsomal deiodination of thyroxine (4). Between 55 and 65 percent of dietary Se is absorbed and the major route of excretion is in the urine, which reflects dietary intakes, as do levels in tissues and blood. Thus the Se 'status' of people correlates with the amount and availability of Se in their diet and the local geochemical environments (1-3).


Requirements

Adults   Blood Se levels in the UK are just above the value (100ng/ml) at which GSHPx activity reaches a plateaU (5,6) suggesting that current levels of Se in diets are adequate. No adverse consequences arise from somewhat lower blood levels of Se or GSHPx which are below saturation (7). However, since intakes that permit functional saturation appear to be the norm in the UK, the RNI has been established at a level to maintain this, at 1.0 µg (13 nmol)/kg. Supplementation studies using DL selenomethionine show that in Chinese males saturation of GSHPx can be achieved on an intake of about 41 µg/d (8). On a body weight basis this would correspond to 50 µg/d in a UK male. However, no evidence of deficiency is seen in populations with intakes of 40 µg/d (7). Since the Se responsive cardiomyopathy, Keshan Disease, is not seen in populations with mean intakes of 19 µ/d (equivalent to 23 µg/d in a UK male) (9), and given the considerable functional reserve at low GSHPx saturations (7), the Panel considered 40 µg/d a suitable LNRI. There is insufficient evidence to suggest that smoking or the use of oral contraceptive agents increase the requirement for Se. Neither is there any convincing evidence that high intakes protect against cancer or cardiovascular disease (3).


Pregnancy and Lactation   Women should have an adequate Se intake prior to becoming pregnant and since adaptive changes in the metabolism of Se occur during pregnancy (10), no advantage is seen in recommending extra Se at this time. Concentrations of Se in colostrum vary from 15 to 80 ng/ml and fall during the first month of lactation to about 8-30 ng/ml, remaining relatively constant thereafter. To maintain infant serum at about 70 ng/ml (whole blood of about 80 ng/ml) a daily intake from breast milk of about 8-10 ng/g is necessary (11), Human milk from the UK has been reported to contain 10-20 ng/ml (12). In the absence of more specific data, a possible extra requirement during lactation has been calculated on the basis of milk with a Se content of about 12 ng/ml and 60 per cent absorption. This gives an increment in intake of about 15 µg (0.2 µmol)/d.


Infants   At birth, blood Se levels resemble those in adults but then fall to a minimum by about 3 months before increasing to reach adult levels at 1-3 years. Breast-fed infants receive 5-13 µg/d (60-160 nmol/d). Intakes from formula are generally low, only 2-4 µg/d and the trend in blood concentrations reflects methods of infant feeding (13,14). In models Se appears to be less well absorbed from infant formulas than from human milk (15). For non-breast fed infants the RNI has been set at 1.5 µg/kg at 4-6 months and 1.0 µg/kg at 7-12 months with an allowance for growth of 0.2 µg/kg weight gain.


Children   Selenium nutrition has not been extensively investigated in children. In the UK, blood Se levels were found to be about 80 per cent of UK adult levels at 1 year, increasing to adult values by 3 years and remaining relatively constant thereafter (14). Similar trends have been reported in New Zealand and West Germany. The RNI has been calculated on a body weight basis from the adult figure, with an additional requirement for growth set at 0.2 ng/g weight gain.


Intakes   Selenium is present in foods mainly as the amino acids selenomethionine and selenocysteine and derivatives. Estimation of adequate Se intake is helped by the recognition of clinical disease with the extremes of naturally occurring dietary intakes of Se. In China, intakes of Se less than 12 µg (0. 15 µmol)/d are associated with an increased incidence of an endemic Se responsive cardiopathy (Keshan Disease). However in New Zealand and Finland where habitual intakes are 15-40 µg/d (0.2-0.5 µmol/d) no Se responsive disease has been identified (1-3). In Southern England Se intakes approximate 65 µg (0.8 µmol)/d (16). Cereals, meat and fish contribute the bulk of Se to the diet with cereals providing about 50 per cent of this (12,16).


Guidance on high intakes   Evidence of disturbed Se homeostasis occurs at intakes above 750 µg (9.5 µmol)/d (17), and early nail dystrophy has been observed in adults ingesting 900 µg (11.4 µmol)/d. Thus, given the absence of any demonstrable benefit from exceeding intakes much lower than these (3), the Panel recommended that the maximum safe Se intake from all sources should be 450 µg (5.7 µmol)/d for adult males, corresponding to 6 µg/kg/d.


References

1   Levander OA.Selenium.1n:Mertz W,ed.Trace Elements in Human and Animal Nutrition.5th ed, vol 2. Orlando, Florida: Academic Press, 1986; 209-279.

2   Levander 0 A. A global view of human selenium nutrition. An Rev Nutr 1987; 7: 227-250.

3   Casey C E. Selenophillia. Proc Nutr Soc 1988; 47: 55-62.

4   Arthur J R, Nicol F, Beckett F J. Hepatic iodothyronine deiodinase: the role of selenium. Biochem J 1990; 272: 537-540.

5   Thomson C D, Rea H M, Doesburg V M, Robinson M F. Selenium concentrations and glutathione peroxidase activities in whole blood of New Zealand residents. Br JNutr 1977; 37: 457-460.

6   Diplock A T, Chaudhry F A. The relationship of selenium biochemistry to selenium-responsive disease in man. In: Prasad A, ed. Essential and Toxic Trace Elements in Human Health and Disease. New York: Alan R Liss, 1988; 211-226.

7   Robinson M F. The New Zealand selenium experience. Am J Clin Nutr 1988; 48: 521-534.

8   Yang G A, Zhu L Z, Liu S J et al. Human selenium requirements in China. In: Combs G, et al eds. Selenium in Biology and Medicine. New York: Nostrand Rheinhold/AVJ, 1987; 589-607.

9   Yang G, Ge K, Chen J, Chen X. Selenium-related endemic diseases and the daily requirement of humans. Wld Rev Nutr Dietet 1988; 55: 98-152.

10   Swanson C A, Reaner D C, Veillon C, King J C, Levander 0 A. Quantitative and qualitative aspects of selenium utilisation in pregnant and non pregnant women: an application of stable isotope methodology. Am J Clin Nutr 1983; 38; 169-180.

11   Smith A M, Picciano M F, Milner J A. Selenium intakes and status of human milk and formula fed infants. Am J Clin Nutr 1982; 35: 521-526.

12   Thorn J, Robertson J, Buss D H, Bunton N G. Trace nutrients. Selenium in British food. Br J Nutr 1978; 39: 391-396.

13   Lombeck 1, Kasperek K, Harbisch H D, Feinendegen L E, Bremer H J. The selenium state of healthy children. Europ J Pediatr 1977; 125: 81-88.

14   Ward K P, Arthur J R, Russell G, Aggett P J. Blood selenium content and glutathione peroxidase activity in children with cystic fibrosis, coeliac disease, asthma and epilepsy. Eur J Pediatr 1984; 142: 21-24.

15   Raghib M H, Chan W Y, Rennert 0 M. Comparative studies of selenium-75 (selenite and selenomethionine) absorption from various milk diets in suckling rats. J Nutr 1986; 116: 1456-1463.

16   Bunker V W, Lawson M S, Stranfield M F, Clayton B E. Selenium balance studies in apparently healthy and housebound elderly people eating self-selected diets. Br JNutr 1988; 59: 171-180.

17   Yang G, Yin S, Zhou L et al. Studies of safe maximal daily dietary Se intake in a seleniferous area in China. Part 11 Relation between Se intake and the manifestation of clinical signs and certain biochemical alterations in blood and urine. J Trace Elem Electrolytes Health Dis 1989; 3: 123-130.