Title: Selenium As An Antioxidant
Key words: selenium, antioxidant, Keshan disease, selenoproteins
Date: July 2000
Category: 3. Micronutrients
Author: Dr van Rhijn
Selenium As An Antioxidant
Potential Health Effects
Selenium has a number of biochemical metabolic functions in the body. Its antioxidant activity is thought to be due to it being a key component of three main functional selenoproteins, glutathione peroxidase, thioredoxin reductase and selenoprotein P.
What is the evidence for the involvement of selenium in the prevention of disease?
Selenium is an integral co-factor of the enzyme glutathione peroxidase (GSHPx)1,2 isoenzyme, which protects against oxidative damage in the body. This attribute accounts for the majority of selenium's health benefits. The mechanism by which this is achieved is by reduction of H2O2 lipid and free phospholipid hydroperoxides3 by using the GSH as the hydrogen donor. H202 + 2GSH ® 2H20 + GSSG. Research has shown that the most potent selenium compound, selenodiglutathione (SDG), a natural metabolite of selenite, does not induce oxidative stress. It is also part of thioredoxin reductase, which is a reducing enzyme (-S-S- bonds in proteins) with peroxidase activity and helps to regulate intracellular redox state. Selenoprotein P is an abundant extracellular selenoprotein that also possibly acts as an antioxidant defence system4. Selenoprotein W is a muscle protein containing selenocysteine. Selenium is an essential element of the glutathione synthase enzyme and a cofactor for the production of superoxide dismutase (SOD).
The enzyme iodothyronine 5’-deiodinase (IDI), required for converting thyroxin (T4) to the more metabolically active triiodothyronine (T3), is a selenium-containing protein5. Coexistence of iodine and selenium deficiency, as in Zaire, result in adverse effects on growth, development and neonatal survival. A lack of dietary selenium is associated with various clinical conditions, the best known of which is Keshan’s disease, a cardiomiopathy endemic in areas of China 6. Although supplementation and general dietary improvements have reduced the incidence of Keshan’s disease significantly7, research suggests the involvement of Vitamin E deficiency as well.
Experimental evidence suggests that Vitamin E and selenium may have a protective role in numerous viral infections8 (HIV9, 10, 11), and stimulation of the immune response. There is also strong epidemiological associative evidence of a protective role for selenium in degenerative conditions such as cancer (lung, bladder, stomach, breast, bowel and prostate). Selenium may act pharmacologically12 in a chemo-preventative role in cancer13 . Epidemiological evidence for its protective role in cardiovascular disease is equivocal14, 15. Low serum selenium may be a risk factor in pancreatitis16. Selenium may also be involved in conditions such as asthma, thrombosis, rheumatoid arthritis, ulcerative colitis and male fertility17.
Selenium is a major player in the antioxidant defence system against oxidative stress. It plays, therefore, a very important protective role in various degenerative conditions and serious viral infections.
1. Rayman, M.P. Dietary selenium: time to act. BMJ, 1997; 314, 387 – 388.
2. Arthur, J.R. and Beckett G.J. New metabolic roles for selenium. Proceedings of the Nutrition society 1994, 53, 615 - 624.
3. Yamamoto, Y. Glutathione peroxidase isolated from plasma reduces phospholipid hydroperoxides. Arch. Biochem. Biophys. 1993; 305; 541 – 545.
4. Burk, R.F. and Hill, K.E. Selenoprotein P: a selenium-rich extracellular glycoprotein. J. Nutr. 1993; 124:1891 – 1897.
5. Arthur, J.R. et al. Selenium deficiency, thyriod hormone metabolism, and the thyroid hormone deiodinases. American Journal of Clinical Nutrition 1993; 57, 236S – 239S.
6. Yang, G. et al. Selenium-related endemic disease and the daily selenium requirement of humans. World Rev. Nutr. Diet. 1988; 55: 98 – 152.
7. Yang, G. et al. The role of selenium in Keshan disease. Adv. Nutr. Res. 1984; 6:203 – 231.
8. Dhur, A. et al. Relationship between selenium, immunity and resistance against infection. Comparative Biochemistry and Physiology. 1990; 96: 271 – 280.
9. Look, M.P. et al. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection. Eur. J. Clin. Nutr. 1997; Apr, 51:4, 266 - 272.
10. Baum, M.K. et al. High risk of HIV-related mortality is associated with Se deficiency. J. AIDS and Human retrovirology. 1997; 15, 370 – 374.
11. Taylor , E.W. HIV-1 encodes a sequence overlapping env gp41 with highly significant similarity to Se-dependent GSHPx. J. Aids and Human Retrovirology. 1997
12. Diplock, A.T. Antioxidant nutrients and disease prevention: an overview. American Journal of Clinical Nutrition 53, 1991; 189S – 193S.
13. Harrison, P.R. et al. Chemopreventive and growth inhibitory effects of selenium. Biomed. Environ. Sci. 1997; Sep, 10:2-3, 235 – 245.
14. Yegin, A. et al. Erythrocyte selenium-glutathione peroxidase activity is lower in patients with coronary atherosclerosis. Jpn Heart J, 1997, Nov, 38:6, 793 - 798.
15. Neve, J. Selenium as a risk factor for cardiovascular disease. J. Cardiovasc. Risk. 1996; 3: 42 – 47.
16. McCloy, R. Chronic pancreatitis at Manchester, UK. Focus on antioxidant therapy. Digestion, 1998; 59 Suppl 4: 36 - 48.
17. Hansen, J.C. and Deguchi, Y. 1993. Selenium and fertility in animals and man--a review. Acta Vet Scand, 1996, 37:1, 19-30
Additional reading: Vitamins Minerals and Health: Fact File No 3: 1997; National Dairy Council. London.