Selenium Deficiency...continued.

Reference from the joint report of FAO/WHO expert consultation of Human Vitamins and Minerals verbatim.

Selenium status and susceptibility to infection

17. Levander, O.A. & Beck, M.A. 1997. Interacting nutritional and infectious ecologies of Keshan Disease. Biol. Trace Elem. Res., 56: 5-21.

As stated earlier, the expressions of the cardiac lesions of Keshan disease probably involve not only the development of selenium deficiency but also the presence of a Coxsackie virus (BA) infection. Animal studies have confirmed that selenium-deficient mice infected with Coxsackie virus (CVB/0) were particularly susceptible to the virus. These studies also illustrated that passage of the virus through selenium-deficient subjects enhanced its virulence (17).

21. Beck, M.A. 1998. The influence of antioxidant nutrients on viral infection. Nutr. Revs., 56: S140-S146.

Myocarditic virulence developed even in strains such as CVB/0 which normally were not myopathogenic. The enhancement of virulence in this RNA virus involves modifications to the nucleotide sequence of the phenotype. These modifications were maintained and expressed even during subsequent passage through animals with normal selenium status (21).

Enhancing the virulence of a virus with a selenium deficiency (resulting either from a nutritional challenge or an increased metabolic demand on tissue selenium depots) appears not to be unique to the Coxsackie viruses. The early pre-clinical stages of development of human immunodeficiency virus (HIV) infection are accompanied by a very marked decline in plasma selenium. Sub-clinical malnutrition assumes increased significance during the development of acquired immune deficiency syndrome (AIDS).

22. Baum, M.K. & Shor-Posner, G. 1998. Micronutrient status in relationship to mortality in HIV-1. Nutr. Revs., 56: S135-S139.

23. Baum, M.K., Shor-Posner, G., Lai, S.H., Zhang, G.Y., Fletcher, M.A., Sanberlich, H. & Page, J.B. 1997. High risk of HIV-related mortality is associated with selenium deficiency. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 15: 370-374.

24. Cirelli, A., Ciardi, M. & DeSimone, C. 1991. Serum selenium concentration and disease progress in patients with HIV infection. Clin. Biochem., 24: 211-214.

25. Dworkin, B.M. 1994. Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). Chem. Bio. Interact., 91: 181-186.

However, for the nutrients affected, there are strong indications that only the extent of the decline in selenium status has predictive value with respect to both the rate of development of AIDS and its resultingmortality (22-25).

26. Taylor, E.W., Nadimpalli, R.G. & Ramanthan, C.S. 1997. Genomic structures of viral agents in relation to the synthesis of selenoproteins. Biol. Trace Elem. Res., 56: 63-91.

The virulence of other RNA viruses such as hepatitis B and those associated with the development of haemolytic anaemias are enhanced similarly by a decline in selenium status. The mechanisms underlying these effects are not yet resolved. There are indications that the loss of protective antioxidant functions dependent on selenium and vitamin E are both involved and that the resulting structural changes in viral nucleotide sequences are reproducible and appear to provoke additional selenoprotein synthesis (26).

27. Zazzo, J.F., Chalas, A. & LaFont. 1988. Is monobstructive cardiomyopathy in AIDS a selenium deficiency-related disease. J. Parenteral Enteral Nutr., 12: 537-538.

28. Kavanaugh-McHugh, A.L., Ruff, A. & Pearlman, A. 1991. Selenium deficiency and cardiomyopathy in acquired immunodeficiency syndrome. J. Parenteral Enteral Nutr., 15: 347-349.

29. Ramanathan, C.S. & Taylor, E.W. 1997. Computational genomic analysis of Hemorrhagic viruses; viral selenoproteins as a potential factors in pathogenesis. Biol. Trace Elem. Res., 56: 93-106.

It is suspected that this further depletes previously diminished pools of physiologically available selenium and accelerates pathologic responses (27-29).

30. Serfass, R.E. & Ganther, H.E. 1975. Defective microbial activity in glutathione peroxidase deficient neutrophils of selenium deficient rats. Nature, 225: 640-641.

31. Boyne, R. & Arthur, J.R. 1986. The response of selenium deficient mice to Candida

albicans infection. J. Nutr., 116: 816-822.

Whatever mechanisms are involved, further understanding is needed of the influenceof selenium status on susceptibility to viral diseases ranging from cardiomyopathies tohaemolytic anaemias. The relationship already illustrates the difficulty of defining nutritional essentiality for nutrients which may primarily maintain defences against infection. Studies of the effects of selenium deficiency in several experimental animal species have shown that the microbicidal activity of blood neutrophils is severely impaired even though phagocyticactivity remains unimpaired (30, 31).

8. Reilly, C. 1996. Selenium in food and health. London, Blackie Academic and Professional.

32. Ip, C. & Sinha, D.K. 1981. Enhancement of mammary tumorigenesis by dietary selenium deficiency in rats with a high polyunsaturated fat intake. Cancer Res., 41: 31-34.

33. Levander, O.A. 1987. A global view of human selenium nutrition. Annu. Rev. Nutr., 7: 227-250.

The complexity of species differences in the influence of selenium status on the effectiveness of cell-mediated immune processes is summarised elsewhere (8).The possibility that increased intakes of selenium might protect against the development of cancer in humans has generated great interest (32). However, a number of epidemiologic studies have now been reported which show no relationship between selenium and cancer risk (33).

34. Birt, D.F., Pour, P.M. & Pelling, J.C. 1989. The influence of dietary selenium on colon, pancreas, and skin tumorigenesis. In: Wendel A., ed. Selenium in biology and medicine. p. 297-304. Berlin, Springer-Verlag.

Moreover, an analysis of the relationship between selenium and cancer suggests that “the question of whether selenium protects against cancer is still wide open”(34).

An increased intake of selenium appears to stimulate tumorigenesis in some animal models of pancreatic and skin cancer. In contrast, the protective effect of higher exposures to selenium observed in several animal studies, together with small but statistically significant differences in selenium blood plasma levels detected in some retrospective-prospective studies of subgroups of people developing cancer, explains the continuing interest in the anticarcinogenic potential of selenium.

33. Levander, O.A. 1987. A global view of human selenium nutrition. Annu. Rev. Nutr., 7:227-250. 

However, the results of prospective-retrospective studies had no predictive value for individuals and could have reflected non-specific influences on groups. The association between low selenium intake and high cancer risk,although clearly of some interest, is in need of further investigation before a conclusion can be reached. Although a biochemical mechanism can be postulated whereby selenium could protect against heart disease by influencing platelet aggregation (through an effect on the prostacyclin-thromboxane ratio), the epidemiologic evidence linking selenium status and risk of cardiovascular disease is still equivocal (33).