Raymond F. Burk
Division of Gastroenterology, Hepatology, and Nutrition and Center in Molecular Toxi- cology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA; [email protected]
Interest in selenium as an essential micronutrient for human beings arose in the 1960s after it had been found to protect against several diet- related conditions in animals. In early human studies, blood and plasma levels of the element were determined in attempts to assess selenium status (Allaway et al.1968, Burk et al. 1967). However, no reference values were available, so interpretation of those results was difficult. Functional measurement of selenium became possible when, in 1973, the element was discovered to be an essential constituent of liver glu- tathione peroxidase (GPX) in the rat (Rotruck et al. 1973). GPX activ- ity was also present in plasma so measurement of it there was used as an accessible biomarker of selenium status in human beings (Yang et al. 1987). Plasma activity has been shown to be due to the extracellular GPX, which was designated as GPX-3. The major tissue form of GPX is a different gene product, GPX-1.
In addition to GPX-3, selenoprotein P is present in plasma (Burk and Hill 2005). Thus, 2 selenoproteins are available in plasma for measure- ment. They serve as ‘functional’ forms of selenium and, together with measurement of selenium, have been used as indexes of selenium nutri- tional status. GPX activities in the red blood cells and platelets have also been used as markers of selenium status but are employed infre- quently.
In 1979 Chinese scientists reported that administration of selenium to children in a low-selenium area prevented the development of Keshan disease, a cardiomyopathy (Keshan Disease Research Group 1979). Following this the U.S. National Research Council listed selenium as essential and indicated that an intake of 50-200 µg per day was safe and adequate (National Research Council 1980).
Based on another study in China carried out in 1983 (Yang et al. 1987), the National Research Council set recommended dietary intake values of 70 µg per day for men and 55 µg per day for women in 1989 (Na-
tional Research Council 1989). These figures were revised in 2000 to 55 µg per day for men and women (Institute of Medicine 2000). In 2001 we carried out a selenium supplementation study in a low- selenium area of China (Xia et al. 2005). Two forms of selenium, se- lenite and selenomethionine, were supplemented at levels up to 66 µg selenium per day for 20 weeks. Both plasma selenoproteins were measured to assess selenium nutritional status.
Plasma GPX activity became optimized with supplementation of 37 µg selenium as selenomethionine. Dietary selenium intake was 10 µg per day so a total intake of 47 µg per day optimized this selenoenzyme, confirming the results of the study done in China in 1983. Selenopro- tein P did not become optimized with supplements of selenomethionine as high as 61 µg selenium per day, however. The effect of selenite was approximately half that of selenomethionine for a given dose of sele- nium.
These results indicate that a higher selenium intake is needed to opti- mize selenoprotein P than is needed to optimize plasma GPX activity. Because these plasma selenoproteins are surrogates for selenoproteins in tissues, the failure to optimize selenoprotein P suggests that some tissue selenoproteins were not optimized by the supplements given. Thus, a higher selenium intake than was given in this study will be needed to optimize all selenoproteins. An additional study will be needed to determine how much selenium is required to optimize seleno- protein P.
In conclusion, it appears from the study published this year that the recommended dietary allowance for selenium will need to be increased. Also, selenium in selenomethionine appears to be more bioavailable than selenium in selenite.
References
Allaway, W.H., Kubota, J., Losee, F. & Roth, M. 1968. Selenium, mo- lybdenum, and vanadium in human blood. Arch Environ Health 16: 342-348.
Burk, R.F., Pearson, W.N., Wood, R.P. & Viteri, F. 1967. Blood sele- nium levels and in vitro red blood cell uptake of 75Se in kwashiorkor. American Journal of Clinical Nutrition 20: 723-733.
Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D. & Hoekstra, W.G. 1973. Selenium: Biochemical role as a component of glutathione peroxidase. Science 179: 588-590.
Yang, G-Q., Zhu, L-Z., Liu, S-J., et al. 1987. Human selenium require- ments in China. In: Combs, G.F., Spallholz, J.E., Levander, O.A., Oldfield, J.E., (eds.). Selenium in biology and medicine. New York: AVI, 1987: 589-607.
Burk, R.F. & Hill, K.E. 2005. Selenoprotein P: An extracellular protein with unique physical characteristics and a role in selenium homeo- stasis. Annual Review Nutrition 25.
Keshan Disease Research Group 1979. Observations on effect of so- dium selenite in prevention of Keshan disease. Chinese Medical Journal 92: 471-476.
National Research Council 1980. Recommended Dietary Allowances. 9th ed. Washington, DC: National Academy of Sciences.
National Research Council 1989. Recommended Dietary Allowances. 10th ed. Washington, DC: National Academy of Sciences.
Institute of Medicine 2000. Selenium: Dietary reference intakes for vi- tamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000: 284-324.
Xia, Y., Hill, K.E., Byrne, D.W., Xu, J. & Burk, R.F. 2005. Effectiveness of selenium supplements in a low-selenium area of China. American Journal of Clinical Nutrition 81: 829-834.