Selenium deficiency leads to decreased concentration and therefore functions of selenoenzymes. Some consequences of this in animals are increased susceptibility to infections, to toxicity of certain drugs and chemicals, and to damage by other nutritional deficiencies. There is evidence for selenium deficiency of varying severity in human populations in Asia, Europe, and Africa. In addition, some people in the U.S. with cirrhosis appear to be selenium deficient. This project aims to acquire the knowledge necessary to assess the need for selenium supplementation of populations and individuals and to formulate cost-effective supplements. In the previous grant period three clinical studies were completed. One, carried out in a selenium-deficient population in China, demonstrated that selenoprotein P concentration was superior to glutathione peroxidase activity as a plasma index of selenium nutritional status. It indicated that the present recommended dietary allowance for selenium is too low and showed that bioavailability of commonly used forms of the element vary widely. A study of healthy subjects in the U.S. demonstrated that selenium supplements did not increase either plasma selenoprotein, indicating that the subjects were selenium replete. Plasma selenium increased but the increase was different with each form of selenium given. An equation was derived that related increase in plasma selenium concentration to selenomethionine intake. The third study showed that some patients in the U.S. with severe cirrhosis are selenium deficient, presumably because they are unable to metabolize dietary selenomethionine. In the coming grant period we propose two studies in China, where a selenium-deficient population is available. One will determine the selenium requirement of healthy subjects based on plasma selenoprotein P and the other will determine the bioavailability of forms of selenium commonly used as supplements. A study of U.S. patients with cirrhosis is proposed to assess the occurrence of selenium deficiency over the disease spectrum and to determine the form and dose of selenium needed to repair it. Finally, characterization of the small-molecule transport form of selenium in plasma and development of an assay for it will be carried out with the expectation that it will serve as a superior index of selenium status. All these studies are aimed at facilitating efforts to determine the health effects of selenium deficiency and to guide supplementation of the element when that is needed. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK058763-07
Application #
7188080
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
May, Michael K
Project Start
2001-05-01
Project End
2011-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
7
Fiscal Year
2007
Total Cost
$402,581
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Burk, Raymond F; Hill, Kristina E (2015) Regulation of Selenium Metabolism and Transport. Annu Rev Nutr 35:109-34
Burk, Raymond F; Hill, Kristina E; Motley, Amy K et al. (2015) Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial. Am J Clin Nutr 102:1126-33
Takata, Yumie; King, Irena B; Lampe, Johanna W et al. (2012) Genetic variation in GPX1 is associated with GPX1 activity in a comprehensive analysis of genetic variations in selenoenzyme genes and their activity and oxidative stress in humans. J Nutr 142:419-26
Takata, Yumie; Kristal, Alan R; Santella, Regina M et al. (2012) Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants. PLoS One 7:e38612
Xia, Yiming; Hill, Kristina E; Li, Ping et al. (2010) Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. Am J Clin Nutr 92:525-31
Hurst, Rachel; Armah, Charlotte N; Dainty, Jack R et al. (2010) Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 91:923-31
MacFarquhar, Jennifer K; Broussard, Danielle L; Melstrom, Paul et al. (2010) Acute selenium toxicity associated with a dietary supplement. Arch Intern Med 170:256-61
Burk, Raymond F; Hill, Kristina E (2009) Selenoprotein P-expression, functions, and roles in mammals. Biochim Biophys Acta 1790:1441-7
Camargo, M Constanza; Burk, Raymond F; Bravo, Luis E et al. (2008) Plasma selenium measurements in subjects from areas with contrasting gastric cancer risks in Colombia. Arch Med Res 39:443-51
Meplan, Catherine; Crosley, Lynne K; Nicol, Fergus et al. (2007) Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J 21:3063-74

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