Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements.
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AbstractBACKGROUND: The relationship between selenium and cancer involves many different aspects. These include the forms of selenium present in the diet and in the body, their functions and mechanisms of action, and methods employed in assessing an individual's selenium nutritional status-both in general, and in epidemiological studies of the risk of cancer in relation to diet, as well as in connection with long-term trials for investigating the disease-preventive potential of selenium supplementation. AIM OF THE REVIEW: To review different aspects on selenium metabolism, the occurrence of different selenoproteins and their use as biomarkers of selenium status, the results of intervention trials of the cancer-preventive effects of selenium supplementation, the mechanisms of action involved, together with epidemiological findings on relations between the selenium status in the body and risk of cancer. RESULTS AND CONCLUSIONS: The rapid advance in the knowledge of different selenoproteins and their biological functions has opened up new possibilities for the understanding of the biological effects of selenium supplementation. A wide variety of effects of different forms and doses of selenium has been observed in a number of experimental systems, and it is at present difficult to pinpoint the mechanism that may explain the positive preventive effects of selenium supplementation observed in some human long-term trials. Moreover, additional such trials are needed to define the benefits and risks of different types and doses of selenium supplements which in the future may be implemented for public health reasons. Another necessary focus for future research is a better understanding of the mechanisms by which selenium interferes with the carcinogenesis process.
CitationEur. J. Nutr. 2008, 47 Suppl 2:29-50
JournalEuropean journal of nutrition
SponsorsThis review was written as a part of the research integration in the Workpackage “Mechanisms of modulation of cancer by dietary factors” in the NoE Environmental Cancer risk, Nutrition and Individual Susceptibility (ECNIS, no. 513943; www.ecnis.org). Additional support was obtained from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, the Lund University Hospital, and the Påhlsson Foundation. We thank Dr. Gunilla Önning for helpful advice. Biomedical Nutrition is also a member of the EU NoE the European Nutrigenomics Organization (NuGO, no. 505944) which partly supported the study.
- Authors: Alexander J
- Issue date: 2007
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Short-term effects of selenium supplementation of cows' feed on the content and distribution of selenium, copper and zinc in bovine milk, whey and blood plasma.Hoac, Tien; Stagsted, Jan; Lundh, Thomas; Nielsen, Jacob H.; Akesson, Bjorn (2008-08)The effect of selenium supplementation of feed on the Se content in bovine milk, whey and plasma, and on the distribution of Se, Zn and Cu in whey and plasma was investigated. In a cross-over study two groups of cows were given a basal feed with 0.16 ppm selenite (approx. 3 mg Se/d) with or without 25 mg yeast Se/d for 2 weeks. In the supplemented group the Se content increased 10-fold in milk, 10-fold in whey and 2-fold in plasma, and after the cessation of the supplementation, selenium in milk decreased with a calculated half-life of 3.5 d. In another experiment, two groups of cows were given either 100 mg yeast Se/d for 1 week or only the basal feed. The increase in Se content in both whole and defatted milk was 40-50-fold, and in whey it was approx. 20-fold. Size-exclusion chromatography of whey using inductively coupled plasma mass spectrometry for detection showed that supplementation increased the proportion of Se in the beta-lactoglobulin-alpha-lactalbumin fraction. Distribution of Cu and Zn was essentially unaffected. In plasma, supplementation increased the Se content in all major Se fractions like selenoprotein P, albumin and low-molecular-weight compounds, but the distribution profiles of Zn and Cu underwent no major changes. The study showed for the first time the rapid kinetics of the Se increase and decrease in milk after the initiation and cessation of supplementation, respectively, and the preferential appearance of Se in the beta-lactoglobulin-alpha-lactalbumin fraction of whey. Milk highly enriched in selenium will be a useful tool for different research purposes.
A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defence regulation.Ravn-Haren, Gitte; Bugel, Susanne; Krath, Britta N.; Hoac, Tien; Stagsted, Jan; Jorgensen, Karina; Bresson, June R.; Larsen, Erik H.; Dragsted, Lars O. (2008-04)Increased Se intakes have been associated with decreased risk of cancer and CVD. Several mechanisms have been proposed, including antioxidant effects through selenoproteins, induction of carcinogen metabolism and effects on the blood lipid profile. In a 4 x 1 week randomised, double-blind cross-over study, healthy young men supplemented their usual diet with selenate, Se-enriched yeast, Se-enriched milk or placebo (Se dose was 300 microg/d for selenate and Se-enriched yeast, and about 480 microg/d for Se-enriched milk) followed by 8-week washout periods. All Se sources increased serum Se levels after supplementation for 1 week. The effect of the organic forms did not differ significantly and both increased serum Se more than selenate. Conversely, thrombocyte glutathione peroxidase (GPX) was increased in the periods where subjects were supplemented with selenate but not in those where they were given Se-enriched yeast or Se-enriched milk. We found no effect on plasma lipid resistance to oxidation, total cholesterol, TAG, HDL- and LDL-cholesterol, GPX, glutathione reductase (GR) and glutathione S-transferase (GST) activities measured in erythrocytes, GPX and GR activities determined in plasma, or GR and GST activities in thrombocytes. Leucocyte expression of genes encoding selenoproteins (GPX1, TrR1 and SelP), and of electrophile response element-regulated genes (GCLC, Fra1 and NQO1) were likewise unaffected at all time points following intervention. We conclude that thrombocyte GPX is specifically increased by short-term selenate supplementation, but not by short-term supplementation with organic Se. Short-term Se supplementation does not seem to affect blood lipid markers or expression and activity of selected enzymes and a transcription factor involved in glutathione-mediated detoxification and antioxidation.
Vitamins and selenium.Dragsted, Lars O.; Loft, Steffen; Moller, Peter; Cook, Marcus S.; Rozalski, Rafal; Olinski, Ryszard; Linseisen, Jakob; Abbas, Sascha; Akesson, Bjorn; Bruzelius, Katharina; Gromadzinska, Jolanta; Reszka, Edyta; Wasowicz, Wojciech (The Nofer Institute of Occupational Medicine, 2007-04)