Selenium is a scarce element that can be found naturally in soil, and it enters the food chain through plants. Se can be supplemented in water and in food, in different chemical forms, organic and/or inorganic ones. Most common inorganic forms are selenite and selenate salts, while organic forms correspond mainly to seleno-amino-acids such as selenomethionine and selenocysteine, where the sulfur atom has been replaced by selenium [14]. The Se level in foods is determined by many factors, such as geochemical, geological and climatic characteristics of the soil where plants are grown and further eaten by cattle, poultry, and other animals, all of them entering in the food chain, as do the plants. Se concentration in plants varies depending on the bioavailability of Se in the soil where they were grown, and also on the plant species [27]. In mammals, Se status depends on a continuous supply of this element, because these organisms have a limited Se storage capacity [9].
The effects of Se to human health strongly depend on its dose and chemical form. The concentration range in which Se is considered toxic or beneficial is very narrow [30]. It was estimated that the intake of foods containing more than 1 mg Se Kg-1 result in toxicity, while a concentration lower than 0.1 mg Se Kg-1 may result in Se deficiency. The dietary recommended allowance of Se for humans depends on region, sex and age; however it is estimated in average as 55 mg (Subcommittee on the tenth Edition of the RDAs, Food and Nutrition Board, National Research Council, 1989).
Se toxicity depends on its chemical form, oxidation state, and dose, and it is manifested as acute or chronic selenosis. Acute exposure to Se may result mainly in bronchitis, pulmonary edema and pneumonia. Chronic exposure to Se instead, results in discoloration of the skin, hair loss, and deformation of nails, weakness and a lack of mental alertness [30]. In general, the health injuries caused by excess of Se are much lower than those caused by Se deficiency.
Selenium deficiency decreases selenoprotein expression, and then it alters the metabolic processes mediated by them [30]. Since Se intake is related to the geographic location, some endemic diseases have been reported in low-Se regions (China and Eastern Siberia): Keshan disease (a cardiomiopathy) and Kashin-Beck disease (a deforming arthritis). Additionally, a form of cretinism associated with hypothyroidism has been attributed to low Se status.
Selenium and Health: Discovering Nutritional Biomarkers 95 Low Se status has been related to immune dysfunction, cardiovascular diseases, low male fertility, and development of some types of cancer [45, 46] It has been demonstrated that increased levels of Se intake produce an enhancement of both cell-mediated and humoral immune responses [17]. Besides, Se deficiency would result in less robust immune responses in experimental animals. The existence of a strong correlation between the risk of cardiovascular disease and a low Se status in humans was shown. Selenium also plays an important role in male fertility, since it is essential for testosterone synthesis [47]. Structural abnormalities and low motility in sperm have been reported in rats fed a Se-depleted diet [48]. In human trials, it has been shown that Se supplementation increases sperm motility and fathering [49].
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ELENIUM ASC
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GENTIn the last twenty years, the main interest has been set on the anticarcinogenic properties of Se [3, 4, 50 – 55]. In 1991 it was carried out the first human intervention trials for cancer prevention with Se [56], resulting in a significant reduction of liver cancer. Later, Clark et al. [3] showed that the supplementation of free-living people with Se (as selenomethionine) resulted in a decrease of 50% in the overall cancer morbidity and mortality. Se supplementation was found to be related with a reduced risk of colorectal cancer, prostate cancer, and lung cancer [57]. In 2001 it began SELECT, the SELenium and vitamin E Cancer prevention Trial, funded by the National Cancer Institute (NCI), U.S.A. The aim of this study was to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in healthy men [58], based on epidemiological and preclinical data that showed the potential of Se and vitamin E in the prevention of prostate cancer [59]. Oral selenium (200 mg/d from L-selenomethionine) and vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) were administered to >50 years old healthy men, during 7 years. Recently, in September 2008, the partial results of SELECT were analyzed, and no decline in prostate cancer could be detected [60]. This unexpected result was attributed to the chemical form of the Se supplement (selenomethionine), and the relatively high initial levels of selenium in the enrolled men. However, the neutral results of the SELECT study do not discredit the hypothesis of cancer prevention by Se [61]. Since selenomethionine did not give the expected results, Se-methylselenocysteine, a naturally occurring selenocompound, seems to be a promising alternative.
Organic Se compounds are the most effective in cancer chemoprotection, especially SMSeC [50]. In human interventions it was demonstrated that at 1 – 3 mg Se/Kg, SMSeC is a more powerful chemoprotective agent that other Se compounds, such as sodium selenite and selenomethionine [42]. The chemoprotective action of SMSeC has been attributed to the generation of monomethylated Se compounds. Since SMSeC is a non-proteinogenic amino acid, it would be totally available for cancer chemo protection [9]. SMSeC exerts its anticarcinogenic properties by serving as precursor of methylselenol and methylseleninic acid, which would be the active anticarcinogenic compounds [62, 63].
Current investigations about the relationship between Se intake and cancer prevention have focused mainly on the chemical form of Se: Se-enriched food and in vitro effect of monomethylated forms of Se. It has been reported that dietary supplementation with selenized
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vegetables, such as garlic and broccoli grown in Se-enriched soil, results in a much higher chemoprotective effect, in comparison with selenite and selenomethionine [50, 64]. These vegetables are capable to store inorganic forms of Se and convert them to an organic form, mainly SMSeC. Additionally, it was shown that the health benefits of Se are achieved when supranutritional doses of this element are administered [65], ranging from 100 up to 200 mg Se/d for humans. A dose of 400 mg Se/d is considered as a safe upper limit. As a consequence, most of the recent interest in Se nutrition has been focused on over- supplementation several times beyond the Recommended Dietary Allowance [37].