Thesis Abstract

Abstract
Selenium is an essential micronutrient that plays a crucial role in human health. Both deficiency and toxicity of selenium can have significant impacts on various physiological processes in the human body. Selenium deficiency is associated with an increased risk of various chronic diseases, such as cardiovascular disease, certain types of cancer, and impaired immune function. On the other hand, selenium toxicity can result in adverse health effects, including gastrointestinal disturbances, hair and nail brittleness, and neurological abnormalities. The effects of selenium deficiency on humans are well-documented. In regions where the soil is deficient in selenium, populations are at a higher risk of developing health problems related to selenium deficiency. Insufficient dietary intake of selenium can lead to decreased activity of selenoproteins, which are essential for antioxidant defense mechanisms and thyroid hormone metabolism. As a result, individuals with selenium deficiency may experience oxidative stress, compromised immune function, and thyroid disorders. Conversely, selenium toxicity is a concern in regions where selenium levels in the soil are high or due to overconsumption of selenium supplements. Chronic exposure to high levels of selenium can lead to selenosis, a condition characterized by symptoms such as garlic odor breath, hair loss, and gastrointestinal disturbances. Selenium toxicity can also impact the nervous system, causing symptoms such as tremors, muscle weakness, and in severe cases, paralysis. The mechanisms underlying the effects of selenium toxicity and deficiency on human health are complex and involve interactions with various biological pathways. Selenium acts as a double-edged sword, where both inadequate and excessive levels can disrupt the delicate balance required for optimal health. Understanding the factors that influence selenium status in individuals, such as dietary intake, genetic variations, and environmental exposure, is crucial for mitigating the risks associated with selenium imbalances. In conclusion, selenium is a micronutrient with a narrow therapeutic range, where both deficiency and toxicity can have detrimental effects on human health. Maintaining an optimal selenium status is essential for supporting overall health and well-being. Further research is needed to elucidate the precise mechanisms by which selenium influences human health and to develop strategies for preventing and managing selenium-related disorders.

Thesis Overview

INTRODUCTION

1.1.          BACKGROUND INFORMATION

Selenium (Se) is an essential trace element having biological functions of utmost importance for human health. Different from the other (semi) metals, it is incorporated into proteins by a co-translational mechanism as part of the amino acid selenocysteine (SeCys), the 21st amino acid used for protein synthesis in humans, whereas only a few of them have been functionally characterized. Most Se-proteins participate in antioxidant defence and redox state regulation, particularly the families of more specific essential roles, such as iodothyronine deiodinases (DIOs) which are involved in thyroid hormones metabolism, GPx4 which is essential for spermatogenesis, and selenophospathe synthetases 2 (SPS2) participating in Se-protein biosynthesis.

Other Se-proteins may be involved in important biological processes, but their exact mechanism of action is still yet to be fully understood. Despite the scarce knowledge of the precise biochemical functions, a very large number of studies have been carried out in the last two decades showing that insufficient Se levels, and particularly Se-proteins, are associated with several human diseases including cancer, diabetes, cardiovascular and immune system disorders. In most cases, the link lies in the contrast to the oxidative stress that may be booth causing or caused by the disease. In this context, it is important to decipher whether and adequate Se status may contrast the risk factors for health disorders, or Se supplementation may improve the therapy when Se metabolism is altered.

Despite many studies that have suggested a beneficial effect from Se supplementation to general health protection, most of them have remarked that it is limited to general health protection, most of them have remarked that it is limited to the initially inadequate Se status. Conversely, care should be taken when using supplements because excessive Se intake leads to toxic effects, and recent studies have shown that even sub-toxic doses may be negatively impacting, for example by increasing the risk of type 2 diabetes.