Project Abstract

Abstract
Selenium is an essential trace element required for various cellular functions in the human body. While selenium plays a crucial role in antioxidant defense systems and thyroid hormone metabolism, both selenium toxicity and deficiency can have significant impacts on human health. This research project aims to investigate the effects of selenium toxicity and deficiency on humans, focusing on the mechanisms involved and potential health outcomes. Selenium toxicity can occur when the intake of selenium exceeds the body's capacity for utilization and excretion. Chronic exposure to high levels of selenium can lead to selenosis, a condition characterized by hair and nail loss, skin lesions, gastrointestinal disturbances, and neurological abnormalities. The underlying mechanisms of selenium toxicity involve oxidative stress, disruption of cellular redox balance, and inhibition of selenoprotein synthesis. Long-term exposure to high levels of selenium has been associated with an increased risk of diabetes, cardiovascular disease, and certain types of cancer. Conversely, selenium deficiency can result from inadequate dietary intake, poor selenium absorption, or increased selenium excretion. The effects of selenium deficiency are wide-ranging and can manifest as impaired immune function, increased susceptibility to infections, cognitive decline, and thyroid dysfunction. Selenium deficiency has been linked to an increased risk of cardiovascular disease, infertility, and certain types of cancer. The mechanisms underlying the adverse effects of selenium deficiency include compromised antioxidant defense mechanisms, impaired thyroid hormone metabolism, and reduced immune function. Understanding the complex interplay between selenium toxicity and deficiency is essential for developing strategies to maintain optimal selenium status and prevent associated health problems. Research has shown that the health effects of selenium depend not only on its intake levels but also on individual genetic factors that influence selenium metabolism and utilization. Therefore, personalized approaches to selenium supplementation may be necessary to address the varying selenium requirements and risks among different populations. In conclusion, selenium is a vital micronutrient that plays a critical role in human health, but both excess and deficiency of selenium can have detrimental effects on various physiological processes. By elucidating the mechanisms through which selenium influences human health, this research project aims to provide valuable insights for the development of targeted interventions to prevent and manage selenium-related health issues.

Project Overview

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.