Abstract
Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.