Selenium: 48-year journey of global clinical trials

Selenium, an essential trace mineral for health, has seen a rise in clinical trials over the past nearly 5 decades. Our aim here is to provide a comprehensive and concise overview of selenium clinical trials from 1976 to 2023. Overall, the evolution of selenium clinical trials over 48 years has advanced through phases of emergence, prosperity, and either stability or transition. The USA plays pivotal roles in establishing large research clusters and fostering strong collaborative ties of selenium clinical trials. Low-selenium levels are noted in a higher proportion of selenium observational trials, while selenium intervention trials are delineated by nine key functional classifications. The emphasis in intervention trials is that selenium product development should be on conducting clinical trials in diseases with higher efficacy, such as those involving antioxidant and endocrine and metabolic disease. Moreover, inorganic forms such as sodium selenite and semi-organic forms like selenized yeast were recognized as primary sources of selenium, while nano-selenium has emerged as a new selenium source in clinical treatments. Selenium is mainly consumed through tablets and oral administration, with a recommended upper limit of 200 µg per day for managing most diseases. In addition, genes encoding selenoproteins or factors of relevance for selenium metabolism, inflammation, and immunity, which have a higher number of records in all trials, are poised to steer future investigations into functional mechanisms of selenium. We believe this review will offer fresh perspectives on selenium clinical trials and identify potential avenues for future selenium research.