Global regulation, application categories, toxicological safety, and analytical methodologies of selenium nutritional fortifiers: a critical review.

Dietary selenium deficiency, driven primarily by geochemical heterogeneity in soil bioavailable selenium, remains a widely recognized public health concern in multiple regions, with food fortification representing one of the main strategies for addressing selenium insufficiency. In this review, the classification, physicochemical properties, metabolic fate, toxicological profiles, global regulatory frameworks, and analytical detection methodologies of mainstream selenium food fortifiers are systematically reviewed and critically discussed. A key conclusion of this review is that selenium speciation serves as a fundamental determinant of the nutritional efficacy, toxicological safety, and industrial applicability of selenium nutritional fortifiers. Specifically, inorganic selenium sources, despite low cost and long-standing use, are constrained by a narrow therapeutic window and intrinsic oxidative reactivity; organic selenium forms are commonly used as fortifiers due to their relatively higher absorption efficiency and systemic retention compared with inorganic forms, although their safety profiles remain compound-dependent and may involve limitations such as compositional heterogeneity and potential risks of chronic accumulation. Selenium nanoparticles are considered promising delivery systems; however, their industrial application remains limited by insufficient chronic safety data and a lack of standardized evaluation frameworks. Furthermore, this review suggests that conventional total selenium quantification may not fully capture selenium speciation relevant to safety assessment in fortified foods, and that cross-regional regulatory differences may pose challenges for the harmonization of selenium fortification practices. Overall, this work provides an integrated framework to support the rational design, standardized regulation, and improved evaluation of selenium food fortifiers.