Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We Go?

Abstract

Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both.

The Role of Nutrition in Neurological Disorders

“…Furthermore, fluctuations in selenium have also been indicated in stroke pathogenesis. The review paper by Liampas et al demonstrated that both excess and decreased levels of selenium and selenoprotein expression can lead to immune and coagulation dysregulation [4]. Selenium has multiple pleiotropic homeostatic roles in human health and mediates its enzymatic functions through selenoproteins, which are known to moderate oxidative stress and coagulation processes such as the arachidonic cascade.…”

“…Selenium's protective role in cardiovascular disease has been proven in various studies showing an inverse relationship between low selenium levels and stroke, especially in elder, white, male populations. Furthermore, it has been shown that each 50 µg/L increase in blood selenium and in dietary selenium leads to a 38% and a 30% reduction in the prevalence of stroke, respectively [4]. Selenium supplementation in acute stroke patients has been shown to improve short-term acute stroke outcomes; however, there is limited evidence of its effects on long-term stroke outcomes, and more studies regarding its efficacy and safety must be conducted as selenium excess may cause dysregulation of glucose metabolism in addition to heightened immune activity [4].…”