Friday, March 17, 2023

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

Ask your doctor to test you.

How can you tell if you are low on selenium?

What are the symptoms?

  1. infertility in men and women.

  2. muscle weakness.

  3. fatigue.

  4. mental fog.

  5. hair loss.

  6. weakened immune system.

The latest here:

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

1
Department of Neurology, Nicosia New General Hospital, Nicosia 2029, Cyprus
2
Second Department of Neurology, School of Medicine, ‘Attikon’ University Hospital, National and Kapodistrian University of Athens, 124 62 Athens, Greece
3
Medical School, University of Cyprus, Nicosia 2024, Cyprus
*
Author to whom correspondence should be addressed.
Nutrients 2023, 15(6), 1405; https://doi.org/10.3390/nu15061405
Received: 14 December 2022 / Revised: 8 March 2023 / Accepted: 9 March 2023 / Published: 15 March 2023
(This article belongs to the Special Issue The Role of Nutrition in Neurological Disorders)

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.

1. Background

Stroke is the second most common cause of death worldwide (11.8% of all deaths) and a major cause of serious long-term morbidity [1,2]. Ischemic stroke (IS) is the most common type of stroke, comprising about 80% of the total cerebrovascular events [3]. Despite the decline of stroke mortality over the years, the number of IS-related deaths and morbidities and overall disability-adjusted life years (DALY) lost remains of great importance and increases in the course of time [4]. Although most risk factors are modifiable, including hypertension, diabetes mellitus, hyperlipidemia, and smoking [5] other non-modifiable variables such as age, sex, and genetics have also been considered as risk factors for stroke [6,7,8]. Studies on nutritional factors affecting stroke risk and outcomes have been generally focused on dyslipidemia, with micronutrients and trace elements being generally underexplored in the literature.
Micronutrients or trace elements refer to nutritional factors required in specific, minute quantities by organisms and affect specific aspects of their physiological functions. One such micronutrient is selenium (Se) [9]. Selenium exerts multiple pleiotropic homeostatic roles on human health, several of which are interwoven with stroke etiopathogenesis and its outcomes, as well as infection. This tripartite relationship is not merely observational; many of the shared pathophysiological substrates that link infection and stroke find common grounds in Se biology.
A central case in point for this concept arises from the observed interrelationships between serum Se concentration, the systemic inflammatory response, and multi-organ failure in sepsis patients. As selenoproteins are known to mitigate oxidative stress, coagulation, and immune fitness, these associations potentially reflect homeostatic adaptations aimed at preserving tissues and organs affected by the stress represented by sepsis [10]. Another example of the pertinence of Se biology arises from host–virus interactions, where host Se biology is actively contested by viruses in order to favor egress, with oxidative stress and hypercoagulable states representing secondary consequences. Moreover, selenium depletion secondary to infection may build up towards a prothrombotic state and impaired immune fitness, a milieu that has been shown to favor viral genomic instability potentially resulting in variants with greater pathogenicity [11].
The purpose of this critical review is to explore state-of-the-art evidence on the epidemiology, potential mechanisms, and possible interventions regarding selenium status, infection, and stroke. Furthermore, we aim to provide a concise report on current concepts regarding selenium supplementation in the specific setting of infectious disease and stroke, as well as their interplay.
 
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