Long-term magnesium supplementation improves glucocorticoid metabolism 95 5 Introduction Low dietary magnesium intake has been associated with increased risk of cardiovascular disease (CVD).1 Specifically, we already observed a clinically relevant improvement in arterial stiffness after long-term oral magnesium supplementation2, which may underlie the beneficial effects of magnesium on CVD events. Previous studies have also suggested a role for cortisol in CVD risk 3,4. For instance, excess levels of cortisol in patients with Cushing’s syndrome have been linked to alterations in the vascular system, including increased arterial stiffness and impaired endothelial function 5,6. Several enzymes, including 11β-hydroxysteroid dehydrogenases (11β-HSDs) and A-ring reductases, regulate intracellular glucocorticoid metabolism and have been suggested to play an important role in the pathogenesis of metabolic syndrome, which is in turn associated with increased risk of CVD 7–9. 11β-HSDs are primarily responsible for the conversion of inert cortisone to active cortisol and vice versa. In fact, two iso-enzymes of 11β-HSD have been identified: type 1 and type 2. The former is mainly expressed in the liver and adipose tissue, and converts the inactive cortisone into the active cortisol 10, while the latter is primarily expressed in the kidney and colon and is responsible for the conversion of cortisol into cortisone 11,12. On the other hand, A-ring reductases regulate the conversion of cortisol and cortisone to their metabolites tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF) and tetrahydrocortisone (THE). The glucocorticoid metabolism is depicted in Figure 1. Enzyme activity of 11β-HSDs and A-ring reductases can be quantified by the ratios of 24-h urinary excretions of cortisol, cortisone and their metabolites, which provides insight into the intracellular production and clearance of cortisol 13,14. Several preclinical studies have shown that magnesium plays a role in glucocorticoid metabolism 15–17. In fact, dietary magnesium restriction resulted in an altered glucocorticoid metabolism.To date,no human intervention trials have addressed effects of oral magnesium supplementation on glucocorticoid metabolism. Here,we performed a post-hoc analysis of a previously performed double-blind placebocontrolled intervention trial with the primary aim to study the effect of magnesium supplementation on arterial stiffness, measured by carotid-to-femoral pulse wave velocity. In the current study, we investigated effects of long-term oral magnesium supplementation on glucocorticoid metabolism, specifically on 24-h urinary excretions of cortisol, cortisone and their metabolites, as well as on enzyme activity of 11β-HSD and A-ring reductases.
RkJQdWJsaXNoZXIy MTk4NDMw