Chapter 1 14 increased blood pressure and suppression of immune system and inflammatory reactions. 11β-hydroxysteroid dehydrogenases (11β-HSDs) are enzymes that catalyze the conversion of active cortisol to inert cortisone and vice versa 49,50. Disturbed activity of these enzymes has been linked to hypertension and insulin resistance, which have been implicated to adversely affect cardiovascular health 51,52. Enzyme activity of 11β-HSDs can be quantified by the ratios of 24-h urinary cortisol, cortisone, and their metabolites. Several preclinical studies have shown a relationship between a magnesium deficient diet and a disturbed glucocorticoid metabolism 53–55. Whether oral magnesium supplementation can modify glucocorticoid metabolism in humans is unknown. OUTLINE OF THE THESIS Previous research mainly focused on total plasma or serum magnesium as a marker of magnesium status. In addition, RCTs addressing potential effects of magnesium supplementation on cardiovascular end points mainly focused on blood pressure, while effects on arterial stiffness have rarely been studied. This thesis aims to compare several analytic methods for the assessment of magnesium status and to investigate health aspects of magnesium status and magnesium supplementation, with emphasis on T2D, glucocorticoid metabolism, blood pressure, and arterial stiffness. Under physiological conditions, magnesium homeostasis is maintained by adjusting urinary excretion equaling the net uptake of magnesium in the gut, with plasma values ranging within the normal range of 0.70 - 1.00 mmol/L 56. Of the total amount of circulating magnesium, 70-80% is available in the free, ionized form, whereas the rest is bound to proteins, citrate, phosphate, and other compounds. So far, most epidemiological studies that focused on the relationship between low total plasma or serum magnesium and disease risk reported weak or absent associations 38,57–59, whereas strong associations of 24-h urinary magnesium excretion, a marker of intestinal magnesium uptake, with hypertension and CVD risk have been reported repeatedly 38,57. Furthermore, total plasma magnesium seems to correlate weakly with 24-h urinary magnesium excretion. Plasma ionized magnesium, on the other hand, may have additional clinical implications, since this form is biologically active and may therefore better reflect the intracellular concentration 60. In fact, several studies have suggested that the measurement of plasma ionized magnesium is superior to the measurement of total plasma magnesium 60–63, although no proper method comparison between plasma ionized and total plasma magnesium has been performed so far 62,63. In addition, not
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