General Discussion 161 7 Intra-erythrocyte magnesium = (whole blood magnesium − plasma magnesium × (1 − hematocrit))/hematocrit We observed a strong correlation between a direct and an indirect method, with only a small degree of bias, which is in line with the findings from the previous study 21. The results of this study suggest that the indirect method can potentially be embedded in current routine of clinical measurements, eliminating labor-intensive washing procedures and high costs required for direct methods. As secondary aim of this chapter, we investigated determinants of intra-erythrocyte magnesium, plasma magnesium and 24-h urinary magnesium excretion and tested their mutual relationships. Intraerythrocyte magnesium was positively associated with plasma magnesium, but not with 24-urinary magnesium excretion, suggesting that dietary magnesium intake is not (directly) reflected in cells, at least not in erythrocytes. Furthermore, we studied determinants of intra-erythrocyte and plasma magnesium. Based on the finding of Chapter 2, we hypothesized that plasma magnesium and intra-erythrocyte magnesium inversely associate with T2D markers, including fasting glucose and HbA1c. Although plasma magnesium was associated with fasting glucose and HbA1c, we found no association between intra-erythrocyte magnesium and these markers. This negative result may at least in part be explained by our study population, which consisted of healthy individuals. Future studies should therefore further elucidate whether cellular magnesium concentrations are associated with glucose and insulin metabolism, preferably in patients with T2D, who are at risk of hypomagnesaemia. Health aspects of magnesium supplementation Over the past decades, an increasing interest in dietary magnesium supplements has emerged. Although numerous magnesium formulations are commercially available, no consensus has been reached with respect to the optimal formulation. Magnesium is involved in many physiological processes in the human body and acts as a natural calcium channel blocker 1. Interestingly, preclinical studies demonstrated a protective role of magnesium in vascular calcification 22–24. In this thesis, we summarized available evidence linking magnesium with blood pressure, using a physiology-based approach in Chapter 4. Further, we addressed the health aspects of magnesium supplementation on glucocorticoid metabolism, arterial stiffness and blood pressure. In Chapter 5, we performed a post-hoc analysis from a previously performed two-arm RCT, comparing magnesium citrate supplements with
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