General Discussion 165 7 assess underlying processes in terms of vascular calcification. Therefore, other tests to measure arterial remodelling should be considered as well. CT imaging provides further information specifically on the potential effect of magnesium supplementation on the coronary artery calcium score. In addition, calciprotein particle maturation time (T50) is a novel blood test that measures the transformation from primary CPPs to secondary CPPs in serum 48. Two RCTs found beneficial effects of magnesium supplementation on slowing vascular calcification progression in patients with CKD stage 3-4 49,50. As with our study, these studies used single end-points to assess effects of magnesium on vascular calcification (either coronary artery calcium score or serum T50). Future studies should therefore include multiple end-points to provide more insights into the exact mechanisms by which magnesium may affect vascular calcification. Conclusions and future perspectives In this thesis, we compared several analytic methods for the assessment of magnesium status and we investigated health aspects of magnesium status and magnesium supplementation. We used data from various large observational cohort studies and we performed a large multi-arm RCT to assess effects of various magnesium formulations on arterial stiffness and blood pressure. We additionally compared the overall bioavailability between the magnesium formulations. We have demonstrated that intra-erythrocyte magnesium can be calculated by means of an indirect method, eliminating labor-intensive sample preparation. Furthermore, our results highlight that ionized plasma magnesium can be accurately obtained from NMR spectra, while testing for routine lipoprotein quantification. This may add to overall cost saving as well as to overall sample saving. We have shown that lower plasma ionized magnesium was associated with increased risk of T2D in women, but not in men. We hypothesized that this specific effect in women could arise from a difference in renal magnesium handling, which might be related to the sex hormone estrogen. However, this hypothesis remains to be further delineated in future studies. To conclude, as magnesium plays an essential role in many physiological functions in the human body, it is important that changes in magnesium status and magnesium deficiencies can be accurately detected. Studies from this thesis showed that indirect intra-erythrocyte magnesium as well as plasma ionized magnesium are promising methods to measure magnesium in the human body. Future large prospective studies should further examine whether these methods can be embedded in clinical practice.
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