General Introduction 13 1 lower risk of developing hypertension among individuals with a higher 24-h urinary magnesium excretion 38. To date, some, but not all randomized controlled trials (RCTs) have shown small effects of oral magnesium supplementation on both systolic and diastolic blood pressure 15,39,40, with greater blood pressure effects in studies using higher dosages of magnesium. Arterial stiffness Arterial stiffness causes dysfunction of the large arteries and is strongly associated with increased risk of coronary heart disease and stroke 41. It is one of the earliest detectable changes in vascular structure and function 42.Arterial stiffness is a non-invasive vascular functionmarker and can bemeasured bymeans of carotid-to-femoral pulsewave velocity (c-fPWV), which is currently the gold standard for the quantification of arterial stiffness 43. c-fPWV is calculated as the time it takes a pulse wave to travel from the carotid to the femoral site divided by the distance. Ageing is a non-modifiable risk factor for arterial stiffness as the large arteries lose their elasticity over time 44, whereas smoking, alcohol use, physical inactivity, and an unhealthy diet are modifiable risk factors 45. One of the most important causes of arterial stiffness is vascular calcification. In-vitro studies have suggested that a high dietary magnesium diet may prevent vascular calcification 46,47, which may in turn improve arterial stiffness. RCTs that addressed effects of oral magnesium supplementation on arterial stiffness are scarce and show inconclusive results 10,13,17. Joris et al. showed a significant improvement of arterial stiffness by 1.0 m/s following oral magnesium supplementation in healthy overweight and slightly obese adults using a total daily magnesium dose of 350 mg/d 17. However, the study was based on a single comparison between magnesium citrate and placebo, and thus, it remains unknown whether the effect was induced by magnesium itself or by the anion citrate. Furthermore, no head-to-head comparison between various magnesium formulations in terms of effects of arterial stiffness has been performed. In this respect, a comparison between magnesium citrate and other formulations might be of interest to investigate whether the effect was induced by magnesium itself or by the anion citrate and whether other formulations have similar effects. Glucocorticoid metabolism Physiological stress is a major, yet modifiable risk factor for CVD 48. During the stress response, the hypothalamic-pituitary-adrenal (HPA) axis is activated, which results in the secretion of cortisol, a glucocorticoid hormone. Elevated cortisol levels cause
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