Magnesium is an essential mineral that acts as a cofactor in hundreds of enzymatic reactions in the human body. It is, therefore, not surprising that insufficient magnesium intake has been associated with a wide variety of metabolic disorders, such as insulin resistance, and common diseases that may result from metabolic deregulations, such as hypertension and ischemic heart disease [
1‐
5]. Foods with relatively high magnesium contents include whole grains, leafy green vegetables, legumes and nuts.
Arterial stiffness is closely related to the extent of atherosclerosis [
6], an independent cardiovascular risk factor [
7], and predictive of future cardiovascular events and mortality [
8]. The gold standard for quantifying arterial stiffness is the carotid–femoral pulse wave velocity (PWV
c–f), a noninvasive method that measures the propagation of the forward pressure wave traveling along the aorta [
8]. Recently, we observed a significant reduction of arterial stiffness, measured by the PWV
c–f, after 24 weeks of oral magnesium citrate supplementation (total daily dose of 350 mg) in the magnesium citrate group compared with the placebo group (8.3 m/s vs 9.1 m/s, respectively) [
9]. Although blood pressure is a major determinant of arterial stiffness [
10], we did not observe any change in blood pressure. This lack of effect on blood pressure could be due to the total daily dose, which may have been too low to detect changes in blood pressure. A meta-analysis by Kass
et al. [
11] indeed showed that supplementation of > 370 mg/day resulted in a more pronounced blood pressure-lowering effect. In addition, we could not differentiate whether the beneficial effect on arterial stiffness was due to the supplementation of magnesium or due to citrate. The mechanism by which magnesium decreases arterial stiffness is not entirely known, but an effect on gut microbiota has been observed [
12‐
14]. Previous studies have shown that magnesium deficient diets resulted in an altered microbiome and, more specifically, decreased microbial diversity in mice [
13,
15,
16]. Gut microbiome diversity has recently been shown to be inversely associated with arterial stiffness, independent of obesity-related traits, such as insulin and visceral fat [
17].
The primary aim of the current study is to replicate the effect of magnesium citrate on arterial stiffness that we found in our previous study. Secondly, we aim to test whether magnesium oxide and magnesium sulfate are noninferior to the effect of magnesium citrate on arterial stiffness and to unravel possible underlying mechanisms, including changes in blood pressure and gut microbiota diversity and metabolites.