Magnesium: an important but underestimate mineral for blood pressure regulation and vascular structure.
Magnesium (Mg) is the second most abundant intra- cellular cation in the body. Studies have demonstrated that Mg deficiency enhances reactivity of arteries to vasoconstrictors, promotes vasoconstriction, and increases peripheral resistance, leading to increased blood pressure. In contrast, Mg supplementation is associated with a significant decrease in blood pres- sure. Mg deficiency is related to vascular struc- tural and functional changes such as media thicken- ing, increased media-to-lumen ratio, and increased contraction, which are characteristic in vitro and in vivo vascular changes. Furthermore, Mg deficiency is associated with inflammation, oxidative stress, and endothelial dysfunction [1].
It is known that magnesium has antiarrhythmic effect and can influence blood pressure levels by modulating vascular tone. Changes in extracellular magnesium content are able to modify the production and release of nitric oxide (NO), resulting in the alteration of arterial smooth muscle tone by affecting calcium concentrations. Magnesium also participates in glucose metabolism and insulin homeostasis. For these reasons, it has been suggested that magnesium deficiency or changes in its metabolism are related to the pathophysiology of hypertension, atherosclerosis, insulin resistance, and diabetes [2].
Increased levels of extracellular magnesium inhibit calcium influx. Conversely, reduced extracellular magnesium activates calcium influx via calcium channels. Low intracellular magnesium concentrations stimulate inositol-trisphosphate-(IP3-) mediated mobilization of intracellular calcium and reduce Ca2+-ATPase activity. Thus, calcium efflux and sarcoplasmic reticular calcium reuptake are reduced, leading to cytosolic accumulation of calcium and increased intracellular calcium concentration, which is a crucial factor for vasoconstriction. Increased intracellular levels of magnesium result in decreased intracellular free calcium concentration promoting vasodilation [3]. The action of magnesium as a calcium channel blocker may also help to reduce the release of calcium and thus reducing vascular resistance. In addition, magnesium also activates the Na-K ATPase pump that controls the balance of these minerals contributing to the homeostasis of electrolytes in cells [4].
High levels of magnesium may increase production of adenosine triphosphate (ATP) and intracellular glucose utilization, since magnesium acts as a cofactor of all reactions involving ATP transfer [5]. Insulin seems to be one of the most important factors that regulate plasma and intracellular magnesium concentrations. It has been suggested that an ATPase-dependent pump is involved in the mechanism by which insulin regulates the erythrocyte magnesium content [6].
Furthermore meta-analyses show that a daily sodium reduction of at least 53 mmol (3.1 g/day as sodium chloride (NaCl)) can lead to a reduction of 4-5 mmHg in systolic BP (SBP) and 2-3 mmHg in diastolic BP (DBP) in hypertensive subjects [7-14]. Instead observational studies have shown that a diet rich in potassium, magnesium, and calcium, present mainly in fruits and vegetables, is associated with lower incidence and mortality from cardiovascular disease. In particular, magnesium has been the target of many studies , considering that there is a significant inverse correlation between serum magnesium levels and incidence of cardiovascular diseases. In addition, hypertensive patients generally exhibit reduced intracellular concentrations of magnesium, while the contents of sodium and calcium are often increased compared to normotensive subjects [2].
Hypertension is also associated with unfavorable changes in elastic properties of large arteries. In an experimental study evaluating the structure of the carotid artery in rats, magnesium deficiency was associated with hypertrophic vascular remodeling, which was attenuated by supplementation of this ion. These findings suggest that magnesium deficiency alters the vascular mechanical properties in young animals and may be a mechanism involved in the pathogenesis of hypertension, atherosclerosis, and other cardiovascular diseases [15].
Other possible mechanisms of magnesium action are anti-inflammation, antioxidion, and modulation of cell growth properties. In fact, the production of reactive oxygen species is usually increased in the vasculature of hypertensive patients, and the involvement of magnesium could occur through the reduction of inflammation and oxidative stress [16]. Magnesium has antioxidant properties that could attenuate detrimental effects of oxidative stress on the vasculature, thereby preventing increased vascular tone and contractility [17]. Magnesium indeed, plays a role in free intracellular Calcium concentration; so Magnesium promotes a vasodilation.
Conclusion
Magnesium is a mineral with important functions in the body, and it is important that their levels are adequate. The conflicting results of studies evaluating the effects of magnesium supplements on blood pressure and other cardiovascular outcomes indicate that the action of magnesium in the vascular system is present but not yet established. Certainly, the lack of definitive conclusions due to heterogeneity of study populations with different clinical profiles and severity of illness, lack of standardization of the type of supplement and the dose, and, finally, very short time of treatment, most often between one and three months, are factors that contribute to the difficulty to achieve the primary objectives. Based on recent studies, although we cannot make categorical statements, it appears that magnesium is more involved in the functional vascular changes, and also on local metabolic stability with no influence on the vascular structure. Therefore, further studies are needed to evaluate the risk of magnesium deficiency and the effects to be considered in this mineral supplementation [2].
References
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Jacopo Cumbo
