May 2019
Paolo Severino, Lucrezia Netti, Marco Valerio Mariani, Annalisa Maraone, Andrea D’Amato, Rossana Scarpati, Fabio Infusino, Mariateresa Pucci, Carlo Lavalle, Viviana Maestrini, Massimo Mancone, and Francesco Fedele
Abstract
Magnesium is an essential mineral naturally present in the human body, where it acts as cofactor in several enzymatic reactions. Magnesium is a key cardiovascular regulator, which maintains electrical, metabolic, and vascular homeostasis. Moreover, magnesium participates in inflammation and oxidative processes. In fact, magnesium deficiency is involved in the pathophysiology of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, endothelial dysfunction, coronary artery disease, cardiac arrhythmias, and sudden cardiac death.
In consideration of the great public-health impact of cardiovascular disease, the recognition of the negative effects of magnesium deficiency suggests the possible role of hypomagnesaemia as cardiovascular risk factor and the use of serum magnesium level for the screening and prevention of cardiovascular risk factors and cardiovascular diseases. Moreover, it might help with the identification of new therapeutical strategies for the management of cardiovascular disease through magnesium supplementation.
Introduction
Magnesium (Mg2+) is an essential mineral naturally present in the human body, where it plays an important role as a cofactor in about 325 enzymatic reactions such as the production of adenosine triphosphate (ATP), the synthesis of nucleotides, glucose, and blood pressure control, and lipid peroxidation [1]. Mg2+ is the second most important intracellular cation after potassium (K+) and is fundamental in muscle contraction, nerve conduction, and bone strength. In an adult human body, there are approximately 0.4 g Mg2+/kg [2], with about 50–60% localized in bones, and the rest distributed in skeletal muscle and soft tissues. Serum Mg2+ represents a little percentage, less than 1% of all Mg2+ in the body [3], and the normal reference range is 0.76–1.15 mmol/L [4]. However, bone Mg2+ is largely exchangeable to counteract acute changes in serum levels of this mineral, while one-third of skeletal Mg2+ accomplishes the same function [5]. We can obtain Mg2+ from different types of food as green leafy vegetables, legumes, cereal and nuts, which have a great Mg2+ content, or fruits, meat, fish, and chocolate, providing a moderate amount of Mg2+. Moreover, water represents an important source of Mg2+, because it contains up to 30 mg/L of Mg2+ [6].
Scientific literature has reported the role of Mg2+ as important cardiovascular regulator, acting to maintain electrical, metabolic, and vascular homeostasis; additionally, Mg2+ modulates inflammation and oxidative processes that are known to be triggers for atherogenesis and cardiovascular diseases (CVDs) [7]. More recently, several data have shown the association between Mg2+ intake and circulating Mg2+ with CV health [7–9]; hypomagnesaemia has been associated to increased risk of type 2 diabetes mellitus (T2D), metabolic syndrome (MetS), arterial hypertension, endothelial dysfunction, and CVD. Hence, new evidences suggest that hypomagnesaemia may have a detrimental effect on CV health and may increase the total risk of developing several metabolic conditions and CVD. Dietary surveys have shown deficient Mg2+ intake in a large proportion of population, probably due to Western dietary habits. Additionally, other known causes of hypomagnesaemia, such as intestinal malabsorption, gastrointestinal losses, and diuretics or lassative assumption, are very frequent in general population but often underestimated and undertreated, particularly among elderly individuals.
The recognition of the possible role of hypomagnesaemia as risk factor for CV health, along with the underestimation of the importance of this mineral in daily clinical practice, makes serum Mg2+ level suitable for the screening and prevention of CVD and opens new therapeutic scenarios with the possibility of reducing CV risk profile and treating CVDs through Mg2+ supplementation.
Conclusions
The present review shows that a relationship between Mg2+ and cardiovascular health has been clearly demonstrated and underlines the possible pathophysiological mechanisms through which Mg2+ deficiency can promote the onset, progression, and maintenance of CVD. In fact, hypomagnesaemia influences negatively the CV health and is associated with an augmented incidence of hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, arrhythmias, and coronary artery disease. In consideration of the great public-health impact of CVD, the recognition of the detrimental effects of Mg2+ deficiency on CV health suggests the possible role of Mg2+ blood levels for the screening and prevention of CV risk factors and CVD and helps the identification of new therapeutical strategies for the management of CVD through Mg2+ supplementation. This concept is even more shareable if framed in a wider and more complete perspective, that aims to embrace in a global way any possible alteration or disease, even noncardiovascular ones, which can damage the heart health and whose treatment or correction can support specific cardiological therapies, from the standard one to the most innovative, in the pursuit of the healing and the well-being of the patients [104–106]. Considering the limitations of the present studies addressing a role of hypomagnesaemia on the development of CVD, large prospective randomized controlled trials are necessary to elucidate this multifaceted relationship, to assess the benefits of routine Mg2+ level assessment in cardiovascular patients and in the general population and the usefulness of Mg2+ supplementation in the prevention and treatment of CVD.
