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Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease.
Dyslipidemia has emerged as a significant threat to public health worldwide, with recent statistics revealing that its prevalence reaches 42.7% in China and 56.8% in the United States of America (USA). In addition, Lu et al. (2018) have pointed out that an alarming rate of the population suffering from this disorder is not aware of its lipid profile (26.7% in the USA versus 80.4% in China), leading to poor treatment and control rates of lipid abnormalities (13.2% and 4.6% in China versus 54.1 and 35.7% in the USA) [1]. Thus, identifying novel strategies to combat dyslipidemia are warranted, particularly due to its involvement in the development of and crosstalk with metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), cardiovascular disease, obesity, hypertension, chronic kidney disease (CKD), and others [1][2][3].
Magnesium (Mg) seems to play a key role in a myriad of disorders, e.g., MetS, T2DM, obesity, hypertension, and its deficiency has been regarded as highly prevalent, with Piuri et al. (2021) ranking it as the most common electrolyte imbalance in high-income countries [4][5][6]. Taking this information into consideration, we may hypothesize that there is a crosstalk between Mg and serum lipids which may impact on the pathogenesis of dyslipidemia and its associated comorbidities, as well as that Mg supplementation might provide health benefits in patients suffering from cardiometabolic disorders.
Mg deficits may arise both from primary (insufficient intake, decreased absorption or elevated excretion) and secondary causes, e.g., disorders that accompany the advancement in age, several comorbidities (T2DM, MetS) or it can occur due to the use of certain medications such as loop diuretics [7]. In addition, particular attention should be given to the methods employed in the measurement of Mg concentrations. Barbagallo et al. (2014) demonstrated that, in elderly patients diagnosed with T2DM, serum ionized rather than total serum Mg may emerge as a superior predictor of the subclinical deficit of this micronutrient. In addition, they also detected that TG may be a confounding factor in the crosstalk between Mg levels and markers of glucose metabolism. For example, after multiple adjustments for TG, BMI, and glomerular filtration rate, the associations of serum total Mg with FPG and HbA1c, respectively, failed to reach statistical significance. However, serum-ionized Mg remained associated with these variables despite multiple adjustments [8]. Moreover, in their recent umbrella review of systematic reviews and meta-analyses of observational and intervention studies focused on the crosstalk between Mg concentrations and health outcomes, Veronese et al. (2019) evidenced that an elevated intake of this micronutrient can result in a reduction of the risk of both stroke and T2DM. However, Mg intake was not linked to any other cardiovascular endpoints based on their results [9].
The potential lipid-lowering effects of Mg warrant further investigation, with a myriad of studies linking the serum concentrations of this micronutrient to cardiometabolic disorders, e.g., obesity, T2DM, MetS, cardiovascular disorders, neurological ailments, and even cancer, all of which are worldwide public health threats [5][10][11]. Mg supplements stand out as one of the most popular supplements in Europe and the United States [12]. In particular, Mg orotate supplementation, due to the Mg-fixing capacity of this salt, has exerted health benefits [12][13]. For example, in an RCT, patients with heart failure who were prescribed Mg orotate had better 1-year survival versus subjects receiving placebo [13]. Similarly, patients diagnosed with concomitant heart failure and hypertension who were administered Mg orotate registered a decrease in both blood pressure and N-terminal (NT)-pro hormone BNP (NT-proBNP) [14].
In terms of Mg supplementation, the most reliable data included in our paper were obtained from 29 RCTs with a total number of 1724 subjects who received different forms of Mg supplementation for a period of time ranging from 4 to 24 weeks [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Overall, the vast majority of the analyzed RCTs reported no variations in HDL-C (n = 19), LDL-C (n = 16), TG (n = 17), TC (n = 14), TC/HDL-C (n = 4), VLDL (n = 2), or LDL-C/HDL-C (n = 1). However, some RCTs reported elevations of the HDL-C (n = 8), apoA1 (n = 1), or HDL-C/TG (n = 1), as well as reductions in LDL-C (n = 7), TC (n = 4), TG (n = 7), TC/HDL-C (n = 2), or VLDL (n = 3) in the participants exposed to the Mg intervention [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43].