Magnesium in disease

Abstract

Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo.

Keywords: cardiovascular disease; diabetes mellitus; magnesium; metabolic syndrome; pre-eclampsia/eclampsia.

Fig. 1.

Association between magnesium intake (for a 100 mg/day increase) and incidence of T2DM. In the various trials, the study-specific relative risk was assessed (squares) [25]. The diamond represents the overall relative risk. Reprinted from Larson et al. [25], Copyright © 2007, John Wiley and Sons. *, Black participants; ^†, White participants; HPFS, Health Professionals' Follow-up Study; NHS, Nurses' Health Study.

Fig. 2.

Race- and gender-specific, age- and body mass index-adjusted average systolic blood pressure according to the serum magnesium level in participants without cardiovascular disease [54]. Magnesium serum levels were inversely related to systolic blood pressure except in black women in whom there was a U-shaped association. Subjects who received anti-hypertensive medication were excluded from the analyses (ARIC study). Reprinted from Ma et al. [54], Copyright (1995), with permission from Elsevier.

Fig. 3.

Magnesium consumption and systolic blood pressure (ARIC study) [54]. Dietary magnesium intake led to considerable effects on systolic blood pressure parameters in white women and in blacks. Race- and gender-specific, age and body mass index-adjusted average systolic blood pressure according to dietary magnesium intake in participants lacking cardiovascular disease. Those on anti-hypertensive medication are also excluded. Reprinted from Ma et al. [54], Copyright (1995), with permission from Elsevier.

Fig. 4.

Vascular effects of magnesium sulphate [66]. Magnesium is a potent vasodilator of uterine and mesenteric arteries as well as the aorta, but has little effect on cerebral arteries. In vascular smooth muscle, magnesium competes with calcium for binding sites, in this case for voltage-operated calcium channels (VOCC). Decreased calcium channel activity lowers intracellular calcium, resulting in relaxation and vasodilation. In the endothelium, magnesium increases production of prostaglandin I₂ which in turn decreases platelet aggregation. Magnesium also increases NO production causing vasodilation. From Euser and Cipolla [66], with permission, adapted.

Fig. 5.

Treatment effects of magnesium administration in patients with (pre-)eclampsia [169]. Magnesium led to consistent effects regardless of severity of pre-eclampsia, stage of gestation and anticonvulsant therapy. Reprinted from Altman et al. [169], Copyright (2002), with permission from Elsevier. PMR, perinatal mortality rate; *Unknown whether prior anticonvulsant treatment was given to 26 women allocated to the magnesium sulphate and 37 allocated to the placebo groups.

Fig. 6.

Associations between low serum magnesium levels and low dietary magnesium intake and an increased risk for diseases such as the metabolic syndrome, T2DM and hypertension and atherosclerosis have been shown in various epidemiological studies. In addition, a beneficial effect of magnesium supplementation has been observed for most of these diseases. However, an indication for the administration of magnesium as a therapeutic could only be confirmed for pre-eclampsia and specific forms of arrhythmias.