Whither Magnesium?

Magnesium is a chemical element with the atomic number 12, an atomic weight of 24, and the common oxidation number 12. Magnesium is an alkaline metal and the eighth most abundant element in the Earth’s crust, where it constitutes about 2% by mass, and ninth in the Universe. Magnesium is easily built up in supernova stars by the sequential addition of three helium nuclei to carbon. Magnesium ion’s high solubility in water helps ensure that it is the third most abundant element dissolved in seawater. Thus, magnesium seems ubiquitous and countless products contain magnesium. My wife swears by her GSR Magnesium IQ skis; I can offer no comment in that regard. A crude facsimile of magnesium is offered in Figure 1. Magnesium is the second most prevalent intracellular cation and the fourth most abundant cation in the body. Magnesium is integral to the function of adenosine triphosphate and plays a role in a host of enzymatic reactions and transport processes, and in the synthesis of proteins, DNA and RNA. Oddly, magnesium gets relatively short shrift in terms of physician education. Disorders of magnesium metabolism made hardly 1.3 pages in my most recent edition of a commonly used Internal Medicine textbook [1]. The topic did a bit better in a textbook devoted solely to fluid and electrolyte metabolism [2]. The lay public seems a bit more aware. They generally know that grains, nuts, milk and green leafy vegetables provide magnesium. They are convinced that magnesium is ‘good for you’. They know for instance that magnesium cures leg cramps, although the Cochrane Review folks are less convinced. Many people travel to the Dead Sea to get at it; presumably they absorb it through the skin, who knows? One of my favourite clinical teachers, Robert Whang, scoured intensive care units of our hospitals checking the patients for magnesium deficiency [3]. In a survey of 1033 serum specimens for electrolyte analysis in an acute-care hospital, he and an associate found that 53% of the patients had magnesium levels <0.74 mmol/L, while the ordering physicians suspected and ordered magnesium levels specifically in only 10% of patients. Whang and Ryder concluded that in many patients, magnesium disturbances were not being detected. They recommended that routine magnesium measurements should be performed in acutely ill patients when electrolyte disturbances are suspected [4]. Whang was also interested in the relationship between magnesium and potassium, particularly intracellular potassium stores. He and an associate drew attention to the close interrelationship of magnesium, calcium and intracellular potassium. Clinically, magnesium deficiency is associated with hypocalcaemia, kaliuresis and hypokalaemia [5]. Decreased Na-K pump density in cells decreases ATPase activity; and increased cell membrane permeability related to intracellular potassium depletion are mechanisms that they implicate. Since the kidneys eliminate magnesium, nephrologists would be expected to know the most about it. The daily intake of magnesium is ~15 mmol of which approximately one third is absorbed. The circulating pool amounts to ~7.6 mmol and is in equilibrium with bone magnesium which is ~530 mmol, muscle magnesium ~270 mmol, other intracellular places ~190 mmol and erythrocytes ~5 mmol. Of the 5 mmol absorbed, the kidneys excrete 4 mmol and the rest is eliminated by other means. Robert Whang recognized that serum measurements, while practicable, were not adequate reflections of total body stores and took to measuring magnesium in mononuclear cells. Erythrocytes are apparently inexact reflectors. Dialysis patients cannot eliminate magnesium via their kidneys. The dialysate is adjusted accordingly. Such patients should be prime candidates of interest regarding magnesium metabolism. The other cations have done pretty well, sodium in terms of volume regulation, potassium in terms of Nernst-Equation problems (like sudden cardiac death) and calcium in terms of bone disease. The relationship between serum magnesium concentrations and renal function is based on a (seminal) study from 40 years ago; the values were all over the map and were typically high. However, the authors did not report that the patients developed any symptoms related to their magnesium levels [6]. I was taught that magnesium, similar to potassium, was ‘dangerous’ in dialysis patients and could cause similar symptoms to hyperkalaemia. Forty years ago, before the advent of histamine receptor-2 blockers and proton-pump inhibitors, gastric disorders were treated with antacids and the favourite was Maalox . The compound contains aluminum hydroxide and magnesium hydroxide to neutralize or reduce stomach acid. Dire were the consequences and limited was the future for any nephrology fellow who did not eliminate Maalox from the treatment venue of any renal patient! Getting fired in those days was relatively Fig. 1. The magnesium atom with its protons, neutrons, and electrons is displayed.