Magnesium: Its proven and potential clinical significance
ABSTRACT: Magnesium is the fourth most abundant cation in the body and is present in more than 300 enzymatic systems, where it is crucial for adenosine triphosphate (ATP) metabolism. Deficiency states result in increased insulin resistance, as well as increased smooth muscle and platelet reactivity. Magnesium deficiency has been shown to correlate with a number of chronic cardiovascular diseases, including hypertension, diabetes mellitus, and hyperlipidemia. Intravenous magnesium has been used therapeutically in critical situations such as status asthmaticus, torsades de pointes, and preeclampsia. Few controlled studies exist regarding the therapeutic uses of oral magnesium supplementation in chronic cardiovascular diseases. Randomized clinical trials are urgently needed to determine whether magnesium supplementation will alter the natural history of these disease states.
THE CLINICAL SIGNIFICANCE of magnesium as an important intracellular cation has been implied for decades. (1) Recently, magnesium deficiency has been implicated in the pathogenesis of a host of clinical disorders. (2) In an editorial, Resnick (3) stated, "A link between magnesium, diabetes mellitus, and hypertension seems established beyond a reasonable doubt."
Magnesium is the fourth most abundant cation in the body. It is involved in more than 300 enzymatic systems, such as adenosine triphosphate (ATP) metabolism, activation of creatine kinase, adenylate cyclase, and sodium-potassium-ATPase. Magnesium deficiency has been implicated in such diseases as diabetes, hypertension, cardiac arrhythmias, acute myocardial infarction, and atherosclerosis. This has come under increasing scrutiny in several recent publications. (3-5)
MAGNESIUM METABOLISM AND PHYSIOLOGY
The total body stores of magnesium are between 21 and 28 g in the average 70 kg adult. Normal serum magnesium usually has a range of 1.7 to 2.5 mg/dL. Most of the body's magnesium is in the skeletal bone mass, which accounts for more than 50% of the body's stores. The remainder is located in soft tissue, of which only 0.3% is located extracellularly. The common nutritional sources of magnesium are green leafy vegetables, legumes, nuts, and animal protein. (6)
Of the total magnesium consumed, approximately 30% to 50% is absorbed, mainly from the upper small intestine. The level of absorption of magnesium varies, depending on endogenous magnesium status. Magnesium is excreted via the kidneys. When magnesium stores are normal, excretion usually equates with absorption. There is a circadian excretory rhythm, with the maximal excretion occurring at night. Approximately one third of serum magnesium is bound to albumin and therefore is not filterable at the glomerulus. A total of 20% of serum magnesium is filtered by the kidneys, from which 50% to 60% is reabsorbed by the ascending loop of Henle, in contrast to other major electrolytes, which are reabsorbed principally at the proximal loop of Henle.
Extracellular magnesium in serum is 33% protein bound, 12% complexed to anions, and 55% in the free ionized form. At the cellular level, magnesium appears to influence the properties of various cell membranes; this process is thought to occur by means of calcium channels and ion transport mechanisms. Calcium flux is inhibited by magnesium from sarcolemmal membranes, through competition for binding sites on actin and...