Magnesium: Its Proven and Potential Clinical Significance

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South Med J. 2001;94(12) 

In This Article

Clinical Signs and Symptoms

Magnesium deficiency is almost always asymptomatic. There are no pathognomonic signs and symptoms of the magnesium deficient state. The situation must be severe if clinical manifestations are to occur. This would also always be accompanied by a low serum magnesium level. Symptoms, when they do occur, generally fall into the categories of cardiac effects, metabolic effects, and neurologic effects (Table 1).

Magnesium has been associated with a number of chronic diseases, such as hypertension, diabetes mellitus, and hyperlipidemia. Studies showing the effect of magnesium supplementation on these clinical states are summarized in Table 2. We found 15 studies in which magnesium supplementation was used to measure the effect on hypertension. Ten of these studies (67%) showed a statistically significant decrease of blood pressure with the use of magnesium. In patients with diabetes, 3 studies looked at the effect of magnesium replacement on hemoglobin A1C. None of these investigations showed a statistically significant effect. Two studies examined the effect of magnesium supplementation on hyperlipidemia. Both of these showed decreased triglycerides, and one of them showed a decreased low-density lipoprotein/high-density lipoprotein ratio.

The clinical correlation between decreased plasma magnesium and the diabetic condition was first proposed by Londono and Rosenbloom[36] in 1971. This was shown in diabetic children after a glucagon injection induced a significant decline in plasma magnesium levels.

The inverse relationship between glycemic control and plasma magnesium levels has been attributed to increased magnesium urinary losses. McNair et al[37] observed that in the presence of hypomagnesemia, magnesium plasma levels were inversely correlated with fasting blood glucose values and urinary magnesium. The conclusion was that net tubular reabsorption of magnesium was decreased in severe hyperglycemia. The relationship between metabolic control and impaired magnesium balance was confirmed by Fugii et al,[38] who analyzed magnesium levels in plasma, erythrocytes, and urine of diabetic patients.

The role of magnesium in the pathogenesis of macroangiopathy and microangiopathy have been the subject of several investigators. Seelig and Heggtveit,[39] as well as Mather,[29] suggested that atherosclerotic disease may be prevented by normal magnesium homeostasis by counteracting the adverse effects of excessive intracellular calcium, thereby retaining intracellular potassium and contributing both to the stabilizing of plasma membrane and maintaining the integrity of subcellular structures.

Considerable evidence suggests a linkage between magnesium deficiency and hypertension. One study showed reduced intracellular free magnesium concentration in hypertensive laboratory animals as well as in human subjects. The researchers described an inverse relationship between intracellular magnesium concentration and blood pressure.[19]

Magnesium has been implicated in a regulatory role in a variety of cellular ion channels and pumps that modulate peripheral vascular tone; these include sodium-potassium-ATPase and calcium-activated potassium channels, as well as calcium calmodulin binding. In each of these instances, low intracellular magnesium levels would potentiate calcium-dependent vasoconstriction.