Magnesium: Its Proven and Potential Clinical Significance

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South Med J. 2001;94(12) 

In This Article

Biologic Mechanisms

A review of the literature reveals three biologic mechanisms that could potentially explain the physiologic effects of magnesium in hypertension, diabetes, and hyperlipidemia. First, magnesium deficiency causes a dysregulation of the Na-Mg exchanger, resulting in higher intracellular sodium and higher blood pressure. Second, a relatively low magnesium level creates an intracellular imbalance between calcium and magnesium, which results in increased vascular tone in the smooth muscle of the artery and therefore increased blood pressure. Third, magnesium deficiency causes insulin resistance, which in turn causes hyperinsulinemia, resulting in hypertension, diabetes, and hyperlipidemia.

A study of cyclosporine toxicity in spontaneously hypertensive rats found that rats placed on a low sodium diet did not get hypertension or nephrotoxicity, but during a high sodium diet, both these diseases occurred. These deleterious effects were blocked by magnesium supplementation,[14] revealing a causal relationship between magnesium and hypertension in spontaneously hypertensive rats. This result has implications for clinical trials because it may be that the hypotensive effect of a rigorously followed low-salt diet obviates the need for magnesium supplementation to improve blood pressure even in the face of magnesium deficiency. Some of the negative clinical trials for magnesium replacement did have patients on low salt diets.[15,16] This defect in the Na-Mg exchanger that results in higher intracellular sodium and lower intracellular magnesium was found in at least three other studies of patients with essential hypertension.[17,18,19]

Again, both rat and human studies confirm that in the presence of decreased magnesium, there is increased intracellular calcium, resulting in increased vascular tone and hypertension. In a basic physiologic study that looked at isolated aortas from both normotensive and desoxycorticosterone acetate (DOCA)-salt hypertensive rats, it was found that "changes in extracellular magnesium concentration differentially alter endothelin-1-induced contraction in aortae from normotensive and hypertensive rats, possibly by interfering with calcium utilization during contraction."[20] In other animal studies, a salt load produced an increase in intracellular calcium with a concomitant decrease in magnesium.[21,22,23] This intracellular imbalance between magnesium and calcium has also been found in human studies.[24,25] There appears to be a clear connection between decreased magnesium, increased vascular tone, and essential hypertension.

Insulin resistance has emerged as a major pathophysiologic mechanism for the creation of atherosclerosis in the body. Magnesium deficiency has clearly been shown to create insulin resistance.[24] This may well be a common link in increased cardiovascular risk, because hyperinsulinemia is related to hypertension, diabetes, and hyperlipidemia.[26]

This discussion shows strong evidence linking magnesium deficiency with altered physiologic states and chronic disease.