Loss of magnesium from the GI tract and the kidneys, as well as cellular uptake, are among the causes.

CLEVELAND—Although magnesium is abundant, “it is the most neglected nutrient cation,” said Zalman S. Agus, MD, at the Cleveland Clinic’s Nephrology Update 2008.

The effect of magnesium depletion, which causes a temporary drop in serum magnesium, is a decrease in urinary magnesium excretion. “It falls and protects the serum so that while we get some magnesium depletion with a magnesium-depleted diet, the serum level doesn’t fall below 1.0 mEq/L, the level at which we usually see symptoms,” said Dr. Agus, emeritus professor of medicine at the University of Pennsylvania School of Medicine in Philadelphia.

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Low serum magnesium causes hypocalcemia by inhibiting parathyroid hormone (PTH) secretion as well as the action of PTH at the bone. Intracellular magnesium has additional effects on intracellular ion channels, activating calcium and potassium channels in both myocardial and ventricular cells and also activating chloride and potassium channels in the nephron’s thick ascending limb.

The prevalence of hypomagnesemia is about 10% in community and Veterans Administration hospitals, affecting 50% of hypokalemic hospitalized patients and 60% of ICU patients.

Causes of hypomagnesemia include loss of magnesium from the GI tract and kidney as well as cellular uptake (e.g., refeeding in alcoholic patients). GI loss can be a result of decreased magnesium absorption, inadequate magnesium intake (from small bowel malabsorption, small bowel bypass, or a disorder known as familial hypomagnesemia with secondary hypocalcemia), increased secretory loss (as with diarrhea), and acute pancreatitis.

Familial hypomagnesemia

Familial hypomagnesemia with secondary hypocalcemia is an autosomal recessive disorder caused by mutations in the magnesium channel, called TRPM6. These mutations result in impaired active absorption of magnesium and may also cause impaired magnesium transport in the distal tubule. The disorder presents shortly after birth with seizures and tetany, predominantly in males.

“It is important to recognize that treatment of familial hypomagnesemia with secondary hypocalcemia is high-dose oral supplementation—the higher you can get the magnesium concentration, the more absorption you can drive passively,” Dr. Agus said. Serum magnesium is dependent on absorption and urinary excretion. Absorption in the small and large bowel is passive; in the large bowel, active transcellular absorption of magnesium also occurs and is mediated by TRPM6.

“In fact, with high-dose oral supplementation, you can bring serum magnesium up to a level that won’t cause hypocalcemia, and if you start early enough, this disease can be treatable.”