What are the causes of hypomagnesemia (low magnesium levels)?

From the Guidelines

Hypomagnesemia is most commonly caused by inadequate dietary intake, increased gastrointestinal losses, certain medications, and kidney disorders, as supported by the most recent evidence from 2021 1. The causes of hypomagnesemia can be multifactorial, including:

• Inadequate dietary intake of magnesium
• Increased gastrointestinal losses through diarrhea or vomiting
• Certain medications, such as diuretics, proton pump inhibitors, antibiotics, and chemotherapy drugs
• Kidney disorders, which can lead to increased magnesium loss
• Chronic conditions like diabetes, malabsorption syndromes, pancreatitis, and hyperparathyroidism According to the 2021 study 1, hypomagnesemia has been reported in up to 12% of hospitalized patients, with an incidence around 60-65% among critically ill patients. The study also highlights the importance of considering the amount of ionized magnesium chelated by citrate when regional citrate anticoagulation is utilized, as this can lead to increased magnesium removal during kidney replacement therapy. The most effective treatment for hypomagnesemia depends on the severity of the deficiency, with intravenous replacement with magnesium sulfate being recommended for severe symptoms, and oral supplementation with magnesium oxide, magnesium citrate, or magnesium glycinate being effective for mild to moderate deficiency 1. It is essential to note that magnesium plays a crucial role in over 300 enzymatic reactions in the body, including energy production, protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation, making its deficiency a significant concern. The 2019 study 1 also emphasizes the importance of monitoring plasma potassium levels and supplementing as required, as hypokalemia can be a complication of hypomagnesemia. Overall, the management of hypomagnesemia requires a comprehensive approach, taking into account the underlying causes, severity of the deficiency, and the patient's overall clinical condition.

From the FDA Drug Label

As plasma magnesium rises above 4 mEq/L, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/L. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of magnesium. Serum magnesium concentrations in excess of 12 mEq/L may be fatal. Early symptoms of hypomagnesemia (less than 1. 5 mEq/L) may develop as early as three to four days or within weeks. Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of magnesium.

The causes of hypomagnesemia are not directly stated in the provided drug labels. However, the labels do mention that hypomagnesemia can arise during the course of total parenteral nutrition (TPN) therapy 2. Additionally, the labels describe the effects of low serum magnesium levels, including neurological symptoms such as muscle irritability, clonic twitching, and tremors, as well as the potential for hypocalcemia and hypokalemia to follow low serum levels of magnesium 2.

From the Research

Causes of Hypomagnesemia

• Inadequate magnesium intake
• Increased gastrointestinal or renal losses
• Redistribution from extracellular to intracellular space 3

Renal Causes

• Genetic or acquired renal disorders
• Barter syndrome and loop diuretics which inhibit sodium chloride transport in the ascending loop of Henle are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypercalciuria 3
• Gitelman syndrome and thiazide diuretics which inhibit sodium chloride cotransporter in the distal convoluted tubule are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypocalciuria 3
• Familial renal magnesium wasting is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis 3

Drug-Induced Causes

• Proton pump inhibitors (PPIs) can cause hypomagnesemia due to impaired intestinal absorption, mainly attributed to reduced transcellular transport of magnesium via transient receptor potential melastatin 6 (TRPM6) and 7 (TRPM7) channels 4, 5
• PPI-induced hypomagnesemia can trigger other concomitant electrolyte derangements, including hypokalemia, hypocalcemia, hypophosphatemia, and hyponatremia 4

Population-Based Studies

• PPI use is associated with hypomagnesemia in the general population, with prolonged PPI use and concomitant loop diuretic use associated with a stronger risk increase 6
• However, another study found that PPIs are not associated with hypomagnesemia, regardless of dose or concomitant diuretic use 7