What are the causes of severe magnesium deficiency?

From the Guidelines

Severe magnesium deficiency is primarily caused by increased gastrointestinal losses, particularly in patients with inflammatory bowel disease (IBD), as evidenced by a study published in 2019 in the journal Gut 1. The causes of severe magnesium deficiency can be multifactorial, including:

• Inadequate dietary intake of magnesium-rich foods
• Gastrointestinal disorders that impair absorption, such as IBD, which has been reported to cause magnesium deficiency in 13–88% of patients 1
• Certain medical conditions, such as chronic diarrhea, which can worsen with oral magnesium supplementation
• Increased renal losses, which can be exacerbated by certain medications
• Other factors, such as poor nutrition, chronic alcoholism, and endocrine disorders like diabetes and hyperaldosteronism It is essential to note that serum magnesium is not an accurate measurement of magnesium status, as less than 1% of magnesium stores are in the blood, and the remainder is in bone, soft tissue, and muscle 1. Symptoms of magnesium deficiency include abdominal cramps, impaired healing, fatigue, and bone pain, and treatment typically involves oral magnesium supplementation or intravenous replacement in severe cases, along with addressing the underlying cause. In patients with IBD, magnesium supplementation can be given orally or intravenously, although oral supplementation can worsen diarrhea, and plasma potassium levels should be monitored and supplemented as required 1.

From the FDA Drug Label

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for magnesium is uncertain. 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 severe magnesium deficiency are not directly stated in the provided drug labels. However, the labels mention that hypomagnesemia (less than 1.5 mEq/L) may develop as early as three to four days or within weeks, and that hypocalcemia and hypokalemia often follow low serum levels of magnesium.

• Key points about magnesium deficiency include:
  • Neurological effects: muscle irritability, clonic twitching, and tremors
  • Electrolyte imbalances: hypocalcemia and hypokalemia
  • Onset of symptoms: as early as three to four days or within weeks 2 2

From the Research

Causes of Severe Magnesium Deficiency

The causes of severe magnesium deficiency can be categorized into several groups, including:

• Inadequate magnesium intake
• Increased gastrointestinal losses, such as:
  • Chronic watery diarrhea
  • Steatorrhea
  • Short bowel syndrome
  • Bowel fistula
  • Continuous nasogastric suctioning
• Increased renal losses, such as:
  • Genetic or acquired renal disorders
  • Use of certain drugs, including:
    • Loop and thiazide diuretics 3, 4, 5
    • Proton pump inhibitors (PPIs) 6, 4, 7
    • Aminoglycosides, cisplatin, pentamidine, and foscarnet 5
• Redistribution from extracellular to intracellular space
• Certain medical conditions, such as:
  • Bartter's syndrome and Gitelman's syndrome 3, 5
  • Post obstructive diuresis, post acute tubular necrosis, renal transplantation, and interstitial nephropathy 5
  • Alcoholism and diabetes 5

Gastrointestinal Causes

Gastrointestinal causes of severe magnesium deficiency include:

• Protein-calorie malnutrition
• Intravenous administration of Mg-free fluids and total parenteral nutrition
• Primary familial Mg malabsorption

Renal Causes

Renal causes of severe magnesium deficiency include:

• Barter syndrome and loop diuretics, which inhibit sodium chloride transport in the ascending loop of Henle 3
• Gitelman syndrome and thiazide diuretics, which inhibit sodium chloride cotransporter in the distal convoluted tubule 3
• Familial renal magnesium wasting, which is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis 3

Drug-Induced Causes

Several drugs can cause severe magnesium deficiency, including:

• Proton pump inhibitors (PPIs), which can lead to hypomagnesemia and hypocalcemia 6, 7
• Loop and thiazide diuretics, which can cause renal magnesium wasting and subsequent deficiency 3, 4, 5