What are the causes of hypomagnesemia, particularly in the elderly or individuals with a history of malabsorption, malnutrition, type 2 diabetes, or gastrointestinal disorders such as Crohn's disease or celiac disease?

Causes of Hypomagnesemia

Hypomagnesemia results from three primary mechanisms: inadequate intake, excessive gastrointestinal losses, or excessive renal losses—with the most common causes being gastrointestinal malabsorption, medication-induced renal wasting, and alcohol use disorder. 1

Gastrointestinal Causes

Direct intestinal losses are a major contributor to magnesium depletion:

• Chronic diarrhea and steatorrhea cause direct magnesium loss through intestinal fluid, with approximately 100 mmol/L sodium and substantial magnesium lost per liter 2
• Short bowel syndrome, particularly with jejunostomy, leads to severe and intractable magnesium losses through both direct loss in intestinal effluent and reduced absorption time due to rapid transit 3, 2, 1
• Inflammatory bowel disease (Crohn's disease and ulcerative colitis) causes magnesium deficiency in 13-88% of patients through malabsorption, increased intestinal losses, and reduced intake 3, 4
• Celiac disease and other malabsorption syndromes reduce magnesium absorption in the small intestine 5, 6
• Chronic nasogastric suctioning depletes magnesium through continuous upper GI losses 2

A critical pitfall: In patients with high-output diarrhea or stomas, sodium and water depletion triggers secondary hyperaldosteronism, which paradoxically increases renal magnesium wasting despite total body depletion—making rehydration with IV saline the crucial first step before magnesium supplementation 2. Hyperaldosteronism increases renal retention of sodium at the expense of both magnesium and potassium, creating a vicious cycle where continued magnesium is lost renally despite oral supplementation 4.

Renal Causes

Medication-induced renal wasting is increasingly recognized as a common cause:

• Proton pump inhibitors cause chronic renal magnesium wasting through incompletely understood mechanisms 2, 1, 7, 6
• Loop diuretics (furosemide, bumetanide) inhibit sodium chloride transport in the ascending loop of Henle, leading to increased renal magnesium wasting 2, 8
• Thiazide diuretics inhibit sodium chloride cotransporter in the distal convoluted tubule, causing renal magnesium wasting 2, 8
• Calcineurin inhibitors (cyclosporine, tacrolimus) increase renal magnesium excretion in transplant patients 2, 1
• Aminoglycosides, cisplatin, cetuximab, pentamidine, and foscarnet directly damage renal tubular magnesium handling 1

Genetic tubular disorders cause chronic renal magnesium wasting:

• Bartter syndrome is characterized by hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypercalciuria 2, 8
• Gitelman syndrome presents with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypocalciuria 8
• Familial renal magnesium wasting is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis 8

Endocrine causes include primary hyperaldosteronism, which directly increases renal magnesium excretion 1.

Inadequate Intake and Increased Requirements

• Malnutrition and starvation lead to inadequate magnesium intake 3, 5
• Alcoholism causes hypomagnesemia through reduced intake, increased gastrointestinal losses, and increased renal excretion—often presenting with the classic triad of hypomagnesemia, hypokalemia, and hypocalcemia 3, 2, 1, 5
• Increased requirements during early childhood, pregnancy, or lactation can precipitate deficiency 5
• Elderly individuals are at risk due to reduced dietary intake, polypharmacy, and age-related decline in renal function 2

Redistribution and Special Circumstances

• Refeeding syndrome in malnourished patients causes magnesium to shift intracellularly during nutritional repletion, leading to severe hypomagnesemia 2, 7, 6
• Continuous renal replacement therapy (CRRT) causes hypomagnesemia in 60-65% of patients, particularly when regional citrate anticoagulation is used, as citrate chelates ionized magnesium 4, 2
• Type 2 diabetes is associated with chronic low magnesium state through increased renal losses 9
• 22q11.2 deletion syndrome is associated with hypoparathyroidism and chronic hypomagnesemia 4, 1

Diagnostic Approach

The serum magnesium level is a poor proxy for total body stores—less than 1% of total body magnesium is found in the blood, so normal serum levels can coexist with significant intracellular depletion 4, 2, 1. Most patients with hypomagnesemia are asymptomatic, and symptoms usually do not arise until the serum magnesium concentration falls below 1.2 mg/dL 8, 6.

To determine the cause of hypomagnesemia:

• Measure fractional excretion of magnesium: The renal response to magnesium deficiency from gastrointestinal loss is to lower fractional excretion to less than 2%; a fractional excretion above 2% in a patient with normal kidney function indicates renal magnesium wasting 8
• Measure urinary calcium-creatinine ratio to distinguish between Bartter syndrome (hypercalciuria) and Gitelman syndrome (hypocalciuria) 8
• Always suspect concurrent hypomagnesemia in patients with refractory hypokalemia or hypocalcemia, as magnesium deficiency causes dysfunction of multiple potassium transport systems and impairs parathyroid hormone release 2, 1, 9, 6

Critical Clinical Pitfalls

• Never attempt to correct hypokalemia or hypocalcemia before normalizing magnesium—these electrolyte abnormalities are refractory to supplementation until magnesium is corrected 4, 1
• Never supplement magnesium in volume-depleted patients without first correcting sodium and water depletion with IV saline—secondary hyperaldosteronism will cause continued renal magnesium wasting despite supplementation 4, 2
• Establishment of adequate renal function is required before administering any magnesium supplementation—magnesium supplementation is absolutely contraindicated when creatinine clearance falls below 20 mL/min due to risk of life-threatening hypermagnesemia 8, 5