What are the causes of low magnesium levels?

Causes of Low Magnesium Levels

Low magnesium levels result from three primary mechanisms: inadequate intake, excessive gastrointestinal losses, or excessive renal losses—with medication-induced renal wasting being the most common cause in hospitalized patients. 1, 2

Gastrointestinal Causes

Gastrointestinal losses are a major contributor to magnesium depletion:

• Chronic diarrhea and high-output stomas cause substantial magnesium loss, with each liter of intestinal fluid containing approximately 100 mmol/L sodium and proportionate magnesium 1, 3
• Short bowel syndrome, particularly with resection of >60-100 cm of terminal ileum, reduces absorptive surface area and causes magnesium chelation with unabsorbed fatty acids 3
• Malabsorption syndromes including inflammatory bowel disease (13-88% prevalence of deficiency), celiac disease, and chronic pancreatitis 3, 4
• Continuous nasogastric suctioning and bowel fistulas 2
• Steatorrhea from any cause 2

Volume Depletion Creates a Vicious Cycle

A critical pitfall: volume depletion from gastrointestinal losses triggers secondary hyperaldosteronism, which increases renal magnesium excretion and creates a self-perpetuating cycle of depletion. 1, 3 This is why rehydration with IV saline must precede magnesium supplementation in these patients. 1, 3

Renal Causes

Renal magnesium wasting (fractional excretion >2% despite deficiency) occurs through multiple mechanisms:

Medications (Most Common)

• Loop diuretics (furosemide, bumetanide) and thiazide diuretics are the most frequent medication causes in hospitalized patients 1, 3, 5
• Proton pump inhibitors cause hypomagnesemia through unclear mechanisms, increasingly recognized as a major cause 1, 6, 7
• Calcineurin inhibitors (tacrolimus, cyclosporine) in transplant recipients 1, 4
• Aminoglycosides, cisplatin, pentamidine, amphotericin B, and foscarnet cause direct renal tubular magnesium wasting 1, 2

Genetic Disorders

• Bartter syndrome (loop of Henle defect): associated with hypokalemia, metabolic alkalosis, hypercalciuria 5
• Gitelman syndrome (distal tubule defect): associated with hypokalemia, metabolic alkalosis, hypocalciuria (distinguishing feature) 5
• Familial renal magnesium wasting: associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis 5

Other Renal Causes

• Post-obstructive diuresis and post-acute tubular necrosis 2
• Renal transplantation (60-65% develop hypomagnesemia on continuous renal replacement therapy) 1, 3
• Diabetic nephropathy with osmotic diuresis 2

Inadequate Intake

• Protein-calorie malnutrition and starvation 8, 2
• Prolonged IV fluids or total parenteral nutrition without magnesium supplementation 2
• Alcoholism (combination of poor intake, increased GI losses, and renal wasting) 2, 7

Redistribution and Increased Demand

• Refeeding syndrome in malnourished patients starting nutrition 3
• Acute stress states: epinephrine release, cold stress, serious injury, or extensive surgery cause acute shift into cells 8
• Pregnancy and lactation increase requirements 8
• Diabetic ketoacidosis with insulin therapy causes cellular uptake 2

Hormonal and Metabolic Feedback

Magnesium deficiency creates a self-perpetuating cycle through hormonal mechanisms:

• Impaired parathyroid hormone (PTH) secretion and activity promotes further renal magnesium loss 3
• Reduced 1,25-hydroxy-vitamin D production (secondary to low PTH) decreases jejunal magnesium absorption 3
• Secondary hyperaldosteronism from volume depletion increases renal magnesium and potassium excretion 1, 3

Diagnostic Approach to Determine Cause

Measure fractional excretion of magnesium (FEMg) and urinary calcium-creatinine ratio to distinguish renal from non-renal causes: 5

• FEMg <2% indicates appropriate renal conservation → gastrointestinal losses or inadequate intake 5
• FEMg >2% (with normal kidney function) indicates renal magnesium wasting 5
• Hypercalciuria suggests Bartter syndrome, loop diuretics, or familial renal wasting 5
• Hypocalciuria suggests Gitelman syndrome or thiazide diuretics 5

24-hour urinary magnesium measurement is ideal for patients with ongoing losses (e.g., jejunostomy) and better reflects total body status than serum levels. 4

Critical Clinical Pitfall

Normal serum magnesium does not exclude deficiency—less than 1% of total body magnesium is in blood, with the remainder stored in bone, soft tissue, and muscle. 3, 4 Symptoms typically don't appear until serum magnesium falls below 1.2 mg/dL. 5