What are the mechanisms of magnesium loss?

Mechanisms of Magnesium Loss

Magnesium is lost through three primary pathways: gastrointestinal losses (both malabsorption and secretory losses), renal losses (either primary or secondary to hormonal dysregulation), and drug-induced losses through both routes. 1

Gastrointestinal Losses

Direct Intestinal Losses

• High-output gastrointestinal secretions result in substantial magnesium depletion, as stomal fluid contains approximately 100 mmol/L of sodium along with significant magnesium concentrations 1
• Patients with jejunostomy lose magnesium directly through stomal output, particularly when output exceeds 2 L/24 hours 1
• Severe diarrheal states and gastrointestinal fistulae cause direct magnesium losses through intestinal secretions 2

Malabsorption Mechanisms

• Chelation with unabsorbed fatty acids is a critical mechanism—when fat malabsorption occurs (particularly after resection of >60-100 cm of terminal ileum), unabsorbed long-chain fatty acids bind to intraluminal magnesium, rendering it unavailable for absorption 1
• Reduced absorptive surface area after intestinal resection directly impairs magnesium absorption capacity 1
• Rapid intestinal transit in patients with jejunostomy prevents adequate contact time for magnesium absorption 1

Renal Losses

Secondary Hyperaldosteronism (Most Important Mechanism)

• Sodium and water depletion triggers secondary hyperaldosteronism, which increases renal retention of sodium at the expense of both magnesium and potassium—this creates a vicious cycle where the more sodium-depleted the patient becomes, the more aldosterone is secreted, and the more magnesium is wasted renally 1, 3
• When hyperaldosteronism is present, the protective renal mechanism of reducing fractional excretion of magnesium to less than 2% is overridden, and magnesium continues to be lost in urine despite total body depletion 3, 4
• This mechanism explains why rehydration to correct secondary hyperaldosteronism is the crucial first step before magnesium supplementation—failure to correct volume depletion first will result in continued magnesium losses despite supplementation 1, 3

Direct Renal Wasting

• Loop diuretics inhibit sodium chloride transport in the ascending loop of Henle, causing renal magnesium wasting 4, 5
• Thiazide diuretics inhibit sodium chloride cotransporter in the distal convoluted tubule, also causing renal magnesium wasting 4
• Proton-pump inhibitors can cause magnesium loss through unclear mechanisms 5
• Gentamicin therapy directly causes renal magnesium wasting 2

Hypomagnesemia-Induced Renal Losses (Self-Perpetuating Cycle)

• Hypomagnesemia reduces the secretion and function of parathormone, which directly increases renal magnesium loss 1
• This parathormone dysfunction indirectly worsens magnesium loss by reducing the manufacture of 1,25 hydroxy-vitamin D, which normally increases jejunal magnesium absorption 1

Drug-Induced Losses

• Diuretics cause both increased renal excretion and potential gastrointestinal losses 5, 2
• Alcohol causes magnesium depletion through multiple mechanisms including malabsorption and increased renal losses 6, 7
• Chemotherapy can reduce magnesium intake through anorexia and cause direct losses 7, 2

Clinical Context and Pitfalls

The most common pitfall is attempting to correct magnesium without first addressing volume depletion and hyperaldosteronism—this will fail because ongoing renal losses will exceed supplementation 3. The correct sequence is: (1) administer intravenous saline to restore sodium and water balance, which reduces aldosterone secretion and stops renal magnesium wasting; (2) then initiate magnesium supplementation 3.

In patients with short bowel syndrome, the combination of direct intestinal losses, malabsorption due to fatty acid chelation, and secondary hyperaldosteronism from volume depletion creates a particularly severe magnesium deficit 1. These patients require aggressive rehydration first, followed by high-dose magnesium supplementation (12-24 mmol daily), preferably given at night when intestinal transit is slowest 1, 3.

Most magnesium salts are poorly absorbed and may paradoxically worsen diarrhea or stomal output, so magnesium oxide should be used in divided doses with monitoring for worsening gastrointestinal symptoms 3, 8.