What Causes Hypermagnesemia
Hypermagnesemia results from either excessive magnesium intake (particularly from magnesium-containing medications like laxatives and antacids) or impaired renal excretion, with the combination of both factors creating the highest risk for severe toxicity. 1
Primary Mechanisms
The kidney normally has enormous capacity to excrete magnesium, filtering 80% of serum magnesium at the glomerulus while excreting only 3% in urine. 1 Therefore, hypermagnesemia typically requires one or both of the following:
1. Excessive Magnesium Intake
- Magnesium-containing laxatives are the most common culprit, particularly magnesium oxide (MgO) and magnesium hydroxide (milk of magnesia). 2, 3
- Over-the-counter antacids containing magnesium hydroxide (such as Maalox) can cause severe toxicity when used frequently. 4, 5
- The small intestine normally absorbs only 30-50% of magnesium intake under basal conditions, but absorption increases with certain gastrointestinal conditions. 1
- Magnesium oxide doses of 1.5 g/day are commonly used therapeutically, though lower doses of 500 mg to 1 g daily are typical in clinical practice. 6
2. Impaired Renal Excretion
- Renal insufficiency is the most critical risk factor, as hypermagnesemia rarely occurs with normal kidney function due to the kidney's large excretory capacity. 1, 3
- Acute or chronic kidney disease dramatically reduces magnesium clearance, and magnesium-containing preparations should be avoided when creatinine clearance is <20 mg/dL. 6, 7
- End-stage renal disease patients are at particularly high risk, even with modest magnesium intake. 2
3. Gastrointestinal Dysfunction
- Bowel obstruction or severe constipation increases magnesium absorption time in the intestinal lumen, allowing greater systemic absorption. 7, 4, 5
- Sigmoid volvulus and other mechanical obstructions can lead to prolonged mucosal contact with magnesium-containing products. 4
- The osmotic gradient created by nonabsorbed magnesium in the GI tract can paradoxically increase absorption when transit is impaired. 6
High-Risk Clinical Scenarios
Elderly Patients with Multiple Risk Factors
- Age >65 years combined with any degree of renal dysfunction creates substantial risk. 3
- Cognitive impairment from dementia or cerebrovascular events prevents patients from reporting early symptoms. 3
- Multiple comorbidities in elderly patients compound risk even with normal baseline renal function. 7
Patients with Normal Renal Function
Hypermagnesemia can occur despite normal kidney function when: 5
- Massive magnesium intake overwhelms renal excretory capacity
- Concurrent bowel obstruction or motility disorders increase absorption
- Unsupervised use of over-the-counter products leads to excessive dosing
Critical Pitfalls to Avoid
- Underestimating OTC medication risk: Magnesium hydroxide and oxide are widely available without prescription, leading to unsupervised use and dose escalation. 2, 4
- Failure to monitor serum magnesium: Most patients taking magnesium-containing laxatives never have their magnesium levels checked, despite being at risk. 3
- Assuming normal renal function is protective: Even mild renal impairment significantly increases risk, and acute kidney injury can develop rapidly in elderly patients. 5
- Missing gastrointestinal dysfunction: Constipation itself may be a sign of impaired motility that increases magnesium absorption. 4
Prevention Strategies
The American Society of Nephrology recommends avoiding magnesium-containing preparations in patients with acute or chronic kidney disease, bowel obstruction, severe constipation, and elderly patients with multiple comorbidities. 7 When magnesium-containing laxatives must be used, ensure adequate renal function and avoid prolonged use. 7 Regular serum magnesium monitoring is essential for high-risk patients after initial prescription or dose increases. 3