Does lithium therapy increase or decrease magnesium levels?

Effect of Lithium on Magnesium Levels

Lithium therapy increases magnesium levels in the serum, with elevated levels persisting throughout the 24-hour period after administration. 1

Mechanism and Evidence

• Lithium administration leads to increased serum magnesium concentration, which has been consistently demonstrated in clinical studies 1, 2
• The increase in magnesium levels occurs throughout the entire 24-hour period after lithium administration, suggesting a sustained effect 1
• Lithium treatment also increases urinary magnesium excretion during daytime hours, indicating altered magnesium handling by the kidneys 1, 2
• These changes in magnesium homeostasis appear to be independent of plasma aldosterone levels 2

Clinical Implications

• Increased magnesium levels may have both beneficial and potentially concerning effects:

  • Magnesium has been associated with benefit in treating torsades de pointes and ventricular arrhythmias 3
  • In patients with heart failure, hypomagnesemia is associated with more frequent ventricular arrhythmias, and magnesium supplementation can significantly reduce premature ventricular contractions 3
  • Monitoring magnesium levels is important in cancer patients and other clinical populations 3

• Despite increased urinary magnesium excretion, lithium treatment produces an overall positive magnesium balance in the body 4

  • This effect on magnesium balance may diminish with long-term lithium treatment, while effects on calcium and phosphate persist 4

Monitoring Recommendations

• Regular monitoring of magnesium levels is advisable in patients on lithium therapy, particularly during the initial treatment phase 1, 4

• Normal serum magnesium levels are typically defined as ≥0.70 mmol/l, with hypomagnesemia classified as:

  • Mild: between 0.76 and 0.64 mmol/l
  • Moderate: between 0.63 and 0.40 mmol/l
  • Severe: <0.40 mmol/l 3

• Particular attention should be paid to patients with:

  • Cardiac conditions, as magnesium plays an important role in cardiac electrophysiology 3
  • Kidney disease, as both lithium and altered magnesium levels can impact renal function 3
  • Concurrent medications that may affect magnesium levels (e.g., diuretics, proton pump inhibitors) 3

Animal Studies Support

• Animal studies have shown varied effects of lithium on magnesium:
  • Some studies show increased serum magnesium levels throughout lithium administration 5
  • Other research indicates lithium may decrease magnesium concentration in tissues like liver, kidney, brain, and femoral muscle after three weeks of administration 5
  • More recent animal research suggests that selenium co-administration may help mitigate some of lithium's effects on mineral homeostasis 6

In conclusion, lithium therapy increases serum magnesium levels while also increasing urinary magnesium excretion. This effect should be considered when monitoring patients on lithium therapy, especially those with conditions where magnesium status is clinically relevant.