Definition:

• Magnesium is an essential mineral and a cofactor for hundreds of enzymes. Magnesium is involved in many physiologic pathways, including energy production, nucleic acid and protein synthesis, ion transport, cell signaling, and also has structural functions. 
• Severe magnesium deficiency can impede vitamin D and calcium homeostasis. Certain individuals are more susceptible to magnesium deficiency, especially those with gastrointestinal or renal disorders, those suffering from chronic alcoholism, and older people. 
• Inadequate dietary intakes and/or low serum concentrations of magnesium have been associated with increased risk of cardiovascular disease, osteoporosis, and metabolic disorders, including metabolic syndrome, hypertension, and type 2 diabetes mellitus. Preliminary studies have shown that magnesium improved insulin sensitivity in individuals at risk for type 2 diabetes mellitus. Randomized controlled trials have also investigated the role of magnesium supplementation in the prevention of complications following a stroke or heart surgery. 
• Magnesium sulfate is used in obstetric care for the prevention of seizures in pregnant women with preeclampsia or eclampsia. Observational studies and randomized controlled trials also support the role of magnesium in preventing brain damage in premature infants. 
• The use of magnesium supplementation is currently being explored in the management of various conditions, including hypertension, cardiovascular disease, type 2 diabetes mellitus, asthma, and pain. 
• About half of the US adult population may have insufficient magnesium intake to support nutritional adequacy. Dietary sources rich in magnesium include green leafy vegetables, unrefined grains, legumes, beans, and nuts.

Drug interactions

• Aminoglycosides (gentamicin, tobramycin, and amikacin) have been reported to cause magnesium deficiency in a high proportion of patients, apparently as a result of renal magnesium wasting.
• Amphotericin B: Treatment with amphotericin B has been reported to cause hypomagnesemia and hypokalemia.
• Angiotensin-converting enzyme (ACE) inhibitors: Angiotensin-converting enzyme (ACE) inhibitors may decrease urinary magnesium excretion. In patients taking ACE inhibitors, magnesium supplements should be used with caution and serum magnesium levels should be monitored.
• Antipsychotics (neuroleptics): Administration of various neuroleptic drugs has been reported to reduce serum magnesium levels. Drug-induced magnesium deficiency may aggravate symptoms such as depression, irritability, agitation, and hallucinations, and magnesium supplementation has been reported to improve psychiatric symptoms in some neuroleptic-treated hypomagnesemic chronic schizophrenics.
• Beta-2 agonists: Administration of the beta-2 agonists, salbutamol and rimiterol, decreased plasma magnesium and potassium levels in healthy volunteers.
• Contraceptives, oral: Some, but not all, studies found that oral contraceptives decreased plasma magnesium levels.
• Treatment with cisplatin appears to induce renal tubular magnesium wasting and causes magnesium deficiency in up to 90% of patients who do not receive prophylactic magnesium supplementation.
• Cyclosporine has been reported to cause hypomagnesemia, apparently as a result of renal magnesium wasting.
• Deficiencies of magnesium and potassium increase the toxic effects of digoxin. Treatment with digoxin may promote magnesium deficiency by increasing urinary excretion of the mineral. Many patients receiving digoxin are at increased risk of developing magnesium and potassium deficiency because of the concomitant use of diuretics and because cardiovascular disease per se is often associated with magnesium deficiency.
• Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) and loop diuretics (e.g., furosemide, bumetanide) increase urinary magnesium excretion and in some cases cause clinically significant magnesium depletion. In contrast, potassium-sparing diuretics (e.g., triamterene, spironolactone) may decrease urinary magnesium excretion.
• Glucocorticoid treatment may increase magnesium loss. Patients taking glucocorticoids may therefore benefit from increasing magnesium intake. However, co-administration of magnesium has been reported to interfere with the absorption of dexamethasone.
• Some forms of magnesium (e.g., magnesium oxide) may inhibit the absorption of levothyroxine. It is recommended that levothyroxine be taken at least 1 hour before or 2–4 hours after the ingestion of substances that interfere with its absorption.
• In a case report, magnesium supplementation reversed lithium-induced prolongation of the QTc interval on

Dosage and administration

• The usual dosage range for oral magnesium supplementation is 100–750 mg/day. With dosages toward the higher end of the range, administering magnesium in 2–3 divided doses per day may decrease the risk of developing diarrhea. Magnesium supplements are typically given with meals.