Magnesium use is indicated for a variety of diseases. This is due to the variety of effects magnesium has within the body. Administration of magnesium can be divided into FDA versus non-FDA approved. Also, magnesium is commonly used in over-the-counter products.[1][2][3][4]

Hypomagnesemia: Magnesium Concentration of Less Than 1.8 mg/dL

• Magnesium depletion can result from inadequate intake, decreased renal absorption, or decreased gastrointestinal (GI) absorption.
• Risk factors for hypomagnesemia include those with GI disease, chronic diarrhea, proton pump inhibitor therapy, alcohol use disorder, and diuretic use, both loop and thiazide. It is common to see hypomagnesemia along with low levels of other electrolytes, such as hypokalemia and hypocalcemia. In patients with refractory hypokalemia or hypocalcemia, hypomagnesemia may be the reason why. It is difficult to correct these electrolyte imbalances without first treating the magnesium imbalance. [5]
• Symptoms of hypomagnesemia correlate with the development of concurrent hypocalcemia. The signs include Trousseau sign, Chvostek sign, hyperreflexia, tremor, and muscle fasciculations. Patients may also experience vague symptoms such as nausea, vomiting, lethargy, and weakness. Severe hypomagnesemia, less than 1.25 mg/dL, can result in generalized tonic-clonic seizures. [5]

Eclampsia or Severe Pre-Eclampsia

• Magnesium is given to those with severe pre-eclampsia to prevent seizures and those with eclampsia to control seizures.[6]

Constipation

• Over-the-counter laxatives, such as Milk of Magnesia, commonly contain magnesium.

Pre-Term Labor (Off-Label Use)

• Magnesium can be given as a tocolytic to stop the progression of preterm labor. [5]

Arrhythmias (Off-Label Use)

• Administration of magnesium is recommended in certain arrhythmias such as torsades de pointes, digoxin-associated arrhythmia, ventricular arrhythmias like ventricular fibrillation, and ventricular tachycardia.[7]

Asthma: Acute Severe Exacerbation (Off-Label Use)

• Magnesium is recommended as adjunctive therapy for patients with severe, life-threatening exacerbation, or refractory cases after 1 hour of intensive conventional therapy. Magnesium allows bronchial smooth muscle relaxation, which aids in patients with status asthmatics.

Migraines: Over the Counter Supplementation 

• The use of magnesium in migraines is limited at this moment. Hypomagnesemia has been found in patients with migraines. Supplemental magnesium is considered an inexpensive, simple preventive treatment option for some. However, the dosage required is above the daily requirement, thus potentially leading to hypermagnesemia. The American Academy of Neurology and the American Headache Society have stated that magnesium therapy is “probably effective” for migraine prevention.[8]

As with other electrolytes, magnesium's role is the body is diverse and complex. The mechanism of action of magnesium is dependent on which organ system is involved.Physiology of Magnesium

• Magnesium is the fourth most common cation in the body. The majority of magnesium is intracellular; it is the second most common intracellular cation following potassium. Magnesium plays a vital role in over 300 reactions involving metabolism. It is involved with hormone receptor binding, muscle contraction, neural activity, neurotransmitter release, vasomotor tone, and cardiac excitability. It is necessary for the active transport of potassium and calcium across the cell membrane. ATP is dependent on magnesium for proper functioning.[5]

Effects of Magnesium

Gastrointestinal

• Oral magnesium promotes defecation via osmotic retention of fluids. It is also used in over-the-counter antacids. [5]

Cardiovascular

• Magnesium acts as a natural calcium channel blocker, and it is a cofactor of the Na-K-ATP pump. Magnesium helps control atrioventricular node conduction. Therefore, hypomagnesemia can cause myocardial excitability resulting in arrhythmias such as ventricular tachycardia and torsades de pointes. [5]

Neurological System

• Magnesium depresses the central nervous system (CNS) while producing anticonvulsant effects. At neuromuscular junctions, it inhibits the release of acetylcholine, thus blocking peripheral neuromuscular transmission. [5]

Reproductive System

• Magnesium is used as a tocolytic during pre-term labor. Magnesium stimulates calcium reuptake by the sarcoplasmic reticulum, which promotes relaxation of muscle and vasodilation. For pre-term labor, magnesium decreases the calcium within the uterine muscle.[5]

Musculoskeletal System

• Magnesium is a cofactor of parathyroid hormone (PTH) synthesis. With hypomagnesemia, concurrent hypoparathyroidism will ensue. Hypoparathyroidism can lead to decreased calcium and eventually leading to osteopenia or osteoporosis. [5]

Respiratory System

• Magnesium administration can cause bronchial smooth muscle relaxation. The cause of smooth muscle relaxation is unclear. It is thought to be either by inhibiting calcium, histamine, or acetylcholine release. There may also be a synergist effect with the concurrent use of beta-agonists. [5]

Hemostasis of Magnesium

• Roughly 50% of magnesium is located within the bone, 25% is within the muscle, and the remainder is in soft tissue, serum, and red blood cells (RBC). Like other electrolytes, it can be classified as ionized, protein-bound, or bound to anions. Ionized magnesium is the most biological activity.
• The intestine, bone, and kidney maintain magnesium homeostasis. Similar to calcium, magnesium is absorbed via the intestine, stored in the bone, excreted via the kidneys. Absorption of magnesium is inversely proportional to the concentration within the body; if there are low magnesium levels within the body, more magnesium will be absorbed.

Administration of magnesium can occur in various ways. Dietary intake is the main source of magnesium for a healthy individual. The recommended daily intake varies with gender and age. Green leafy vegetables, fish, legumes and whole grains are good sources of magnesium.

• Treatment can be with oral magnesium salts or with intravenous (IV) or intramuscular (IM) magnesium sulfate. IV or IM magnesium sulfate is given for severe hypomagnesemia or those who are not able to tolerate or adhere to oral therapy.
• Patients with alcohol use disorder are treated empirically to avoid hypomagnesemia. For patients with renal insufficiency, an increase in dose must be made to adjust for the increase in renal loss. [5]
• Concurrent hypokalemia or hypocalcemia should also be addressed.

Adverse reactions are associated with magnesium’s effect on the neuromuscular and cardiovascular system. Effects can include flushing, hypotension, vasodilation, and hypermagnesemia.[9]

For contraindications, factors to consider are renal function, pregnancy, and neuromuscular disease.

• It is important to assess renal function before giving magnesium. Renal failure can cause decreased magnesium excretion leading to toxicity. Closely monitor magnesium levels in patients with reduced renal function. [2]
• Patients with neuromuscular disease, such as myasthenia gravis, need to be monitored closely if they are given magnesium. Magnesium inhibits the release of acetylcholine which can cause deterioration.
• Magnesium is considered class D for pregnancy. Skeletal demineralization, hypocalcemia, and hypermagnesemia are seen with long-term use, more than 5 to 7 days, of magnesium, which is needed in pre-term labor treatment.
• There are no contraindications for magnesium supplements with other prescriptions. However, various drugs increase or decrease the concentration of either magnesium or the prescribed drug.