Magnesium

Overview

Magnesium is essential to many metabolic reactions, including lipid metabolism, amino acid activation, the glycolytic cycle, and the citric acid cycle. Its primary function is as an enzyme cofactor, thus producing energy, synthesizing lipids and proteins, regulating calcium flow and parathyroid hormone (PTH) secretion, forming urea, and relaxing muscles. Vitamin B₆ works with magnesium in many enzyme systems and assists in the body's accumulation of magnesium.

Dietary intake is generally thought to be insufficient, although clinical depletion is rare in Americans. One problem in determining actual dietary intake is that a number of foods have not been thoroughly analyzed, and laboratory analysis of magnesium contents often do not agree with food composition tables. However, inadequate dietary intake is not usually the sole cause of deficiency. Proper balance also depends on efficient intestinal and renal absorption and excretion. Risk factors for depletion include gastrointestinal disorders, such as inflammatory bowel disease, pancreatitis, fatty acid malabsorption, ileal dysfunction, and gastrointestinal infections (viral, bacterial, or protozoan) that result in malabsorption or vomiting and diarrhea; renal dysfunction with excessive urine loss; nephrotoxic and diuretic drugs; and endocrine disorders, such as hyperthyroidism, diabetes mellitus, and hyperparathyroidism with hypercalcemia.

Magnesium deficiency most severely affects cardiovascular, neuromuscular, and renal tissues, and has been linked to agitation, anemia (hemolytic), anorexia, anxiety, ataxia, cardiac arrhythmias, confusion, Crohn's disease, depression, disorientation, fasciculations, hallucinations, heart disease, heart attacks resulting from coronary artery spasm, heart failure from defibrillation, hyperactivity, hypertension, insomnia, irritability, kidney stones, muscle pains, muscular weakness, nausea and vomiting, nervousness, nystagmus, neuromuscular irritability, organic brain syndrome, paresthesias, pronounced startle response, restlessness, seizures, sonophobia, tachycardia, increased triglyceride levels, and vertigo.

Increased levels of magnesium sulfate from treatment of preeclampsia or other problems of pregnancy have been associated with significantly reduced risks of cerebral palsy and possibly mental retardation in very-low-birth-weight infants; however, a preliminary report of a recent study is contradictory. Use of magnesium to prevent premature labor at less than 34 weeks' gestation in women who are not preeclamptic is disputed. In a recent study, use of MgSO4 (magnesium sulfate) as a randomized treatment for such women was associated with higher infant mortality, and the study was stopped.

Dietary Sources

• Rich sources: tofu, legumes, whole grains, green leafy vegetables, wheat bran, Brazil nuts, soybean flour, almonds, cashews, blackstrap molasses, pumpkin and squash seeds, pine nuts, black walnuts
• Good sources: peanuts, whole wheat flour, oat flour, beet greens, spinach, pistachio nuts, shredded wheat, bran cereals, oatmeal, bananas, baked potatoes (with skin)
• Many herbs, spices, and seaweeds supply magnesium (e.g., agar seaweed, coriander, dill weed, celery seed, sage, dried mustard, basil, cocoa powder, fennel seed, savory, cumin seed, tarragon, marjoram, poppy seed)

Constituents/Composition

The magnesium ion (Mg²⁺) forms complexes with many types of organic molecules. It binds with phosphates, and weakly with carboxylates and hydroxyls. Magnesium stabilizes many ribonucleotides and deoxyribonucleotides, inducing important physicochemical changes.

Commercial Preparations

Supplementary magnesium is available in several varieties of salts.

• Magnesium citrate, magnesium gluconate, and magnesium lactate are more soluble and bioavailable than magnesium oxide.
• Magnesium chloride is more soluble than magnesium oxide, gluconate, citrate, hydroxide, and sulfate, and does not require stomach acid for solubility, but its use is limited due to its hygroscopic properties.
• Magnesium hydroxide (milk of magnesia)
• Magnesium sulfate (Epsom salts)

Therapeutic Uses

• Cardiovascular: to prevent atherosclerosis and myocardial infarction, reduce high blood pressure, treat angina, prevent strokes, improve cholesterol and triglyceride levels
• Cardiac arrhythmia: to inhibit triggered beats arising from early afterdepolarizations, treat congenital long QT syndrome (torsade de pointes)
• Lung function: to halt acute asthma attacks and acute exacerbations of chronic obstructive pulmonary disease, reduce recurrence of apnea in infants
• Diabetes: to improve insulin action and glucose metabolism, decrease insulin need, ease diabetic blood pressure
• Hearing: to prevent noise-induced hearing loss
• Glaucoma: to improve peripheral circulation and visual field
• Fatigue: to improve sleep, restore normal energy level
• Mental health: to reduce nervousness, anxiety, and depression
• Migraines: to treat food allergy–induced migraine headaches using ionized magnesium
• Pregnancy: to lower blood pressure, prevent preeclampsia and eclampsia
• Renal: to prevent kidney stones
• Menstruation and premenstrual syndrome (PMS): to relieve menstrual cramps, irritability, fatigue, depression, and water retention

Dosage Ranges and Duration of Administration

Recommendations for adequate magnesium intake promulgated by the Food and Nutrition Board of the Institute of Medicine in 1997:

Infants:

• Birth to 6 months: 30 mg/day
• 6 months to 1 year: 75 mg/day

Children:

• 1 to 3 years: 80 mg/day
• 4 to 8 years: 130 mg/day
• 9 to 13 years: 240 mg/day

Adolescents:

• 14 to 18 years (boys): 410 mg/day
• 14 to 18 years (girls): 360 mg/day

Adults:

• 19 to 30 years (men): 400 mg/day
• 19 to 30 years (women): 310 mg/day
• 31+ years (men): 420 mg/day
• 31+ years (women): 320 mg/day

Pregnant women: 

• Up to 18 years: 400 mg/day
• 19 to 30 years: 350 mg/day
• 31 to 50 years: 360 mg/day

Lactating women:

• Up to 18 years: 360 mg/day
• 19 to 30 years: 310 mg/day
• 31 to 50 years: 320 mg/day

These represent significant increases for adolescents and adults from the recommended dietary allowance promulgated by the National Academy of Sciences in 1989. Supplementation should be in small doses three to six times throughout the day with a full glass of water to reduce chance of diarrhea.

Side Effects/Toxicology

Nutritional toxicity is rare. Symptomatic magnesium excess may occur in patients with gastrointestinal disorders and renal insufficiency when magnesium-based laxatives or antacids are taken. With increasing hypermagnesemia, the effects are lowered blood pressure, nausea, vomiting, brachycardia, and urinary retention (serum levels as low as 3 mEq/L), mental status changes, electrocardiographic changes (longer PR and QT intervals), central nervous system depression, severe respiratory depression, coma, and cardiac arrest (at or near 15 mEq/L).

Warnings/Contraindications/Precautions

Individuals with severe heart disease (such as high-grade atrioventricular block) should take magnesium only on the advice of their physician.

Individuals with kidney disease should not take more than 3,000 mg per day.

Overuse of magnesium hydroxide (milk of magnesia) as a laxative or antacid, or magnesium sulfate (Epsom salts) as a laxative and tonic, may cause deficiencies of other minerals or lead to toxicity.

Interactions

Alendronate; Tiludronate

Magnesium salts or magnesium-containing antacids interfere with absorption of tiludronate, a bisphosphonate drug similar to alendronate (PDR 1998). This interaction has not been reported with alendronate. However, calcium and other minerals should be taken at least two hours before or after alendronate administration to minimize interference with the absorption of the drug.

Calcium Channel Blockers

Magnesium sulfate may interact with calcium channel blockers and decrease cardiac function, particularly in pregnant women (Davis et al. 1997). However, another report indicates that using magnesium-enriched salt as a substitute for sodium enhances the cardiovascular effects derived from the combination of low dose felodipine and ramipril in rats (Mervaala et al. 1998).

Digoxin

Hypomagnesemia increases the risk of cardiac glycoside toxicity (Whang et al. 1985). Digoxin decreases the reabsorption of magnesium from the kidneys, which leads to increased excretion in the urine (Crippa et al. 1999). However, adequate amounts of magnesium enhance the antiarrhythmic activity of this drug, particularly by diminishing the ventricular response during atrial fibrillation. One case report describes a patient with digoxin toxicity associated with ventricular tachycardia (Kinlay and Buckley 1995). Treatment with magnesium sulfate (two doses of 10 mmol IV) resulted in a more stable junctional rhythm. Normal magnesium levels should be maintained during digoxin treatment.

Estrogens; Progestins

In a controlled clinical study with 25 healthy women at or past menopause and 15 healthy women of child-bearing age, serum levels of magnesium were inversely related to the serum level of estrogen in both groups (Muneyyirci-Delale et al. 1999). Another group of postmenopausal women treated with conjugated estrogens and medroxyprogesterone for one year had reduced urinary excretion of zinc and magnesium (Herzberg et al. 1996). The clinical significance of this interaction is unknown.

Glipizide; Glyburide

Concomitant ingestion of magnesium hydroxide with both glipizide and glyburide has been shown to increase the rate and extent of absorption of these medications (Kivisto and Neuvonen 1991; Lehto et al. 1996; Neuvonen and Kivisto 1994). The faster rate of absorption may result in increased early insulin and glucose responses (Kivisto and Neuvonen 1991). This effect was observed with magnesium hydroxide antacids, not dietary supplements.

Insulin Preparations

Supplementation with magnesium in patients with type II diabetes mellitus enhances insulin sensitivity and secretion (De Valk 1999). In rats predisposed to type II diabetes, supplementation with oral magnesium diminished the progression of the disease.

Nitrofurantoin

Magnesium salts decrease the rate and extent of absorption of nitrofurantoin (Naggar and Khalil 1979). It is not known if dietary supplements containing magnesium will have a similar effect on nitrofurantoin absorption.

Penicillamine

Penicillamine can inactivate magnesium, particularly when high doses are used over a long period of time (Seelig 1982). However, supplementation with magnesium and other nutrients in over 50 patients on penicillamine therapy for the treatment of autoimmune disorders resulted in fewer adverse reactions than those commonly experienced in patients treated with the drug alone.

Quinolone Antibiotics

Quinolone antibiotics form chelates with metal cations, such as aluminum, magnesium, calcium, iron, zinc, copper, and manganese (Kara et al. 1991; Li et al. 1999), which significantly reduces the absorption of these medications (Balfour and Wiseman 1999; Brouwers 1992; Campbell and Hasinoff 1991). Dietary supplements and antacids containing aluminum and magnesium should be taken two to four hours before or after administration of these antibiotics (Hines Burnham et al. 2000).

Tetracycline Derivatives

Tetracyclines form chelates with divalent and trivalent cations, including iron, aluminum, magnesium, and calcium (Neuvonen 1976). It has been reported that these chelates are poorly soluble and can significantly reduce the absorption and efficacy of tetracyclines (Hines Burnham et al. 2000; Neuvonen 1976). However, one study reports that magnesium-tetracycline complexes may be more bioavailable than uncomplexed tetracycline due to a higher degree of membrane diffusion (Lambs et al. 1984).

References

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