Magnesium & Disease Treatment

The use of pharmacologic doses of magnesium to treat specific diseases is discussed below. Although many of the studies cited utilized supplemental magnesium in doses considerably higher than the tolerable upper level of intake (UL) of 350 mg/day recommended by the Food and Nutrition Board for healthy individuals, it is important to note that they were all conducted under medical supervision. Because of the potential risk of high doses of supplemental magnesium, especially in the presence of impaired kidney function, any trial of magnesium supplementation for disease treatment higher than the UL should be conducted under medical supervision.

Hypertension (high blood pressure)

The results from intervention studies using magnesium supplements to treat hypertension have been conflicting. In uncontrolled trials, hypertensive patients on thiazide diuretics experienced decreases in blood pressure when given magnesium supplements. In general, placebo-controlled trials have not been supportive of a blood pressure-lowering effect for magnesium supplementation. Modest but significant blood pressure-lowering effects have been reported in two placebo-controlled studies using 485 mg/day of supplemental magnesium in individuals with mild to moderate hypertension for at least 2 months, but a number of other studies failed to find any blood pressure-lowering effects with magnesium supplementation. One double blind placebo-controlled study found magnesium supplementation to be beneficial in lowering the blood pressure of individuals with low magnesium status, suggesting that oral magnesium supplementation may be helpful in hypertensive individuals who are depleted of magnesium due to chronic diuretic use, inadequate dietary intake, or both.

Preeclampsia-eclampsia (toxemia of pregnancy)

Preeclampsia-eclampsia is a disease that is unique to pregnancy, and may occur anytime after 20 weeks of pregnancy and up to 6 weeks after birth. Approximately 7% of pregnant women in the U.S. develop preeclampsia-eclampsia. Preeclampsia is defined as the presence of elevated blood pressure, protein in the urine, and severe swelling (edema) during pregnancy. Eclampsia occurs with the addition of seizures to the above triad of symptoms. Approximately 5% of women with preeclampsia go on to develop eclampsia, which is a significant cause of maternal death. For many years, high dose intravenous magnesium sulfate has been the treatment of choice for preventing eclamptic seizures that may occur in association with preeclampsia-eclampsia late in pregnancy or during labor. Magnesium is believed to relieve cerebral blood vessel spasm, increasing blood flow to the brain.

Cardiovascular Diseases

Myocardial infarction (heart attack): Results of a meta-analysis of randomized placebo-controlled trials indicated that an intravenous (IV) magnesium infusion given early after suspected myocardial infarction (MI) could decrease the risk of death. The most influential study included in the meta-analysis was a randomized placebo-controlled trial in 2,316 patients that found a significant reduction in mortality (7.8% vs. 10.3% in the placebo group) in those patients who were given intravenous magnesium sulfate within 24 hours of suspected myocardial infarction. Follow up from one to five years after treatment revealed that the mortality from cardiovascular disease was 21% lower in the magnesium treated group. However, a larger placebo-controlled trial that included more than 58,000 patients found no significant reduction in 5-week mortality in those patients treated with intravenous magnesium sulfate within 24 hours of suspected myocardial infarction, resulting in controversy regarding the efficacy of the treatment. A more recent survey of the treatment of more than 173,000 patients with acute MI in the U.S. found that only 5% were given IV magnesium in the first 24 hours after the MI, and that mortality was higher in those patients treated with IV magnesium. Thus, the use of IV magnesium sulfate in the therapy of acute MI remains controversial.

Endothelial dysfunction: Vascular endothelial cells line the walls of arteries where they are in contact with the blood that flows through the circulatory system. Normally functioning vascular endothelium promotes vasodilation when needed, for example, during exercise, and inhibits the formation of blood clots. With cardiovascular disease, arteries develop atherosclerotic plaque. Atherosclerosis impairs normal endothelial function, increasing the risk of vasoconstriction and clot formation, which may lead to a heart attack or a stroke. Recent research indicates that pharmacologic doses of oral magnesium may improve endothelial function in individuals with cardiovascular disease. A randomized double blind placebo-controlled trial in 50 men and women with stable coronary artery disease found that 6 months of oral magnesium supplementation (730 mg/day) resulted in a 12% improvement in flow-mediated vasodilation compared to placebo. In other words, the normal dilation response of the brachial (arm) artery to increased blood flow was improved. Magnesium supplementation also resulted in increased exercise tolerance during an exercise stress test compared to placebo. In another study of 42 patients with coronary artery disease who were already taking low dose aspirin (an inhibitor of platelet aggregation), 3 months of oral magnesium supplementation (800-1,200 mg/day) improved some laboratory measures of the propensity of their blood to form clots. Although preliminary, these studies suggest that magnesium may be of benefit in improving endothelial function in individuals with cardiovascular diseases.

Diabetes mellitus

Magnesium depletion is commonly associated with both insulin dependent (IDDM) and non-insulin dependent (NIDDM) diabetes mellitus. Between 25% and 38% of diabetics have been found to have decreased serum levels of magnesium (hypomagnesemia). One cause of the depletion may be increased urinary loss of magnesium as a result of the increased urinary excretion of glucose that accompanies poorly controlled diabetes. Magnesium depletion has been shown to increase insulin resistance in a few studies and may adversely affect blood glucose control in diabetes. Dietary magnesium supplements (400 mg/day) were found to improve glucose tolerance in elderly individuals. Presently, there is little scientific evidence supporting routine magnesium supplementation for diabetics. However, a few studies suggest that correcting magnesium depletion in elderly and diabetic individuals may improve glucose tolerance.

Osteoporosis

Although decreased bone mineral density (BMD) is the primary feature of osteoporosis, other osteoporotic changes in the collagenous matrix and mineral components of bone may result in bones that are brittle and more susceptible to fracture. Magnesium comprises about 1% of bone mineral and is known to influence both bone matrix and bone mineral metabolism. As the magnesium content of bone mineral decreases, bone crystals become larger and more brittle. Some studies have found lower magnesium content and larger bone crystals in bones of osteoporotic women compared to non-osteoporotic controls. Inadequate serum magnesium levels are known to result in low serum calcium levels, resistance to parathyroid hormone, and resistance to some of the effects of vitamin D, all of which can lead to increased bone loss (see Calcium). A recent study of over 900 elderly men and women found higher dietary magnesium intake to be associated with increased bone mineral density at the hip in both men and women. However, because they are present in many of the same foods the effect of dietary magnesium could not be separated from the effect of dietary potassium. Few studies have addressed the effect of magnesium supplementation on bone mineral density or osteoporosis in humans. In a small group of postmenopausal women with osteoporosis, magnesium supplementation of 750 mg/day for the first 6 months followed by 250 mg/day months for 18 more months resulted in increased BMD at the wrist after one year, with no further increase after two years of supplementation. Another study found that supplementation with 500 mg/day of magnesium and 600 mg/day of calcium in postmenopausal women who were also taking estrogen replacement therapy and a multivitamin resulted in increased bone density at the heel compared to postmenopausal women receiving only estrogen replacement therapy. Presently, the potential for increased magnesium intake to influence calcium and bone metabolism warrants more research with particular attention to its role in the prevention and treatment of osteoporosis.

Migraine headaches

Individuals who suffer from recurrent migraine headaches have been found to have lower intracellular magnesium levels (demonstrated in both red blood cells and white blood cells) than individuals who do not experience migraines. Oral magnesium supplementation has been shown to increase intracellular magnesium levels in individuals with migraine, leading to the hypothesis that magnesium supplementation might be helpful in decreasing the frequency and severity of migraine headaches. Two placebo-controlled trials have demonstrated modest decreases in the frequency of migraine headaches after supplementation with 600 mg/day of magnesium compared to placebo. However, another placebo-controlled study found no benefit compared to placebo of 485 mg/day of magnesium in reducing the frequency of migraine headaches. Although no serious adverse effects were noted during these migraine headache trials, the investigators did note adverse effects such as diarrhea and gastric (stomach) irritation in about 20% to 40% of the individuals taking the magnesium supplements.

Asthma

Several clinical trials have examined the effect of intravenous magnesium infusions on acute asthma attacks. One double blind placebo-controlled trial in 38 adults, who did not respond to initial treatment in the emergency room, found improved lung function and decreased likelihood of hospitalization when IV magnesium sulfate was infused compared to a placebo. However, in another placebo-controlled double blind study in 48 adults IV infusion of magnesium sulfate did not improve lung function in patients experiencing an acute asthma attack. Measurements of serum and red blood cell levels of magnesium have not been found to be lower in asthmatic patients than nonasthmatic individuals even during acute asthmatic attacks. At present, available evidence indicates that intravenous magnesium infusion may have a minimal role in the treatment of acute asthma, but oral magnesium supplementation is of no known value in the management of chronic asthma.

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