The Magnesium Report
Clinical, Research, and Laboratory News for Cardiologists
December 1999
Oral Magnesium for Cardiac Arrhythmias: Current Clinical Perspective
EZRA A. AMSTERDAM, MD
The relationship between magnesium and the heart—specifically, the influence of low levels of magnesium on cardiac rhythm—has been studied for more than 60 years. Magnesium has an essential role in normal cardiac electrophysiology, and inadequate concentrations of this cation contribute to a variety of cardiac arrhythmias. Most important among these are ventricular tachycardia (VT), ventricular fibrillation (VF), long QT and torsades de pointes, and atrial and ventricular premature beats (Table 1), all factors in sudden cardiac death.Magnesium deficit in the setting of congestive heart failure (CHF), which affects some 4 million Americans, and in the setting of hypertension, which affects more than 30 million, is particularly important and worrisome.
Clinical magnesium deficiencies and subclinical magnesium deficits have a number of causes (Table 2) and appear to promote cardiac electrical instability by affecting ion transport across cell membranes.
Magnesium and CHF
Between 400 000 and 700 000 patients are newly diagnosed with CHF every year. Patients with CHF have a very high propensity for ventricular arrhythmias, which are an important cause of death in this group. In fact, a majority of patients referred for the treatment of CHF have ambient ventricular arrhythmias, which are frequently linked to hypomagnesemia.
In patients with CHF, magnesium deficiencies may develop as a result of increased urinary excretion, which is a consequence of diuretic and digoxin therapy, and of elevated circulating levels of catecholamines, aldosterone, and vasopressin. Treatment with diuretics, except for those that spare potassium and magnesium, increases urinary magnesium excretion by 25% to 400%. This increased magnesium loss in patients with CHF impairs their response to digitalis therapy, necessitating as much as twice the amount of digitalis as patients with normal serum magnesium levels to control the ventricular rate in atrial fibrillation. Magnesium administration can reduce the amount of digitalis required in these patients and, thus, decrease the risk of its toxicity.
Clinical Hypomagnesemia
Hypomagnesemia is among the most common electrolyte disorders. Low serum magnesium has been reported in 7% to 11% of hospitalized patients, in approximately 40% of patients with hypokalemia, and in over one third of patients with CHF who use diuretics. Elderly hypertensive men treated with diuretics have a higher frequency of coronary artery disease and arrhythmias than those not treated or receiving nondiuretic therapy for hypertension.
Despite the prevalence and potential seriousness of magnesium deficit, however, the frequent absence of serum magnesium analysis from routine electrolyte panels means the diagnosis is too often delayed— or missed entirely. To complicate matters, even though magnesium status is most commonly determined by measuring serum levels directly, less than 1% of the total body magnesium is in the serum. This is because magnesium is primarily an intracellular ion, and intracellular levels do not correlate with serum levels. Moreover, intracellular levels are difficult and expensive to measure, so it is necessary to suspect magnesium deficit based on clinical settings (eg, diuretic use, poor nutrition, or both).
Role of Magnesium Replacement
Arrhythmias associated with magnesium depletion can often be minimized or eliminated with magnesium replacement. Studies that have examined the effects of pharmacologic doses of intravenous (IV) magnesium on heart rate and rhythm suggest that sudden death from arrhythmias might be reduced by maintaining adequate magnesium levels. Thus, in patients with low magnesium levels, administration of magnesium (parenterally or orally) should be considered.
Parenteral use of magnesium boasts a long history in the treatment of arrhythmias. Candidates for IV magnesium therapy include patients with ventricular tachyarrhythmias that have been incompletely responsive or refractory to conventional antiarrhythmic treatment. These patients may have CHF, idiopathic dilated cardiomyopathy, acute myocardial infarction, or have undergone cardiac surgery. Infusions of magnesium have also been suggested as a preferred therapy for patients with torsades de pointes.
Parenteral Magnesium: The Data. In 1994, Sueta and colleagues reported on 30 arrhythmic patients with symptomatic CHF who were treated acutely with IV magnesium (0.3 mEq/kg as a bolus over 10 minutes followed by a maintenance infusion of 0.08 mEq/kg/h for 24 hours). This therapy doubled serum magnesium concentrations after 24 hours. The treatment also significantly decreased total ventricular ectopy, couplets, and episodes of VT as well as the rate of the most rapid episode of VT.
A prospective evaluation of the electrophysiologic and antiarrhythmic effects of parenteral magnesium was conducted in patients with reentrant paroxysmal supraventricular tachycardia. In this 1990 study, Sager and associates administered IV elemental magnesium and found that tachycardia cycle length increased from 319 ± 39 msec to 348 ± 43 msec, reflecting a decrease in ventricular tachycardia rate.
As far back as the 1930s, arrhythmias precipitated by digitalis were found to be reversed by injections of magnesium. Patients with digitalis-related paroxysmal tachycardia and bidirectional VT had long lasting responses to IV magnesium in a study by Szekely and colleagues in 1951. In a 1984 report of a potentially fatal case of massive digitalis intoxication and recurrent VF, French and associates reported suppression of VF in response to IV magnesium after lidocaine or phenytoin were ineffective.
A diagnosis of hypomagnesemia is not required before parenteral magnesium therapy is given. Magnesium administration can—and often should—be considered for patients with symptomatic or life-threatening arrhythmias even when serum magnesium levels are normal. In patients with apparently normal serum digoxin and magnesium levels but low lymphocyte levels of magnesium and potassium, VT responded to parenteral magnesium therapy, as reported by Cohen and associates in 1993.
Oral Magnesium: Clinical Studies. Investigations have shown that the use of oral magnesium may decrease the risk of arrhythmias associated with cardiac disease and medication use. For example:
• In 1978, Davis and coworkers administered oral magnesium tablets to patients with long QT (LQT). Subjects experienced statistically significant declines in QTc and QUc intervals, as well as normalization of ST-segment and T-wave abnormalities.
• In 1993, Bashir and colleagues studied patients with stable CHF secondary to coronary artery disease who were taking long-term loop diuretics. Oral magnesium markedly decreased the incidence of asymptomatic ventricular arrhythmias. The frequency of ventricular couplets declined by 52%, and nonsustained VT episodes declined by 24%.
• In 1981, in a controlled study by Krasner and associates, patients scheduled for mitral valve replacement received either oral magnesium or placebo before surgery. Effects on QTc intervals became significant after 4 days of oral magnesium supplementation, and only patients receiving placebo developed LQT and arrhythmias postoperatively.
Magnesium Plus Potassium. Because both magnesium and potassium play roles in preserving electrical stability of the heart, researchers have studied the effect of increasing the oral intake of both electrolytes.
• A 1989 Finnish study by Kohvakka and colleagues examined the effects of magnesium and potassium on hydrochlorothiazide treated patients with chronic compensated CHF. Patients received either an oral potassium supplement or an oral magnesium-potassium combination in a double-blind, crossover protocol. Potassium chloride alone did not correct hypokalemia. Treatment with the combination of magnesium and potassium increased serum concentrations of both ions significantly; this trend continued (although to a lesser degree) during 4 weeks of observation.
• A 1997 study by Zehender and associates evaluated oral magnesium and potassium supplements in patients with stable, frequent ventricular arrhythmias to determine the potential antiarrhythmic effects of increasing the daily recommended minimal dietary intake of magnesium and potassium by 50%. Compared to placebo pretreatment, 3 weeks of supplementation with oral magnesium (6 mmol/d) and potassium (12 mmol/d) produced a median 17.4% decline in premature beats. The suppression rate was 2.4 times greater in the treatment phase compared to placebo.
The investigators concluded that the simplicity, cost-effectiveness, and safety of increasing the daily intake of magnesium and potassium salts suggest that such supplementation is a first-line option for treating patients with frequent but not life-threatening ventricular tachyarrhythmias.
Oral Magnesium Recommendations
Magnesium can be consumed in a number of common foods. Legumes and whole grains are excellent sources of magnesium, as are green vegetables, nuts, shellfish, and dried fruit (Table 3).
Foods particularly rich in magnesium, however, are not major components in the diets of many people. In fact, surveys indicate that American diets tend to be deficient in magnesium. As a result, patients at risk for arrhythmias may have magnesium needs in excess of their dietary intake. These patients are candidates for oral magnesium supplementation.
The recommended dosage of oral magnesium may vary, depending on the severity of magnesium deficiency and the urgency of the clinical circumstances. When an individual increases his or her calcium consumption, magnesium intake also should be increased. These adjustments are based on the need to maintain a balance between the two cations.
Diarrhea, which has been encountered in about one third of patients started on full supplemental doses of magnesium, usually can be eliminated or mitigated by starting with lower doses and gradually increasing to the level of intestinal intolerance. There is a low incidence of serious adverse effects associated with the use of oral magnesium supplements.
Suggested Reading
Gottlieb SS. Importance of magnesium in congestive heart failure. Am J Cardiol. 1989;63:39G-42G.
Iseri LT, French JH. Magnesium: nature’s physiologic calcium blocker. Am Heart J. 1984;108:188-193.
Seelig M. Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations—magnesium and chloride loss in refractory potassium repletion. Am J Cardiol. 1989;63:4G- 21G.
Zehender M, Meinertz T, Faber T, et al. Antiarrhythmic effects of increasing the daily intake of magnesium and potassium in patients with frequent ventricular arrhythmias. J Am Coll Cardiol. 1997;29:1028-1034.
Q&A: Using Oral Mg for Cardiac Arrhythmias
Q: Do you recommend oral magnesium?
DR. AMSTERDAM: Yes, usually when a patient is taking a diuretic or if there is high digitalis requirement or digitalis toxicity.
Q: Which patients at risk for arrhythmias are most likely to benefit?
DR. AMSTERDAM: In addition to those taking diuretics, patients with documented magnesium deficiency, digitalis-induced arrhythniias, torsades de pointes associated with long QT, and premature ventricular complexes may benefit.
Q: Is the mechanism known?
DR. AMSTERDAM: No, but a number of different mechanisms contribute. Magnesium at physiologic concentrations has a rhythm-stabilizing effect on the heart and is important in calcium homeostasis. Hypomagnesemia increases the electrical instability of the heart and results in intracellular hypokalemia. Magnesium prolongs the PR and QRS intervals and shortens the QT interval, which is important in opposing arrhythmias related to long QT syndrome (such as torsades de pointes).
Q: Do you ever recommend that a patient boost dietary magnesium intake?
DR. AMSTERDAM: Yes. Good dietary sources are legumes—peas and beans such as pinto, soy, garbanzo, kidney, lima, and lentil. Spinach, kale, collard greens, and mustard greens are high in magnesium. Oatmeal, brown rice, wheat germ, and whole wheat are also helpful. Many patients still need oral magnesium supplements, though.
Q: What formulations of oral magnesium preparations do you recommend, and in what dosages?
DR. AMSTERDAM: I recommend magnesium oxide, 400 mg/d to 800 mg/d. Magnesium chloride, 1 g/d to 2 g/d, may be used instead. For patients who require diuretic therapy, consider magnesium-sparing and potassium-sparing agents such as spironolactone, amiloride, or triamterene.
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The above article is from the "The Magnesium Report", December 1999. Blaine Pharmaceuticals is the manufacturer of Mag-Ox 400 and Uro-Mag magnesium supplements.
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