The Magnesium Web Site



Healthy Water
  The Magnesium
  Online Library

The Magnesium Online Library
The Magnesium Online Library More

Center for Magnesium Education & Research, LLC

Magnesium Symposium at Experimental Biology 2010

Program Announcement, April 24, 2010, Anaheim Convention Center

Featured Editorial from Life Extension Magazine, Sept. 2005:

How Many Americans Are Magnesium Deficient?

Complete Book by
Dr. Mildred S. Seelig:

Mg Deficiency in the Pathogenesis
of Disease

Free ebook
edited by Robert Vink and Mihai Nechifor
University of Adelaide Press

Magnesium in the Central Nervous System

John Libbey Eurotext

Magnesium Research
Archives, 2003-Present

The legal battle for recognition of the importance of dietary magnesium:

Legal documents

Healthy Water Association

HWA Button Healthy Water Association--USA
AHWA Button Arab Healthy Water Association



Paul Mason, Editor
P.O. Box 1417
Patterson, CA 95363

Send Email to The Magnesium Online Library
Go to our Main Menu



In American Journal of Cardiology 63:4G-21G, 1989


Mildred S. Seelig, M.D., M.P.H.

New York Medical College, Valhalla, and the American College of Nutrition, Scarsdale, New York

The section headers of this paper are as follows:


Dietary magnesium (Mg) deficiency is more prevalent than generally suspected, and can cause cardiovascular lesions leading to disease at all stages of life. The average American diets is deficient in Mg, especially in the young, in alcoholic persons, and in those under stress or with diseases or receiving certain drug therapies, who have increased Mg needs. Otherwise normal, Mg deficient diets cause arterial and myocardial lesions in all animals, and diets that are atherogenic, thrombogenic and cardiovasopathic, as well as Mg-deficient, intensify the cardiovascular lesions, whereas Mg supplementation prevents them. Diuretics and digitalis can intensify an underlying Mg deficiency, leading to cardiac arrhythmias that are refractory unless Mg is added to the regimen. Potassium (K) depletion in diuretic-treated hypertensive has been linked to an increased incidence of ventricular ectopy and sudden death. K supplementation alone is not the answer. Mg has been found to be necessary to intracellular K repletion in these patients. Because patients with congestive heart failure and others receiving diuretic therapy are also prone to chloride loss, leading to metabolic alkalosis that also interferes with K repletion, the addition of Mg and Cl supplements in addition to the K seems prudent.


It is paradoxical that many physicians do not consider magnesium (Mg) a nutrient, inadequacy of which has many overt consequences (Table I),

Cardio Table 1

precisely because it has long been recognized as a very effective drug for the treatment of convulsions and hypertension of eclampsia,(1-3), and for cardiac arrhythmias, including those that are refractory without Mg therapy.(1,4-9) Realization that its efficacy in these life-threatening conditions might be a reflection of repair of its deficiency, as well as of its pharmacologic activity, has been gradual. Basic studies have clarified mechanisms by which Mg deficiency can disrupt arterial and cardiac integrity; Mg plays many roles at the mitochondrial level, activating numerous enzymes and preserving both function and structure. (10,11) The heart, with its dense mitochondrial structure and high enzymatic activity,(12) is particularly vulnerable to Mg loss. There is substantial evidence that long-term Mg deficiency in animal species, including monkeys, causes cardiovascular histologic and functional abnormalities.(13) Whereas Mg deficiency in all experimental models increases vulnerability to cardiotoxic agents, and intensifies arterial and cardiac damage caused by other dietary factors (such as excesses of fat, calcemic agents and inorganic phosphate) Mg supplementation has a protective effect.(1,13,14) The epidemiologic evidence that populations consuming more Mg from hard water or diet are less prone to cardiovascular disease and sudden death, than those with lower Mg intakes,(15-19) substantiates the relevance of the animal findings to human atherosclerosis, hypertension and its treatment, myocardial infarction, and sudden cardiac death.(1,20) Both Mg loss and hypochloremic alkalosis interfere with potassium (K) repletion(21-24) and contribute to the risk of sudden death among hypertensive and cardiac patients treated with Mg- and K-losing diuretics.(25)


It is widely assumed, especially in the United States where the food intake is generally ample, that Mg inadequacy is unlikely. However, the foods that are highest in Mg - vegetables (especially legumes and dark green leafy vegetables), fish (including shellfish, and whole grains and nuts (Table II(26))

Cardio Table 2

are not major constituents of the average American diet. Nutrients that are high in the American diet, such as fat, sugar, salt, vitamin D, inorganic phosphate, proteins and more recently supplemented calcium (Ca) and fiber, all increase the dietary requirement of Mg.(26,27)

Recommended dietary allowances for adults: The recommended dietary allowance is defined as: the amount of a nutrient that maintains a balance of intake and output in healthy adults, and is sufficient to assure health - as determined from studies performed long enough for adjustment to be made to altered intakes.(26) Analysis of worldwide metabolic balance studies of free-living young adults, showed that when 4-<5 mg/kg/day of Mg (the content of typical American diets) is taken, men tended to be in negative Mg balance, whereas women remained in equilibrium(26). (Figure 1)

Cardio Figure 1

The analysis also disclosed that in countries (i.e. in the Orient) where the Mg intake is higher (6>8 mg/kg/day), both men and women were in positive Mg balance during the studies. The decision that the recommended dietary allowance for Mg in the stable adult should be 5 mg/kg/day(28) was derived from the finding that maintenance of Mg equilibrium was unreliable on lower intakes.(28)

However, many factors: dietary imbalance, normal anabolism as during growth and development, and psychologic and physical stress, including that of athletic training and competition, all increase the need for Mg. Diseases and drugs that decrease Mg absorption or increase renal Mg loss increase vulnerability to Mg deficiency(27). (Figure 2)

Cardio Figure 2

To assure adequacy of Mg to meet increased needs, the optimal intake of adults may be 6-8 mg/kg/day.

Dietary surveys - magnesium intakes below recommended dietary allowance: Large scale dietary surveys have disclosed that the dietary Mg intake of most Americans falls below the recommended dietary allowance.(27,29-31) Vegetarians' Mg intake is much higher, which could be a factor in their lower incidence of cardiac and vascular disease. Self-selected meals of students in American and Canadian high schools and colleges were found to provide less than the recommended dietary allowance for Mg, but more than the recommended dietary allowances for Ca and phosphate(27,32-34). (Figure 3)

Cardio Figure 3


Diets high in saturated fat:

Overconsumption of saturated fat, which is accepted as a key factor in the high morbidity and mortality from cardiovascular disease, increases the need for Mg. Mg deficiency alone has been shown to cause cardiac and arterial pathologic changes in every species of animal in which it has been induced.(1,13,35-38) High fat/low Mg intakes appear to be conjoint pathogenic factors. The arterial lesions of high fat diets in several species are intensified by simultaneous Mg deficiency, and protected against by Mg repletion.(1,13,35-42)

Fats form soaps with Ca and Mg, in the gut, thereby decreasing absorption both of fat and divalent cations. However, the protection afforded by high oral Mg intake, against both hyperlipidemia and cardiovascular lesions, entails more than diminution of fat absorption. Mg supplementation decreases the enhanced thrombogenesis caused by high fat intake(36,43) (see later).

Recent demonstration of the importance of Mg in fat metabolism in rats(36-38,44,45) suggests that increased Mg intakes may also exert a favorable influence on adverse effects of diets too high in fat, even in humans. The increase in low-density lipoproteins, very low density lipoproteins, and decrease in high-density lipids seen in Mg deficient rats - on a diet providing 20% casein, that was relatively low in fat (5% corn oil), but high in sucrose (70%) (Table III),

Cardio Table 3

was reversed with Mg supplementation.(38,44) Triglyceride plasma levels were also higher in Mg deficient rats than in controls (same diet, but with adequate Mg) - an effect that was shown to be caused by its impaired clearance.(38,44,45) A marked decrease in esterified cholesterol (but no change in total cholesterol) was reported in Mg deficient dogs on a high butter fat diet in a 1933 study.(46) Fifty years later, the reduction in esterified cholesterol of rats maintained on the aforementioned high sucrose/5% oil/Mg deficient diet was shown to be caused by decreased activity of lecithin-cholesterol acyl-transferase.(38) It may be the subnormal lecithin-cholesterol acyl-transferase activity that is responsible for the depression of high-density lipoproteins in Mg deficiency - the high-density lipoproteins being the major substrate for esterification by this enzyme.(47)

A pilot clinical study of the effect of oral supplements of MgCl2 on blood lipoproteins of 16 patients with abnormally low high-density lipoprotein/very low density + low densitylipoprotein ratios, showed that a mean daily dose of 17.9 mM for a mean period of 118 days significantly raised the ratio.(48)

Sugar: These animal studies showing the effects of Mg deficiency on lipoproteins were with high sucrose diets.(36-38,44,47) In humans, sugar loading causes magnesiuresis,(49) possibly converting a marginal intake to a deficient one. Diabetes mellitus, which causes Mg wasting, especially during periods of decompensation,(50,51) is marked by hyperlipidemia and lesions of small blood vessels,(52,53) that resemble those seen in experimental Mg deficiency.(1,13)

Calcemic Agents and Phosphates: Among the other nutrients, of which the usual diet is likely to provide more than is required, and excesses of which increase Mg needs and are cardiovasopathic, vitamin D is of interest as both a calcemic and hyperlipidemic sterol,(54-59) that has been shown to be a steroid hormone.(60) Its requirements are individually variable, and the amount provided to prevent rickets (in milk, by addition to many foods, and in multivitamins), is enough to cure rickets, even in those with high requirements, and is close to the toxic dose for those whose need is low.(56-58) Vitamin D is often one of the components of experimental cardiovasopathic diets against which Mg is protective.(61) Inorganic phosphate which is plentiful in the American diet (though cola beverages and processed foods) is another component of cardiovasopathic regimens.(16,62) Excess Ca is included in some of the cardiovasopathic models, and elevated myocardial Ca is characteristic of cardiac damage.(1,13,14) Finland, with the world's highest dietary Ca/Mg ratio, has the world's highest cardiovascular morbidity and mortality and incidence of sudden death among young men.(16,63) A similar ratio may become a problem in the United States, where Ca supplementation is increasing. Similarly, unsupervised excess intake of fiber (organic phosphate), which can reduce availability of Mg, as well as of other divalent cations, may require mineral supplementation to correct fiber-induced losses.(27)

Alcohol: Ethyl alcohol increases Mg needs, even when taken in moderate quantities, through its enhancement of renal Mg excretion.(64-66) The efficacy of Mg treatment of neuromuscular and cardiac disorders of alcoholism was early attributed to correction of the Mg deficiency.(67) Chronic alcoholics become profoundly Mg depleted as a result of long-term magnesiuresis, superimposed on poor intake; those with cirrhosis also lose Mg as a result of secondary aldosteronism.(68,69) During the stress of alcohol-withdrawal, the fatty acids released as a result of catecholamine-induced lipolysis magnify the problem by binding serum and cellular Mg.(70) Unless the concomitant Mg deficiency is repaired during treatment of alcoholism (which entails repair of thiamin deficiency) there may be faulty response to administered vitamin B1 because of the Mg-dependence of thiamin-activated enzymes.(71-74) In thiamin- and Mg deficient rats, thiamin administration without correction of the Mg deficiency intensifies tissue Mg depletion.(73)


Pregnancy, growth and development: Studies show that Mg intake in pregnant women has been falling, while their intakes of Ca, phosphate, and vitamin D have risen(1). (Figure 4)

Cardio Figure 4

The lowest reported Mg intake and repeated negative Mg balances during a long-term study of a pregnant woman were in Finland,(75) (the country with the lowest Mg intake and the highest Ca/Mg dietary ratio, as well as the highest cardiovascular morbidity and mortality rates in relatively young men.(16,63) Mg intakes of white, middle class pregnant American women have disclosed that low dietary Mg results in negative Mg balance during pregnancy.(76,78,79) This is a potentially dangerous situation during a time when new tissue formation in mother and fetus mandates an adequate supply. It is possible that Mg deficiency may be a factor in peripartal cardiomyopathy and arrhythmias, which often occur in women with conditions that increase Mg requirements: maternal immaturity, multiple births, high parity especially when rapidly successive, and diabetes mellitus. The lesions resemble those of Mg deficiency.(1) That Mg inadequacy during pregnancy might cause fetal arterial injury is suggested by reports of coronary arterial lesions and generalized arteriosclerosis, detected at autopsy in infancy and atherosclerosis and cardiac damage early in childhood.(1,59) A few studies of Mg requirements of very young children and adolescents suggest that Mg needs during growth and development are higher than they are in adults. Might inadequate Mg intakes at times of high need contribute to cardiovascular disease?

Aging: The Mg intake of the elderly tends to be low, and their susceptibility to Mg deficiency is intensified by diminished intestinal absorption and increase urinary output of Mg.(80-83) Elderly persons, who are subject to disorders that impair absorption and renal function, and who may be taking Mg-wasting medications, are likely to be particularly vulnerable to Mg deficiency.(80)

Whether long-standing Mg deficiency affects the health of the aged, and increases their susceptibility to adverse cardiac reactions to disease and drugs that cause Mg-wasting deserves investigation. Transient ischemic cerebral attacks, to which the elderly are particularly prone, might be intensified by Mg deficiency. Subjects who have Mg added to their diets have been reported to be less likely to have transient ischemic events,(84)

That the tolerance of old subjects to stress might be improved by Mg supplementation is suggested by a study of rats maintained on diets low in Mg from the time of weaning to death from old age.(85) They adapted to the deficiency and ceased to show the acute signs, that occurred at the outset (which caused death in convulsions in some). However, the Mg-depleted survivors had shorter lives and died with cardiac damage under conditions of stress tolerated by controls.

Stress: A variety of stresses, both psychological and physical, increase Mg requirements and cause increased cellular Mg loss(27). (Figure 5)

Cardio Figure 5

Stress and Mg deficiency are mutually enhancing. Experimental Mg deficiency has been shown to cause hypertrophy of the juxtaglomerular index,(86) which results in mineralocorticoid secretion, which in turn increases Mg loss.(69,87) In vitro studies have shown that catecholamine secretion is increased by low Mg/Ca ratios, and decreased by high Mg/Ca ratios in suspensions of catecholinergic cells of the adrenal cortex(88) and of ganglionic nerve endings(89. (Figure 6)

Cardio Figure 6

In vivo rat studies have shown that hypomagnesemic noise-stressed rats excrete more catecholamines than do control-fed stressed rats.(90,91)

A vicious cycle can thereby develop, because exogenous or endogenous catecholamines secreted as a result of stress cause mobilization of cellular Mg, particularly from the myocardium - from which 12-39% losses have been reported, in association with uptake of Ca.(91-96) The loss of myocardial Mg precedes cardiac damage and Ca accumulation.(14,93-95) It has been postulated that catecholamines also block Mg ingress across a proposed Mg-channel.(97,98) This theory is in accord with data suggesting that catecholamines block Mg-uptake via a Mg-channel by lymphoma cells.(99) The highly protective effect of verapamil, the Ca-channel blocking agent, against catecholamine-induced cardiac necrosis, has been associated both by reduction of Ca-uptake and of Mg-loss.(92,97)

These effects may explain the transitory increase in serum Mg that has been shown in noise-stressed rats and in guinea pigs stressed by overcrowding. They exhibited decreased erythrocyte Mg and increased serum Mg that derived from released intracellular Mg, and then increased urinary excretion of Mg.(90) The longer-term fall in Mg levels during the stress of exposure to cold of ruminants transferred from barn to early spring pasture,(100) alcohol withdrawal,(70) and myocardial infarction(101) has been attributed to stress hormone induced release of fatty acids, with resultant inactivation of Mg in the serum and tissues. Another interpretation is that epinephrine, which increases Mg-binding in adipocytes,(102) a reaction that is coupled to adrenergic lipolysis,(103) might be responsible for the reduction in serum Mg.

Subjects with Type A personalities, who have increased urinary catecholamines and circulating free fatty acid levels, been shown to have lower erythrocyte Mg levels than do those with more phlegmatic Type B personalities, who are less vulnerable to stress-related cardiovascular disease.(104-107) Patients with latent tetany associated with Mg deficiency - may be especially vulnerable to stress-induced catecholamine release. This condition is diagnosed more frequently in Europe than in the United States, and has received detailed consideration.(108) Whether those presenting with nervous complaints, with or without latent tetany, might be especially vulnerable to heart disease as a result of catecholamine induced increase of Mg requirements (as are Type A subjects) is moot. Among (130) children with "nervous" complaints related to psychosocial and school stresses 16% had hypomagnesemia, and 41.5% had hypocalcemia; 62% improved with oral Mg aspartate HCl supplementation.(109) Among 842 children, diagnosed as having latent tetany and respiratory alkalosis, who had comparable complaints, satisfactory improvement was achieved in 56% by oral treatment with MgCl2, and there was partial amelioration in 32%.(110)

Stresses to which normal young people are subject include those experienced during competition (athletic and career-oriented), crowding and subjection to flickering lights and vibration - as in subways or discoteques. Those with genetic predisposition to poor tolerance of psychological stress,(104-109), or others exposed to physical or psychological stress, are at particular risk of Mg inadequacy.(1,27,74,78) The close interrelations of suboptimal Mg intake, coupled with the Mg loss induced by excess release of stress-hormones, suggest the desirability of Mg supplementation, as a reasonable means of reducing the risk of cardiovascular disease culminating in chronic disease, myocardial infarction, or sudden unexpected death from cardiac arrhythmia.


Histologic Lesions:

Diets delivering amounts of Mg sufficient to prevent death in experimental animals but insufficient for optimal growth and development, have caused arterial and cardiac lesions, the nature of which differs depending on other dietary factors.(1,13,35) In animals fed Mg deficient, but otherwise acceptable diets, early myocardial lesions develop predominantly in the small coronary and intramyocardial arteries.(1,13,35,111,112) There are pathologic sarcosomal and mitochondrial alterations, with Ca accumulation before the cell dies and multifocal necrosis develops.(111,112) There are many Mg-dependent processes in the heart that entail interactions with Ca.(10,11) Mg modulates Ca uptake by myocardial mitochondrial,(113,114) thereby protecting against conditions and drugs that increase Ca ingress and damage to the heart.(1,93,113,114) The lesions of the mitochondria of the heart caused by Mg deficiency resemble those of myocardial ischemia and of catecholamine induced cardiopathy; in experimental models, and in fatal clinical ischemic heart disease, the first alteration is loss of Mg from the heart.(1,13,14,93,95,111,115-119)

Intensification of Atherogenesis by Mg Deficiency: Atherosclerosis is frequently produced by feeding animals diets high in fat/cholesterol. The Mg deficiency induced lesions of the small and medium sized arteries in several animal species are characterized by edematous and thickened intima, and thinned, split, and fragmented internal elastica sometimes with lipid droplets(1,13,35). (Figure 7)

Cardio Figure 7

Coronary arteriopathy: hyperplasia of smooth muscle cells, fibrinoid necrosis, and chronic medial and adventitial inflammation develop in the hamster, a rodent that is particularly vulnerable to Mg deficiency, when fed a Mg deficient diet.(120) When, in addition to low Mg the diet includes excesses of saturated fat and/or calcemic agents, or both, larger arteries are affected, and atherosclerosis develops(1). (Figure 8)

Cardio Figure 8

(Figure 9)

Cardio Figure 9

The lesions are intensified over those seen in the absence of Mg deficiency.(1,13,35,39-41)

Coagulation, and Thrombosis: The possibility that early lesions of atherosclerosis are mediated by organization and fatty changes in mural thrombi at sites of arterial damage(121) calls attention to the possible role of Mg deficiency, which increases intra-arterial coagulation. Mg deficient animals had significantly shorter thrombin clotting time than did controls.(122) Hypercoagulability caused by a thrombogenic diet rich in fat was counteracted by oral supplements of MgCl2.(43) Most of the in vitro studies showing that Mg inhibits coagulation factors: prothrombin, thrombin, and Factors V, VII, and IX, have been with unphysiologically high Mg concentrations.(1,108)

The anti-thrombotic effect of high concentrations of Mg has been investigated in animals receiving standard diets, with artificially induced intimal lesions. The suppression of platelet aggregation by local application of a MgSO4 solution (6%) was demonstrated at areas of arterial injury caused by holding or pinching with a forceps.(123) Repeated intravenous infusions of isotonic MgCl2 also suppressed thrombus formation(123). (Figure 10)

Cardio Figure 10

The effect of high doses (50 mg/kg) of intravenously administered MgSO4 (25%) on platelet deposition in arteries with suture ligation of arteries causing 40-60% constriction has been reported.(124) (Dogs) with a narrowed major coronary artery, and rabbits with a narrowed carotid artery, pretreated with Mg, showed marked diminution of platelet aggregation at the site of constriction, and absence of microthrombi in the arteries distal to the ligation. It has been suggested that these findings have potential therapeutic or prophylactic implications - in Prinzmetal's variant angina where arterial spasm is the principal factor, and in coronary thrombosis.(124) There is some evidence that these findings may be applicable to the clinical situation.

Patients with thromboembolic disease, associated with latent tetany, have responded to Mg therapy by correction of hypercoagulability caused by excess adenosine diphosphate-induced platelet aggregation.(125,126) Increased platelet aggregability has been demonstrated in myocardial infarction patients, in association with decreased serum Mg levels.(127) In addition, Mg therapy has yielded benefit in patients with Prinzmetal angina(128) and in post-myocardial infarct patients (see later).

Fibrotic Changes in Thrombi and Myocardium: Fibrosis constitutes a large portion of the occlusive thrombi, examined from cases of fatal myocardial infarction.(129). Since increased fibrosis and slowed collagen resorption has been reported in tissues damaged by experimental Mg deficiency,(36,37) it is plausible that Mg deficiency may be a factor in clinical cardiomyopathies. Fibrotic cardiomyopathy has been associated with abnormalities during the perinatal period (in mother as well as infant) alcoholism, protracted diarrhea, protein calorie malnutrition, in hypercalcemic states, such as hyperparathyroidism and vitamin D hyperreactivity or toxicity, and in congestive heart failure.(130) All are conditions associated with Mg deficiency, as a result of the disease, or of treatment.

Myocardial Ischemia of Coronary Insufficiency or Occlusion: Ischemic heart disease, which is responsible for about a third of all deaths in the Western world, is caused by coronary atherosclerosis with or without thrombosis that gives rise to myocardial infarction, arteriospasms, and resultant arrhythmias. Many theories have been propounded as to the pathogenesis of this widespread disease-complex.(118,131) Inadequacy of Mg is a common denominator in some of the proposed mechanisms. The cited damaged intima, and lipid infiltration of Mg deficient animals, and their increased blood coagulability bear on the endothelial injury/lipid infiltration/mural thrombosis theory of atherogenesis.(132) The cited role of Mg in reversing low high-density/high-density ratios may also be germane to that theory. The importance of optimal Mg levels in counteracting arteriospastic agents - neurohormonal and electrolyte ultimately affects angina pectoris and peripheral arterial spastic disease.(118,119)

Pertinent to the effect of Mg on the damage to the myocardium caused by coronary occlusion, are the demonstrations in rats that its extracellular depletion causes impaired postischemic cardiac function and metabolism,(133) and its dietary inadequacy in dogs results in increased infarct size after coronary artery occlusion.(134) It has been proposed that the protective effects of Mg during myocardial ischemia entails not only its limiting the loss of cellular Mg and K, and militating against Ca-overload, but restricting the cellular loss of Mg-adenosine triphosphate the essential substrate for many cellular reactions.(135-137) The experimental findings suggest that early myocardial changes after an ischemic event (perhaps during the first 20-30 minutes) might be reversible, and that applying the findings to patients with a recent MI might result in better preservation of the ischemic myocardium and limitation of the size of the infarct.(137)

Electrophysiologic Cardiac Findings: With Mg deficiency severe enough to produce convulsions in rats, the electrocardiogram first disclosed tachycardia, followed by marked arrhythmia and then bradycardia just before the seizures started.(46) During post-convulsive unconsciousness, a sinoauricular block developed, with occasional skipped or ectopic ventricular beats.(138) In young dogs with average serum Mg of 0.4 mEq/liter, the PQ interval and QRS were markedly shortened, with lesser shortening of the QT interval, and an increased incidence of negative T waves.(139) With a semisynthetic diet that lowered the serum Mg to < 0.5 mEq/liter without seriously affecting serum K or Ca, there was sinus tachycardia, but little change in PR, QRS or QT intervals.(140) Less severe Mg deficiency in dogs and monkeys produced changes like those of extracellular hyperkalemia (as K shifted out of cells): marked sinus tachycardia, peaking of T waves, and ST depression.(41,141)

Electrocardiographic similarities among magnesium, potassium and calcium abnormalities - experimental and clinical: The electrocardiographic changes of Mg deficiency differ, depending on the degree of the deficiency which further influences K and Ca intracellular and extracellular levels. Therefore, it is not surprising that there are similarities between the electrocardiograms of Mg deficiency and those of Ca or K abnormalities(1,142), (Figure 11).

Cardio Figure 11

The loss of myocardial K (with transitory elevation of extracellular K) that results from myocardial Mg loss can contribute to electrophysiologic changes of Mg deficiency that resemble that of moderate hyperkalemia: a T-wave that is peaked but narrower than that of Mg deficiency.(1,142,143)

The common pushing of K therapy to overcome the (often undiagnosed) hypomagnesemia-associated refractory hypokalemia(21,22) can intensify Mg deficiency(144) and be associated with the electrocardiogram of K-depletion. With long-standing Mg deficiency, the electrocardiogram with its flattened T-wave (and sometimes a U-wave) is more similar to that of hypokalemia, with which it is associated.(142-144)

Early hypomagnesemia can be accompanied by hypercalcemia that may be caused by transient hyperparathyroidism(145) and that might contribute to the broader T wave peak (than that of hyperkalemia) seen with moderate Mg deficiency. More severe Mg deficit is associated with hypocalcemia, in association with both impaired release of parathyroid hormone and blunting of the target organs to its action.(145) At that stage, the electrocardiogram of Mg deficiency also resembles that of Ca deficiency. However, at that stage, there is a shift of Ca into the myocardium. Much of the protective effect of Mg against arrhythmic stimuli is being attributed to its being a physiologic Ca blocker.(118,119,146)

Many of the clinical conditions, in which electrocardiographic changes of hypomagnesemia have been reported, have been associated with electrocardiograms characteristic of hypokalemia or hypocalcemia. Basic to the role of Mg in maintaining or restoring cardiac rhythmicity is its role in maintaining K and Ca homeostasis. In brief, the electrocardiogram associated with clinical hypomagnesemia is usually characterized by increased sino-atrial discharge rate, with a tendency towards abnormal impulse formation, and ventricular ectopic beats.(8,147) Prolongation of the PR and QT intervals reflect the arrhythmogenic potential of Mg deficiency. Widening of the QT may indicate a lengthened repolarization phase, caused by altered membrane transport of K, associated with aberrant conduction, reentry, and lowered threshold for ventricular fibrillation.

Arrhythmias: The efficacy of intravenously administered Mg in control of clinical arrhythmias has been reported at intervals during the past half century. Since the early 1970s when this effect was associated with correction of Mg deficiency, (6,7) a variety of dysrhythmias incompletely responsive or refractory to conventional treatment have been controlled by parenteral Mg therapy (Table IV).(8)

Cardio Table 4

Although the Mg-responsive arrhythmias are often not associated with low serum Mg levels, better tests for Mg deficiency(42) have shown it to be implicated in the conditions in which cardiac dysrhythmias develop.(6-9,148-159)

Dysrhythmias responsive to Mg occur in alcoholism - particularly during alcohol withdrawal,(6,8,64,65,154-159) during long-term administration of parenteral fluids lacking or inadequate in Mg, or in those undergoing postsurgical drainage of gastrointestinal fluids, or a combination of all 3.(1,65,154,160-162) They have been reported in patients with Mg deficiency caused by chronic diarrhea or short bowel.(7,160-163) The diarrhea of protein calorie malnutrition can be a predisposing factor to the arrhythmias seen in victims of starvation, especially during refeeding with formulas inadequate in Mg.(164).

The arrhythmias during exchange transfusions(165,166) and after open-heart surgery are partially caused by hypomagnesemia resulting from the use of anticoagulants such as acid-citrate-dextrose, that bind Mg as well as Ca (only Ca usually being repleted)(167). (Figure 12)

Cardio Figure 12

The use of Mg in the postcardiotomy period has decreased the incidence of arrhythmia.(168-171) Addition of Mg to cardioplegic solutions used in the pump-prime during cardiac surgery has proved to be the single most effective component of the protective infusates tested(172), (Figure 13)

Cardio Figure 13

Myocardial Infarction: Treatment of myocardial infarct patients with parenteral Mg salts was reported to decrease arrhythmias and improve survival in uncontrolled studies in South Africa, Australia and Europe from 1958 through the 1960s.(1) Recent controlled studies have verified the improvement in management and survival after acute myocardial infarction achieved by intravenous Mg therapy.(173-177) There is growing evidence that Mg deficiency may be a predisposing factor for myocardial infarction and subsequent complications,(8,23,91,147-153,178) Addition of Mg to the postmyocardial infarction regimen parenterally in the early phase, and orally subsequently - needs serious consideration.

Congestive Heart Failure: The most arrhythmogenic disease, congestive heart failure,(179-182) is responsible for many unexpected sudden deaths - not from progressive circulatory failure, but suddenly and unexpectedly, at a rate even higher than among patients in the first 12 months after myocardial infarction.(179) This has been attributed to the dysrhythmias caused by the electrolyte disturbances produced both by compensatory mechanisms and by treatment of the disease. (Figure 14)

Cardio Figure 14

The compensatory mechanisms resulting from reduced cardiac output cause increased secretion of vasoconstrictor and volume regulating hormones: catecholamines, renin-angiotensin-aldosterone, and anti-diuretics,(180,183) Catecholamine and aldosterone secretion is increased by underlying Mg deficiency - which is increased by both diuretic and digitalis therapy (see before), which further stimulate the neurohormones.(180,183) Loss of K and Mg, caused by diuretics and aldosterone, increases arrhythmias, which are intensified by angiotensin's stimulation of aldosterone secretion and potentiation of the sympathetic nervous system.(180,183)

Correction of secondary aldosterone- andtreatment-induced losses of both K and Mg is responsible for the favorable immediate response of heart failure patients with digitalis arrhythmias. When both cations are deficient, repletion of Mg is necessary for the repair of Mg and K tissue levels and the dysrhythmias.(23,180-182) Infusion of K before Mg infusion had a much weaker anti-arrhythmic effect than did Mg infusion alone; in several patients, the K infusion actually caused more ectopic beats, that were largely corrected by the Mg infusion.(184)

Rapid electrolyte depletion might explain the precipitation of lethal arrhythmias in patients with left heart failure with myocardial fibrosis, ventricular wall stress and elevated circulating neurohormones.(182) Hypokalemia is most often recognized in this condition, and in patients with congestive heart failure resuscitated after in-hospital cardiac arrest. It has been suggested that the only antiarrhythmic intervention needed to prevent recurrence of cardiac arrest may be repletion of K and Mg.(182)

Mitral Valve Prolapse: The electrocardiogram patterns and arrhythmias of mitral valve prolapse that are like those seen in Mg deficiency(185) are those present in a condition frequently seen in many patients with latent tetany of Mg deficiency.(108,185,186) The finding of decreased red blood cell Mg levels in patients with the human leukocyte antigen haplotype HLA haplotype HLA-Bw35,(187) has been associated with mitral valve prolapse,(188) supports the premise that there is a relation. Additional theories as to how Mg deficiency might participate in the pathogenesis of this disease have been considered.(108,186)

Hypertension: Hypertension is the most prevalent risk factor for premature cardiovascular diseases in the United States; it is estimated that over 30 million are affected.(189) Reviews of the dietary changes recommended for its prevention and treatment summarize strengths and weaknesses of past and current recommendations: caloric and sodium (Na) restriction, and K, Ca, and Mg supplementation.(189,190) The premise that dietary Ca deficiency is an important factor in the pathogenesis of hypertension,(190) and the evidence as to the proposed mechanisms that might be involved have been analyzed and found questionable.(191)

Unlike Ca, high serum levels of which increase blood pressure,(191) hypermagnesemia produced by Mg administration in pharmacologic doses has long been found efficacious in the treatment of severe hypertension, as in toxemias of pregnancy,(2,3) There is substantial experimental evidence that dietary Mg deficiency increases arterial contractility, and that elevating Mg decreases blood pressure.(1,118,192-194) However, severe experimental Mg depletion reduces the activity of vasopressive neurohypophyseal peptides.(1,192) This may explain the hypotension of patients with renal Mg wasting.(195)

The fact that hypertensive patients with low plasma renin activity (who have higher than average serum Mg levels) respond to administration of Ca, while those with high renin activity (who have lower serum Mg levels) respond to Mg treatment(196) does much to clarify the roles of Mg and Ca in hypertension. Of particular interest is the evidence of low levels of free Mg in erythrocytes in both forms of hypertension.(197,198)

It was found that Mg infusions - in patients with congestive heart failure and with hyponatremia, increased muscle Na and Cl, and subnormal muscle K and Mg and with increased resistance to diuretics - corrected the electrolyte abnormalities.(199) Comparable results were obtained with oral Mg supplements in CHF and hypertensive patients taking long-term diuretics.(200)



The first demonstration of the anti-arrhythmic effects of Mg was in the treatment of digitalis toxicity, more than 50 years ago.(201) Almost 30 years later, low serum Mg levels (1.38 mEq/liter +/- 0.13) were found in patients with arrhythmias of digitalis toxicity.(202) These findings have been repeatedly confirmed.(5,203,204) Patients with normal serum Mg levels, but decreased lymphocyte Mg, have also been shown to respond to intravenous Mg therapy by correction of the arrhythmias.(205) Hypomagnesemia has been reported more frequently than hypokalemia in patients with digitalis toxicity.(206) Among patients with symptomatic atrial fibrillation 20% were found to be hypomagnesemic; these required twice as much digoxin to control the arrhythmia as did those with normal serum Mg.(207)

The mechanisms by which Mg deficiency increases digitalis toxicity and by which Mg administration protects against digitalis arrhythmias, have been elucidated by animal and in vitro experiments. In vitro studies of isolated calf cardiac Purkinje fibers(208) suggested that excess digoxin poisons the membrane Na and K-adenosine triphosphatase with resultant inhibition of the Na-K pump, which is Mg dependent.(10,11). As a result, there is a reduction in the intracellular K/Na ratio that causes phasic movement of Ca in and out of the myoplasm, and transient inward current and spontaneous depolarizations. Low Mg levels potentiate these currents, while high Mg levels block them.(8.208) A study of digitalis-induced arrhythmias in dogs did not confirm the hypothesis that Mg reactivated digoxin-inhibited Na-K adenosine triphosphatase, suggesting that Mg directly affects Ca and K fluxes across the cell membrane.(209) A study of the efficacy of repeated intravenous infusions of MgCl2 in intact dogs given doses of digitalis that induced ventricular tachycardia showed that Mg corrected the arrhythmia, or when given before the digitalis, prevented it.(210)

Digitalis toxicity has also developed in patients with congestive heart failure who had hypermagnesemia as a result of concomitant renal impairment.(203) This seems contradictory to the evidence that Mg deficiency increases digitalis toxicity. However renal failure patients may have Mg deficiency, despite their higher than normal serum Mg levels, as indicated by subnormal skeletal muscle Mg concentrations.(211-213)

Diuretics: With regard to the risk of arrhythmia, most classes of diuretics have long been known to cause Mg as well as Na and K loss. Although the loop diuretics are the main offenders in treatment of congestive heart failure, patients receiving long-term treatment with such agents as the thiazides, are at risk, especially the elderly,(214-216) Serum Mg determinations are less reliable than tissue values.(42) In a study of muscle and serum Mg and K levels in 34 patients in whom ventricular ectopic beats developed while taking long-term diuretic therapy, Mg infusions more effectively reduced the ectopic beats than did K infusions.(184) In a larger study among 297 patients with congestive heart failure who had received long-term diuretic treatment, serum Mg was subnormal in 37%, and skeletal muscle Mg was subnormal in 43% (almost all of whom also had low muscle K(23)).

The increase of mortality among those participants, receiving diuretics, in large-scale anti-hypertension studies has called attention to the possibility that Mg loss, as well as K loss (which is usually watched for and corrected) may be at fault. Mg loss, in contrast, is usually undetected. In the extensive randomized Multiple Risk Factor Intervention Trial (MRFIT), that was sponsored by the National Institutes of Health, there was poorer survival in a subgroup who had had baseline electrocardiogram abnormalities and had been treated with thiazide diuretics, than in those not so treated.(217,218) In a study of mildly hypertensive patients 165 of whom (n = 287) had ambulatory electrocardiography, ventricular ectopic beats occurred more frequently in thiazide-treated patients than in placebo-treated controls.(219) A higher mortality rate due to fatal myocardial infarction and sudden deaths had been reported earlier in elderly hypertensive men, treated with diuretics, than in comparable patients treated only with salt restriction or beta-adrenergic blocking agents.(220) This is contrast to the European double-blind multicenter study, in which the study group was given diuretics plus Mg and Ksparers; survival of that group of subjects was 15% better than it was in the control groups.(221)

In two of the Multiple Risk Factor Intervention Trial centers, the serum Mg levels of 300 participants, aged 35-57 years, were analyzed after 4 to 5 years of treatment with relatively low dose chlorthalidone or hydrochlorthiazide.(222) About 15% of these had persistently lower Mg levels on 2 samples taken 4 months apart, than did those not taking diuretics. The investigators noted that the small differences might reflect the inadequacy of serum Mg as an index of Mg loss, and that further study is indicated, using better indices of the Mg status.

Hypochloremic metabolic alkalosis interferes with potassium repletion: Diuretic-induced Cl loss is less frequently noted than is hypokalemia, with or without Mg loss. Metabolic alkalosis can develop, especially in patients with congestive heart failure, but also appears in hypertensive patients receiving long-term diuretics. In an update of complications of thiazide diuretic therapy, in which the above disappointing results in large scale antihypertensive intervention trials were summarized, emphasis was placed, not only on Mg and K losses, but on the metabolic alkalosis caused by diuretic- and aldosterone induced Cl loss as a contributory factor in intracellular K depletion, and refractoriness to K repletion.25 Patients with metabolic alkalosis, associated with volume contraction and Cl loss induced by diuretics and secondary aldosteronism, require large doses of KCl to repair the cellular K deficit. A patient with renal Mg wasting developed hypokalemic hypochloremic alkalosis while being treated with a diuretic for edema of unknown derivation, despite administration of KCl.(195) Only when MgCl2 was added was normal electrolyte status restored.

Reports, in which the importance of Mg in repleting intracellular K is considered, sometimes refer to the concomitant existence of metabolic alkalosis, that intensifies K loss, but usually only in passing.(23,180,181,204) Problems of metabolic alkalosis are usually considered in reports on acid/base disorders.(24) The diuretics in common use promote cation excretion almost exclusively in association with Cl. Because patients receiving diuretics are often advised to consume low salt diets, that are thus also low in Cl, metabolic alkalosis - often not diagnosed - may exist. At first, the alkalosis was considered the result of K depletion; however, subsequent studies showed the K deficit often encountered in metabolic alkalosis (as high as 300 to 500 mEq) is a consequence of the alkalosis rather than its cause.(24) In 1955, acute metabolic alkalosis induced by removal of Cl was shown to increase K excretion in rats.(223) In a study of dogs made alkalotic by a diet low in K and Cl, and by administration of a mineralocorticoid and sodium bicarbonate, Cl was shown to be critical in repair of alkalosis.(224) Full correction of the hypokalemia required sufficient Cl to repair the hypochloremia. The importance of Cl in repair of hypokalemic alkalosis in humans was then shown by balance studies performed in normal human volunteers with alkalosis induced by Na nitrate, and in patients with diuretic-induced metabolic alkalosis.(225) Both in the experimentally induced and the diuretic induced alkalosis, liberal intakes of K had no effect on plasma bicarbonate and little effect on body K, if the Cl deficiency was not corrected.

One of the patients with metabolic alkalosis studied by metabolic balance(225) had chronic obstructive pulmonary disease. A series of such patients, who had a tendency towards metabolic alkalosis, rather than respiratory acidosis, had multifocal atrial tachycardia that responded to Mg sulfate infusions.(226) Four of the 9 patients with chronic pulmonary disease had serum Mg levels below 1.5 mEq/ liter and 5 had levels higher than 1.8. Even those with normal serum Mg retained substantial amounts of infused Mg, indicating deficiency. Possibly, their respiratory insufficiency might have caused sufficient hypoxia to mobilize tissue Mg, raising serum levelsas has been shown to result from too long application of a tourniquet, while withdrawing blood samples,(227), and as has been seen in birth asphyxia.(228)

Alkalotic patients had greater vulnerability to digitalis toxicity, even though they had therapeutic digitalis blood levels lower than the nonalkalotic patients.(229) They improved with KCl treatment, even though they were normokalemic, an effect that was attributed to correction of decreased intracellular K that had been caused by metabolic alkalosis. Their serum Mg levels were not reported.

Risk of intensifying alkalosis by repletion of non-Cl salts: Among the studies that showed that Cl is critical to repair K loss and alkalosis, were case studies that showed worsening of alkalosis when buffered K rather than KCl was provided,(225) In another instance, a patient who abused Mg cathartics, developed hypochloremic, hypokalemic metabolic alkalosis, believed to have resulted from conversion of the Mg oxide to MgCl2 in the stomach, and fecal excretion of endogenous Cl.(230)

Animal studies of the intestinal absorption of different Mg salts have shown a tendency towards hypochloremic alkalosis with all of the Mg organic compounds and inorganic salts, except those containing Cl (Table V).(231)

Cardio Table 5

Rats fed MgCl2 had a slight tendency towards hyperchloremic acidosis, which might be useful in subjects with diuretic induced hypochloremic alkalosis.

Improvement in intestinal absorption of Mg, and correction of extracellular alkalosis, with use of Cl-containing Mg compounds was credited with the greater cardioprotective effect of MgCl2 and Mg aspartate hydrochloride in adrenergic cardiopathy (Table VI).(231-234)

Cardio Table 6

The experimental model employed a mixed gluco-mineralcorticoid, that is a very potent agent for inducing hypochloremic alkalosis and marginal Mg deficiency, and that in combination with epinephrine or with dietary Mg deficiency, or both, lowers the myocardial Mg and raises the myocardial Ca before development of necrosis.(234) Feeding a Cl containing Mg compound (Mg aspartate hydrochloride) protected against cardiac electrolyte changes and necrosis.

Early studies of the electrolyte-steroid-cardiac necrosis and stress rat models showed that MgCl2 and KCl were the most potent protectors against cardiac damage.(62) In a comparative study of old and young stressed rats, it was found that Cl-deficiency particularly intensified the risk of cardiac necrosis in old rats.(235)

Repair of intracellular potassium deficits associated with deficiencies of magnesium and chloride: Most of the foregoing data deals with evidence that when Mg and K deficiencies coexist, repletion of Mg is necessary for repair of the cellular K loss. Since hypochloremic alkalosis has also been shown to interfere with K repletion, it seems appropriate to provide Mg and Cl, as well as the K that is usually provided, to patients with diseases and those subjected to treatments that cause loss of all 3 ions (Table VII).

Cardio Table 7

Because of the hygroscopic nature of MgCl2, it must either be supplied as a solution for oral use or in protectively coated tablets.

In addition to the response of a patient with Mg-deficient latent tetany to elixir of MgCl2,(195) there is a report of satisfactory improvement of most of 842 children diagnosed as having latent tetany and respiratory alkalosis on treatment with orally administered MgCl2.(110) There are several preliminary reports on the efficacy of an enteric coated MgCl2 preparation in cardiovascular disorders.(48,236,237) Doses of 4-6 tablets, each containing 0.5 g MgCl26H20, given for 6 weeks to 2 years, were effective in decreasing QTc and QUc intervals in 25 patients.(236) The same preparation was found to improve the antihypertensive response to a thiazide diuretic of 21 hypertensive patients aged 42 to 82 years.(237) Abnormally high low-density lipoprotein levels were reduced in 16 patients given 6-10 coated MgCl2 tablets daily for a mean period of 118 days.(48)


There is substantial experimental evidence of the vital role of Mg in maintaining cardiovascular integrity and normal function. Large-scale dietary surveys have shown that American diets are usually Mg deficient, inadequately meeting requirements under conditions of growth and development, stress, or disease and drug therapy that cause Mg loss. Mg has long been used for parenteral treatment of convulsions and hypertension of eclampsia, and more recently, as a therapeutic modality in refractory cardiac arrhythmias (although usually as a last resort). Mg has potential value in the management of cardiovascular diseases treated with Mg-wasting drugs that intensify Mg deficiency. Such diseases and treatment also predispose to Cl loss induced metabolic alkalosis, which with Mg deficiency, contribute to refractory cellular K depletion.

The fact that chronic Mg deficiency is silent and difficult to diagnose - serum Mg levels being an unreliable index of the cellular Mg status, has militated against early treatment or supplementation with Mg. Studies should further assess the Mg status in persons with conditions that may cause Mg deficiency or those being treated with Mg- and K-wasting drugs. All of the ions that are lost should be repleted - Mg, K, and Cl (to prevent or correct metabolic alkalosis). It is further proposed that optimal Mg intake throughout life, and especially under conditions of normal anabolism and stress, may reduce the risk of cardiovascular disease, and even of sudden unexpected cardiac death.


1. Seelig MS. Magnesium Deficiency in the Pathogenesis of Disease. Early Roots of Cardiovascular, Skeletal, and Renal Abnormalities. Plenum Publ Corp, NY, 1980.

2. Lazard EM. A preliminary report on the intravenous use of magnesium sulphate in puerperal eclampsia. Am J Obst Gynec 1925;26:647-656.

3. Pritchard JA. The use of magnesium in the management of eclamptic toxemias. Surg Obst Gynec 1955;100:131-140.

4. Boyd LJ, Scherf D. Magnesium sulfate in paroxysmal tachycardia. Am J Med Sc 1943;206:43-48.

5. Szekely P. The action of magnesium on the heart. Brit Heart J 1946; 8:115-124.

6. Iseri LT, Freed J, Bures AR. Magnesium deficiency and cardiac disorders. Am J Med 1975;58:837-846.

7. Chadda KD, Lichstein E, Gupta P. Hypomagnesemia and Refractory arrhythmia in a nondigitalized patient. Am J Cardiol 1973;31:98-100.

8. Iseri LT. Magnesium and Dysrhythmias. Magn Bull 8: 223-229, 1986.

9. Packer M, Gottlieb SS, Kessler PD. Hormone-electrolyte interactions in the pathogenesis of lethal cardiac arrhythmias in patients with congestive heart failure, basis of a new physiologic approach to control of arrhythmia. Am J Med 1986;80 (Suppl 4A):23-29.

10. Wacker WEC. "Magnesium and Man", Harvard University Press, Cambridge, MA 1980.

11. Aikawa JK. "Magnesium: Its Biologic Significance", CRC Press, Boca Raton, FL, 1981

12. Green DE, Fleischer S. The mitochondrial system of enzymes. in "Metabolic Pathways", Academic Press, 1980

13. Seelig MS, Heggtveit HA. Magnesium interrelationships in ischemic heart disease. Am J Clin Nutr 1974;27:59-79.

14. Lehr D. Tissue electrolyte alteration in disseminated myocardial necrosis. Ann NY Acad Sci 1969;156:344-378.

15. Schroeder HA. Relations between mortality from cardiovascular disease and treated water supplies. JAMA 1960:172:1902-1908.

16. Karppanen H, Neuvoenen PJ. Ischemic heart disease and soil magnesium in Finland (letter). Lancet 1973;2.1390.

17. Marier JR. Role of magnesium in the "hard water story". Magnesium Bull 1986;8:194-198.

18. Anderson T, Neri LC, Schreiber GB, Talbot F, Zdrowjewski A. Ischemic heart disease, water hardness, and myocardial magnesium. Can Med Assoc J 1975;113:199-203.

19. Anderson TW, LeRiche WH: Sudden death from ischemic heart disease in Ontario and its correlation with water hardness and other factors. Can Med Assoc J 1971;105:155-160.

20. Altura BM, Altura BT, Carella A, Prasad DMV. Hypomagnesemia and vasoconstriction: possible relationship to etiology of sudden death ischemic disease and hypertensive vascular disease. Artery 1981;9:212-213.

21. Whang R, Flink EB, Dyckner T, Wester PO, Aikawa JK, Ryan MP. Magnesium depletion as a cause of refractory potassium repletion. Arch Intern Med 1985;145:1686-1689.

22. Ryan MP: Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82(Suppl 3A):38-47.

23. Dyckner T, Wester PO. Potassium/magnesium depletion in patients with cardiovascular disease. Am J Med 1087;82(Suppl 3A):11-17.

24. Cohen JJ, Kassirer JP. Acid base metabolism. In Maxwell MH, Kleeman CR, eds. Clinical Disorders of Fluid and Electrolyte Metabolism. New York:McGraw-Hill Book Co, 1980:1812-232.

25. Field MJ, Lawrence JR. Complications of thiazide therapy: an update. Med J Aust 1986;144:641-644.

26. Seelig MS: The requirement of magnesium by the normal adult. Am J Clin Nutr 1964;14:342-390.

27. Seelig MS: Magnesium requirements in human nutrition. Magnesium Bull 1981;3 (Suppl 1A):26-47.

28. Committee on Dietary Allowance: Recommended dietary allowances. Magnesium. 9th Revised Edition. National Academy of Sciences, Washington, D.C., 1980, pp 134-136.

29. USDA. Food and nutrient intakes of individuals on 1 day in the U.S., Spring 1977. Nationwide Food Consumption Survey 1977-1978. Preliminary Report #2, Washington DC, 1980.

30. Morgan KJ, Stampley GL, Zabik ME, Fischer DR. Magnesium and calcium intakes of the U.S. population. J Am Coll Nutr 1985;4: 195-206.

31. Lakshmanan FL, Rao RB, Kim WW, Kelsay JL. Magnesium intakes, balances, and blood levels of adults consuming self-selected diets. Am J Clin Nutr 1984;40:1380-1389.

32. Walker M, Page L. Nutritive content of college meals. III. Mineral elements. J Am Diet Assoc 1977;70:260-266.

33. Srivastava US, Nadeau MJ, Guennou L. Nutrition Reports Intl 1978;18:235-242.

34. White HS. Inorganic elements in weighed diets of girls and young women. J Am Diet Assoc 1969;55:38-43.

35. Seelig MS, Haddy FJ. Magnesium and the arteries. I. Effects of magnesium deficiency on arteries and on the retention of sodium, potassium and calcium. in Cantin M, Seelig MS, eds. Magnesium in Health and Disease. New York: SP Med & Sc Books, 1980:605-638.

36. Rayssiguier Y. Magnesium and lipid interrelationships in the pathogenesis of vascular diseases. Magnesium Bull 1981;3:165-177.

37. Rayssiguier Y. Lipoprotein metabolism: importance of magnesium. Magnesium Bull 1986;8:186-193.

38. Rayssiguier Y, Gueux E. Magnesium and lipids in cardiovascular disease. J Am Coll Nutr 1986;5:507-519.

39. Vitale JJ, White PL, Nakamura M, Zamcheck N, Hellerstein EE. Interrelationships between experimental hypercholesterolemia, magnesium requirements, and experimental atherosclerosis. J Exp Med 1957;106:757-766.

40. Hellerstein E, Vitale JJ,White PL, Hegsted D, Zamcheck N, Nakamura M. Influence of dietary magnesium on cardiac and renal lesions of young rats Fed an atherogenic diet. J Exp Med 1957: 106:767-775.

41. Vitale JJ, Velez H, Guzman C, Correa P. Magnesium deficiency in the cebus monkey. Circ Res 1963;12:642-650.

42. Elin RJ: Magnesium Metabolism in Health and Disease. Disease-a- Month 34: 161-218, 1988.

43. Szelenyi Y, Rigo R, Ahmen BO, Sos J. The role of magnesium in blood coagulation. Thromb Diath Haemaorrh 1967;18:626-633.

44. Rayssiguier Y, Gueux E, Weiser D. Effect of magnesium deficiency on lipid metabolism in rats fed a high carbohydrate diet. J Nutr 1981;111:1876-1883.

45. Rayssiguier Y, Gueux E. The reduction of plasma triglyceride clearance by magnesium-deficient rats. Magnesium 1983;2:132-138.

46. Kruse H, Orent E, McCollum E. Studies on magnesium deficiency in animals. III. Chemical Changes in the blood following magnesium deprivation. J Biol Chem 1933;100:603-643.

47. Gueux E, Rayssiguier Y, Piot M-C, Alcindor L: Reduction of plasma lecithin-cholesterol acyl-transferase activity by acute magnesium deficiency in the rat. J Nutr 1984;114:1479-1483.

48. Davis WH, Leary WP, Reyes AJ, Ohlaberry JV: Monotherapy with magnesium increases abnormally low high density lipoprotein cholesterol: a clinical assay. Curr Ther Res 36;1984:341-344.

49. Lindeman RD, Adler S, Yiengst MJ, Beard ES. Influence of various nutrients on urinary divalent cation excretion. L Lab Clin Med 1967;70:236-245.

50. Martin HE.: Clinical magnesium deficiency. Ann NY Acad Sci 1969;156:891-900.

51. Martin HE, Wertman M. Serum potassium, magnesium and calcium levels in diabetic acidosis. J Clin Invest 1947;26:217-228.

52. Ditzel J. Morphologic and hemodynamic changes in the smaller blood vessels in diabetes mellitus. I. Considerations based on the literature. New Engl J Med 1954;250:551-546.

53. James TN. Pathology of small coronary arteries. Am J Cardiol 1967;20:679-691.

54. Linden V. Correlation of vitamin D intake to ischemic heart disease, hypercholesterolemia, and renal calcinosis. In Seelig MS ed. Nutritional Imbalances in Infant and Adult Disease: Mineral, Vitamin D and Cholesterol. New York, Spectrum Pub 1977: 23-42.

55. Linden V, Seelig MS. Multiple factors in the hyperlipidemia of hypervitaminosis D (letter). Br Med J 1975;4:166.

56. Harris LJ. The mode of action of vitamin D. The "parathyroid" theory: clinical hypervitaminosis. Lancet 1932;1:1031-1038.

57. Forfar JO, Tompsett SL, Forshall W. Biochemical studies in idiopathic hypercalcemia in infancy. Arch Dis Childh 1959;34: 525-537.

58. Seelig MS. Vitamin D and cardiovascular, renal, and brain damage in infancy and childhood. An NY Acad Sci 1969;147: 537-582.   59. Seelig MS. Magnesium deficiency with phosphate and vitamin D excesses: role in pediatric cardiovascular disease? Cardiovasc Med 1978;3:637-650.

60. Norman AW, Henry H. 1,25-dihydroxycholecalciferol - a hormonally active form of vitamin D3. Rec Prog Horm Res 1974;30:431-430. 61. Sos J. An investigation into nutritional factors of experimental cardiopathy. In Bajusz E & Rona G, eds.Electrolytes and Cardiovascular Disease: Fundamental Aspects. Baltimore: Williams & Wilkins, 1965:161-180.

62. Selye H. The Pluricausal Cardiomyopathies. Springfield IL: Charles C Thomas, 1961.

63. Karppanen H. Epidemiologic studies on the relationship between magnesium intake and cardiovascular diseases. Artery 1981;9: 190-199.

64. Kalbfleisch JM, Lindeman RD, Ginn HE, Smith WO. Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subjects. J Clin Invest 1963;42:1471-1475.

65. McCollister RJ, Prasad AS, Doe RP, Flink EB. Normal renal magnesium clearance and the effect of water loading, chlorthiazide and ethanol on magnesium clearance. J Lab Clin Med 1958;52:928.

66. McCollister RJ, Flink EB, Lewis MD. Urinary excretion of magnesium in man following the ingestion of alcohol. Am J Clin Nutr 1963;12:415-420.

67. Flink EB, Stutzman FL, Anderson AR, Konig T, Fraser R: Magnesium deficiency after prolonged parenteral fluid administration and after chronic alcoholism complicated by delirium tremens. J Lab Clin Med 1954;43:956-968.

68. Flink EB: Magnesium deficiency in alcoholism. Clin Exp Res 1986; 10:590-594, .

69. Horton R, Biglieri EG. Effect of aldosterone on the metabolism of magnesium. J Clin Endocrin Metab 1962;22:1187-1192.

70. Flink EB, Shane SR, Scobbo RR, Blehschmidt NG, McDowell P. Relationship of free fatty acids and magnesium in ethanol withdrawal in Dogs. Metabolism 1979;28:858-865.

71. Zieve L. Influence of magnesium deficiency on the utilization of thiamine. Ann NY Acad Sci 1969;162:732-743.

72. Itokawa Y, Tseng L-F, Fujiwara M. Thiamine metabolism in magnesium-deficient rats. J Nutr Sc Vit 1974;20:249-255.

73. Itokawa Y, Inoue K, Natori Y, Okazaki K, Fujiwara M. Effect of thiamine on growth, tissue magnesium and thiamine levels and on transketolase in magnesium deficient rats. J Vitaminol 1972;18: 159-164.

74. Seelig MS. Nutritional status and requirements of magnesium. Magnesium Bull 1986;8:170-185.

75. Hoffstrom KA: Phosphor, Calcium and Magnesium. Skand Arch Physiol 1916;23:326-420.

76. Franz KB: Magnesium intake during pregnancy. Magnesium 1985;6: 18-27.

77. Endres JM, Sawicki M, Casper JA. Dietary assessment of pregnant women in a supplemental food program. J Am Diet Assoc 1981;79: 121-126.

78. Ashe JR, Schofield FA, Gram MR. The retention of calcium, phosphorus and magnesium during pregnancy: the adequacy of prenatal diets with and without supplementation. Am J Clin Nutr 1979;32:286-291.

79. Johnson NE, Phillips CA: Magnesium contents of pregnant women. In Cantin M, Seelig MS, eds. Magnesium in Health & Disease, New York: SP Med & Sci Books 1980: 827-831.

80. Seelig MS: Possible roles of magnesium in disorders of the aged. In Regelson W, Sinex FM, eds. Intervention in the Aging Process, Part A: Quantitation, Epidemiology, Clinical Research. New York: AR Liss, Inc, 1983:279-205.

81. Johansson G. Magnesium metabolism. Studies in health, primary hyperparathyroidism and renal stone disease. Scand J Urol Nephrol 1979;51:1-47.

82. Mountakalakis TD. Effects of aging, chronic disease, and multiple supplements on magnesium requirements. Magnesium 1987:6:5-11.

83. Vir SC, Love AHG. Nutritional status of institutionalized and non-institutionalized Aged in Belfast. Am J Clin Nutr 1979;32: 1934-1947.

84. Fehlinger R, Fauk D, Seidel K. Hypomagnesemia and transient ischemic cerebral attacks. Magnesium Bull 1984;6:100-104.

85. Heroux O, Peter D, Heggtveit A. Long-term effect of subnormal magnesium on magnesium and calcium contents of organs, on cold tolerance and on lifespan and its pathological consequences in rats. J Nutr 1977;107:1640-1652.

86. Cantin M. Relationship of juxtaglomerular apparatus and adrenal cortex to biochemical and extracellular fluid volume changes in magnesium deficiency. Lab Investig 1970;22:558-568.

87. Mader IJ, Iseri LT. Spontaneous hypopotassemia, hypomagnesemia, alkalosis and tetany due to hypersecretion of corticosterone- like mineralocorticoid. Am J Med 1955;19:976-988.

88. Douglas WW, Rubin RP. The Effects of alkaline earths and other divalent cations on adrenal medullary secretion. J Physiol 1964;175:231-241.

89. Boullin D.J. The action of extracellular cations on the release of the sympathetic transmitter from peripheral nerves. J Physiol 1967;89:85-99.

90. Ising H. Interaction of noise-induced stress and Mg decrease. Artery 1981;9:205-211.

91. Ising H, Bertschat F, Ibe K, Stoboy V, Goossen C, Hengst G. Stress-induced Ca/Mg shifts and vascular response in animals and men; comparison to electrolyte alterations in myocardial infarction patients. Magnesium Bull 1986;8:95-103.

92. Ebel H, Guenther T: Role of magnesium in cardiac disease. J Clin Chem Clin Biochem 1983; 21:249-256.

93. Lehr D, Krukowski M, Colon R. Correlation of myocardial and renal necrosis with tissue electrolyte changes. JAMA 1966; 197:105-112.

94. Kraikitpanitch S, Haygood CC, Baxter DJ, Yunice AA, Lindeman RD. Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs. Am Heart J 1976;92:615-622.

95. Lehr D. Magnesium and cardiac necrosis. Magnesium Bull 1981; 3(1A):178-191.

96. Abraham AS, Baron E, Eylath U. Changes in the magnesium content of tissues following myocardial damage in rats. Med Biol 1981;59: 99-102.

97. Fleckenstein A, Janke J, Doering HJ, Pachinger O. Myocardial fiber necrosis due to intracellular Ca overload - a new principle in cardiac pathophysiology. Rec Adv Stud Card Struct Metabol 1972;4:563-580.

98. Spah F, Fleckenstein A. Evidence of a new preferentially Mg- carrying transport system besides the fast Na and the slow Ca channels in the excited myocardial sarcolemma membrane. J Mol Cell Cardiol 1979;11:1109-1129.

99. Maguire ME, Erdos JJ. Magnesium but not calcium accumulation is inhibited by B-adrenergic stimulation in S49 lymphoma cells. J Biol Chem 1978;253:6633-6635.

100. Rayssiguier Y. Hypomagnesemia resulting from adrenalin infusion in ewes: its relation to lipolysis. Horm Metab Res 1977;9:309-314.

101. Flink EB, Brick JE, Shane SR: Alterations of long-chain free fatty acid and magnesium concentrations in acute myocardial infarction. Arch Intern Med 1981;141:441-443.

102. Elliott DA, Rizak MA. Epinephrine and adrenocorticotropic hormone-stimulated magnesium accumulation in adipocytes and their plasma membranes. J Biol Chem 1973;249:3985-3990.

103. Vormann J, Foerster R, Guenther T, Ebel H. Lipolysis-induced Mg uptake into fat cells. Magnesium Bull 1983;5:39-41.

104. Altura BT. Type A behavior and coronary vasospasm: a possible role of hypomagnesemia. Med Hypoth 1980;6:753-757.

105. Henrotte JG. Type A behavior and magnesium metabolism. Magnesium

106. Simon J, Kruzej E, Svarc V, Krizk M. Correlation of A B behavior pattern, alcohol intake, HDL-cholesterol and serum magnesium levels in middle-aged men. Act Nerv Super 1983;25:105-107.

107. Henrotte JG, Plouin PF, Levy-Leboyer G, Moser G, Sideroff- Girault N, Franck G, Santarromana M, Pineau M. Blood and urinary magnesium, zinc, calcium, free fatty acids and catecholamines in type A and type B subjects. J Am Coll Nutr 1985;4:165-172.

108. Durlach J (Transl by D Wilson). Magnesium in Clinical Practice. London: J Libbey & Co, 1988.

109. Classen H-G, Classen O, Fischer G, Fischer H, Helbig J, Rummler HG, Schimatschek H. Magnesium: Prevention of stress-induced cardiovascular damage. Magnesium Bull 1986;8:140-144.

110. Ducroux T: L'Enfant spasmophile. Aspects diagnostiques et therapeutiques. Magnesium Bull 1984;6:9-16.

111. Heggtveit HA. The cardiomyopathy of Mg-deficiency. In Bajusz E, ed. Electrolytes and Cardiovascular Diseases, Vol 1. New York: S Karger, 1965:204-220.

112. Heggtveit HA, Tanser L, Mishra RK. Cardiac necrosis and calcification in experimental magnesium deficiency. Am J Path 1964;45:757-782.

113. Sordahl LA. Effects of magnesium, ruthenium red, and the antibiotic ionophore A-23187 on initial rates of calcium uptake and release by heart mitochondria. Arch Biochem Biophys 1974;167:103-115.

114. Sordahl LA, Silver BB. Pathological accumulation of calcium by mitochondria: modulation by magnesium. Rec Adv Structure & Metabolism 1975;6:85-93.

115. Janke J, Fleckenstein A, Hein B, Leder O, Sigel H. Prevention of myocardial Ca overload and necrotization by Mg and K salts or acidosis. Rec Adv Stud Card Struct Metab 1975;6:33-42.

116. Lehr D, Chau R, Irene S. Possible role of magnesium loss in the pathogenesis of myocardial fiber necrosis. Rec Adv Stud Card Struct Metab 1975;6:258-273.

117. Heggtveit HA. Contribution of electron microscopy to the study of myocardial ischemia. WHO 1971;41:865-872.

118. Altura BM, Altura BT. New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system, I. Clinical aspects. Magnesium 1985;4:226-244.

119. Altura BM, Altura BT. New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system. II. Experimental aspects. Magnesium 1985;245-271.

120. Bloom S. Coronary arterial lesions in Mg-deficient hamsters. Magnesium 1985:4:82-95.

121. Duguid JB. Thrombosis as a factor in the pathogenesis of coronary atherosclerosis. J Pathol Bacteriol 1946;58:207-212.

122. Stevenson MM, Yoder I. Studies of platelet aggregation, plasma adenosine diphosphate breakdown, and blood coagulation in magnesium deficient calves and rats. Thromb Diath Hemorrh 1972; 23:299-305.

123. Adams JH, Mitchell JRA: The effect of agents which modify platelet behavior and of magnesium ions on thrombus formation in vivo. Thrombos Haemostas 1979;42:603-610.

124. Gertz SD, Wajnberg RS, Kurgan A, Uretzky G. Effect of magnesium sulfate on thrombus formation following partial arterial constriction: implications for coronary vasospasm. Magnesium 1987;6:225-235.

125. Durlach J. Magnesium deficiency thrombosis (letter). Lancet 1967;1:1967.

126. Durlach J. Pilule, et thrombose (des plaquettes, des estrogens et du magnesium). Rev Fr Endocrinol Clin 1970;11:45-54.

127. Hughes A Tonks RS. Platelets, magnesium and myocardial infarction. Lancet 1965;1:1044-1046.

128. Cohen L, Kitzes R. Prompt termination and/or prevention of coldpressor-stimulation-induced vasoconstriction of different beds by magnesium sulfate in patients with Prinzmetal's angina. Magnesium 1986;5:144-149.

129. Roberts WC, Buja LM. The frequency and significance of coronary arterial thrombi and other observations in fatal acute myocardial infarction. Am J Med 1972;52:425-443.

130. Hudson REB. The cardiomyopathies: order from chaos. Am J Cardiol 1970;25:70-77.

131. Altura BM, Ischemic heartdisease and magnesium. Magnesium 1988; 7:57-67.

132. Ross R, Glomsett JA. The pathogenesis of atherosclerosis. N Engl L Med 1976;195:420-425.

133. Borchgrevink PC, Oksendal AN, Jynge P. Acute extracellular magnesium deficiency and myocardial tolerance to ischemia. J Am Coll Nutr 1987;6:125-130.

134. Chang C, Varghese PJ, Downey J, Bloom S. Magnesium deficiency and myocardial infarct size in the dog. J Am Coll Cardiol 1985;5: 280-289.

135. Hearse DJ, Stewart DA, Braimbridge MVL. Myocardial protection during ischemic cardiac arrest. The importance of magnesium in cardioplegic infusates. J Thor Cardiavasc Surg 1978;75:877-885.

136. Shattock MJ, Hearse DJ, Fry CH: The ionic basis of the anti- ischemic and anti-arrhythmic properties of magnesium in the heart. J Am Coll Nutr 1987;6:27-33.

137. Mansford KRL, Hearse DJ. Metabolic approaches to myocardial infarction. In Hems DA, ed.Biologically Active Substances: Exploration and Exploitation. Chichester: John Wiley & Sons, 1977:239-264.

138. Greenberg D, Tufts E. The nature of magnesium tetany. Am J Physiol 1938;121:416-423.

139. Syllm-Rapoport I, Strassburger I, Gruneberg D, Zirbel C. Electrocardiographic studies in dogs with experimental magnesium deficiency. J Paediat 1962; 60:801-804.

140. Wener J, Pintar K, Simon MA, Motola R, Friedman R, Mayman A, Schucher R. The effects of prolonged hypomagnesemia on the cardiovascular system in young dogs. Am Heart J 1964;67:221-231.

141. Vitale JJ, Hellerstein EE, Nakamura M, Lown B. Effects of magnesium-deficient diet upon puppies. Circ Res 1961;9:387-394.

142. Seelig MS. Electrocardiographic patterns of magnesium depletion appearing in alcoholic heart disease. Ann NY Acad Sci 1969; 162:906-917.

143. Burch GE, Giles TD. The importance of magnesium deficiency in cardiovascular disease. Am Heart J 1977;4:649-657.

144. Sheehan JP, Seelig MS. Interactions of magnesium and potassium in the pathogenesis of cardiovascular disease. Magnesium 1984;301- 314.

145. Rude RK, Oldham SB, Sharp CF, Singer FR. Parathyroid hormone secretion in magnesium deficiency. J Clin Endocrinol Metab 1978; 47:800-806.

146. Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J 1984;108:188-193.

147. Dyckner TH, Wester PO. Magnesium-electrophysiological effects. Magnesium Bull 1986;8:219-222.

148. Kulick DL, Hong R, Ryzen E, Rude RK, Rubin JN, Elkayam U, Rahimtoola SH, Bhandari AK. Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease. Am Heart J 1988;115:367-373.

149. Abraham AS, Rosenman D, Meshulam Z, Zion M, Eylath U. Serum, lymphocyte, and erythrocyte potassium, magnesium, and calcium concentrations and their relation to tachyarrhythmias in patients with acute myocardial infarction. Am J Med 1986;81:983-988.

150. Ising H, Guenther T, Bertschat F, Ibe K, Stoboy V, Heldman E. Alterations of electrolytes in serum and erythrocytes after myocardial infarction. Magnesium 1987;6:192-200.

151. Abraham AS. Potassium and magnesium status in ischaemic heart disease. Magn Res 1988;1: 53-57.

152. Rasmussen HS, McNair P, Goransson L, Balslov S, Larsen OG, Aurup P. Magnesium deficiency in patients with ischemic heart disease with and without acute myocardial infarction uncovered by an intravenous loading test. Arch Intern Med 1988;148:329-332.

153. Ryzen E, Elkayam U, Rude RK. Low blood mononuclear cell magnesium in intensive cardiac care unit patients. Am Heart J 1986;111: 475-480.

154. Randall RE Jr, Rossmeisl EC, Bleifer KH. Magnesium depletion in man. Ann Intern Med 1959;50:257-287.

155. Brigden W, Robinson J. Alcoholic heart disease. Br Med J 1964; 2:1283-1289.

156. Fankushen D, Raskin D, Dimich A, Wallach S. The significance of hypomagnesemia in alcoholic patients. Am J Med 1964;37:802-812.

157. Loeb HS, Raymond P, Gunnar RM, Tobin JR. Paroxysmal ventricular fibrillation in two patients with hypomagnesemia. Treatment by transvenous pacing. Circulation 1968;37:210-215.

158. Ricketts HH, Denison EK, Haywood IJ. Unusual T-wave abnormality. Repolarization alternans associated with hypomagnesemia, acute alcoholism and cardiomyopathy. JAMA 1969;207:365-366.

159. Luomanmaki K, Heikkila J, Hartikainen M. T-wave alternans associated with heart failure and hypomagnesemia in alcoholic cardiomyopathy. Europ J Cardiol 1975;3:167-170.\

160. Kellaway G, Ewen K. Magnesium deficiency complicating prolonged gastric suction. New Zeal Med J 1962;61:137-142.

161. Thoren L. Magnesium deficiency in gastrointestinal fluid loss. Acta Chir Scand 1963;Suppl 306:1-65.

162. Levine SR, Crowley TJ, Hai HA. Hypomagnesemia and ventricular tachycardia. Chest 1982;81:244-247.

163. Lim P, Jacob E. Tissue magnesium level in chronic diarrhea. J Lab Clin Med 1972;80:313-321.

164. Caddell JL. The effect of magnesium therapy on cardiovascular and electrocardiographic changes in severe protein-calorie malnutrition. Trop Geogr Med 1969;21:33-38.

165. Dooling ED, Stern L. Hypomagnesemia with convulsions in a newborn infant. Report of a case associated with maternal hypophosphatemia. Can Med Assc J 1967;97:827-831.

166. Bajpai PC, Hasan M, Gupta AK, Kunwar KB. Electrocardiographic changes in hypomagnesemia. Indian Heart J 1972;24:271-276.

167. Killen DA, Grogan EL II, Gower IE, Collins IS, Collins HA. Effect of ACD blood prime on plasma calcium and magnesium. Ann Thorac Surg 1972;18:371-380.

168. Scheinman MM, Sullivan RW, Hyatt KH. Magnesium metabolism in patients undergoing cardiopulmonary bypass. Circulation 1969;39- 40(Suppl I);40:1235-1241.

169. Holden MP, Ionescu MI, Wooler GH. Magnesium in patients undergoing open-heart surgery. Thorax 1972;27:212-218.

170. Holden MP. The value of magnesium supplements during open-heart surgery. A double-blind trial. In Naito KH, ed. Nutrition and Heart Disease. SP Press 1982:273-283.

171. Khan RMA, Hodge JS, Bassett HFM. Magnesium in open-heart surgery. J Thorac Cardiovasc Surg 1973;66:185-191.

172. Hearse DJ, Stewart DA, Braimbridge MV. Cellular protection during myocardial ischemia. The development and characterization of a procedure for the induction of reversible ischemic arrest. Circulation 1976;54:193-202.

173. Morton BC, Smith FM, McKibbon TJ, Nair RC, Poznanski WJ. Magnesium therapy in acute myocardial infarction. Magnesium Bull 1981;3(1A):192-194.

174. Morton BC, Smith FM, Nair RC, McKibbon TG, Poznanski WJ. The clinical effects of magnesium sulphate treatment in acute myocardial infarction. Magnesium Bull 1984;4:133-136.

175. Rasmussen HS, McNair P, Norregard P, Backer V, Lindeneg O, Balslev S. Intravenous magnesium in acute myocardial infarction. Lancet 1986:234-236.

176. Abraham AS, Rosenman D, Kramer M, Balkin J, Zion MM, Farbstein H, Eylath U. Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction. Arch Intern Med 1987;147:753-755.

177. Rasmussen HS. Justification for intravenous magnesium therapy in acute myocardial infarction. Magn Res 1988;1:59-73.

178. Dyckner T. Serum magnesium in acute myocardial infarction. Acta med scand 1980;207:59-66.

179. Packer M. Sudden unexpected death in patients with congestive heart failure: a second frontier. Circulation 1985;72:681-685.

180. Wester PO, Dyckner T. Intracellular electrolytes in cardiac failure. Acta Med Scand 1986;707Suppl:33-36.

181. Wester PO, Dyckner T. Magnesium in cardiac failure and diuretic treatment. Magnesium Bull 1986;8:204-209.

182. Packer M, Gottlieb SS, Blum MA. Immediate and long-term pathophysiologic mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. Am J Med 1987;82 (Suppl 3A):4-10, 1987.

183. Francis GS. Neurohumoral mechanisms involved in congestive heart failure. Am J Cardiol 1985;55:15A-21A.

184. Dyckner T, Wester PO: Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment. Am Heart J 1979;97:12-18.

185. Luccioni R, Frances Y, Kiegel P, Collet F. Prolapsus valvulaire mitral - spasmophilie et deficit magnesien. Magnesium Bull 1982;4:62-67.

186. Galland LD, Baker SM, McLellan RK. Magnesium deficiency in the pathogenesis of mitral valve prolapse. Magnesium 1986;5:165-174.

187. Henrotte JG. The variability of human red blood cell magnesium level according to HLA groups. Tissue-Antigens 1980;15:419-430.

188. Braun WE, Ronan JA, Schachter B, Gardin J, Isner J, Greek D. HLA antigens in mitral valve prolapse. Transplant Proc 1977;9:1869- 1871.

189. Kaplan NM: Dietary aspects of the treatment of hypertension. Ann Rev Public Health 1986;7:503-519.

190. McCarron DA, Morris CD, Cole C. Dietary calcium in human hypertension. Science 1982;267-269, .

191. Kaplan NM, Meese RB. The calcium deficiency hypothesis of hypertension: a critique. Ann Intern Med 1986;105:947-955.

192. Haddy FJ, Seelig MS. Magnesium and the Arteries. II. Physiologic effects of electrolyte abnormalities on arterial resistance. In Cantin M, Seelig MS, eds. Magnesium in Health and Disease. New York: SP Med & Sc Books, 1980:639-657.

193. Altura BM. Altura BT. Interactions of Mg and K on blood vessels - aspects in view of hypertension. Review of present status and new findings. Magnesium 1984;3:175-194.

194. Altura BM, Altura BT. Role of magnesium ions in contractility of blood vessels ans skeletal muscles. Magn Bulletin 1981;3:102-114.

195. Seelig MS, Berger AR, Avioli LA. Speculations on renal hormonal, and metabolic aberrations in a patient with marginal magnesium deficiency. In Cantin M, MS Seelig, eds. Magnesium in Health and Disease. New York: SP Med & Sc Books, 1980:459-468.

196. Resnick LM, Laragh JH, Sealy JE, Alderman MH. Divalent cations in essential hypertension. New Engl J Med 1983;309:888-891.

197. Resnick LM, Gupta RK, Laragh JH. Intracellular free magnesium in erythrocytes of essential hypertension: relation to blood pressure and serum divalent cations. Proc Natk Acad Sci USA 1984;81:6511-6515.

198. Resnick LM. Uniformity and diversity of calcium metabolism in hypertension. A conceptual framework. Am J Med 1987;82(suppl 1B): 16-26.

199. Dyckner T, Wester PO. Effects of magnesium infusions in diuretic induced hyponatremia. Lancet 1981;1:585-586.

200. Dyckner T, Wester PO. Effect of magnesium on blood pressure. Br Med J 1983;286:1847-1849.

201. Zwillinger L. On magnesium's effect on the heart. Klin Wochenschr 1935;14:1429-1433. (in German)

202. Kim YW, Andrews CE, Ruth WE. Serum magnesium and cardiac arrhythmias with special reference to digitalis intoxication. Am J Med Sci 1961;242:87-92.

203. Beller GA, Hood WB Jr, Smith TW, Abelmann WH, Wacker WEC. Correlation of serum magnesium levels and cardiac digitalis intoxication. Am J Cardiol 1974;33:225-229.

204. Iseri LT. Potassium, magnesium, and digitalis toxicity. In Whang R, ed. Potassium: Its Biologic Significance . Boca Raton FLa: CRC Press, 1983:125-135 .

205. Cohen L, Kitzes R. Magnesium sulfate and digitalis toxic arrhythmias. JAMA 1983;249:2808-2810.

206. Whang R, Oei TO, Watanabe A. Frequency of hypomagnesemia in hospitalized patients receiving digitalis. Arch Intern Med 1985; 145:655-656.

207. DeCarli C, Sprouse G, LaRosa JC. Serum magnesium levels in symptomatic atrial fibrillation and their relation to rhythm control by intravenous digoxin. Am J Cardiol 1986;57:956-959.

208. Kass RS, Lederer WJ, Tsien RW, Weingart R. Role of calcium ions in transient inward current and after contraction induced by strophanthidin in cardiac Purkinje fibers. J Physiol (London) 1978;281:187-208.

209. Specter MJ, Schweizer E, Goldman RH. Studies on magnesium's mechanism of action in digitalis induced arrhythmias. Circulation 1975;52:1001-1005.

210. Ghani MF, Smith JR. The effectiveness of magnesium chloride in the treatment of ventricular tachyarrhythmias due to digitalis intoxication. Am Heart J 1974;88:621-626.

211. MacIntyre I, Hanna S, Booth CC, Read AE. Intracellular magnesium deficiency in man. Clin Sci 1961;20:297-305.

212. Lim P, Jacob E, Dong S, Khoo OT. Values for tissue magnesium as a guide for detecting magnesium deficiency. J Clin Path 1969; 22:417-421.

213. Merrill JP, Hampers CL. Uremia (Med Progr Series). N Engl J Med 1970;282:1014-1021.

214. Sheehan J, White A. Diuretic-associated hypomagnaesemia. Br Med J 1982;285:1157-1159.

215. Martin BJ, Milligan K: Diuretic-associated hypomagnesemia in the elderly. Arch Intern Med 1987;1768-1771.

216. Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82 (Suppl 3A):30-37.

217. Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial: risk factor changes and mortality results. JAMA 1982;248:2465-2477.

218. Sherwin R. Sudden death in men with increased risk of myocardial infarction - the MRFIT Program. Drugs 1984;28 (Suppl 1):46-53.

219. Whelton PK. Diuretics and arrhythmias in the Medical Research Council Trial. Drugs 1984;28 (Suppl 1):54-65.

220. Morgan TO, Adams WR, Hodgson M, Gibberd RW. Failure of therapy to improve the prognosis in elderly males with hypertension. Med J Aust 2: 27-31, 1980.

221. Amery A, Birkhager W, Brixko P.: Mortality and morbidity results from the European Working Party on high blood pressure in the elderly. Lancet 1985;1:1249-1354.

222. Kuller L, Farrier N, Caggiula A, Borhani N, Dunkle S. Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Facor Intervention Trial. Am J Epidemiol 1985;122:1045-1059.

223. Holliday MA, Lukenbill A, Hancock C. Acute metabolic alkalosis: its effect on potassium and acid excretion. J Clin Invest 1955; 34:428-433.

224. Atkins EL, Schwartz WB: Factors governing correction of the alkalosis associated with potassium deficiency; the critical role of chloride in the recovery process. J Clin Invest 1962;41: 218-229.

225. Kassirer JP, Berkman PM, Lawrenz DR, Schwartz WB. The critical role of chloride in the correction of hypokalemic alkalosis in man. Am J Med 1965;38:172-190.

226. Iseri LT, Fairshter RD, Hardemann JL, Brodsky MA. Magnesium and potassium therapy in multifocal atrial tachycardia. Am Heart J 1985;110:789-794.

227. Whang R, Wagner R. The influence of venous occlusion and exercise on serum magnesium concentration. Metabolism 1966;15:608-612.

228. Engel RR, Elin RJ. Hypermagnesemia from birth asphyxia. J Pediat 1970;77:631-637.

229. Brater DC, Morrelli HF. Systemic alkalosis and digitalis related arrhythmias. Acta Med Scand 1981;647:79-85.

230. Urakabe S, Nakata K, Ando A, Orita Y, Abe H. Hypokalemia and metabolic alkalosis resulting from overuse of magnesium oxide. Jpn Circ J 1975;39:1135-113.

231. Schimatschek HT, Classen HG, Thoni H, Haubold W. Acid-base changes in rats kept on highly magnesium enriched diets using different magnesium compounds. Magn Bulletin 1987;9:161-176. (in German)

232. Classen H-G, Marquardt P, Spaeth M, Ebel H, Schumacher K-A. Improvement by chlorine of the intestinal absorption of inorganic and organic Mg-compounds and their protective effect against adrenergic cardiopathy. Rec Adv Stud Card Struct Metab 1975;111-119.

233. Classen H-G. Magnesium and potassium deprivation and supplementation in animals and man: aspects in view of intestinal absorption. Magnesium 1984;2:257-264.

234. Classen H-G, Fischer G, Jacob R, Marx J,Schimatschek H, Stein C. Prenecrotic electrolyte alterations of the adrenergic cardiopathy: potentiation by magnesium depletion and prevention by high dietary magnesium levels and verapamil. Magnesium Bulletin 1986;8: 82-92.

235. Bajusz E. Age factor and myocardial necrosis: experimental studies on the sensitizing effect of K-, Mg-, and Cl- deficiencies. Gerontologia 1963;8:66-80.

236. Davis WH, Ziady F. The effect of oral magnesium chloride therapy on the QTc and QTu intervals of the electrocardiogram. S Afr Med J 1978;53:591-593.

237. Reyes AJ, Leary WP, Acosta-Barrios TN, Davis WH. Magnesium supplementation in hypertension treated with hydrochlorthiazide. Curr Ther Res 36:332-340, 1984.

This page was first uploaded to The Magnesium Web Site on October 18, 1995