Magnesium Trace Elem 1990;9:143-151
Sudden cardiac death - Coronary heart disease
Abstract: Magnesium may be important in the pathogenesis of coronary heart disease and sudden death. To study the role of magnesium, 400 high risk individuals were asked to volunteer either for a magnesium-rich diet (group A, 206) or for our usual diet (group B, 194) for 10 years in a randomized fashion. The age groups were between 25 and 63 years and the majority (374) of them were males. At entry to the study, age, sex, incidence of hypertension, diabetes, hypercholesterolemia, smoking, coronary disease and diuretic therapy were comparable. Dietary magnesium intake in group A (1, 142 ± 233 mg/day) was higher than in group B (418 ± 105 mg/day). Total complications in group A (59; 28.6%) were significantly (p < 0.01) less compared to group B (117; 60.3 %). Sudden deaths were one and a half times more common in group B than in group A. Total mortality in group A (22; 10.7%) was significantly (p < 0.01) less than in group B (34; 18.0%). A greater number of complications and increased mortality in group B subjects was consistent with a higher incidence of hypokalemia, hypomagnesemia and coronary risk factors in group B patients. Mean serum magnesium levels in group B participants were significantly (p < 0.01) lowered compared to the mean magnesium level in group A participants who were administered the magnesium-rich diet. It is possible that increased intake of dietary magnesium in association with the general effects of a nutritious diet can offer protection against cardiovascular deaths among high-risk individuals predisposed to coronary heart disease.
Introduction An increased incidence of sudden cardiac death (SCD) has been observed in soft water areas with lowered water content of magnesium [1a, 2, 3, 20, 22, 23]. A lowered myocardial magnesium content has also been demonstrated in victims dying of SCD and in road accidents in these areas compared to other areas [12, 22, 23]. The magnesium content of the infarcted portion of the myocardium was found to be lowered compared to noninfarcted myocardium . Clinical and experimental studies emphasize that hypomagnesemia may be associated with arrhythmias and replacement of magnesium ions has been suggested [2, 3, 7, 13, 26, 27] and proposed [24, 28] to be useful in the prevention of sudden deaths due to cardiac arrhythmias. Diuretic-induced loss of cations can predispose to sudden deaths among patients with hypertension and coronary disease, particularly in the setting of acute myocardial infarction [7, 13].
Epidemiologic studies [14, 181 showed a significant positive correlation between incidence of ischemic heart disease (IHD) and the calcium/magnesium ratio of food and water ingested. A positive correlation was also noted between dietary sodium/magnesium ratio and incidence of hypertensive heart disease. A magnesium-deficient diet has been reported to cause a rise in blood pressures in Wistar rats [lb]. Magnesium deficiency can influence electrolyte transport across the cell membrane and enhance coronary artery tone [2, 28]. It may also predispose to increased adrenergic activity, enhanced vascular reactivity, spasm, platelet dysfunction and thrombosis [2, 3, 6). Magnesium administration in acute myocardial infarction can reduce arrhythmias and mortality .
In view of these observations, the purpose of this study was to examine the effect of dietary magnesium in the prevention of IHD and SCD among high-risk free living individuals.
The study dietitian recruited urbanized adults with major or minor risk factors, with or without cardiovascular disease, by advertisements in the local clubs and newspapers. Respondents having cancer, chronic renal failure, chronic diarrhea and dysentery or who felt unable to participate were excluded from this study. Clinical, electrocardiographic, radiologic and laboratory data were obtained in all the participants during 2 weeks of surveillance before admission to the study. Exercise electrocardiograms were done to confirm the presence or absence of IHD in all the participants. Blood pressures were measured after 5 min of rest lying comfortably in a supine position, by a mercury sphygmomanometer by the same person. Korotkoff sounds, phase V, were recorded for diastolic blood pressure. Hypertension was diagnosed in the presence of blood pressures above 150/95 mm Hg, diabetes by a positive glucose tolerance test, smoking by consumption of more than 10 cigarettes/day, obesity by 10 % more weight than normal for that age and sex. Hypercholesterolemia was diagnosed in the presence of fasting serum cholesterol of more than 250 mg/dl. Presence of these major and/or minor risk factors of IHD was considered a high risk for the study population. The diagnosis of IHD, arrhythmias, ischemia, prolonged Q-T interval, left ventricular strain or elements and physical inactivity was based on criteria laid down by the WHO .
Laboratory data included blood urea, sugar, total cholesterol, low- and high-density lipoprotein cholesterol, total blood leukocytes, hemoglobin, serum sodium potassium , magnesium , calcium  and albumin. The criteria of SCD was death occurring within 1 h either due to IHD or without any apparent cause. The study dietitian divided all the participants into two groups alternately in a randomized fashion after informed consent and the physician responsible was blinded to dietary regimens. Group A included persons on a magnesium-rich dietary protocol and group B included persons on our usual diet. Participants who discontinued the trial during follow-up were excluded. Only those participants who completed a minimum of 10 years have been included in the analysis of the data.
The aim during the study period was to achieve a stable body weight on the lower side of normal weight for that age, sex and height. The diets for the obese and hyperlipidemic persons were lower in total fat content and had the same ratio of polyunsaturated fatty acids to saturated fatty acids that are recommended for group A subjects. Consumption of energy by different individuals ranged from 1,200 kcal to 2,500 kcal, and nutrients were adjusted accordingly in both of the groups. The distribution of various nutrients in the diet taken by the two groups (obtained by food composition tables ) is shown in table 1. In the magnesium-rich diet, fruits, green vegetables, cereals and nuts were given to group A participants.
Dietary advice was reinforced vigorously and regularly at 1-4 weekly visits to all participants in particular to those with risk factors for coronary disease, e.g., diabetes, hypertension, hypercholesterolemia, myocardial infarction and angina. All of the participants completed dietary diaries beginning at week 2, week 4, week 6, week 12 and then every 12 weeks (biannually in asymptomatic subjects without risk factors) to assess dietary compliance. Each participant was asked regularly to follow, closely, the dietary advice and fill out a questionnaire regarding dietary intakes at separate counseling sessions by the dietitian and the physician, respectively. The dietitian also made home visits to educate housewives regarding the maintenance of dietary compliance. Apart from dietary diaries, evidence of dietary compliance of the experimental diets, in both groups, was obtained by measuring the serum magnesium in some randomly selected patients at the beginning of weeks 0. 4 and later once per year. We noted a sustained rise in the amount of serum magnesium confirming dietary compliance with the experimental diet.
Follow-up in all symptomatic participants and those with major risk factors for coronary artery disease was made at weeks 1-4 for the entire period and in others at weeks 6-12 for 1 year and later on a biannual basis for 10 years. In those healthy participants who were reluctant to come, details were obtained by telephone, letter and personal visits, whichever was applicable.
Of the 442 respondents, 12 were excluded and 30 cases left the trial before it was completed. The dietary specifications, clinical and laboratory data in the remaining 206 group A and 194 group B patients exhibiting alteration in risk factors are shown in tables 1-3. At entry to the study, there was no significant difference in the proportion of patients in age groups, sex, risk factors, coexisting complications of atheromatous diseases, dietary factors, miscellaneous factors and drugs between the two groups. The incidence of patients with hypomagnesemia and hypokalemia was similar as were other laboratory data in all the patients. A similar rehabilitation program for risk factor modification was followed in both of the groups. The differences in the dietary intakes are shown in table 1. Intervention diet (group A) included increased intake of fruits, vegetables, cereals and nuts which amounted to around 2.5 times more intake of magnesium and potassium in this group compared to control group B. Smoking, alcoholism and drug therapy remained comparable in both the groups. Study of the pattern of risk factor modification showed that smoking was reduced or stopped in 24 patients in group A and 28 patients in group B. Obesity was corrected for 23 patients in group A and 17 in group B. Hypercholesterolemia was corrected for 19 patients in group A and 14 in group B. Alcohol intake was occasional in 12 patients in group A and 15 in group B. Hypokalemia  and hypomagnesemia  became more common in group B, whereas there was no such deficit in group A at end of the study.
Initial mean serum cholesterols were in the high to normal range without a significant difference between the two groups (table 3). After 10 years of magnesium-rich dietary therapy in group A, and our usual diet in group B, there was a significant fall in serum cholesterol in both groups compared to basal levels but without a significant difference between the two groups. There was no significant difference in the incidence of hypokalemia, hypomagnesemia, IHD, angina and arrhythmias between the two groups, initially. However, after 10 years, the incidence of predisposing factors such as hypokalemia, hypomagnesemia and total complications such as IHD, angina and arrhythmias were significantly higher in group B compared to the intervention group (tables 2-4).
There was a rise in serum magnesium and potassium in participants with deficiency of these cations in group A compared to no such rise in group B participants with a similar deficit. The majority of these patients with mineral deficits, particularly hypokalemia and hypomagnesemia, were hypertensives receiving diuretics. The mean serum magnesium and potassium levels after the study in total number of mineral-rich-diet-supplemented group A patients were also significantly higher compared to the mean levels of these cations in group B patients given our usual diet (table 3).
The incidence of sudden death and deaths due to IHD in group A (19; 10.2 %) was significantly (p < 0.02) less compared to such deaths (30; 1 5.2 %) in group B (table 4). This complication occurred mostly in males between 51 and 60 years of age. The majority of them had IHD or risk factors for coronary disease. A few victims in group B had frank hypomagnesemia (2 cases) and hypokalemia (3 cases) in contrast to the absence of such changes in the intervention group.
During the last five decades, there has been a sharp increase in the prevalence of cardiovascular diseases and sudden IHD deaths following increased intake of saturated fat, refined and preserved food and diminished intake of fruits, vegetables and cereals [1a, 22]. Underlying this syndrome is the tremendous increase in the incidence of atherosclerosis, hypertension and acute myocardial infarction in young age groups. One experimental study  showed that a diet rich in saturated fat, cholesterol, vitamin D, sodium, phosphate, animal proteins and low in magnesium, potassium and polyunsaturated fat given to rats was associated with an increased number of myocardial infarctions, coronary atherosclerosis and hypertension, factors which are now considered to predispose to SCD [la, 10, 24, 25]. Animals on such an experimental diet retained more body sodium, 12% more myocardial calcium and a drop of 19% magnesium and 33 % potassium in the myocardium and 20% of both cations in the serum [26). In a more recent study for dietary prevention of coronary heart disease, there was a significant reduction in the incidence of sudden death in the intervention group compared to control subjects .
Recently, major attention has been paid to antiarrhythmic measures and myocardial factors which produce arrhythmias contributing to SCD . Indeed, more attention should be given to the total spectrum of sudden death cases which involves occurrence of arrhythmias in the setting of IHD [15, 21]. It is possible that changes in life-style and dietary habits which reduce blood cholesterol and IHD mortality might diminish SCD [10, 251. In view of the above studies, showing the relation of nutritional factors and IHD with sudden death, the observations of the present study seem to be logical. It is possible that correction of magnesium and potassium deficiency and increased body status of these cations in association with blood cholesterol reduction offered protection to group A participants against IHD and SCD. Similarly, a low cation status in the presence of hypomagnesemia and hypopotassemia, particularly in the setting of IHD, left ventricular dysfunction and arrhythmia could have precipitated a greater incidence of total complications, sudden deaths and total mortality in group B. Increased intake of dietary magnesium and pharmacological magnesium administration have been found to be protective against atheromatous diseases [1a, 22, 23] and mortality in patients with acute myocardial infarction . It was not possible in our study, however, to separate the effect of hypocholesterolemia and hypokalemia in group A patients from that of hypomagnesemia. Reduction in cholesterol showed no influence upon mortality from SCD [15, 21 ] but the reduction in blood cholesterol in group A on total mortality seems to be important .
In the majority of SCD, the underlying mechanism is ventricular fibrillation which involves electrophysiologic changes due to metabolic and biochemical alterations, occurring across the myocardial cell membrane. These factors in turn may be under the influence of nutrients in the serum and the cells [1a, 2]. One experimental study  showed that coronary arterial reperfusion may be associated with an increase in myocardial tissue water and potassium, loss of magnesium and minimal changes in calcium and sodium ions. A clinical study  showed cellular deficiency of magnesium, potassium and zinc during exercise and stress in type A personality subjects. These studies and observations of the present work indicate that magnesium in association with other dietary factors may have a role not only in the pathogenesis of IHD and SCD but also in their prevention, particularly in patients with major risk factors for IHD.
I am grateful to Vipin for secretarial help and to Sushav, Reema and Kartick for support.
1a Altura, B.M.: Ischemic heart disease and magnesium. Magnesium 7: 57-67 (1988).
1b Altura, B.M.; Altura, B.T.; Gebrewold, A.; Ising, H.; Gunther, T.: Magnesium deficiency and hypertension, correlation between magnesium deficient diet and microcirculatory changes in situ. Science 223: 1315-1317 (1984).
2 Altura, B.M.; Altura, B.T.: Magnesium electrolyte transport and coronary vascular tone. Drugs 28: 120-142 (1984).
3 Altura, B.M.; Altura, B.T.: New perspective on the role of magnesium in the pathophysiology of cardiovascular system. Clinical aspects. Magnesium 4: 226-244 (1985).
4 Basuk, W.L; Reimer, K-L; Jennings, R.B.: Effect of repetitive episodes of ischaemia on cell volume, electrolytes and ultrastructure. J. Am- Coll. Cardiol. 8: 33A-41A (1986).
5 Bigger, J.T.; Fleiss, J.L; Kleiger, R.L; Miller, J.R.; Rolnitzsky, LM.; the multicentre postinfarction research group: T'he relationship among ventricular arrhythmias, left ventricular dysfunction and mortality in two years after myocardial infarction. Circulation 69: 250-255 (1981).
6 Chadda, K-D.; Essman, E.J.; Schultg, N.: Alpha adrenergic receptors and induced hypomagnesemia. Magnesium 2: 125-131 (1983).
7 Dyckner, T.; Wester, P.O.: Clinical significance of diuretic-induced magnesium loss. Pract. Cardiol. 10: 124-133 (1984).
8 Gindler, E.M.; King, J.D.: Determination of calcium in plasma. Am. J. clin. Path. 58: 376-386 (1972).
9 Gopalan, C.; Rama Sastri, B.V.; Balasubramanium, S.C.: Nutrition value of Indian foods (National Institute of Nutrition. Publication, Hyderabad 1976).
10 Hajermann, I.; Holm, I.; Gyre, K.V.; Leren, R.: Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo study group of a randomized trial in healthy men. Lancet i.: 1303-1310 (1981).
11 Henrotte, J.G.; Ploin, P.F.; Levy, L.D.; et al.: Blood erythrocyte and urinary magnesium, zinc, calcium, free fatty acids and catecholamines in type A and B subjects. J. Am. Coll. Nutr. 4: 165- 172 (1985).
12 Johnson, C.J.; Peterson, D.R.; Smith, E.K.: Myocardial tissue concentrations of magnesium and potassium in men dying suddenly from ischemic heart disease. Am. J. clin. Nutr. 32: 960-967 (1971).
13 Kaplan, N.M.: Our appropriate concern about hypokalemia. Am. J. Med. 77: 1-5 (1984).
14 Karppanen, N.: Epidemiological studies on the relationship between magnesium intake and cardiovascular disease. Artery 9: 190-199 (1981).
15 Kannel, W.B.; Schatskin, A.: Sudden death: lesions from subsets in population studies. J. Am. Coll. Cardiol. 5: suppl. 6, p. 141B (1985).
16 Kesteloot, H.: Nutrition and cardiovascular disease. Acta cardiol. 42: 73-77 (1987).
17 Khayam-Bashi, H.; Liu, TJ.; Walter, B.: Determination of serum magnesium by calorimetric method. Clin. Chem. 23: 289-300 (1977).
18 Marier, J.L: Role of environmental magnesium in cardiovascular disease; in Wanto, Nutrition and heart disease, pp. 31-59 (Medical and Scientific Books, New York 1982).
19 Rasmussen, H.S.; McNair, P.K.; Morregord, P.; et al: Intravenous magnesium in acute myocardial infarction. Lancet i: 234-236 (1986).
20 Schroeder, H.A.: Municipal drinking water and cardiovascular death rates. JAMA 95: 125-135 (1966).
21 Schatskin, A.; Cupples, LA.; Heeren, T.; Moreleck, S.; Mucatcl, M.; Kannel, W.B.: The epidemiology of sudden unexpected death: risk factor for men and women in the Framingham Heart Study. Am. Heart J. 107: 1300-1310 (1984).
22 Seelig M.S.; Heggtvcit, H.A.: Magnesium interrelationships in ischaemic heart disease. Am. J. clin. Nutr. 27: 59-75 (1974).
23 Singh, R.B.; Singh, V.P.; Cameron, E.A.: Magnesium in atherosclerotic cardiovascular disease and sudden death. Acta cardiol. 36: 411-429 (1981).
24 Singh, R.B.: Effect of dietary minerals on the incidence of sudden cardiac death. Trace Elem. Med. 7: 19-24 (1990).
25 Singh, R.B.: Multifactorial risk factor intervention for sudden cardiac death: the Indian diet heart preliminary study. J. Adv. Med. 2: 475-485 (1989).
26 Sos, J.: An investigation into the nutritional factors of experimental cardiopathy. Electrolytes cardiovasc. Dis. 1: 167-180 (1965).
27 Szclenyi, I.: Physiological interrelationship between magnesium and the heart; in Durlach, International Symposium on Magnesium, Vittel 197 1, pp. 195-21 1.
28 Turlapaty, P.D.M.V.; Altura, B.M.: Magnesium deficiency produces spasms of coronary arteries: relationship to etiology of sudden cardiac death. Science 208: 198-200 (1980).
29 Varley, H.; Gowealock, A.H.; Bell, M.: Sodium, potassium and chloride by flame photometer. Prac. Clin. Biochem., pp. 850-900 (Heinemann Medical Books, London 1980).
30 World Health Organization: Rehabilitation and comprehensive secondary prevention after acute myocardial infarction, pp. 5-15 (WHO, Geneva 1983).
R.B. Singh, MD, FICN
Director, Cardiologist and
Professor of Clinical Nutrition (Hon.)
Moradabad 10 (India)
This page was first uploaded to The Magnesium Web Site on June 19, 1996