Magnesium, Antioxidants and Myocardial Infarction
The retrospective dietary study and hospital admission and
follow-up laboratory and clinical investigation of 505 patients
with suspected acute myocardial infarction (AMI), as reported in
this issue by Singh et al [1], provides insight into
epidemiologic observations that have suggested different
explanations of geographic and ethnic differences in incidence of
coronary arterial disease (CAD). Their findings support the
established implication of high intake of cholesterol and total
fat by those developing AMI and other CAD, and also support the
premise that low magnesium (Mg) levels increase the risk of
arrhythmias. Although Mg intakes of the cardiac patients were
only moderately lower than that of noncardiac patients, the serum
Mg levels that were marginally low in almost all of the patients
were lowest in patients with rhythm disturbances.
Their observations also suggest that the etiology is
multifactorial, implicating not only excess fat and low Mg, but
also low potassium (K), fiber, and antioxidant intakes. Group A
(335 patients) had enzymatic and electrocardiographic proof of
AMI; Group B (64 patients), the patients with convincing chest
pain but lower enzyme levels, and those with unstable angina
(Group C: 42 patients), had had significantly greater fat,
cholesterol, and carbohydrate intakes, and somewhat lesser Mg, K,
and fiber intakes than did those (Group D: 42 patients) who had
no characteristics of CAD. Notable is the higher pre-study intake
of fiber from fruit and vegetables in the group free of CAD than
in the cardiac patients. In a study recently published elsewhere
[2], Singh et al reported cardiac improvement in post-AMI
patients consuming fruits, legumes and other vegetables and nuts
(foods rich in antioxidants, as well as in Mg and fiber).
In the paper published in this issue, Singh et al make brief
reference to the relationship of increased catecholamine levels,
found in AMI patients, and accept the premise that the reduction
of serum Mg they observed in their arrhythmic patients might have
been caused by a shift of circulating Mg to ischemic cells,
caused by their increased metabolic requirements for Mg.
However, the high myocardial oxygen consumption—which
has been attributed to catecholamine-induced lipolysis with
increased free fatty acid (FFA) levels, through an energy wasting
triglyceride—fatty acid cycle-has been blamed for the
prevalence of post-infarction arrhythmias and sudden cardiac
death [3,4]; this has been correlated with FFA binding of Mg [5].
Furthermore, the risk of catecholamine-induced arrhythmias is
greater when the Mg status is suboptimal. Mg deficiency increases
secretion of catecholamines [6-9]. Additionally, the initial
change in intracellular myocardial Mg after AMI and/or increased
catecholamine secretion is likely to be decreased, rather than
increased. Administration to rats of a single dose of
catecholamine just sufficient to cause multifocal micronecrosis
in the heart, rather than the large areas of necrosis that are
produced by high dosage (a model of massive AMI) resulted in loss
of myocardial Mg an hour after the injection—the earliest
electrolyte derangement—which was followed by decreased K
and increased calcium and sodium in the myocardial cells [10,
11]. On the other hand, elevation of myocardial Mg might result
from mitochondrial damage caused by ischemia [12], with Mg
present as non-functional crystalline deposits, in which the Mg
is bound to inorganic phosphates [13], rather than from increased
metabolic activity.
It is uncertain whether there is necessarily correlation of
myocardial Mg levels with blood cell levels, which are influenced
by genetic factors that also impact on vulnerability to
cardiovascular disease. For example, type A subjects, who have
lower erythrocyte Mg levels than do type B subjects, exhibit
increased catecholamine secretion in response to stress, as well
as greater prevalence of heart disease [14,15].
Freedman et al have shown that vitamin E protects against Mg
deficiency cardiomyopathy (CMP) [16] and that
catecholamine-induced CMP is intensified by Mg deficiency, which
they propose is caused by reduction in the threshold antioxidant
capacity, that is caused by Mg deficiency [17]. Mg supplements,
especially when vitamin E supplements were also given, were
protective against catecholamine cardiotoxicity [17]. The
protection afforded by vitamin E against damage to the heart
caused by catecholamines might be explained by the demonstration
by Singal et al [18] that catecholamine auto-oxidation generates
highly toxic free radicals that participate in the CMP process.
In a study designed to test the hypothesis that a free
radical-mediated mechanism is involved in both catecholamine- and
Mg deficiency-induced cardiac damage, the research groups of
Weglicki and Bloom [19] concluded that since Probucol, a drug
with both antilipidemic and antioxidant effects, was effective
against both types of cardiac damage, each of which entails free
radical damage, it was the antioxidant activity that was
protective.
The observation by Singh et al that the cardioprotective diets
they studied were rich in antioxidants [2], and that the patients
with acute manifestations of cardiac disease had consumed diets
low in these substances, as well as in Mg [1], provides important
supportive clinical evidence.
REFERENCES
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Nutr 13:139-143,1994.
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experiment with nutritional modulation in acute myocardial
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free fatty acids and arrhythmias and death after acute myocardial
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15. Henrotte JG: Recent advances on genetic factors regulating
blood and tissue magnesium concentrations; relationship with
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Health and Disease." London: Libbey, pp 285-289, 1989.
16. Freedman AM, Atrakshi AH, Cassidy MM, Weglicki WB:
Magnesium deficiency-induced cardiomyopathy; protection by
vitamin E. Biochem Biophys Res Commun 170:1102-1106, 1990.
17. Freedman AM, Cassidy MM, Weglicki WB: Magnesium-deficient
myocardium demonstrates an increased susceptibility to an in vivo
oxidative stress. Magnesium Res 4:185-189, 1991.
18. Singal PK, Kapur N, Dhillon KS, Beamish RE, Dhall NS: Role
of free radicals in catecholamine-induced cardiomyopathy. Can J
Physiol Pharmacol 60:1390-1397, 1982.
19. Atrakchi AH, Bloom S, Dickens BF, Mak IT, Weglicki WB:
Hypomagnesemia and isoproterenol cardiomyopathies: protection by
probucol. Cardiovasc Pathol 1:155-160, 1992.
Mildred S. Seelig, MD, MPH, Master ACN
Editor Emeritus
Received November 1993.
Journal of the American College of Nutrition, Vol. 13, No.2,
116-117 (1994) Published by the American College of Nutrition
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