Mildred S. Seelig

Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).

Stress intensifies release of catecholamines and corticosteroids that increase survival of normal animals when their lives are threatened. When magnesium (Mg) deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death (SCD). In affluent societies, severe dietary Mg deficiency is uncommon, but dietary imbalances such as high intakes of fat and/or calcium (Ca) can intensify Mg inadequacy, especially under conditions of stress. Adrenergic stimulation of lipolysis can intensify its deficiency by complexing Mg with liberated fatty acids (FA), A low Mg/Ca ratio increases release of catecholamines, which lowers tissue (i.e. myocardial) Mg levels. It also favors excess release or formation of factors (derived both from FA metabolism and the endothelium), that are vasoconstrictive and platelet aggregating; a high Ca/Mg ratio also directly favors blood coagulation, which is also favored by excess fat and its mobilization during adrenergic lipolysis. Auto-oxidation of catecholamines yields free radicals, which explains the enhancement of the protective effect of Mg by anti-oxidant nutrients against cardiac damage caused by beta-catecholamines. Thus, stress, whether physical (i.e. exertion, heat, cold, trauma--accidental or surgical, burns), or emotional (i.e. pain, anxiety, excitement or depression) and dyspnea as in asthma increases need for Mg. Genetic differences in Mg utilization may account for differences in vulnerability to Mg deficiency and differences in body responses to stress.

Benefits and Risks of Sex Hormone Replacement in Postmenopausal Women

Because cardiovascular disease (CVD), which is far less common in young women than in men, but increases in prevalence in the postmenopausal years to that of men, estrogen repletion therapy (ERT) or combined hormone replacement therapy (HRT), has been widely used to protect against development of both CVD and osteoporosis, and possibly to delay or prevent cognitive loss or Alzheimer’s disease (AD). To test the validity of favorable findings in many small-scale studies, and in clinical practice, a large-scale trial: the Women’s Health Initiative (WHI) was undertaken by the National Institutes of Health (NIH), a trial that was prematurely ended because of increased CVD complications, despite some lessening of hip fractures. This paper suggests that the customary high intake of calcium (Ca)—advised to protect against osteoporosis, and the marginal magnesium (Mg) intake in the USA, might well be contributory to the adverse CV effects, that were all thromboembolic in nature. The procoagulant effect of estrogen is intensified by Ca; Mg—which counteracts many steps in the coagulation cascade and inhibits platelet aggregation and adhesion—is commonly consumed in sub-optimal amounts. The high American dietary Ca/Mg ratio might also be contributory to the WHI failure to confirm ERT’s favorable mental effects. Discussed are mechanisms by which Mg enhances estrogen’s central nervous system protective effects. Mg’s improvement of cerebral blood flow, which improves brain metabolism, can also enhance removal of the beta amyloid peptide, accumulation of which is implicated in AD.

Is there a place for magnesium in the treatment of acute myocardial infarction

Infusions of solutions of magnesium sulfate for patients with acute myocardial infarction were shown by a meta-analysis of seven small studies and a larger study of 2316 patients (LIMIT-2) to have clinical efficacy. However, the ISIS-4 study of 58,050 patients found no improvement in short-term mortality rates with magnesium therapy in patients with acute myocardial infarction. In this article we explore the following four differences between the ISIS-4 study and the earlier studies: (1) Time of initiation of magnesium treatment after acute myocardial infarction and thrombolytic therapy; (2) dosage of magnesium in the first 24 hours after acute myocardial infarction; (3) duration of magnesium infusion after acute myocardial infarction; and (4) differences in patient risks in control and treatment groups. These four differences may explain the different outcomes among these studies and indicate the type of additional studies that are needed to define the clinical utility of magnesium infusion in the treatment of patients with acute myocardial infarction.

Magnesium in acute myocardial infarction: Scientific, statistical, and economic rationale for its use

~ Cardiovascular Division, Brigham and Womens Hospital Boston, MA; 2School of Public Health, University of North Carolina, Chapel Hill, NC; 3Division of Clinical Care Research, New England Medical Center, Boston, MA; 4Division of Cllnical Epidemiology, Brigham and Womens Hospital Boston, MA; S Channing Laboratory, Harvard Medical School Boston, MA; 6Department of Statistics, Harvard University, Cambridge, MA, USA