MAGNESIUM DEFICIENCY IN THE PATHOGENESIS OF DISEASE

Early Roots of Cardiovascular, Skeletal
and Renal Abnormalities

Mildred S. Seelig, M.D., M.P.H., F.A.C.N.

Goldwater Memorial Hospital
New York University Medical Center
New York, New York
1980

Preface

There is a large and rapidly growing body of literature on the importance of magnesium in biochemical and physiological processes. There is also much evidence that magnesium deficiency, alone and in combination with agents that interfere with its utilization, is associated with functional and structural abnormalities of membranes, cells, organs, and systems. The manifestations of the changes caused by magnesium deficiency depend upon its extent and duration and on variable factors. Among the conditions that increase the risk of magnesium deficiency are (1) metabolic factors that affect the absorption, distribution, and excretion of this mineral; (2) disease and therapy; (3) physiologic states that increase requirements for nutrients; and (4) nutritional imbalances. Excesses of nutrients that interfere with the absorption or increase the excretion of magnesium-such as fat, phosphate, sugar, and vitamin D-can contribute to long-lasting relative magnesium deficiency. All have been implicated in several of the diseases considered in this book. Whether their influence on the need for magnesium is a common denominator remains to be investigated further.

Unfortunately, means of diagnosing clinical magnesium deficiency of a lesser degree than that associated with overt signs such as convulsions or cardiac arrhythmias or other electrocardiographic changes are not readily accessible. Plasma magnesium levels are unreliable as an index of its cellular inadequacy. More complicated means of evaluating the magnesium status are considered in the Appendix, as are their limitations and need for convenient determinants. Until magnesium clinical methodology is improved and made available, the importance of correcting magnesium deficiency in man's diet and of preventing intensification of a deficit when needs are increased by physiologic or pathologic processes and drugs will have to be inferential-based on experimental and epidemiologic observations. Because magnesium has pharmacologic activities that have been recognized for many years, demonstration of the correction of abnormal acute neurologic and cardiac signs (even though such signs are characteristic of acute magnesium deficiency) are not readily accepted as evidence that magnesium deficiency can contribute to diseases in which such magnesium-responsive signs are seen. With notable exceptions, there has been clinical neglect of magnesium in most medical centers and certainly in private practice. This is unfortunate because many of the pathologic changes produced by experimental magnesium deficiency or loss resemble many of those of chronic diseases that are responsible for intractable medical problems.

This book develops the premise that magnesium deficiency during gestation is more common than generally believed and that it may be contributory to some disorders of pregnancy and infancy. It draws parallels between cardiovascular and skeletorenal lesions of infancy and childhood and those produced by magnesium deficiency-especially when intensified by dietary excesses of vitamin D and of phosphate, which are commonly consumed in the United States and other Occidental countries. It suggests that the most severe lesions (of magnesium deficiency ± vitamin D ± phosphate excess) resemble those of some congenital abnormalities. Lesions that develop later in infancy might provide the nidus for chronic cardiovascular and renal diseases of later childhood and adult life. Epidemiologic evidence is considered, having provided inferential evidence that magnesium deficiency (as in soft-water areas) contributes to the higher rate of sudden cardiac deaths (than in hard-water areas). Although differences in trace mineral and calcium contents of hard and soft water are also considered contributory, the most convincing evidence is that magnesium in hard-water areas is protective. Such a premise is subject to criticism because there are always concomitant factors that cloud the issue. Other dietary and environmental, as well as genetic, differences make it unlikely that there is a single provocative factor.

This book constitutes a plea for the objective examination of the evidence and for the exploration of the possibility that the prophylactic use of magnesium-especially in geographic areas where the intake is low, in families whose members have a high incidence of cardiovascular disease, and in high-risk individuals (e.g., diabetics and patients with a personal history of cardiac or vascular disease)-might be effective. Reevaluation of the use of vitamin D and of phosphate in foods is justifiable. The use of magnesium in the treatment of cardiac and renal diseases has been claimed by some investigators to be an important adjunct to therapy. More controlled studies should be done to obtain further evidence as to the extent to which experimental evidence and pilot clinical trials, indicative of benefits produced by magnesium, are applicable to more extensive treatment and prevention of human disease.

The substantial data on drugs (such as diuretics, cardiotonics, and antibiotics) that cause magnesium loss or inactivation are referred to only in the context of the theme of this volume and are so indexed. Further development will be provided elsewhere.

Appreciation is expressed to Harriet Nathan, May Becker, Marie Bennett, and Doris Wallace for typing the manuscript and to Dr. A. R. Berger for approving this employment of the secretarial staff of the Medical Service of Goldwater Memorial Hospital.

Mildred S. Seelig

New York