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EPIDEMIOLOGICAL STUDIES ON THE RELATIONSHIP BETWEEN MAGNESIUM INTAKE AND CARDIOVASCULAR DISEASES

Heikki Karppanen

Department of Pharmacology
University of Helsinki
Siltavuorenpenger 10
SF-00170 Helsinki 17, Finland



ABSTRACT: Data are reviewed which suggest that dietary intake of magnesium may be lower than needed in the industrialized nations in the world. This low dietary intake of Mg appears to be related to the high incidence of ischemic heart disease (IHD) in these nations. Dietary supplementation of individuals in these industrialized nations with Mg is recommended to prevent risk of IHD and other cardiovascular diseases.

INTRODUCTION

In the incidence of cardiovascular diseases great differences between various countries exist (1). Moreover, within each country there may be marked geographic differences in the mortality from these diseases. In Finland, for example, the average mortality from ischemic heart disease (IHD) is very high (1). The mortality has a clear-cut geographic distribution. Eastern Finland has one of the highest, if not the highest, mortality rate from IHD in the whole world. The mortality rate decreases continuously toward south and west. The difference in IHD mortality between the eastern and southwestern parts of Finland is nearly two-fold (2, 3).

The high incidence of some diseases in certain geographic areas is explained by particular geochemical environments. Before the enrichment of table salt, with iodine, endemic goitre, due to iodine deficiency in the soil, had in Finland its highest incidence in the same eastern areas where the death rates from IHD are highest (4). It has been proposed that mineral elements may play an important role also in the etiology of cardiovascular diseases and that differences in the intake of certain minerals, due to different geochemical environments, may partly account for the geographic differences in their incidence (for review, see 3). A lot of evidence has accumulated to suggest that inadequately low intake of magnesium in the industrialized countries in general, and in certain geographic areas in particular, may be one of the reasons for the present high incidence of cardiovascular diseases.

RECOMMENDED INTAKE OF MAGNESIUM

Table I represents the magnesium intake recommended by the U.S. National Academy of Sciences (NAS 1974). In West Germany the recommended daily allowance for adults is 360 mg magnesium per day (5). For adult patients maintained on parenteral nutrition, the infusion of 400 mg of magnesium daily has been recommended (6, 7). Seelig (8) has recommended that the daily intake of magnesium should be 6 mg/kg. It has also been emphasized that several factors increase magnesium requirements (9).

Estudies Table I

PRESENT LEVELS OF MAGNESIUM INTAKE

In the past half century, magnesium intakes have fallen considerably in industrialized countries whereas the intakes of protein, fat, sugar, and calcium which increase magnesium requirements have risen (10). However, the exact levels of magnesium intake in most populations are not known. The intake of magnesium has been measured only in few studies and in relatively small groups of people (11). Table II summarizes some magnesium surveys. As compared to the recommended daily allowance, the intake of magnesium appears to be adequate in Ireland but suboptimal in other regions studied. Some results suggest that the intake of magnesium is quite low also in Sweden (12). Furthermore, Seelig (10) and Ashe et al. (13) reported that the average magnesium intake of pregnant women was only 45-60% of the recommended daily allowance. Some investigators in Finland have estimated that the daily intake of magnesium is about 400 mg (14). The average excretion of magnesium in 24 hour urine In Finland appears to be about 125 mg, thus suggesting that magnesium may be poorly absorbed from the Finnish diet, or that the estimates of intake are too high (H. Karppanen, J. Tuomilehto and J. Vuori, unpublished results).

Several studies therefore suggest that the dietary intake of magnesium may be sub-optimal in many industrialized countries.

Table II

RELATION OF WATER HARDNESS, AND MAGNESIUM CONTENT OF WATER AND SOIL,
TO CARDIOVASCULAR DISEASES

Regional death rates from IHD or other cardiovascular diseases in several countries are inversely related to the hardness and thus the mineral content of the local drinking water (11). Similar inverse correlation between regional IHD mortality and the content of certain minerals, especially magnesium, in the soil has been observed (3, 15).

Magnesium and calcium are the main elements contributing to the hardness of the water. As calcium is usually present in larger amounts, there has been more attention paid to the possibility that calcium is the protective "water factor". In fact, inverse correlations between the calcium content of water or dietary intake of calcium and IHD have been observed (16, 17). However, in Finland, a country with an exceptionally high death rate from IHD the intake of calcium is higher than in most other countries (31). Therefore the situation found in Finland does not support the hypothesis that a high intake of calcium protects against IHD. Allen (18) reported that magnesium in the drinking water was more effective than total hardness, which in turn was more effective than calcium in favourably influencing the rate of sudden deaths from IHD. Residents of soft-water areas have lower concentrations of magnesium in heart muscle (19) and coronary arteries (20) than do residents of hard-water areas. In addition, a diminished content of myocardial magnesium has been found after a sudden death from heart disease (21). In fact, of the minerals that are deficient in soft water, magnesium is the only element that has been found to be lowered in the cardiac muscle of victims of sudden death from IHD (see 22). It has also been found that the exchangeable magnesium per kg body weight is lower in IHD patients than in their controls (23). The decrease in magnesium content may have serious consequences since it has been shown that deficiency produces spasms of coronary arteries (22). Moreover, the decrease in myocardial magnesium may increase cellular excitability, thereby contributing to the development of ventricular arrhythmias (24). The lower tendency to ventricular arrhythmias in the hard-water areas (11) could well be due to water-borne magnesium since magnesium administrations have proved effective in the treatment of cardiac arrhythmias of various etiologies (24). Moreover, the fall of the magnesium content in the heart of residents of soft-water areas suggests that the content of magnesium in the diet is inadequately low. The amount of magnesium provided by hard drinking water is able to correct at least a mild deficit (11), thereby preventing the tissue levels from decreasing.

FACTORS POSSIBLY INFLUENCING THE ROLE OF MAGNESIUM IN CARDIOVASCULAR DISEASES

Certain factors increase magnesium requirements and may therefore intensify magnesium deficiency or induce relative magnesium deficiency in the presence of marginal intake (9, 10). Such factors include, for example, a high intake of protein, calcium, vitamin D, phosphorus, fats, carbohydrates or alcohol. Expansion of the extracellular space and increased diuresis induce the loss of magnesium in the urine. Therefore, high intake of salt (sodium) and diuretics may induce magnesium deficiency (25). The metabolism, functions and effects of magnesium, calcium, sodium and potassium are in many ways closely interconnected (24, 26, 27, 28, 29). Statistically, there is a positive correlation between IHD mortality and the estimated calcium to magnesium ratio of the diet in various OECD countries (Fig. 1), thus suggesting that a high calcium to magnesium ratio in the diet may be harmful. High intake of salt (sodium) and, especially, a high sodium to potassium ratio in the diet increase the risk of arterial hyper tension (26, 29, 30). Statistically there is a very strong positive correlation between the average value ofEstudies formulain the diet and mortality from IHD in various OECD countries (Varo, personal communication). These observations suggest that, in addition to the level of magnesium intake, also the relation of magnesium to the abundance of certain other nutrients in the diet may be important for the long-term maintenance of human health.

Figure 1

CONCLUSIONS

In conclusion, there is evidence that the present levels of magnesium intake may be inadequately low in industrialized countries. The available evidence also suggests that the low intake of magnesium may increase the risk of IHD. Therefore it may be warranted to study the effect of a long-term magnesium supplementation in areas with high IHD mortality and soft, magnesium-deficient drinking water. Unfortunately, no such studies have been done. However, a magnesium supplementation study was recently started in the high IHD mortality area of eastern Finland.

In this study the supplementation of magnesium to the population is effected by replacing the use of regular table salt as extensively as possible by a new type of salt with reduced sodium concentration and enriched with magnesium and potassium salts (Mineral SaltR, Salvo-Companies, Helsinki; see 29). More studies are certainly needed to examine whether the incidence of cardiovascular diseases can be reduced and the death rate from IHD decreased by increasing the level of magnesium intake.

REFERENCES

1. Keys, A. (ed.) 1970. Coronary heart disease in seven countries. Am. Heart Ass. Monogr. No. 29, New York.

2. Puska, P. 1972. Sydän- ja verisuonisairauksien aiheuttaman kuolleisuuden alueelliset erot. I. Tilanne vuoden 1969 tilastojen valossa. Suomen Lääkärilehti 27: 3071-3075.

3. Karppanen, H., R. Pennanen, and L. Passinen. 1978. Minerals, Coronary heart disease and sudden coronary death. Adv. Cardiol. 25: 9-24.

4. Uotila, U., J. Raekallio, and W. Enmrooth. 1958. Goitre and arteriosclerosis. Lancet ii: 171-173.

5. Holtmeier, H.J., and M. Kuhn. 1972. Zink und magnesium Mangel beim Menschen. Therapiewoche 22: 4536-4546.

6. Freeman. J.B., and M.F. Wittine. 1977. Magnesium requirements are increased during total parenteral nutrition. Surgical Forum 28: 61-62.

7. Hauer, E.C., and M.V. Kaminski. 1978. Trace metal profile of parenteral nutrition solutions. Amer. J. Clin. Nutr. 31: 264-268.

8. Seelig, M.S. 1964. The requirements of magnesium by the normal adult. Amer. J. Clin. Nutr. 14: 342-390.

9. Seelig, M.S. 1971. Human requirements of magnesium; factors that increase needs; In: Durlach ler Symp. Int. sur le déficit magnésique en pathologie humaine Vol. 1, Vittel, pp. 11-38.

10. Seelig, M.S. 1978. Magnesium deficiency with phosphate and vitamin D excesses: Role in pediatric cardiovascular disease? Cardiovasc. Med. 3: 637-650.

11. Marier, J.R., L.C. Neri, and T.W. Anderson. 1979. Water hardness, human health, and the importance of magnesium. National Research Council Canada. NRCC No. 17581.

12. Mohamed, A. 1976: Dietary intake of electrolytes and trace elements in the elderly. Nutr. Metab. 20: 187.

13. Ashe, J.R., F.A. Schofield, and M.R. Gram. 1979. The retention of calcium, iron, phosphorus, and magnesium during pregnancy: The adequacy of prenatal diets with and without supplementation. Amer. J. Clin. Nutr. 32: 286-291.

14. Koivistoinen, P. (ed.) 1980. Mineral element composition of Finnish foods. I-XIII. Acta Agr. Scand. Suppl. in press.

15. Karppanen, H. and P.J. Neuvonen. 1973. Ischaemic heart—disease and soil magnesium in Finland. Lancet ii: 1390.

16. Knox, E.G. 1973. Ischaemic heart disease mortality and dietary intake of calcium. Lancet i: 1465-1467.

17. Elwood, P.C., M. Abemethy, and M. Morton. 1974. Mortality in adults and trace elements in water. Lancet ii: 1470-1472.

18. Allen, H.A.J. 1972. An investigation of water hardness, calcium and magnesium in relation to mortality in Ontario. Thesis University of Waterloo, Ontario.

19. Anderson, T.W., L.C. Neri, G. Schreiber, F.D.F. Talbot, and A. Zdrejewski. 1975. Ischemic heart disease, water hardness, and myocardial magnesium. Canad. Med. Assoc. J. 113: 199203.

20. Crawford, T. and M.D. Crawford. 1967. Prevalence and pathological changes of ischaemic heart disease in a hard-water and in a soft-water area. Lancet i, 229-232.

21. Chipperfield, B. and J.R. Chipperfield. 1973. Heart-muscle magnesium, potassium, and zinc concentrations after sudden death from heart disease. Lancet ii: 293-296.

22. Turlapaty, P.D.M.V. and B.M. Altura. 1980. Magnesium deficiency produces spasms of coronary arteries: Relationship to etiology of sudden death ischaemic heart disease. Science 208: 198-200.

23. Boddy, K., I. Robertson, M.E. Mahaffy, D.S. Katoch, R.G. Murray, F.G. Dunn, and I. Hutton. 1978. Magnesium metabolism in patients with coronary heart disease. Eur. J. Clin. Invest. 8: 87-91.

24. Seelig, M.S. and H.A. Heggtveit. 1974. Magnesium interrelationships in ischemic heart disease: a review. Am. J. Clin. Nutr. 27: 59-79.

25. Lim, P. and E. Jacob. 1972. Magnesium deficiency in patients an long-term diuretic therapy for heart failure. Brit. Med. J. iii: 620-622.

26. Meneely, G.R. and H.D. Battarbee. 1976. High sodium-low potassium environment and hypertension. Am. J. Cardiol. 38: 768-785.

27. Whang, R. and J.K. Aikawa. 1977. Magnesium deficiency and refractoriness to potassium repletion. J. Chron. Dis. 30: 65-68.

28. Dyckner, T. and P.O. Wester. 1978. Intracellular potassium after magnesium infusion. Brit. Med. J. i: 822-823.

29. Karppanen, H. 1979. Rational of New Salt (Mineral Salt). Vientipaino Oy Exportprint Ltd. Helsinki

30. Farquhar, J.W., P.D. Wood, W.L. Haskelt, P. Williams, and S.P. Fortman. 1978. Relationship of urinary sodium/potassium ratio to systolic blood pressure The Stanford three community study. Abstracts from the Eighteenth Conference on Cardiovascular Disease Epidemiology.

31. Varo, P. 1974. Mineral element balance and coronary heart disease. Int. J. Vit. Nutr. Res 44: 267-273.


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