MAGNESIUMDEFICIENCY INANIMALS Experimental magnesium deficiency has been produced in many animal species. Many of the data pertain to work on rats, but magnesium deficiency has frequently been observed in sheep and cattle, species in which the syndrome develops spontaneously. In 1932 Kruse, Orent and McCollum70 induced magnesium deficiency in' weanling rats by feeding a diet containing 0.09 mEq per kilogram of the element. In these animals hyperemia and progressive neuromuscular irritability developed, culminating in generalized and sometimes fatal seizures. These early experiments have been confirmed and extended by many workers. Hypomagnesemia, accompanied by diminution in red cell, muscle, bone and total carcass magnesium1'1"'71'73 occurs. Magneskim deficiency has a profound influence on other metals and metabolites. In adult rats hypercalcemia, decrease in potassium and increase in sodium in muscle and liver and azotemia have been reported.71'74'75 Soft tissue potassium depletion and sodium increase have been correlated with loss of cellular noncollagen nitrogen, indicating cellular atrophy.75 Available evidence suggests that with sufficient magnesium depletion the pumping mechanisms that maintain normal intracellular Na+ and K+ gradients falter, resulting in these changes. The mechanism of hypercalcemia in these circumstances is elusive. Although it is tempting to invoke increased parathyroid function, there is no concomitant hypophosphatemia71 or decrease in bone calcium. 75 The azotemia is also unexplained. Glomeru-lar filtration rates were not determined in these studies. Among the multiple pathologic lesions nephrocalcinosis, myocardial necrosis and calcification and lipid deposition in the aorta have been most striking.'•"'•72-74'7(i'77 Hypomagnesemic tetany occurs spontaneously in calves fed for a long time on a pure milk diet. 1'ln'78'711 A gradual reduction of serum magnesium results in hyperirritability and tetany, the latter appearing at concentrations below 1 mEq per liter. Defective absorption of magnesium has been documented as this diet is maintained.78'79 Magnesium supplements prevent the disease.1'8" It should be noted that milk is a relatively poor dietary source oi magnesium. Fresh whole cow's m i l k contains 11.5 mEq per kilogram, whereas human milk contains 1.9 mEq per kilogram. Most meats, grains and raw green vegetables have magnes ium in excess of 20 mEq per kilogram.81'82 A second and more puzzling form of magnesium deficiency known as "grass tetany" occurs in adult luctating sheep and cattle.K:i Neuromuscular irritability, tetany and convulsions develop in the affected animals, sometimes within two days, when the element. Again, magnesium administration can reverse or prevent the disease.83"85 The acute hypomagnesemia is thought to be related to peculiar conditions of their forage, and may be due to fertilization with ammonium salts. Severe hypomag-nesemia will develop in a few days in lactating cows given artificial rations low in magnesium unless magnesium supplements are provided. The regulation of serum magnesium under these circumstances appears critically dependent on the daily intake, a phenomenon not found in other species. Magnesium content of grass from heavily fertilized fields does not differ from that ot normal pastures. The protein content of grass from fields topdressed with ammonium salts is increased, however, and this has been implicated as a factor causing grass tetany.8fi In view of the absence of magnesium depletion it appears that there is a failure to mobilize tissue stores under these circumstances. In animals the serum magnesium concentration at which tetany appears varies with the nutritional status. Thus, when sheep are made magnesium deficient, then treated by magnesium administration and allowed to become deficient a second time, tetany occurs only after the serum magnesium has fallen considerably below the level at which it occurred the first time.* 7 This observation has important implications for human magnesium deficiency since the onset of symptoms cannot be correlated directly with the concentration of magnesium in serum. (To be continued) REFERENCES 1. Wacker, W. E. C., and Vallee, B. L. Magnesium metabolism. /Vt jir E n g . J . Med. 259:431-438 and 475-482, 1958. la.ldem. Magnesium. In Mineral Metabolism: An advanced ireaiise: Vol. 2. The elements, Parts A-B. Part A. Edited by C. L. Comar and F. Bronner. New York: Academic Press, 1964. Pp. 483-521. 2. Vallee, B. L. Simultaneous determination of sodium, potassium, calcium, magnesium, a nd .strontium by new m u l t i c h a n n e l flame spectrometer. Nature (London) 174:1050, 1954. 3. Wacker, W. E. C., and Vallee, B. L. Stud y of magnesium metabolism in acute renal failure employing multichannel flame spectrometer. New En g . J. Med. 257:1254-1262, 1957. 4. Walsh, A. Application of atomic absorption spectra to chemical analysis. Spectrochim. ucta 7:108-1 17, 1955. 5. Willis, j. B. Determination of metals in blood serum by atomic absorption spectroscopy. 11. Magnesium. Spi'ctroi-liini. actn 16:273278, 1960. 6. Dawson, }. B., and Heaton, F. W. Determination of magnesium in biological materials by atomic absorption spectrophotometry. Bu>cliem.J. 80:99-106. 1961. 7. Horn, D. B., and Latner, A. L. Estimation of magnesium by atomic absorption spectrophotometry. Clin. cliim. acta 8:974-976, 1963. 8. Stewart, W. K., Hutchinson, F., and Fleming, L. W. Estimation of magnesium in serum and urine by atomic absorption spectrophotometry. J. Lab. & Clin. Med. 61:858-872, 1963. 9. Wacker, W. E. C., lida, C., and Fuwa, K. Accuracy of determinations of serum magnesium by flame emission and atomic absorption spectrometry. Nature (London) 202:659-661, 1964. 10. lida, C., Fuwa, K.., and Wacker, W. E. C. General method for magnesium analysis in biological material by atomic absorption spectroscopy. Analytical Biochein. 18:18-26, 1967.