Among offbalance D inducing elements of the II A series of the periodic chart, we first studied magnesium, which belongs to the metazoic compartment and thus, is related to the sea as original environment. Much of the activity of this element can be interpreted as D inducing activity. Mg in many respects is antagonistic to Na, the cation of the same compartment, a member of a series with an opposite A inducing character. High values of Mg found in blood were related to adrenal insufficiency, (127) while low Mg levels usually occur when blood cholesterol is high. (128)

Excess of Mg was seen to induce adrenal deficiency. We explained this action through the antagonism between Mg and Na. We could thus counteract the salutary effect of NaCl in adrenalectomized rats through administration of magnesium sulfate parenterally. A similar effect was obtained even with oral use of magnesium thiosulfate. (Note 9)

The relationship of magnesium to the defense mechanism is of special interest. Mg seems to intervene in the lytic effect of sera upon ascites cancer cells (extensively studied in our laboratory by R. Willheim, P. Fluss and M. Auber) (129) which, as we have seen, represents a characteristic feature of D inducing activity. Similarly, magnesium prevents thrombosis, acting as an antithrombocytic agent. Not only does it prevent the appearance of fibrin, partly preventing the destruction of thrombocytes (130); but it also favors the lysis of already existing thrombi. (131) It appears, therefore, to be a valuable agent in the treatment of thrombosis. (132) Its concomitant action against cholesterol has led to its use in the prevention and treatment of coronary thrombosis.

Magnesium appears to be part of another defense mechanism, the non specific one, represented by the properdin system. Properdin is active only in the presence of magnesium; neither Ca nor Na can replace it. (133) Higher amounts of magnesium increase properdin activity.

Magnesium sometimes is seen to parallel the action of Cu, another D inducing element. In animals fed milk too long, leading to a type A off balance, the amount of magnesium falls along with the amount of Cu. The quantity of magnesium in the blood is low in humans with convulsion. (134) Mg appears to be especially effective in the prevention and treatment of "grass tetany" in animals, which often follows feeding on grass with high potassium content. (135)

Magnesium has a similar antagonism toward K and this can explain its activity in cancer. Lower than normal values of magnesium are found in cancer, as opposed to high amounts of potassium which is an A inducing element, and the low Mg seems to favor cancer growth. Moisture increases the amount of K and lowers the amount of Mg in plants, a fact related to cancer frequency in various geographic regions. (136) The difference between the preventive and curative actions of magnesium is of special interest. Administered after a carcinogen has been applied, magnesium reduces the percentage of cancers induced. (137, 138) It has minimal influence, however, once the tumor has appeared or upon transplanted or spontaneous tumors. We will discuss this occurrence below together with the effect of other elements.

It is necessary to bear in mind, when we have to choose nonspecific combinations in which to administer it, that the D inducing activity of magnesium is particularly manifested at the metazoic level. Magnesium sulfate appears to be suitable for parenteral use, while the thiosulfate appears to be suitable for oral administration. In these forms, Mg has been found to induce marked local alkalosis in the second day wound crust pH and to produce salutary effects upon pain of the acid pattern. A marked influence upon thiamine induced convulsions in rats and mice has led us to use magnesium thiosulfate as a tool not only in tetany but in the treatment of convulsions. It appears to be effective in preventing epileptic seizures and valuable even in cases of status epilepticus. We have utilized the same preparation successfully in cancer when pain and preterminal conditions corresponding to an A offbalance were present. Less important effects are seen for magnesium sulfate and magnesium thiosulfate at lower levels.