HTPER\nTAMlN-<->SI>i D 679 



causing calcification developed out of all proportion to its antirachitic 

 property. This so-called toxisterol possessed no \-itamin D action."" 

 In addition to toxisterol. two other compounds ^vithout an antirachitic 

 action and possessing some toxicity are formed by over-irradiation of 

 \-itamin D.'*' These are known as suprasterol I and suprasterol II.'*' 

 These earlier results, therefore, could not be regarded as proof of the tox- 

 icity of large doses of ^■itamin D per se. The toxicity was rather a result 

 of impurities in the early preparations. At one time it was considered 

 that the toxic effects of excessive amounts of \itamin D were due entirely 

 to the presence of toxic by-products.-^' 



However, PfannenstieP*- and Kreitmair and MolP*' described, almost 

 simultaneously, toxic effects ascrihable to the \-itamin D itself when given 

 in large doses to animals. Harris and co-workers'*-*"'^ reported that s\-mp- 

 toms of hypervitaminosis D could be provoked even on a diet poor in 

 calcium, but that the symptoms were aggravated when the diet was rich 

 in this substance.'^ Furthermore, in the latter case, less \-itamin was 

 required to elicit the manifestations of hypervitaminosis. 



(1) Symptoms of Hypervitaminosis D 



The chief featiu-e of the hypervitaminotic state is the dissolution of 

 bone already formed. In the early stages the bones may exhibit accelerated 

 calcification of the so-oalled "pro\-isional zone of calcification." together 

 with a thickening of the periosteum. However, in more ad\-anced stages 

 of the hv-per^-itaminosis D. a diffuse demineralization of the bones occurs. '^^ 

 The t\'pe of osteoporosis resulting from hypervitaminosis D differs from 

 that caused by an excess of parathormone (parath\Toid extract), in that 

 the resorbed areas are not replaced by fibrous tissue.'*^ The calcium 

 content of the bone is reduced concomitantly with an increased concentra- 

 tion of calcium and phosphorus in the plasma.** According to Le\-y, 

 Sapir, and Mignon.'^" the serimi phosphate increases much more rapidly 



» C. E. BUls, E. M. Hone\-^-eU. and W. M. Cox. /. Biol. Chem., SO, 557-563 (1928). 



»i .\. Windaus. J. Gaede. j. Kdser. and G. Stein. Ann., 4S3. 17-30 (1930"). 



»' W. Pfannenstiel. Munch, med. Wochschr., 75, 1113-1114 (1928). 



«^ H. Kreitmair and T. Moll. Munch, med. Wochschr., 7-5, 637-639 (1928). 



*"■ L. J. Harris and T. Moore. Biochem. J., 22, 1461-1477 (1928\ 



« L. J. Harris and T. Moore, Biochem. J., 23, 261-273. 1114-1121 (1929). 



*« L. J. Harris and J. R. M. Innes. Biochem. J., 25, 367-390 (1931). 



»• L. J. Harris and C. P. Stewart, Biochem. J., 23, 206-209 (1929). 



'** D. H. Shelling, The Parathyroids in Health and Disease, Mosbv. St. Louis, 1935, p. 

 271. 



"'S. Freeman, P. S. Rhoads. and L. B. Yeager. /. .4m. Med. Assoc., ISO, 197-202 

 (1946). 



"^^ M. Lew. M. Sapir. and S. Mignon. Bull. soc. chim. Biol., 31, 300-321 - la-ioy 



