680 X. VITAMINS D 



after toxic doses of vitamin D are given orally to human adults than does 

 the serum calcium. The results were approximately the same, irrespective 

 of whether 15, 30, or 90 mg. of the vitamin were given. These investi- 

 gators"** conclude that plasma phosphorus is a more sensitive index of 

 hypervitaminosis D than is serum calcium. When an excess of vitamin D 

 is administered to rachitic rats, the hypertrophic cartilage becomes densely 

 calcified; this occurs simultaneously wth a dissolution of the bone al- 

 ready formed. 



(2) The Effect on Specific Tissues 



Obviously a generalized effect, involving all tissues, occurs after the 

 administration of toxic doses of vitamin D. There is a generaUzed cal- 

 cinosis, which affects the joints, synovial membranes, kidneys, myocar- 

 dium, pulmonary alveoli, parathyroid glands, pancreas, skin, lymph glands, 

 large and medium-sized arteries, the conjunctiva and cornea, and also the 

 acid-secreting portion of the stomach. '^'^ The abnormal calcification in 

 these tissues appears as a white chalky deposit. 



According to Nicolaysen and Eeg-Larsen,^ the most dominant toxic 

 effect is noted in the kidney, due to the precipitation of calcium phosphate 

 in the tubules. Guldager"^ states that no damage occurs in the kidneys 

 until the precipitation of calcium salts occurs. Toxicity results because 

 the blood is overloaded with minerals which the kidneys are unable to 

 excrete \vith sufficient rapidity. 



(3) Levels of Vitamin D Found Toxic 



Although toxicity symptoms in man have usually resulted when dos- 

 ages exceeded 100,000 I.U. daily, much lower amounts have been shown 

 to be harmful under certain conditions. According to Kramer and Kanof ^^* 

 as little as 400 I.U. daily have been known to produce fatal results. The 

 shortest period of administration of vitamin D before demonstrable cal- 

 cification was produced in fourteen days. On the basis of linear growth 

 in childhood as an index of the action of vitamin D, Jeans and Stearns"^ 

 reported that harmful effects could be produced by as small a dosage as 

 1800 I.U. daily. The tolerance of the human adult for vitamin D before 

 toxicity developed was found to vary considerably in different individuals. 



3'i A. Guldager, Hypervitaminosis D., A. Busck, Nyt Nordisk Forlag. K0benhavn, 

 1936; cited by R. Nicolaysen and N. Eeg-Larsen, Vitamins and Hormones, 11, 29-60 

 (1953), p. 53. 



3" P. C. Jeans and G. Stearns, J. Pediat., 13, 730-740 (1938). 



