G18 IX. CAROTENOIDS AND VITAMINS A 



metabolism in animals suffering from hypervitaminosis A. Van Bruggen 

 and Straumfjord^^" found a normal vitamin C content in the serum of a 

 man who had received 100,000 I.U. of vitamin A/day for three years. 



e. Interaction with Vitamin D. In view of the disturbed bone formation 

 and the effect on blood clotting in hypervitaminosis A, it seemed that it 

 might have some relationship to the action of vitamin D. In fact, it was 

 early reported that vitamin A interferes with the curative effect of vitamin D 

 in rickets. '^^^ In addition, Javillier and Emerique-Blum^^"^^ reported that 

 the onset of experimental rickets was accelerated in rats given an overdose 

 of vitamin A. 



Conversely, Vedder and Rosenberg^ ^^^ noted that the toxicity of large 

 doses of vitamin A could be reduced by the administration of a high 

 dosage of vitamin D. The antirachitic vitamin likewise counteracted the 

 adverse effects of high doses of vitamin A on blood clotting, i^''^ Accordmg 

 to Maddock and co-workers, ^^^^ hypervitaminosis A was accompanied by 

 hemorrhages only when the experimental rats were receiving a rachitogenic 

 diet. 



However, hypervitamuiosis A and avitaminosis D differ. Vitamin D2 

 will not prevent the appearance of bone fractures in A-hypervitaminotic 

 rats.^^^^ On the other hand, corneal injury produced by the external ap- 

 phcation of vitamin A was inhibited by the application of vitamin D.^-"^ 

 Rodahl^'*^ concluded (in 1950) that neither the prophylactic effect nor the 

 curative action of vitamin D was affected by hypervitamuiosis A. On the 

 other hand, A-hypervitaminotic symptoms appeared to develop more 

 rapidly m rats with avitammosis D than in animals having a normal supply 

 of the antirachitic vitamin. There is therefore little question that an mter- 

 action does exist between \dtamins A and D, but more experimental work 

 will be necessary before an explanation of the mechanism is forthcoming. 



f. Interaction with Vitamin K. A hypoprothrombinemia in A-hyper- 

 vitaminosis was reported by Light and co-workers, ^-"^ and by Walker et 

 aU^^^ This is believed to be related to the characteristic hemorrhages in 

 this condition. According to Maddock and associates, ^'^^ who also ob- 

 served a hypoprothrombinemia in hypervitaminosis A, the clottmg time of 

 rats was increased from a normal value of twenty-five seconds to 70 to 183 

 seconds simply by the feeding of excessive doses of vitamin A/day for five 



1201 M. Javillier and L. Emerique-Blum, Compt. rend., 212, 289-292 (1941); Chem. 

 Zentr., 113, Parti, .3112 (1942). 



1202 Y. Raoul and N. Ragheb-Hanna, Compt. rend. soc. bioL, lU, 17-19 (1950). 



'203 w. J. Kapuschinski and J. Zebrowski, Klin. Oczna {Warsaw), 20, 328-331 (1950); 

 Chem. Abst., 46, 5158 (1952); Am. J. Ophthalmol., 35, 283 (1952). 



1204 R. F. Light, R. P. Alscher, and C. N. Frey, Science, 100, 225-226 (1944). 



