VITAMIN K HYPOVITAMINOSIS 773 



mice by proving that a somewhat prolonged bleeding time existed in this 

 species following a vitamin K-free diet. Oleson and co-workers^^^ reported 

 a vitamin K-like deficiency in rats fed synthetic diet apparently devoid of 

 vitamin K. This condition was characterized by subcutaneous hemor- 

 rhages or by purpura in the paAvs and bleeding from the nose. Dam and 

 Glavind-"" later proved that this condition in rats was a true avitaminosis 

 K. They were able to demonstrate a characteristic vitamin K deficiency 

 in seven out of fifteen rats on a vitamin K-free diet, within fifteen to 

 eighty days. The symptoms were alleviated by intravenous injections of 

 vitamin K. Thus, it would appear certain that avitaminosis K can be 

 provoked in rabbits, rats, and mice solely by dietary restriction of this 

 food component. Plasma and tissue extracts from chickens on a diet 

 devoid of vitamin K, tested""' by the blood-clotting method, exhibited 

 analogous results. 



b. Inhibition of the Synthesis of Vitamin K in the Gastrointestinal Tract. 

 The method by which vitamin K deficiency is most readily established in 

 all species is by the inhibition of normal synthesis of vitamin K in the gut, 

 following the administration of a diet free from vitamin K. The intestinal 

 bacteria constitute the largest and most steady source of vitamin K under 

 most conditions. "'^^ Escherichia coli is an important bacterial source of 

 vitamin K." According to Dam,-"^ the farnesyl type of vitamin K (K2) 

 originates as a result of the action of intestinal bacteria. However, 

 Taveira^*^* reported the recovery of phytyl-vitamin K (Kci) from this 

 source. Further investigation is needed to clarify these discordant views. 



Sulfonamides produce a marked reduction of vitamin K synthesis in 

 the gastrointestinal tract by virtue of their bacteriostatic and bactericidal 

 action. The comparative effectiveness of the sulfonamides in depressing 

 vitamin K synthesis^"'* (from the most potent to the weakest) is as follows: 

 sulfapyrazine, sulfadiazine,^^ sulfathiazole,^*^^ sulfasuxidine,^^ sulfanil- 

 amide,^"^ and sulfaguanidine.^^ When p-aminobenzoic acid is given, either 

 orally or parenterally, it concentrates in the intestinal tract and prevents 

 the depression of vitamin K synthesis by the intestinal flora after the 

 administration of sulfonamides.^^ The effect of the sulfonamides upon 



'" J. J. Oleaon, H. R. Bird, C. A. Elvehjem, and E. B. Hart, J. Biol. Chem., 127, 23-42 

 (1939). 



200 H. Dam and J. Glavind, Z. Viiaminforsch., !), 71-74 (1939). 



201 H. Dam and J. Glavind, Biochem. J., 32, 1018-1023 (1938). 

 2°2 H. Dam, Med. Welt., 20, 958 (1951). 



'"'••' M. Taveira, Arm. pharm. franc, 9, 344-347 (1951 ). 

 2°^ W. H. Sebrell, Harvey Lectures, 39, 288-315 (1943-1944). 



^"^ B. M. Braganca and M. V. Radhakrishna Rao, Indian J. Med. Research, 35, 15-21 

 (1947). 



