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Journal of Nutrition Vol. 23 No. 6 June 1942, pp. 589-602
Copyright © 1942 by American Society for Nutrition
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Studies on the Hemorrhagic Sweet Clover Disease

IX. The Effect of Diet and Vitamin K on the Hypopro-Thrombinemia Induced by 3,3'-Methylenebis (4-Hydroxycoumarin) in the Rat1

One Figure

Ralph S. Overman, John B. Field, Carl A. Baumann and Karl Paul Link

Department of Biochemistry, College of Agriculture, University of Wisconsin, Madison

1. The ingestion of 3,3'-methylenebis (4-hydroxycoumarin) induced a hypoprothrombinemia in rats. A single dose of 2.5 mg. to an adult rat lowered the prothrombin activity to 22% of normal in 24 hours, when maximum lowering was observed.
2. The maximum effectiveness of the anticoagulant was observed on rations low in vitamin K. Factors which counteracted the anticoagulant were present in a grain ration, in fish meal and in alfalfa. The factor in alfalfa could be extracted with petroleum ether.
3. Vitamin K counteracted the hypoprothrombinemia induced by the anticoagulant, whether given before the anticoagulant, with it, or 12 hours later. All forms of the vitamin studied were active: 2-methyl 1,4-naphthoquinone, 2-methyl 1,4-naphthohydroquinone diacetate, vitamin K1 and the water-soluble 2-methyl 1,4-naphthohydroquinone 3 sodium sulfonate.
4. The continued administration of the anticoagulant resulted in severe spontaneous hemorrhages which caused the death of the animals. Their survival times could be prolonged by the ingestion of vitamin K but not by such dietary supplements as choline, ascorbic acid, wheat germ oil, hydrogenated fat, or condensed milk.

1 Published with the approval of the Director of the Wisconsin Agricultural Experiment Station. Cooperative studies with the Division of Forage Crops and Diseases, U. S. D. A., Washington, D. C., through Dr. E. A. Hollowell. Personnel and supply assistance since July 1, 1938, in part through the Natural Science Research Project No. 65-1-53-2349 of the Federal Works Progress Administration (Madison), and since July 1, 1940, through special grants from the Graduate Research Committee of the University.

Manuscript received 29 January 1942.


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