Evaluation of Vitamin K₃ Feed Additive for Prevention of Sweet Clover Disease

Abstract

Abstract. Sweet clover poisoning in cattle is caused by an anticoagulant (dicumarol) that is formed in moldy sweet clover hay. Previous experiments with vitamin K 3 and vitamin K 3 in therapy trials indicated that vitamin K 3 was effective in reducing prothrombin times but vitamin K 3 was not. As a possible alternative in the use of toxic sweet clover hays, vitamin K 3 was evaluated to see if it would prevent hemorrhagic crises when fed to cattle consuming toxic sweet clover hay. Vitamin K 3 levels of 0, 0.45, 4.5, 11, and 45 mg/kg body weight/day were fed to 173-235-kg steers consuming toxic (40-50 ppm dicumarol) sweet clover. The 45-mg K 3 /kg/day supplement was not palatable and had to be discontinued. The 0.45, 4.5, and 11-mg K 3 /kg/day supplements did not significantly reduce the prothrombin times as compared to the 0-mg K 3 /kg/day group.Sweet clover poisoning is a common livestock problem in the northern plains. It is caused by dicumarol, a fungal metabolite produced from substrates in sweet clover hay. 3,7,9 Despite the potential toxicity of sweet clover, it is still fed to animals in the northern plains as it compares favorably with alfalfa hay in quality, utility, and cost.2 Previously, North Dakota State University investigated the analytical, toxicologic, and treatment aspects of sweet clover poisoning. 1,4 In treatment trials it was observed that vitamin K 3 was not effective, in any form, whereas vitamin K 1 was effective.' A previous report 6 indicated that oral vitamin K 3 might be antagonistic to moldy sweet clover hay. The purpose of this study was to determine if vitamin K 3 would prevent hemorrhagic crises when used as a feed additive with cattle consuming toxic sweet clover hay. Materials and methodsCalves and treatment. Twelve dairy calves weighing 173-235 kg were allotted to 4 separate groups so each group had a similar average weight. All calves were treated with an antibiotic a and a sulfaquinoxaline b prior to the start of the experiment. A number of core specimens were taken from sweet clover bales and analyzed for dicumarol content.5 Based on these values, bales that were considered toxic were ground and mixed to provide equal dicumarol levels to each of the 4 groups. The ground sweet clover was sampled on a bidaily basis to verify the dicumarol levels consumed. Each calf received 1.1 kg/day of concentrate (Table 1) that contained the vitamin K 3 supplement, plus 6.8 kg/day of ground sweet clover. The actual dicumarol levels in the sweet clover were approximately 40-50 ppm and were considered toxic. 4 All animals were fed alfalfa plus the vitamin K 3 feed additive for 10 days before they were started on the toxic sweet clover hay. The vitamin K 3 concentrate was initially supplied as a premix' and was mixed with ground corn and soybean flour (Table 1) to provide vitamin K 3 supplement levels of 0, 0.45, 4.5, and 45 mg vitamin K 3 /kg body weight/day. The compositions of the 4 primary concentrates are described in Table 1. When an 11-mg vitamin K 3 concentrate was later required, the...

Review: Drug Discovery and Development of Warfarin

“…At that time, healthy cattle suddenly became dying of internal bleeding and the cause was unknown 11 .Karl Link and his students started the isolation of the active substance from the coumarin that caused the bleeding and found 3,3'methylene-bis-[4-hydroxycoumarin], naturally oxidized coumarin was found in hay fed to livestock 12 . The bleeding disease is also known as -sweet clover disease‖ because livestock eat sweet clover that has been infected with the fungus 13. In research, it was found that natural coumarin is oxidized in moldy hay, to form a substance better known as dicoumarol 13 . The discovery of the bioactive properties of dicoumarol resulted from the investigation of a mysterious livestock disease in the 1940s and later developed as a drug in the 1950s as warfarin 14. Warfarin was first used in 1948 as a rodenticide before the US Food and Drug Administration (FDA) approved it for medical use for anticoagulants in 1954.…”