Variation in the response of human beings to vitamin K₁

The effect of vitamin K₁ on the response of 6 healthy volunteers to the anticoagulant, warfarin, was measured. When warfarin (40 mg.) and vitamin K₁ (1 mg.) were administered simultaneously, there was a marked variation between individuals in the ability of the vitamin to antagonize the anticoagulant effect. One subject showed no antagonism; two showed complete antagonism; others showed an intermediate response. When vitamin K₁ was administered 24 hours prior to warfarin, less variation was noted between individuals. One subject continued to show no antagonism; the others showed an intermediate effect. When vitamin K₁ was administered 48 hours after warfarin, at the height of the anticoagulant response, there was a marked variation between individuals in the time required for clotting activity to return to normal. Two subjects appeared to synthesize or release vitamin K-dependent clotting factors rapidly; another subject appeared to synthesize or release it slowly; and others released it at an intermediate rate. These experiments indicate that there is considerable variation in the normal population in response to vitamin K₁ and suggest that this variation is due to a number of factors: differences in rates of metabolism or excretion of vitamin K₁, differences in receptor site affinity in the liver for vitamin K₁, and differences in the rate of synthesis or release of vitamin K-dependent clotting factors.