Toxicity
Although allergic reaction is possible, there is no known toxicity associated with high doses (dietary or supplemental) of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K (42). The same is not true for synthetic menadione (vitamin K3) and its derivatives. Menadione can interfere with the function of glutathione, one of the body's natural antioxidants, resulting in oxidative damage to cell membranes. Menadione given by injection has induced liver toxicity, jaundice, and hemolytic anemia (due to the rupture of red blood cells) in infants; therefore, menadione is no longer used for treatment of vitamin K deficiency (5). No tolerable upper intake level (UL) has been established for vitamin K (42).
Nutrient interactions
Large doses of vitamin A and vitamin E have been found to antagonize vitamin K (8). Excess vitamin A appears to interfere with vitamin K absorption, whereas vitamin E may inhibit vitamin K-dependent carboxylase activity and interfere with the coagulation cascade (99). One study in adults with normal coagulation status found that supplementation with 1,000 IU/day of vitamin E for 12 weeks decreased γ-carboxylation of prothrombin, a vitamin K-dependent protein (100). Individuals taking anticoagulatory drugs like warfarin and those who are vitamin K deficient should not take vitamin E supplements without close medical supervision because of the increased risk of hemorrhage (excessive bleeding) (101).