Vitamin E Injections Decrease Tissue Vitamin K in Rats

To test the mechanism by which α‐tocopherol (α‐T) decreases vitamin K status, rats were fed for 2.5 w phylloquinone (PK) or menadione (MN)‐containing diets (2 μmol/kg). From 10 d, rats were subcutaneously injected daily with α‐T (100 mg/kg) or vehicle, then sacrificed 24 h after the 7 th injection. Urine collected during the injection period was analyzed for vitamin metabolites; tissue PK and menaquinone‐4 (MK‐4), and hepatic expression of enzymes and transporters were also analyzed. Irrespective of diet, α‐T injections decreased MK‐4 in brain, lung, & kidney; and PK in kidney and lung. However, these decreases were not accompanied by increased urinary 5C‐ or 7C‐aglycone, or MN excretion; however, α‐T metabolite excretion increased ≥100 fold. Moreover, α‐T down‐regulated gene expression of various cytochrome P450s and up‐regulated expression of xenobiotic transporters. Thus, high doses of α‐T decrease tissue vitamin K concentrations, but these decreases are not likely a result of increased metabolism, but rather reflect an increased gene expression of xenobiotic transporters, which could potentiate tissue vitamin K loss and increase its biliary excretion. Grant Funding Source : USDA NRI‐2008‐01875