Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.

SCOPE: The mechanism for increased bleeding and decreased vitamin K status accompanying vitamin E supplementation is unknown. We hypothesized that elevated hepatic α-tocopherol (α-T) concentrations may stimulate vitamin K metabolism and excretion. Furthermore, α-T may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4). METHODS AND RESULTS: In order to investigate these hypotheses, rats were fed phylloquinone (PK) or menadione (MN) containing diets (2 µmol/kg) for 2.5 weeks. From day 10, rats were given daily subcutaneous injections of either α-T (100 mg/kg) or vehicle and were sacrificed 24 h after the seventh injection. Irrespective of diet, α-T injections decreased MK-4 concentrations in brain, lung, kidney, and heart; and PK in lung. These decreases were not accompanied by increased excretion of urinary 5C- or 7C-aglycone vitamin K metabolites, however, the urinary α-T metabolite (α-CEHC) increased ≥ 100-fold. Moreover, α-T increases were accompanied by downregulation of hepatic cytochrome P450 expression and modified expression of tissue ATP-binding cassette transporters. CONCLUSION: Thus, in rats, high tissue α-T depleted tissue MK-4 without significantly increasing urinary vitamin K metabolite excretion. Changes in tissue MK-4 and PK levels may be a result of altered regulation of transporters.

Shift of serum osteocalcin components between cord blood and blood at day 5 of life.

Vitamin K deficiency is a relatively common condition in neonates. However, the role of vitamin K in neonatal bone metabolism remains to be determined. Osteocalcin (OC) is the most abundant noncollagenous protein in bone, and is regulated to be gamma-carboxylated by vitamin K. In this study, we measured gamma-carboxylated osteocalcin (Gla-OC) and non- or undercarboxylated osteocalcin (Glu-OC) separately, and examined the effects of vitamin K on osteocalcin metabolism. Eighteen full-term healthy neonates were enrolled in this study. In the cord and d-5 blood samples, the OC levels were determined by three different methods to examine the intact OC by immunoradiometric assay (IRMA), Gla-OC, and Glu-OC. Serum vitamin K fractions, hepaplastin test, and type 1 procollagen carboxyl extension peptide were also determined. Urine samples were also collected from the first voiding and on d 5 to determine urinary pyridinoline, deoxypyridinoline, and gamma-carboxylated glutamic acid. Serum levels of phylloquinone (PK) and menaquinone (MK)-4 increased on d 5 following vitamin K administration and increased intake in breast milk and/or formula. The OC levels determined by IRMA did not change between cord and d-5 blood samples, but the Gla-OC level increased remarkably and Glu-OC reduced to a negligible level. OC in cord blood is mainly Glu-OC, and Glu-OC is replaced with Gla-OC within 5 d of life after vitamin K supplement. The IRMA assay fails to distinguish Gla-OC from Glu-OC and caution is needed to estimate bone turnover with this method in the perinatal period.