Excretion of the Urinary 5C- and 7C-Aglycone Metabolites of Vitamin K by Young Adults Responds to Changes in Dietary Phylloquinone and Dihydrophylloquinone Intakes

Abstract

The physiological function and putative health roles of vitamin K-dependent proteins now extend beyond their classical role in hemostasis and include bone mineralization, arterial calcification, apoptosis, phagocytosis, growth control, chemotaxis, and signal transduction. Current assessments of vitamin K status do not reflect the variety of molecular forms of vitamin K. We assessed whether urinary excretion of 2-methyl-3-(5´-carboxy-3´-methyl-2´-pentenyl)-1,4-naphthoquinone (7C-aglycone) and 2-methyl-3-(3´-3´-carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone), vitamin K metabolites common to both phylloquinone and the menaquinone series, reflect dietary vitamin K intake. In a randomized crossover study, 9 adults resided in a metabolic unit for two 30-d periods separated by a free-living period of ≥4 wk. During each residency, subjects consumed 3 sequential diets: a control diet (93 μg phylloquinone/d) for 5 d, a phylloquinone-restricted diet (11 μg/d) for 15 d, followed by a randomly assigned repletion diet for 10 d with either phylloquinone (206 μg/d) or dihydrophylloquinone (240 μg/d). During the second residency, the alternative repletion diet was assigned. Urinary excretion of the 5C- and 7C-aglycones was measured in sequential 24-h collections. The 5C-aglycone accounted for ∼75% of total excretion and declined in response to phylloquinone restriction (P = 0.001) to ∼30% of that during the control diet period. Repletion with phylloquinone and dihydrophylloquinone doubled the excretion rate of the major 5C-aglycone by 24 h (P < 0.001), and tripled excretion by 4 d. There was a linear relationship between the logarithm of total urinary excretion and dietary vitamin K intake (r = 0.699, P < 0.001). We conclude that the urinary excretion of vitamin K metabolites reflects dietary phylloquinone intake and offers the first candidate marker of global vitamin K status.