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3 The Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London SE1 7EH, UK and 4 Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111
* To whom correspondence should be addressed. E-mail: domonic.harrington{at}gstt.nhs.uk.
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.
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