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Urinary γ-Carboxyglutamyl Residues

After protein catabolism, γ-carboxyglutamyl (Gla) residues contained in the vitamin K-dependent proteins are not further metabolized and are excreted via urine (Shah et al., 1978). As a result, urinary Gla excretion has been used as an indicator of vitamin K status. Urinary Gla responds to alterations in dietary intake, but periods of several days are needed before any change can be observed (Ferland et al., 1993; Suttie et al., 1988). In a study by Suttie and coworkers (1988), 10 college-age men were asked to eliminate the major sources of vitamin K from their diet, thereby reducing their intake to less than 40 μg/day of phylloquinone. Urinary Gla excretion decreased 22 percent after 3 weeks and returned to baseline values 12 days after supplementation with 50 or 500 μg of phylloquinone. In a recent study, increasing phylloquinone intakes from 100 μg/day to a range of 377 to 417 μg/day for 5 days did not induce significant changes in urinary Gla (Booth et al., 1999a).

Response of urinary Gla to vitamin K intake alterations appears to be age-specific. In a study by Ferland and coworkers (1993), 32 subjects were divided into four groups of eight (men or women, 20 to 40 or 60 to 80 years old) and housed in a metabolic research unit. They were fed 80 μg of phylloquinone for 4 days followed by a low vitamin K diet (approximately 10 μg phylloquinone/day) for 16 days. At the end of the depletion period, urinary Gla excretion had decreased significantly in the younger, but not the older subjects. Short-term supplementation with 45 μg/day of phylloquinone reversed the decline to near baseline values. In another study involving 263 healthy individuals (127 men, 136 women) aged 18 to 55 years, urinary Gla/creatinine excretion ratios increased significantly with age in both men and women with values 20 percent higher in women over the age span (Sokoll and Sadowski, 1996). To date, there are insufficient data for using urinary Gla excretion for estimating an average requirement.

Undercarboxylated Prothrombin

In humans, an insufficiency of vitamin K leads to the secretion into plasma of biologically inactive, under-γ-carboxylated forms of the vitamin K-dependent clotting factors. These proteins are referred to as protein induced by vitamin K absence or antagonism (PIVKA). In reference to prothrombin (factor II), the term used is PIVKA-II. This protein has been measured by specific immunoassay (Blanchard et al., 1981), by thrombin generation after the removal



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