Human biomarkers for measuring vitamin K intake and status
Biomarkers of vitamin K status have been reviewed in (3). To date, population surveys including assessment of vitamin K intake have relied on dietary intake and food frequency questionnaires, however the data generated are inconsistent (9). There is currently no single biomarker of vitamin K status for use in population studies (3, 9), and data are complex to interpret (3).
Of the available biomarkers of vitamin K activity, whilst they respond to phylloquinone repletion following a period of depletion there are none for which a dose-response relationship with phylloquinone intake has been firmly established (3).
Phylloquinone
Circulating vitamin K can be measured in serum/plasma as phylloquinone, and most available data are related to phylloquinone (3). Phylloquinone is readily detected in the circulation, and levels respond to intake, however the relatively short half-life means that circulating concentrations reflect recent intake only (9), and no cut-off values to determine adequate vitamin K status are, to date, available (3).
Because of their strong association consideration should be given to the adjustment of plasma phyllooquinone concentration relative to triacylglyceride concentration (3).
Method
HPLC with fluorescence detection, on fasting blood samples. Download the SOP Vitamin K by HPLC.
Sample type: Phylloquinone may be measured in plasma or serum.
Quality control: Analytical procedures should be performed under subdued lighting and samples stored at <20°C.
Other methods
Menanoquinones: The menanoquinones can be measured by HPLC but circulating concentrations are generally much lower than phylloquinone except in specific population groups or in people taking menaquinone-containing supplements and thus have not been adopted for population assessment (9).
Undercarboxylated vitamin K-dependent proteins can be measured to assess vitamin K status. When vitamin K is insufficient, the post-translational carboxylation of vitamin K-dependent proteins, such as prothrombin, is reduced. The undercarboxylated (inactive) fraction rises and can be detected.
Undercarboxylated prothrombin, PIVKA-II, is measureable in circulation, however is not used as a population biomarker as the commercially-available kits have a low sensitivity in detecting variation, except in individuals with chronic kidney disease (9). It is most often used in clinical settings.
Osteocalcin: An alternative is to measure osteocalcin, a vitamin K dependent protein synthesised uniquely during bone formation. Osteocalcin is detectable in serum, and the undercarboxylated portion of the protein is responsive to changes in vitamin K intake (9). It is thought to be a more sensitive indicator for individuals in the community than PIVKA-II (9). Osteocalcin is measured by immunoassay ormass spectrometry(9).
Urinary biomarkers of vitamin K status are available, which measure urinary γ-carboxyglutamic acid (Gla) and menadione, but these are restricted to a clinic setting, since 24h urine collection is required (9).
Prothrombin time is the only vitamin K biomarker for which a change (increase) has been associated with vitamin K deficiency (3). It is used in a clinical setting.