Dietary phylloquinone depletion and repletion in older women

Biological markers indicative of poor vitamin K status have been associated with a greater risk for hip fracture in older men and women. However, the dietary phylloquinone intake required to achieve maximal carboxylation of hepatic and extrahepatic vitamin K-dependent proteins is not known. In an 84-d study in a metabolic unit, 21 older (60-80 y) women were fed a phylloquinone-restricted diet (18 mug/d) for 28 d, followed by stepwise repletion of 86, 200 and 450 mug/d of phylloquinone. Plasma phylloquinone, urinary gamma-carboxyglutamic acid excretion and gamma-carboxylation of hepatic (prothrombin) and extrahepatic proteins (osteocalcin) decreased in response to phylloquinone restriction (P < 0.001), demonstrating the production of subclinical vitamin K deficiency. The gamma-carboxylation of prothrombin was restored to normal levels in response to phylloquinone supplementation at 200 mug/d. In contrast, all other biochemical markers of vitamin K status remained below normal levels after short-term supplementation of up to 450 mug/d of phylloquinone. These data support previous observations in rats that hepatic vitamin K-dependent proteins have preferential utilization of phylloquinone in response to phylloquinone dietary restriction. Moreover, our findings suggest that the current recommended Adequate Intake levels of vitamin K (90 mug/d) in women do not support maximal osteocalcin gamma-carboxylation in older women.