Effect of phylloquinone supplementation on biochemical markers of vitamin K

Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women

Susanne Bügel, A Dorthe Sørensen, Ole Hels, Mette Kristensen, et al. The British Journal of Nutrition . Cambridge: Feb 2007. Vol. 97 , Iss. 2; pg. 373, 8 pgs

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Abstract (Summary)

While current intakes of phylloquinone (vitamin K1) in many populations are believed to be sufficient to maintain normal blood coagulation, these may be insufficient to cover the requirements for optimal bone metabolism. Therefore, the objective of the present study was to investigate the effect of increasing phylloquinone intakes above the usual dietary intake for 6 weeks on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Thirty-one postmenopausal women completed this 3 × 6-week randomised cross-over study, in which volunteers were supplemented with 0 (placebo), 200, and 500 μg phylloquinone/d.

In addition, the volunteers were given 10 μg vitamin D3/d throughout the study period. With increasing phylloquinone intake, the concentration of serum γ-carboxylated and under-γ-carboxylated osteocalcin was significantly increased and decreased, respectively, in a dose-dependent manner (P < 0·001). Mean serum phylloquinone concentration was significantly (P < 0·001) higher with daily supplementation with 500 μg phylloquinone/d compared with that during either of the placebo or 200 μg phylloquinone/d supplementation periods, which did not differ (P = 0·15). Serum total osteocalcin was significantly (P < 0·001) increased in response to daily supplementation with 500 (but not 200) μg phylloquinone compared with placebo.

Serum bone-specific alkaline phosphatase as well as the urinary markers of bone resorption (N-telopeptide cross-links of collagen, pyridinoline and deoxypyridinoline) and urinary γ-carboxyglutamate were unaffected by phylloquinone supplementation. In conclusion, while daily supplementation with 200 and 500 μg phylloquinone/d for 6 weeks increased vitamin K status in postmenopausal women, it had no effect on bone turnover.

In conclusion, the findings of the present study showed that increasing phylloquinone intake of postmenopausal women by 200 and 500 [mu]g/d significantly increased the degree of [gamma]-carboxylation of OC and, consequently, led to a reduction in concentrations of ucOC, an independent risk factor for osteoporotic fracture (Szulc et al. 1993, 1996; Vergnaud et al. 1997).

The reduction in ucOC concentration (and ucOC:cOC ratio) achieved by phylloquinone supplementation, however, had no apparent modulating effect on bone turnover. This may be explained by an apparently adequate habitual intake of phylloquinone and it is possible that very large doses of phylloquinone are required to see a response.

Therefore, further research is warranted to investigate the mechanisms of action of phylloquinone on BMD and fracture risk, as well as further clarification of the physiological and clinical relevance of submaximal [gamma]-carboxylation of OC, including its role as a status indicator for vitamin K nutriture.

This issue is of importance for further consideration of the dietary requirement for phylloquinone, as the findings of the present and other studies would suggest that usual dietary intakes of several population sub-groups provide inadequate phylloquinone to allow maximal [gamma]-carboxylation of OC.