A high phylloquinone intake is required to achieve maximal osteocalcin γ-carboxylation

Background: Dietary vitamin K is usually inadequate to maximize serum osteocalcin gamma-carboxylation. Phylloquinone supplementation increases osteocalcin gamma-carboxylation; however, the amount required to maximize carboxylation is not known. Objective: This study assessed the ability of various doses of phylloquinone (vitamin K1) to facilitate osteocalcin gamma-carboxylation. Design: Healthy adults aged 19-36 y participated in 2 substudies. In an initial dose-finding study (substudy A), 6 women and 4 men received a placebo daily for 1 wk and then phylloquinone daily for 3 wk: 500, 1000, and 2000 micrograms during weeks 2, 3, and 4, respectively. Osteocalcin and undercarboxylated osteocalcin were measured at baseline and after each week of supplementation. Subsequently, to further delineate the gamma-carboxylation response of osteocalcin to various doses of vitamin K, 58 women and 42 men were randomly assigned to receive placebo or phylloquinone supplementation (250, 375, 500, and 1000 μg/d) for 2 wk (substudy B). The percentage of undercarboxylated osteocalcin (%ucOC) was measured at baseline and weeks 1 and 2. Results: In substudy A, %ucOC decreased with phylloquinone supplementation (P < 0.0001); a greater reduction was observed with 1000 and 2000 micrograms than with 500 μg (P < 0.05). In substudy B, %ucOC decreased in all supplemented groups by week 1 (P for the trend < 0.0001), which was sustained through week 2. Phylloquinone supplementation decreased %ucOC dose-dependently; %ucOC was significantly different between the 250-micrograms and the placebo groups and between the 1000- and 500-micrograms groups but not between the 250-, 375-, and 500-μg groups. Conclusion: A daily phylloquinone intake of ≈1000 μg is required to maximally γ-carboxylate circulating osteocalcin.