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American Journal of Clinical Nutrition, Vol. 76, No. 5, 1055-1060, November 2002
© 2002 American Society for Clinical Nutrition


Original Research Communication

A high phylloquinone intake is required to achieve maximal osteocalcin {gamma}-carboxylation1,2,3

Neil C Binkley, Diane C Krueger, Tisha N Kawahara, Jean A Engelke, Richard J Chappell and John W Suttie

1 From the Institute on Aging, Department of Medicine (NCB, DCK, and TNK), Department of Biochemistry (JAE and JWS), and Department of Biostatistics (RJC), University of Wisconsin, Madison.

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 µg 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 µg 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-µg and the placebo groups and between the 1000- and 500-µg groups but not between the 250-, 375-, and 500-µg groups.

Conclusion: A daily phylloquinone intake of {approx}1000 µg is required to maximally {gamma}-carboxylate circulating osteocalcin.

Key Words: Vitamin K • phylloquinone • osteocalcin • undercarboxylated osteocalcin • {gamma}-carboxylation




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