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Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose–response study

Eriko Nakamura, Mami Aoki, Fumiko Watanabe and Ayako Kamimura*

Author Affiliations

Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD, 2 Miyukigaoka, Tsukuba, Ibaraki 305-0841, Japan

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Nutrition Journal 2014, 13:85  doi:10.1186/1475-2891-13-85

Published: 27 August 2014



Menaquinone-4 is a type of vitamin K that has a physiological function in maintaining bone quality via γ-carboxylation of osteocalcin. However, little is known about the beneficial effect of intake of dosages below1500 μg/day.


Fifteen healthy males aged 25.0 years (median) participated in a non-placebo-controlled dose-examination study. They received menaquinone-4 daily for 5 weeks at 0, 300, 600, 900, and 1500 μg/day in weeks 1, 2, 3, 4, and 5, respectively. Compared with baseline, serum γ-carboxylated osteocalcin levels were significantly greater at an intake of 900 μg/day or more; serum undercarboxylated osteocalcin levels and the ratio of serum undercarboxylated osteocalcin to γ-carboxylated osteocalcin were significantly lower than baseline at doses of 600 μg/day or more.


This preliminary graded-dose study suggested that menaquinone-4 supplementation at 600 μg/day or more is likely to be important in terms of vitamin K requirements for bone health.

Menaquinone-4; Osteocalcin; Vitamin K