Summary Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin g-carboxylation. Study 1 was a doubleblind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 mg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 mg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 mg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 mg groups compared with the 0 mg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 mg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake $100 mg was suggested to improve osteocalcin g-carboxylation. Key Words carboxylated osteocalcin, undercarboxylated osteocalcin, blood coagulation, recommended daily intake Vitamin K is a fat-soluble vitamin with a naphthoquinone skeleton and various lipophilic side chains (1, 2). There are two main vitamin K compounds, which differ with respect to their side chain. Vitamin K1 has a phytyl group and is found mainly in leafy green vegetables and vegetable oils (3). Menaquinones (MKs) have isoprenoid side chains with 4-14 repeats and are found in animal products; they are also produced in various bacterial fermentation processes and are, therefore, found in fermented products such as cheese and pickles (3). Vitamin K acts as a cofactor for post-translational carboxylation, in which g-glutamyl carboxylase converts certain protein-bound glutamate residues into g-carboxy glutamate (Gla) (2, 4). At least 14 types of proteins with glutamate residues, designated vitamin K-dependent Gla-proteins, have been discovered. Well-known Gla-proteins are involved in blood coagulation (factors VII, IV, and X), which are synthesized in the liver (4, 5). Gla-proteins that are not involved in coagulation include osteocalcin, a bone modulator (1), and matrix Gla protein, an inhibitor of vascular calcification (6). Osteocalcin has a structural function wherein it binds to hydroxyapatite because of g-carboxylation (7), depositing calcium on bone for b...

Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7.