Low Dose Daily Intake of Vitamin K2 (Menaquinone7) Improves Osteocalcin γ-Carboxylation: Double-Blind, Randomized, Controlled Trials (Inaba N et al.)

Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. Observational studies in Japan showed that fracture frequency was inversely correlated with high consumption levels of natto, which contains large amounts of menaquinone7 (MK7). Moreover, vitamin K2 as menaquinone-4 (45mg/day) is also used for osteoporosis medication in Japan. Clinical studies collectively showed that daily vitamin K2 intake improves bone metabolism, bone mineral density and bone strength, consequently decreasing fracture risk. To that end, researchers investigated the effective minimum daily menaquinone-7 (MK-7) dose for improving osteocalcin γ-carboxylation.

Study 1 was a double-blind, randomized, controlled, dose-finding trial where 60 postmenopausal women aged 50–69 years were allocated to one of four dosage groups and consumed 0, 50, 100, or 200 mcg MK-7 daily for 4 weeks, 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 years were allocated to the placebo or MK-7 group and consumed 0 or 100 mcg MK-7 daily for 12 weeks, 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 mcg MK-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 mcg groups compared with the 0 mcg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 mcg MK-7 group compared with the placebo group (Study 2).

The authors ultimately concluded that daily menaquinone-7 intake of 100 mcg was suggested to improve osteocalcin γ-carboxylation.

But Dr. Katarzyna Maresz, president of the International Science and Health Foundation, pointed out the following: “The present study demonstrated that the dosage equal or higher than 100mcg/day of MK-7, in addition to ordinary meals, could improve osteocalcin activation. Furthermore, inactive form of osteocalcin (ucOC) decreased even over short period of intake.

“The researchers suggests that a longer time period of MK7 intake would be expected to maintain activation of osteocalcin and bone metabolism, leading to improve bone health,” she noted, adding that 3-year clinical study performed in Maastricht, showed the “bone effect” (improved bone mineral density and strength) might be reached after longer time of supplementation (2-3 years).


Inaba N, Sato T, Yamashita T. Low-Dose Daily Intake of Vitamin K2 (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials. J Nutr Sci Vitaminol, 61, 471–480, 2015.

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