K2 dose-finding study: MK-4 requires higher dose than MK-7 for bone benefits

Menaquinone-4 (MK-4) is a type of vitamin K that has a physiological function in maintaining bone quality via γ-carboxylation of osteocalcin. A study published in Nutrition Journal examined the beneficial effect of intake of dosages below 1500 mcg/day.

Fifteen healthy males aged 25 years (median) participated in a non-placebo-controlled dose-examination study. They received MK-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.

Researchers concluded that this preliminary graded-dose study suggested that vitamin K2 as MK-4 supplementation at 600 μg/day or more is likely to be important in terms of vitamin K requirements for bone health.

While this study brings new insight to effective doses of Vitamin K2 as MK-4, Dr. Katarzyna Maresz, president of the International Science and Health Foundation, expressed that it in fact makes a stronger argument for the use of Vitamin K2 as MK-7.

“Studies that give us insight to the optimal dose of Vitamin K2 for bone benefits are always welcomed. However, the Knappen et al. study that published in Osteoporosis International showed that the optimal dose of Vitamin K2 as MK-7 to decrease inactive osteocalcin was 180 mcg/day, which is much lower than the required dose for MK-4, which this study showed was 600 mcg/day or more,” said Dr. Maresz. “This is due to MK-7’s higher bioavailability, which is an important consideration to keep in mind when selecting the best Vitamin K2.”

Reference: Nakamura E, Aoki M, Watanabe F, Kamimura A. Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose-response study. Nutr J. 2014 Aug 27;13:85.

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