Menatetrenone

Biology

MK-4 is the major form of Vitamin K in vertebrate animals, including humans and common forms of meat animals. It is produced via conversion of vitamin K1 in the body, specifically in the testes, pancreas and arterial walls. The conversion is not dependent on gut bacteria, occurring in germ-free rats and in parenterally-administered K1 in rats. Tissues that accumulate high amounts of MK-4 have a capacity to convert up to 90% of the available K1 into MK-4.

K1 is converted to MK-4 in three steps:

• Removal of the phytyl tail to form menadione (K3; unknown enzyme);
• Reduction of menadione to menadiol (likely NQO1);
• Attachment of GGPP tail to form menaquinol-4, the reduced form of MK-4 (UBIAD1)

The second and third steps are known to happen in target tissue. The first step is proposed to happen mainly in the intestines.

As a medication

Menatetrenone is approved in Japan for second-line treatment of postmenopausal osteoporosis. Evidence is restricted to small-scale RCTs; the minimum effective dose (for bone mass parameters) is 45 mg, much higher than the Daily Value for vitamin K (80 μg).

Bioavailbility and dose

420 μg of oral MK-4, in a single-dose or spread out over 7 days, does not cause detectable changes in serum MK-4 level in healthy women, whereas MK-7 produces the expected increases in MK-7 levels.

The minimum effective oral dose to change serum osteocalcin levels is 1500 μg/d, where as oral MK-7 is effective on this parameter at 45 μg/d, a level more in line with nutritional intake. In addition, rat studies show that oral MK-7 is better at increasing extrahepatic tissue levels of MK-4 than oral MK-4.

References

References

1. (October 2008). "Metabolism and cell biology of vitamin K". Thrombosis and Haemostasis.
2. (February 1998). "Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria". The Journal of Nutrition.
3. (January 1998). "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat". Biochimica et Biophysica Acta (BBA) - General Subjects.
4. (September 1994). "Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4". The British Journal of Nutrition.
5. (December 1992). "Comparative metabolism and requirement of vitamin K in chicks and rats". The Journal of Nutrition.
6. (March 2014). "Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis". Journal of Lipid Research.
7. (May 2014). "Vitamin K₂ therapy for postmenopausal osteoporosis". Nutrients.
8. (November 2012). "Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women". Nutrition Journal.