Menatetrenone

Menatetrenone (INN), also known as menaquinone-4 (MK-4), is one of the nine forms of vitamin K2.

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.