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 K
1 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 K
1 in rats.
Tissues that accumulate high amounts of MK-4 have a capacity to convert up to 90% of the available K
1 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.[
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