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Vitamin K tends to be supplemented in one of three forms; Vitamin K1 (phylloquinone) or one of two possible Vitamin K2s (menaquinones), MK-4 or MK-7. Phylloquinone tends to have the standard vitamin-like action of supporting vitamin K dependent proteins, while MK-4 and MK-7 have alternate mechanisms of action.
Vitamin K1 (phylloquinone) or one of the two vitamin K2 variants (MK-4 or MK-7) are the most common vitamin K supplements to be used. Vitamin K3 (menadione) is not commonly used
MK-4 is the most popular menaquinone to supplement, synonymous with the name menatetrenone. 100mcg of MK-4 is equivalent to 225nmol (molar mass of 444.65). Supplementation of MK-4 increases bodily levels of MK-4, but either has no influence or lowers bodily concentrations of phylloquinone.
MK-4 is a supplement that appears to have benefits at a dose of around 1,500mcg but is usually used in pharmacological doses of 45mg. At least one study using dosages of MK-4 found in food (420mcg) failed to find any increases in blood concentrations of MK-4, suggesting that 1,500mcg is the bare minimum and that food sources of MK-4 may not contribute to bodily menaquinone storages easily. Supplementation of MK-4 does not appear to reliably increase circulating concentrations of phylloquinone (a spike observed at week two was no longer present at week four) despite increasing serum concentrations of MK-4 and improving carboxylation of proteins (osteocalcin and MGP), thus MK-4 can act as a vitamin.
For its unique properties, MK-4 appears to induce differentiation of leukemic cells (a property useful in differentiation therapy potently at 1µM, which is not observed with phylloquinone. It has been speculated that MK-4 has a direct action independent of the vitamin K cycle either through proteins (direct binding rather than carboxylation) or acting upon a receptor. There are also differences in transportation and distribution between menaquinones and phylloquinone (elaborated on in the pharmacology section), which can be summed up with menaquinones being better partitioned to the periphery and not the liver, and MK-4 appears to have a unique role on osteoclasts that is not seen with phylloquinone or MK-7 (and perhaps underlies why superloading of MK-4 is used rather than other menaquinone sources).
MK-4 (Menatetrenone) does not appear to increase the amount of active vitamin K in the body, although still appears to be active in carboxylating proteins. It requires higher dosages than phylloquinone, and although 45mg (a very high pharmacological dose) is used it is possible that 1,500mcg is also effective. MK-4 may have a unique role on inducing bone growth that is not seen with phylloquinone or MK-7 *
