Vitamin K2 (Menaquinone)

Vitamin K2 (menaquinone) is a fat-soluble vitamin belonging to the vitamin K family, distinguished by a side-chain of varying length (MK-4 to MK-13). It functions primarily as a co-factor for γ-glutamyl carboxylase, an enzyme that activates several proteins involved in calcium metabolism, blood clotting, and cellular signaling. Unlike vitamin K1 (phylloquinone), which is plant-derived and mainly supports hepatic clotting factors, vitamin K2 is more active in extra-hepatic tissues such as bone, vasculature, and the brain, where it helps regulate mineral deposition and cellular health.

• Vitamin K2 refers to a family of menaquinones differing in the length of their isoprenoid side chain (n = 4–13).
• The most studied forms are MK-4 (menatetrenone) and MK-7 (menatetrahydroquinone).
• General molecular formula: C₍2n+7₎H₍4n+10₎O₂ (e.g., MK-7 = C₄₆H₆₈O₂, MW = 649.9 g·mol⁻¹).
• IUPAC name for MK-7: (5E)-5,6-dihydro-2-methyl-3-(1,3,5,7-octatetraenyl)-2-pyrone.
• The core naphthoquinone ring (1,4-naphthoquinone) carries a methyl group at position-2 and a polyisoprenyl side chain at position-3, which determines lipophilicity and tissue distribution.
• MK-4 is produced via a post-translational conversion of vitamin K1 in animals, whereas MK-7 is produced by bacterial fermentation (e.g., Bacillus subtilis).
• Both forms are stable in acidic, but not alkaline, environments; MK-7 is more resistant to oxidation, making it favorable for supplement formulations.

• Natural vitamin K2 originates primarily from fermented foods (e.g., natto, a Japanese fermented soy product rich in MK-7) and certain animal tissues (e.g., liver, egg yolk, butter) which contain MK-4.
• Commercially, MK-7 is most commonly obtained via fermentation of Bacillus subtilis or Bacillus natto on a nutrient-rich medium, followed by extraction, purification (often via chromatography), and spray-drying for capsule or tablet use.
• MK-4 is typically produced by chemical synthesis from menadione followed by hydrogenation, or via enzymatic conversion of K1 from plant sources.
• Quality considerations include confirming the specific menaquinone isoform (e.g., ≥90 % MK-7), absence of residual bacterial endotoxins, and stability (protect from light and heat).
• GMP-certified manufacturers that provide third-party testing (e.g., USP, NSF) ensure consistent potency and minimal contaminants.