Menaquinone-4 (MK-4)

Category: vitamin

Aliases: Vitamin K2 MK-4, Menatetrenone

Pharmacological Mechanism

Carboxylates extrahepatic Gla proteins — matrix Gla protein (inhibits vascular calcification), osteocalcin (binds bone Ca²⁺), Gas6 (axon regeneration). Short (4-isoprenoid) side chain gives MK-4 a shorter plasma t½ (~1 h) than MK-7 but higher tissue turnover. Extrahepatically synthesised from K1 via side-chain conversion — dietary MK-4 supplements the tissue pool directly.

Half-Life (t½)

PO: 1h

Dosing Guidelines

• PO: Typical 133 mcg (Range: 100–200 mcg)

Target Organ Systems

• musculoskeletal

Interactions

• Vitamin D3 (synergistic): D3 raises Ca²⁺ absorption; K2 directs deposition to bone vs. vasculature. Classic bone-health pair.
• Warfarin (major): Antagonises warfarin. Avoid or monitor INR closely. [Holbrook 2005]
• Menadione (synergistic): Menadione is the circulating precursor of tissue MK-4. Supplemental MK-4 bypasses menadione's redox toxicity.
• Menaquinone-7 (MK-7) (synergistic): Same family; MK-7 is longer-acting. Generally pick one.

Pathways It Modulates

• Vitamin D receptor genomic signaling (VDR) (cofactor) — VDR/K-axis crosstalk (Gla-osteocalcin requires K₂)
• Vitamin K cycle (γ-carboxylation) (substrate) — menaquinone-4 (vitamin K2)

Chemical Identifiers

• PubChem CID: 5282367
• Formula: C31H40O2
• Molecular weight: 444.65 g/mol
• InChIKey: DKHGMERMDICWDU-GHDNBGIDSA-N
• SMILES: CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C

References

• PMID 23140417
• PMID 15911722