Vitamin K2 (MK-7)

Vitamin K is the generic name for a family of fat-soluble compounds that share a common chemical structure and serve as essential cofactors for the enzyme gamma-glutamyl carboxylase, which activates a group of proteins (gamma-carboxyglutamate, or "Gla" proteins) involved in blood coagulation, bone metabolism, and the regulation of vascular calcification.¹ The two principal forms are vitamin K1 (phylloquinone), found primarily in green leafy vegetables, and vitamin K2 (menaquinones), which exists in several sub-forms designated MK-4 through MK-13 based on the length of their side chains.¹

Menaquinone-7 (MK-7) is the form of vitamin K2 most commonly used in dietary supplements. It is produced by bacterial fermentation, most notably during the production of natto (a traditional Japanese fermented soybean food), which is one of the few rich dietary sources of MK-7. Compared with K1, MK-7 has a longer half-life in circulation and is more efficiently transported to tissues outside the liver, including bone and vascular wall.¹

Vitamin K's most well-established role is in blood coagulation: it is required for the post-translational activation of clotting factors II, VII, IX, and X. Vitamin K deficiency causes impaired clotting and is medically corrected with vitamin K supplementation; newborns routinely receive a vitamin K1 injection at birth to prevent vitamin K deficiency bleeding.¹

Vitamin K2 has been studied for its role in extra-hepatic Gla proteins, including osteocalcin (involved in bone matrix formation) and matrix Gla protein (which inhibits vascular calcification). Observational studies have associated higher dietary menaquinone intake with lower rates of coronary calcification and lower coronary heart disease mortality, but these are correlational findings; randomized controlled trials of MK-7 supplementation for cardiovascular outcomes are limited.¹ The NIH ODS fact sheet on vitamin K notes that few intervention trials have investigated vitamin K supplementation for arterial calcification or coronary heart disease risk, and that the existing observational evidence has not yet been confirmed in randomized trials.¹

Some intervention studies have shown that MK-7 supplementation improves markers of bone metabolism (such as carboxylation of osteocalcin) and may modestly affect bone mineral density measures in some populations, but evidence for fracture-prevention benefit at typical supplemental doses is limited.¹

The Institute of Medicine established an Adequate Intake (AI) — rather than an RDA — for vitamin K, based on representative dietary intakes in the U.S. population:¹

• Men 19 years and older: 120 mcg/day
• Women 19 years and older: 90 mcg/day
• Pregnancy and lactation (19 years and older): 90 mcg/day

The AI applies to total vitamin K from all sources, predominantly K1 from dietary sources. No separate intake recommendation has been established for K2 or MK-7 specifically.¹

Common MK-7 supplement doses range from 45 mcg to 180 mcg per day. No Tolerable Upper Intake Level has been established for vitamin K, because available evidence has not identified a specific upper intake level associated with adverse effects in healthy individuals.¹ However, individuals on warfarin require careful dietary and supplemental vitamin K consistency (see considerations below).

Oral. Vitamin K2 is fat-soluble, and absorption is improved when taken with a meal containing some fat.

Standard storage in a cool, dry place out of direct light. MK-7 supplements typically have shelf-life dating on the label that should be observed.

The most important interaction for vitamin K2 — and the reason this compound requires particular caution — is its effect on warfarin (Coumadin) and other vitamin K antagonist anticoagulants.¹ Warfarin works by inhibiting the regeneration of vitamin K, and so directly opposes the effect of supplemental vitamin K. Patients on warfarin who begin or change vitamin K-containing supplements (including K2) can experience altered INR control, which carries clinical risk in both directions (bleeding from over-anticoagulation or clotting from under-anticoagulation). Anyone on warfarin should not start or stop vitamin K-containing supplements without direct coordination with the prescribing clinician managing their anticoagulation.¹

Vitamin K2 does not appear to meaningfully interact with the newer direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, dabigatran, or edoxaban, which do not work through the vitamin K pathway.¹

Other documented interactions or considerations:¹

• Bile acid sequestrants (cholestyramine, colestipol) can reduce vitamin K absorption
• Orlistat can reduce absorption of fat-soluble vitamins including K2
• Long-term broad-spectrum antibiotics can affect gut bacterial vitamin K2 production, though the clinical significance for most individuals is uncertain