90–180 µg/day (MK-7), with a meal containing fat. A good partner for vitamin D.
Supports bone density, especially together with vitamin D and calcium.
View the study (RCT) →May slow arterial calcification; promising data.
View the study (RCT) →⏱ 4 min read
Vitamin K2, or menaquinone, is one of the two main natural forms of vitamin K, along with vitamin K1 (phylloquinone) found in leafy green vegetables; although both share the basic function of serving as a cofactor of gamma-glutamyl carboxylase (the enzyme that converts glutamate residues into functional gamma-carboxyglutamate in several key proteins), they have very different pharmacokinetic and tissue distribution profiles that result in partially different and, in some cases, complementary clinical applications.
K2 exists in several subforms designated with the MK-n nomenclature according to the length of their isoprenoid side chain: MK-4 (predominant in animal foods such as liver, egg yolk, whole-fat dairy), MK-7 (found mainly in the Japanese fermented soybean natto, where it reaches exceptional concentrations), and MK-8 to MK-13 (of bacterial origin, found in aged cheeses and some fermented foods); MK-7 is the form with the longest plasma half-life (3 days vs. 1.5 hours for MK-4) and the best studied as a supplement because of its pharmacokinetic profile, which is favorable for once-daily dosing.
The indication with the most solid mechanistic basis is the prevention of vascular calcification: K2 is an essential cofactor for activating matrix Gla protein (MGP), one of the main endogenous inhibitors of calcification of arteries and other soft tissues; functional K2 deficiency produces uncarboxylated (inactive) MGP, which is associated with greater arterial calcification and higher cardiovascular risk in prospective observational studies.
The Rotterdam study, with more than 4,800 participants followed for 7-10 years, showed that high dietary consumption of K2 (not K1) was associated with significant reductions in coronary arterial calcification, cardiovascular mortality, and all-cause mortality, a robust association that was not observed with K1; intervention trials with supplemental doses of K2 over 3 years have shown a reduction in the progression of arterial stiffness in postmenopausal women, promising data although still limited to a few cohorts.
In postmenopausal osteoporosis and fracture prevention, several Japanese trials with pharmacological doses of MK-4 (45 mg/day as the drug Glakay) have shown significant reductions in vertebral and non-vertebral fractures with treatment over years; European trials with MK-7 at supplemental doses (180-360 micrograms/day for 3 years) have shown significant improvements in biochemical bone markers and reductions in bone mineral density loss at the femoral neck.
The mechanism is the activation of osteocalcin (bone Gla protein, the most abundant non-collagenous protein in bone), which captures calcium to deposit it properly in the bone matrix; this bone function of K2 is complementary to but distinct from that of vitamin D, and the clinical synergy between the two vitamins in bone health is a frequent argument for using them together (especially when supplementing high-dose vitamin D, a context in which some specialists recommend simultaneous K2 to direct mobilized calcium to bone rather than arteries).
In type 2 diabetes and insulin resistance, several small studies have documented improvements in insulin sensitivity with high-dose supplementation over months, attributed to the activation of osteocalcin (which has an endocrine function on glucose metabolism in addition to its bone role); the data are interesting but still preliminary.
The doses studied as a supplement vary by form: MK-7 at 90-360 micrograms daily (low doses are more than sufficient because of its long half-life); MK-4 at supplemental doses of 1-15 mg/day (the Japanese pharmacological doses of 45 mg/day require a medical prescription); with or without food, ideally with some fat to optimize absorption; quality products declare the specific form (MK-4 vs MK-7), the amount per dose, and, ideally, the origin (natto-derived MK-7 is the best studied).
Generally very well tolerated at the supplemental and pharmacological doses studied; the adverse effects described are rare and mild (digestive discomfort, occasionally headache); the most important clinical consideration is the interaction with anticoagulants such as warfarin or acenocoumarol: vitamin K is the direct antagonist of these drugs and supplementation can significantly alter the INR, requiring dose adjustment or absolute avoidance depending on the case; people taking these anticoagulants should not start K2 without consulting their anticoagulation specialist; those taking direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) do not have this interaction and can take K2 safely; in pregnancy and breastfeeding, dietary doses are safe and moderate supplementation is as well; cheap products may have a lower K2 content than declared; it is advisable to choose products with stabilized, trans-isomeric MK-7 (the cis form is biologically inactive).
Information, not medical advice. Scientific evidence reflects the quality of the studies.