Vitamin K2 (Menaquinone)
vitamin · also known as Menaquinone, MK-7, MK-4
This is general information, not medical advice. Supplements can interact with medicines and health conditions. Always check with your doctor or pharmacist before starting or changing supplements.
What it is
Vitamin K2 (menaquinone) is a fat-soluble vitamin that activates proteins involved in calcium handling, most notably osteocalcin, which helps direct calcium into bone, and matrix Gla protein, which helps keep calcium out of blood vessel walls. It differs from vitamin K1 (phylloquinone), the form found in leafy greens that mainly supports liver clotting factors; K2 is made by gut bacteria and found in fermented foods and animal products, and circulates in the body longer than K1. People take vitamin K2 supplements hoping to support bone density and arterial health, often alongside vitamin D3, since the two work together in calcium metabolism. The two common supplemental forms, MK-7 and MK-4, differ substantially in half-life and typical dose: MK-7 is dosed in micrograms and persists in circulation for days, while MK-4 clears within hours and studies using it for bone health have generally used much larger doses. Because vitamin K2 is a form of vitamin K, it can also counteract warfarin and other vitamin K antagonist anticoagulants.
Which form to choose
Grades here rate how well the evidence supports choosing a form, which is not the same as how much that form has been studied: a well-studied form can be graded low precisely because the studies argue against it. This is a different scale from the claim grades below — see our editorial policy.
Long circulating half-life (on the order of days), attributed to incorporation into LDL particles; effective at microgram doses taken once daily.
Graded on trial use, and it is the form the trials behind this monograph actually used at doses a supplement realistically delivers. Two three-year randomised placebo-controlled trials in postmenopausal women used MK-7 at microgram doses, one reporting reduced bone loss and the other effects on bone mineral density and microarchitecture. Held at B rather than A because the effect sizes are modest and the vascular calcification evidence remains mixed.
Much shorter half-life than MK-7, cleared from circulation within hours, so sustained effects require larger and/or more frequent dosing; clinical trials using MK-4 for bone health have generally used milligram-range doses, far higher than typical MK-7 supplement doses.
Graded on trial use, with a dose caveat that is the whole reason it sits below MK-7. MK-4 does appear in the osteoporosis evidence base and is included in the systematic review this monograph cites, but the trials used milligram doses, roughly a thousand times the microgram doses typical of consumer MK-7 products, and its short half-life means those results do not transfer to a once-daily microgram supplement. So the evidence supports a drug-like dosing regimen rather than the product a reader is likely to be holding.
Evidence-based benefits
- Grade B· Limited evidence[1]
Vitamin K2 supplementation produces a small improvement in lumbar spine bone mineral density in postmenopausal women, particularly when combined with calcium and vitamin D.
A meta-analysis of 16 randomised controlled trials (6,425 postmenopausal women) found a statistically significant but modest improvement in lumbar spine bone mineral density with vitamin K2, most consistent when combined with calcium and vitamin D; heterogeneity across included trials was high.
- Grade B· Limited evidence[1]
MK-7 supplementation may help slow age-related bone density and microarchitecture loss in postmenopausal women with osteopenia.
A 3-year randomised, placebo-controlled trial of 375 mcg/day MK-7 in postmenopausal women with osteopenia found reduced age-related decline in bone mineral density and microarchitecture compared with placebo, alongside a reduction in circulating undercarboxylated osteocalcin (a marker of vitamin K status).
- Grade B· Limited evidence[1]
MK-7 at 180 mcg/day over three years reduced the age-related decline in bone mineral density and bone strength at the lumbar spine and femoral neck in healthy postmenopausal women.
A 3-year randomised, placebo-controlled trial in 244 healthy postmenopausal women given 180 mcg/day MK-7 found improved vitamin K status and a significantly reduced age-related decline in bone mineral content and bone mineral density at the lumbar spine and femoral neck, though not at the total hip; femoral-neck bone strength indices were also favourably affected. The authors cautioned that the results cannot be extrapolated to other populations, such as children and men, without further study. This is the lowest MK-7 dose with a multi-year randomised trial behind it, and unlike the 375 mcg/day osteopenia trial it falls inside the dose range this monograph publishes for MK-7.
- Grade B· Limited evidence[1]
Vitamin K supplementation may slow progression of coronary artery calcification on average, though effects are inconsistent across specific patient populations.
A meta-analysis of 14 randomised controlled trials (1,533 participants) found vitamin K supplementation slowed progression of coronary artery calcification scores on average, but several individual trials -- particularly in hemodialysis and other high-calcification-burden populations -- found no significant benefit, so the effect is not consistent across all groups.
- Grade B· Limited evidence[1]
MK-4 (menatetrenone) at 45 mg/day -- a prescription-level dose roughly 30 times the top of the over-the-counter MK-4 range below -- increased lumbar spine and trochanter bone mineral density over one year in postmenopausal women with osteoporosis, performing comparably to alfacalcidol.
A 1-year multicentre, randomised, double-blinded, double-dummy, positive-drug-controlled non-inferiority trial in 236 Chinese postmenopausal women with osteoporosis compared menatetrenone 45 mg/day against alfacalcidol 0.5 mcg/day, both with calcium 500 mg/day. Bone mineral density rose significantly from baseline in the menatetrenone group (1.2% lumbar spine, 2.7% trochanter), with no significant difference between the two groups and no change in femoral neck density in either; undercarboxylated osteocalcin fell further with menatetrenone. New fractures were too few to compare (2 of 108 versus 4 of 105). This is the dose level meant by "pharmacological" MK-4 dosing, and it is a clinician-supervised treatment regimen rather than a supplemental dose.
Risks & contraindications
Vitamin K2, like other forms of vitamin K, can reduce the effectiveness of warfarin and other vitamin K antagonist anticoagulants and destabilise INR control.
Vitamin K intake directly antagonises warfarin's mechanism of action. A study of patients on long-term warfarin found that for every 100 mcg increase in daily dietary vitamin K intake, INR fell by about 0.2 on average; the authors concluded that keeping vitamin K intake consistent could help reduce variability in anticoagulation response. This means inconsistent or added vitamin K, including from supplements, can measurably reduce and destabilise anticoagulant control. Anyone on a vitamin K antagonist should not start, stop, or change vitamin K2 supplementation without medical supervision.
Dosage & how to take it
- Menaquinone-7 (MK-7): 90–200 mcg/day, any time of day, with food. Fat-soluble; take with a meal containing fat. Often paired with vitamin D3 supplementation. On sourcing: 180 mcg/day sits inside this range and is the lowest MK-7 dose with a multi-year randomised trial behind it (PMID 23525894, three years, healthy postmenopausal women). The 375 mcg/day used in this monograph's osteopenia trial (PMID 33030563) is above the top of this range, so someone dosing to 200 mcg/day is taking a little over half the dose of that trial. The bounds themselves are not taken from any trial: 90 and 200 mcg reflect the strengths commonly sold, not a studied minimum or maximum.
- Menaquinone-4 (MK-4): 1000–1500 mcg/day, any time of day, with food. Stated plainly: this range reflects the strengths commonly sold over the counter as MK-4 and is not pinned to a trial -- no study cited on this monograph used a dose inside it. For scale, the pharmacological MK-4 dose studied for osteoporosis treatment is 45 mg/day (PMID 24426779), about 30 times the top of this range, and it is a clinician-supervised treatment regimen rather than a supplemental dose. Given MK-4's short half-life, there is no evidence that a microgram-range MK-4 dose reproduces the bone effects seen either at 45 mg/day MK-4 or at microgram doses of the much longer-lived MK-7; if the aim is the better-evidenced option at supplemental doses, that is MK-7.
Interactions
Bile acid sequestrants like cholestyramine bind bile acids in the gut, and bile acids are what your intestine needs to absorb fat-soluble vitamins, including vitamin K2. A clinical reference on this drug class specifically names vitamin K among the fat-soluble vitamins it depletes, recommending vitamins be taken a full 4 hours before the sequestrant dose; a separate clinical reference on cholestyramine specifically gives the more general rule of spacing other oral substances 1 hour before or 4 hours after it. Rather than track two slightly different windows, the safest and simplest instruction is to keep a full 4-hour gap between your vitamin K2 dose and your sequestrant dose, on either side. A published case report describes vitamin K deficiency and bleeding after 25 years of cholestyramine use, though that patient also had a separate liver condition (intrahepatic cholestasis) that can itself impair clotting-factor production, so the case doesn't isolate cholestyramine's effect alone -- it's illustrative rather than conclusive.
Take at least 4h apart from Bile acid sequestrants.
Warfarin and other vitamin K antagonists work by blocking your body's use of vitamin K to make clotting factors. Taking a vitamin K2 supplement directly opposes that mechanism: a study of people on long-term warfarin found that every extra 100 mcg/day of dietary vitamin K lowered INR by about 0.2 on average, meaning added vitamin K measurably weakens and destabilises anticoagulant control. Because supplement doses (90-200+ mcg/day for MK-7, 1000+ mcg/day for MK-4) are large and variable compared with typical dietary intake, and because starting or stopping them can swing INR outside the safe range, do not start, stop, or change vitamin K2 supplementation while on a vitamin K antagonist without your prescriber's involvement and close INR monitoring.
Our medication coverage is not exhaustive. Absence of a warning here is not evidence of safety. Always confirm with your pharmacist.
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