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Vitamin K2 (MK-4)

MK-4 is a licensed osteoporosis drug in Japan at 45 mg/day — but that is pharmacology, not supplementation. At the microgram-to-milligram doses sold as supplements, MK-4 barely registers in the bloodstream, and its very short half-life makes MK-7 the more practical form.

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What the science says

  • Reduces fractures at pharmacological doses Limited evidence

    A 2006 meta-analysis of vitamin K trials — nearly all Japanese studies of MK-4 at 45 mg/day — reported striking reductions in vertebral (odds ratio 0.40), hip (OR 0.23) and all non-vertebral fractures (OR 0.19). Those numbers are almost certainly too good: the constituent trials were small, unblinded or poorly blinded, and the effect has not been reproduced in larger, better-controlled Western trials. Treat it as a hypothesis from one country's literature, not an established effect.

  • Supplement doses raise vitamin K2 status Limited evidence

    Mostly they do not. In a bioavailability study in healthy women, a single 420 µg dose of MK-4 produced no detectable increase in serum MK-4, while the same dose of MK-7 raised serum MK-7 substantially. MK-4's circulating half-life is a matter of hours versus roughly three days for MK-7. A 100 µg or 1 mg MK-4 capsule taken once daily is unlikely to change your measurable K2 status at all.

  • Directs calcium into bone and away from arteries Limited evidence

    The mechanism — gamma-carboxylation of osteocalcin and matrix Gla protein — is real biochemistry. The clinical claim is not supported for MK-4: no randomised trial of MK-4 has shown reduced arterial or valvular calcification, and the trials that did test this hypothesis used MK-7 and were largely negative.

  • MK-4 is superior to MK-7 because it is 'the human form' Limited evidence

    MK-4 is indeed the menaquinone tissues make from K1 and other menaquinones, and it is the form found in some tissues. But that argument works against oral MK-4, not for it: your body already converts, and the oral molecule barely reaches circulation. If you want to change vitamin K status with a supplement, MK-7 is the form with the pharmacokinetics to do it.

Dosage & safety

Studied doseThe Japanese prescription regimen is 45 mg/day (15 mg three times daily) taken with food — a dose roughly 500x what supplement capsules contain. Supplements supply 100 µg to 5 mg/day. Adequate intake for vitamin K overall is 90–120 µg/day and is met by leafy greens as K1. MK-4 requires dietary fat and frequent dosing to achieve anything; a once-daily microgram dose is largely inert.
SafetyNo toxicity is known even at 45 mg/day, and vitamin K has no established upper limit. The one serious interaction is decisive: any vitamin K supplement antagonises warfarin, acenocoumarol and other vitamin K antagonists and can destabilise INR — do not start or stop one without your prescriber, and if you take a VKA, consistency of intake matters more than avoidance. No interaction with DOACs (apixaban, rivaroxaban). Most supplemental MK-4 is synthetic, typically derived from geranylgeraniol; 'natural' MK-4 in meaningful quantity is rare in food. Pharmacological 45 mg dosing has not been established as safe in pregnancy or lactation. Not banned in sport.

How to take it

TimingSplit across the day — MK-4 has a short half-life, which is why the Japanese regimen dosed three times daily.
With food?With a fat-containing meal; MK-4 needs dietary fat to be absorbed at all.
Worth knowingA once-daily microgram capsule is largely inert — if you want the effects MK-4 was studied for, the dose and the frequency both have to change, and that is a prescription-scale decision.

Interactions

With medications

  • warfarin, acenocoumarol and other vitamin K antagonists

    vitamin K directly opposes the drug and destabilises INR do not start or stop it without your prescriber; if you take a VKA, steady intake matters more than avoidance

  • orlistat and bile-acid sequestrants

    they block absorption of fat-soluble vitamins including K separate by at least 2 hours

Well-established interactions only — this is not a complete list. Always tell your doctor and pharmacist what you take.

Frequently asked questions

Does vitamin K2 MK-4 prevent fractures?

The evidence is limited. The striking fracture reductions come from small, poorly blinded Japanese trials of MK-4 at a prescription dose of 45 mg/day, and they have not been reproduced in larger, better-controlled trials.

Is MK-4 or MK-7 the better form of vitamin K2?

MK-7 is the more practical supplement. A single 420 mcg dose of MK-4 produced no detectable rise in blood MK-4, while the same dose of MK-7 raised blood MK-7 substantially; MK-4's half-life is hours versus roughly three days for MK-7.

Does vitamin K2 MK-4 keep calcium out of arteries?

Not on current evidence. No randomised trial of MK-4 has shown reduced arterial or valve calcification, and the trials that tested this hypothesis used MK-7 and were largely negative.

Can I take vitamin K2 MK-4 with warfarin?

Any vitamin K supplement, including MK-4, opposes warfarin and other vitamin K antagonists and can destabilise your INR. Do not start or stop it without your prescriber; there is no interaction with DOACs such as apixaban or rivaroxaban.

Scientific references

Where to buy

Nutricost, Vitamin K2 MK-4, 100 mcg, 240 Capsules

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