Vitamin K2 (MK-4 and MK-7): Bone and Heart Evidence, Sources and Natto

If you take warfarin, read this first

Vitamin K changes how warfarin works. The NHS (UK) says not to take vitamin K supplements while on warfarin, and that foods high in vitamin K can affect it; you can still eat them, but talk to your warfarin clinic. [1] In a study of healthy volunteers on an anticoagulant (acenocoumarol), 45 mcg a day of MK-7 lowered the clotting test (INR) by about 40%, and the authors concluded MK-7 supplements need to be avoided in people on this type of drug. [2] Do not stop or change a prescribed medicine on your own; ask your anticoagulation clinic or pharmacist. See vitamins and blood thinners and medication interactions.

The short answer

Vitamin K2 is a family of compounds called menaquinones. Trials of K2 on bones and arteries are mixed. Most show effects on blood markers; results on fractures and heart outcomes are unclear. For the K1 and K2 contrast, see vitamin K1 vs K2 and the main profile, Vitamin K.

Evidence labels used: established nutritional role, mixed, promising but limited, insufficient evidence, no good evidence of benefit, and "Proper evidence not found". Biomarker change (a blood marker moving) is kept separate from outcomes like fractures.

What K2 is: MK-4 and MK-7

MedlinePlus lists phylloquinone (K1) and menaquinone (K2) as forms of vitamin K, and notes bacteria in the lower intestine also make vitamin K. [3] In a Japanese analysis of 58 foods, K1 was in green vegetables, MK-4 was widely found in animal products, and MK-7 was characteristic of fermented soybean foods such as natto. [4] MK-7 is the long-chain form with a very long half-life, which gives more stable blood levels. [5] Results for one form do not transfer to another.

Food sources and natto

In that analysis natto contained 939 mcg of MK-7 per 100 g. [4] The analysis was Japanese and of the foods tested; amounts differ by product. Because natto is such a concentrated source, people on warfarin should ask their anticoagulation clinic before eating it. Proper evidence not found in the sources we read for a study of natto itself with warfarin. For K1 foods see foods high in vitamin K.

Official intake figures

EFSA set its figure for phylloquinone only, because evidence on menaquinones was insufficient. [6] So no official body we read sets an intake figure for K2 itself. EFSA lists no adequate data to derive an upper level for vitamin K. [9] The NHS says there is not enough evidence to know what high-dose supplements do, and that 1 mg or less a day is unlikely to cause harm. [7] Lack of an upper level does not prove high doses are safe.

Bones

An earlier review found large fracture reductions, but all seven trials with fracture data were Japanese and used menaquinone-4. [15] The 2019 update noted that the integrity of some of the earlier evidence had been questioned. [13] The NHS says there is some evidence vitamin K may help keep bones healthy. [7] Osteoporosis treatment is clinician-led; see osteoporosis and bone health and vitamin D, falls and fractures.

Heart and arteries

Calcium scores and artery stiffness are markers; none of these trials showed that K2 prevents heart attacks. [20] See vitamin supplements and heart disease and D3 with K2 versus D3 alone.

Kidney disease and dialysis

A meta-analysis of 11 dialysis trials (830 people) found vitamin K had no effect on mortality and no significant benefit in reversing calcification scores. [21] A 96-patient trial found 375 mcg a day of MK-7 did not change arterial stiffness overall, though it did in a diabetes subgroup. [22] People with kidney disease should only use vitamin K supplements under their kidney team; we did not find a source on liver disease and K2, so ask your care team.