Vitamin K2: What It Is and How It Works

Vitamin K used to be thought of purely as the "clotting vitamin". Research over the past three decades has shown that one branch of the family, vitamin K2, may also matter for where calcium ends up in the body — in bone, where we want it, or in artery walls, where we do not. Supplements combining vitamin D3 and K2 have become popular in UK pharmacies and gyms. Our editorial team looks at what K2 actually is, how it works and how solid the evidence really is.

The vitamin K family

Vitamin K is a group of fat-soluble compounds sharing a common chemical ring structure. Vitamin K1 (phylloquinone) comes mainly from green leafy vegetables such as kale, spinach and broccoli and is the dominant form in the British diet. Vitamin K2 is a collective name for menaquinones, abbreviated MK-n, where "n" describes the length of the side chain.

The two forms most often discussed are MK-4 and MK-7. MK-4 is found in small amounts in animal foods such as egg yolk, butter and chicken, and the body can also make it from K1 in some tissues. MK-7 and other long-chain menaquinones are produced by bacteria during fermentation. The richest known source is natto, a Japanese fermented soybean dish; hard and soft cheeses also provide meaningful amounts.

The side chain length affects how the vitamin behaves. MK-7 has a much longer half-life in the blood than K1 or MK-4, measured in days rather than hours, so steady blood levels can be achieved with modest daily doses.

The UK does not set a separate reference intake for K2. The government's long-standing guidance is that about 1 microgram of vitamin K per kilogram of body weight per day is adequate, and most people meet this through diet.

How vitamin K2 works in the body

All forms of vitamin K act as a cofactor for one enzyme: gamma-glutamyl carboxylase. This enzyme modifies specific proteins by adding a carboxyl group to glutamate residues, turning them into "Gla" residues that can bind calcium. Without this step, the proteins are produced but remain largely inactive.

In the liver, the vitamin K-dependent proteins are clotting factors II, VII, IX and X. Outside the liver, two proteins attract most interest:

• osteocalcin, made by bone-forming cells and involved in bone mineralisation;
• matrix Gla protein (MGP), produced in blood vessel walls and cartilage, a powerful local inhibitor of calcification.

The theory is that the liver takes priority for vitamin K, so with marginal intake clotting stays normal while extrahepatic proteins remain partly undercarboxylated. K2, especially MK-7, appears to reach these tissues more effectively than K1.

Supplementation with K2 reliably lowers the fraction of undercarboxylated osteocalcin and dephosphorylated-uncarboxylated MGP in blood. Whether this biochemical change translates into fewer fractures or less arterial disease is the key question.

What the research shows

Bone health is the most studied area. In Japan, high-dose MK-4 (45 mg per day, a pharmacological dose) is licensed for osteoporosis, and Japanese trials reported fewer fractures. Western trials have been less consistent. A three-year Dutch study in postmenopausal women found that 180 micrograms of MK-7 daily slowed age-related bone loss at some sites and preserved bone strength, but large fracture trials are lacking.

Cardiovascular findings come mostly from observational research. The Rotterdam Study found that higher dietary menaquinone intake was associated with less aortic calcification and lower coronary heart disease mortality. Observational associations, however, cannot prove cause and effect.

Randomised trials of K2 in people with established vascular calcification or chronic kidney disease have so far produced largely neutral results. For athletes specifically, a few small studies have explored MK-7 and cardiac output, but the data are too preliminary to support performance claims.

Vitamin K2 and vitamin D3

The popularity of D3 plus K2 products rests on a logical argument. Vitamin D increases calcium absorption from the gut and stimulates production of vitamin K-dependent proteins, which then need vitamin K to be activated. In theory, combining the two helps direct calcium to bone rather than soft tissue.

The argument is plausible, but it remains largely theoretical for healthy people taking ordinary vitamin D doses. UK government advice to take 10 micrograms (400 IU) of vitamin D daily during autumn and winter does not include K2, and there is no evidence that standard vitamin D supplementation causes vascular calcification in people with normal kidney function.

The combination is unlikely to cause harm in healthy adults and may be convenient. It is simply wise to understand that the K2 component is an optional extra rather than a necessity.

People who take high-dose vitamin D under medical supervision, or who have kidney disease, should discuss any K2 product with their doctor rather than self-prescribing.

Safety, interactions and practical use

No tolerable upper intake level has been set for vitamin K by the European Food Safety Authority, because adverse effects have not been observed at high intakes in healthy people. Typical supplement doses of MK-7 range from 45 to 200 micrograms per day; these amounts are within the range used in published studies.

The critical exception is anyone taking warfarin or other vitamin K antagonists. These drugs work precisely by blocking vitamin K recycling, and even small amounts of MK-7 can alter the INR because of its long half-life. Do not start, stop or change a K2 supplement while on warfarin without speaking to the anticoagulation clinic. Direct oral anticoagulants such as apixaban do not interact in the same way, but medical advice is still sensible.

As a fat-soluble vitamin, K2 is best taken with a meal containing some fat. Practical food-based options include eggs, hard cheese, chicken thighs and, for the adventurous, natto.

When choosing a product, look for the form (MK-7 "all-trans" is the most studied), the dose per capsule and the absence of unnecessary additives. As with any supplement, competitive athletes should prefer batch-tested products.

Editorial team's conclusions

Vitamin K2 is a genuine nutrient with a clear biochemical role in activating calcium-regulating proteins in bone and blood vessels. Evidence that supplements reduce fractures or heart disease in healthy people remains limited, and it is not a performance enhancer. For most adults a varied diet suffices; a modest MK-7 supplement is low-risk, except for those on warfarin, who must seek medical advice first.

For a fuller picture of bone and vascular nutrition, consider reading our articles on vitamin D3 for women, calcium intake in athletes, and magnesium forms and their absorption.

References

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2. Knapen MH, Drummen NE, Smit E, et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013;24(9):2499–2507.
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