Vitamin D3 and K2

Short answer

There is no clinical evidence that D3 must be taken together with K2 to be effective. There are bone and vascular health studies for K2, but results are mixed and limited: in healthy postmenopausal women, bone density loss was reduced with MK-7, but when MK-7 and D were given together, progression of aortic valve calcification was not reduced. ^{[4] [5]} For people using a vitamin K antagonist such as warfarin, products containing K are a serious interaction issue. ^[1]

What is vitamin D3, and does it differ from D2?

Vitamin D exists in two main forms: D2 (ergocalciferol; from mushroom and plant sources) and D3 (cholecalciferol; animal foods and the form produced in the skin by sun). According to the NIH, both raise serum 25(OH)D levels and appear equivalent in curing rickets; however, most of the evidence shows that D3 raises the level more and has maintained it longer. ^[2]

In the meta-analysis of randomized trials by Tripkovic and colleagues, D3 raised 25(OH)D more effectively than D2; this difference was marked in trials giving a single high dose and disappeared with daily use. ^[3] The “D3” label therefore describes the vitamin form; it does not say that the product contains K2 or is better. The amount of D3 on the product box is written in IU or µg (1 µg = 40 IU); the two units can make the same product look different.

What is vitamin K2? What do MK-4 and MK-7 mean?

Vitamin K is divided into two groups: phylloquinone (K1) is the main dietary form found in green leafy vegetables; menaquinones (K2) are mostly of bacterial origin and are named from MK-4 to MK-13 according to side-chain length. They are found in modest amounts in animal and fermented foods. The most-studied menaquinones are MK-4, MK-7, and MK-9. MK-4 is distinguished by being convertible from K1 in the body without bacterial involvement. ^[1]

All vitamin K forms are cofactors of the K-dependent carboxylase enzyme; this enzyme is necessary, in addition to clotting proteins, for the function of osteocalcin in bone and matrix Gla protein (MGP) found in vessels, bone, and cartilage. The NIH states that MGP is of interest because it may reduce abnormal calcification. ^[1] This biological rationale is the basis of the marketing sentence “D3 brings calcium into the blood, K2 directs it to the bone.” However, a biological mechanism does not prove that supplementation shows this effect in healthy people.

The most striking difference between MK-7 and K1 is MK-7’s very long half-life: in the healthy volunteer study by Schurgers and colleagues, MK-7 gave much more stable levels in serum and accumulated at 7–8 times higher levels than K1 with continuous intake. ^[7]

Has the claim “calcium goes to bone, not the artery” been proven?

No, the claim has not been proven in this form. The sources give different results:

Bone. In the randomized trial by Knapen and colleagues, 244 healthy postmenopausal women took 180 µg MK-7 per day or placebo for 3 years. MK-7 reduced loss of bone mineral density at the lumbar spine and femoral neck, but there was no difference at the total hip; the results apply to healthy postmenopausal women and cannot be carried over to men or children. ^[4] The reported results are indicators of density and bone strength; a reduction in fractures is not a finding in this study’s summary.

Vessel and valve. In the double-blind trial by Diederichsen and colleagues, 365 men (mean age 71) with a high aortic valve calcium score (above 300 AU) took 720 µg MK-7 plus 25 µg vitamin D per day or placebo for 24 months. The increase in aortic valve calcification was 275 AU in the treatment group and 292 AU in the placebo group; the difference was not significant (P=0.64). Progression of aortic and coronary calcification also did not differ. MK-7 plus D lowered the blood dp-ucMGP level; that is, the biological marker changed, the clinical outcome did not. ^[5] This trial is one of the few randomized trials that directly test the combination idea; even so, it was conducted in a specific patient group (older men with valve calcification).

Dialysis patients. In the Valkyrie trial, in 132 dialysis patients, vitamin K status improved in the group given high-dose K2 (2,000 µg three times a week) for 18 months, but changes in coronary, aortic, and valve calcification and in pulse wave velocity did not differ significantly between groups. ^[6] This is a special population with kidney disease and cannot be generalized to healthy people.

In summary, the claim that K2 reduces vascular calcification or directs calcium to bone together with D3 was not confirmed with clinical outcomes in these randomized trials. This also does not mean that K2 is useless under all conditions; a positive clinical effect has simply not been shown within the population and duration limits of these sources. A separate evidence table for vitamin D’s fracture outcomes is on the vitamin D benefits page.

Why does K2 matter for people using warfarin?

This heading is the most critical safety issue of the combination. The NIH states that warfarin and similar anticoagulants (including those used in Europe, such as phenprocoumon and acenocoumarol) reduce K-dependent clotting factors by blocking the effect of vitamin K; that people using these medications should keep vitamin K intake from food and supplements consistent, because sudden changes can increase or decrease the anticoagulant effect. ^[1]

With menaquinone supplements the risk is not theoretical: Schurgers and colleagues reported that preparations providing 50 µg and above of MK-7 per day can clinically significantly disrupt oral anticoagulant treatment. ^[7] For this reason, in people using warfarin or a similar medication, adding or stopping a product containing K, including a D3+K2 combination, is evaluated together with the physician. Direct oral anticoagulants (such as rivaroxaban) have a different mechanism of action; on this matter the knowledge of the physician who prescribed the drug should be relied upon.

Are D3 and K2 needed together?

There is no evidence that they are needed:

• The NIH’s vitamin D summary does not mention a vitamin K requirement for vitamin D’s function, adequacy values, or supplementation recommendations. ^[2]
• Vitamin K is obtained from foods (especially green leafy vegetables); in the NIH’s K table, natto (MK-7) and dark green vegetables are seen to provide very high amounts. ^[1]
• There is no randomized evidence, in the studies examined here, that the combination reduces fractures or vascular events in healthy people. ^{[4] [5]}

If vitamin D supplementation is needed, a separate D product is generally sufficient; adding K2 requires a separate decision and should be made after reviewing drug interactions, diseases, and diet. What to look for on the label of which D form and product is covered on the vitamin D drugs and supplements page. The risks of high intake are covered on the vitamin D excess page.

Is K2 safe, and who should be careful?

According to the NIH, the Food and Nutrition Board has not set an upper limit for vitamin K because of its low toxicity potential, and reports that there are no reports of adverse effects in humans or animals from vitamin K obtained from food or supplements. ^[1] This does not mean “risk-free for everyone”: the main safety problem is drug interactions.

Apart from warfarin, the NIH states that bile acid sequestrants and drugs that reduce fat absorption such as orlistat can reduce vitamin K absorption, and that orlistat together with warfarin can markedly prolong prothrombin time. Long-term antibiotic use can also affect K production by gut bacteria. ^[1] In people using such medications, the suitability of a product containing K2 is evaluated with a physician or pharmacist.

How is the label of a combination product read?

With combination products, three separate questions are asked: is the D3 amount in IU or µg; is the K2 form MK-4 or MK-7 and how many µg; is the serving one capsule or several drops. The K2 amount is especially important for interaction in warfarin users. If the label carries a promise such as “directs to the bone” or “cleans the arteries,” this should be read as a statement that does not match the evidence above. This guide does not recommend products or brands and does not give a personal dose.

Detailed guideVitamin D forms and reading labels→ Detailed guideProven and unproven benefits of vitamin D→ Detailed guideExcess: symptoms and upper limit→

Main guide: What is vitamin D?