Vitamin K2 (Menaquinone)

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.

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]

  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.

Risks & contraindications

• Grade B· Limited evidence[1], [2]

  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.
• Menaquinone-4 (MK-4): 1000–1500 mcg/day, any time of day, with food. Reflects typical over-the-counter MK-4 supplement dosing. This is far below the 45 mg/day pharmacological dose used in some clinical trials for osteoporosis treatment, which is a prescription-level regimen not represented by this range.

Interactions

• Separate timingBile acid sequestrants(medication class)[1], [2], [3]

  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.

• Avoid combiningVitamin K antagonists(medication class)[1], [2]

  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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