Menaquinone (vitamin K2)

Vitamins. γ-glutamyl carboxylase cofactor

ATC code: B02BA-K2 (Menaquinone (vitamin K2) – local code)

Brand names – supplements

Quality of Life Vitamin K2 MenaQ7, Thorne Vitamin K, Life Extension Super K, Doctor's Best Vitamin K2

Supplements are not tested in clinical trials and are not registered as medications.

Mechanism of action

Vitamin K2 (menaquinone, mainly MK-7 and MK-4) is a γ-glutamyl carboxylase cofactor. It activates Gla proteins: osteocalcin (bone mineralisation), matrix Gla protein (inhibitor of vascular calcification), and clotting factors II, VII, IX, X. Unlike vitamin K1 (phylloquinone) with a predominant role in coagulation, K2 has a more pronounced effect on bone and vascular calcium metabolism. The long half-life of MK-7 (72 hours) allows once-daily dosing.

Indications

Postmenopausal osteoporosis

Not recommended

EFSA 2009 approved the claim “vitamin K contributes to bone health maintenance” for labelling. Evidence on oral K2 in postmenopausal osteoporosis is limited: the 2008 Booth RCT did not show a significant effect on bone mineral density or fractures. Endocrine Society 2019 does not include K2 in osteoporosis treatment standards. Standard therapy: bisphosphonates, denosumab, teriparatide + calcium + vitamin D.

Japanese guidelines for postmenopausal osteoporosis include MK-4 at 45 mg daily, but this is a narrow local practice not supported by international consensus.

Sources

Anti-aging and longevity (marketed indication)

Not recommended

Vitamin K2 for slowing ageing or extending lifespan is not mentioned in international guidelines. The marketing position of “longevity hormone” lacks evidence. In healthy people on a varied diet, supplemental K2 has not shown clinical effects on lifespan or age-related disease incidence.

Sources

Cochrane: Vitamin K supplementation for the primary prevention of cardiovascular disease (2020)

Cardiovascular calcification prevention

Not recommended

Cochrane 2020 found no evidence for vitamin K (including K2) in primary cardiovascular prevention. The 2021 JAHA RCT in patients with coronary calcification showed some slowing of progression – not reproduced in larger RCTs. ESC, AHA do not include K2 in cardiology recommendations. The marketing position “K2 prevents vascular calcification” outpaces the evidence.

Sources

Practical notes

Timing and administration

Take with food, preferably one containing fat – K2 is fat-soluble and absorption increases 2–3 fold with dietary fat. MK-7 has a long half-life (72 hours) and is taken once daily. MK-4 is taken 2–3 times daily.

Dose titration

Standard supplement dose: 90–180 µg MK-7 daily. RCTs evaluating efficacy used 180–360 µg MK-7 or 45 mg MK-4 daily. Daily allowance for vitamin K (total K1 and K2): 90–120 µg in adults. Most people on a varied diet meet daily needs from food.

Monitoring

No special monitoring at standard doses. In patients on warfarin, vitamin K intake (including K2) substantially changes anticoagulation stability – warfarin dose adjustment under INR monitoring is required. In patients on direct oral anticoagulants (rivaroxaban, apixaban, dabigatran), vitamin K does not affect the effect.

Food and drinks

Dietary K2 sources: fermented foods (natto – the richest source, hard cheese, aged dairy), chicken egg yolk, liver, chicken meat. Fermented soybean natto contains 800–1,000 µg MK-7 per 100 g. In people who regularly consume natto, K2 deficiency is extremely rare. Vegetarians without fermented foods in the diet have lower K2 levels.

Common myths

Myth: “K2 prevents vascular calcification and heart attacks”. Fact: large RCTs did not confirm an effect on cardiovascular morbidity or mortality. Marketing outpaces science.

Myth: “K2 must be taken with D3”. Fact: D3+K2 combinations in supplements are a marketing approach. Evidence that concurrent intake improves vitamin D effects or prevents hypercalcaemia is absent. In patients on adequate D3 doses with a varied diet, additional K2 is not needed.

Myth: “MK-7 is significantly better than MK-4”. Fact: MK-7 has a longer half-life and is more convenient. Clinical advantages over MK-4 in the general population are not proven. Japanese osteoporosis guidelines actually use MK-4.

Safety

Contraindications

Concomitant warfarin therapy – requires anticoagulant dose adjustment
Hypersensitivity to components
Severe hepatic impairment

Serious adverse effects

Destabilisation of warfarin anticoagulation with thrombotic event risk

Common adverse effects

Side effects at standard doses are rare

Uncommon adverse effects

Mild dyspepsia
Allergic reactions (rash, pruritus)

PregnancyFDA C

Pregnancy data are insufficient. Vitamin K at physiological doses from dietary sources is safe. Supplemental K2 in pregnancy is not recommended.

Breastfeeding

Low K2 content in breast milk is physiological. Newborns routinely receive a single dose of vitamin K1 to prevent haemorrhagic disease of the newborn. Maternal K2 supplementation does not affect infant status.