Vitamin K2
PromisingDirects calcium to bones and away from arteries.
Not medical advice
Nutripedia summarises published peer-reviewed research. This content is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before taking any supplement.
Vitamin K2 (menaquinone) is a fat-soluble vitamin essential for the activation of Gla-proteins — chiefly osteocalcin in bone and matrix Gla-protein (MGP) in vascular tissue. These proteins require vitamin K–dependent carboxylation to become biologically active. Osteocalcin binds calcium into the bone matrix; MGP inhibits arterial calcification. Dietary sources include fermented foods (natto, aged cheese, certain fermented dairy). The most studied supplemental forms are MK-4 and MK-7, which differ markedly in pharmacokinetics. The strongest interaction concern is warfarin — K2 directly opposes its mechanism.
Mechanistic evidence is compelling: K2 activates osteocalcin and MGP, both relevant to bone mineralisation and arterial health. Three-year RCT data (Knapen, PMID: 23525894) show reduced bone loss and improved arterial stiffness with 180 mcg/day MK-7. The Rotterdam Study (PMID: 15514282) associates higher menaquinone intake with 41% lower coronary heart disease mortality. Fracture endpoint RCTs in European populations are limited. Clinically significant interaction with warfarin.
Osteocalcin Carboxylation (Mechanistic Marker)
12 studies · 450 participants
Bone Health & Fracture Risk
19 studies · 6,759 participants
Arterial Calcification & Cardiovascular Risk
8 studies · 4,800 participants
The Evidence
16 peer-reviewed papers, updated 5 days ago
4 meta-analyses · 3 systematic reviews · 6 RCTs · 2 cohort studies · 1 regulatory document
Effects of vitamin K supplementation on bone mineral density at different sites and bone metabolism in the middle-aged and elderly population: a meta-analysis and systematic review of randomized controlled trials
Xie C, Gong J, Zheng C et al.
Bone & Joint Research
Meta-analysis of 17 RCTs (n=4,800) found vitamin K supplementation, particularly K2, maintains or enhances lumbar spine BMD primarily by increasing conversion of undercarboxylated to carboxylated osteocalcin, with no significant effects on other skeletal sites or additional bone turnover markers.
Vitamin K – a scoping review for Nordic Nutrition Recommendations 2023
Arja T Lyytinen, Allan Linneberg
Food & Nutrition Research
Scoping review for the 2023 Nordic Nutrition Recommendations found insufficient evidence to establish separate dietary reference values for menaquinones. It remains unclear whether menaquinones are more effective than phylloquinone for carboxylation of vitamin K-dependent proteins, and dietary menaquinone data across Nordic and Baltic populations is limited.
Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials
Te Li, Yun Wang, Wei-ping Tu
Frontiers in Nutrition
Meta-analysis of 14 RCTs (1,533 participants) found vitamin K supplementation shows significant therapeutic benefit for coronary artery calcification progression and significantly lowers dp-ucMGP levels. Safety profile is good; more rigorously designed long-term RCTs are needed to confirm outcomes.
Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials
Ming-ling Ma, Zi-jian Ma, Yi-lang He et al.
Frontiers in Public Health
Meta-analysis of 16 RCTs (6,425 participants) found VK2 supplementation positively maintains and improves lumbar spine BMD in postmenopausal women, reduces undercarboxylated osteocalcin, and may decrease fracture incidence, with no significant adverse effects reported.
Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adults: Systematic Review and Meta-Analysis
Salma, Syed Sufian Ahmad, Shahid Karim et al.
Biomedicines
Analysis of 20 studies found vitamin K2 significantly reduces vertebral fracture risk (OR 0.42) and clinical fractures (OR 0.44). Vitamin K decreases general fracture risk and can counter bone loss disorders, though its effect on femoral neck BMD remains inconclusive.
Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial
Diederichsen ACP, Lindholt JS, Möller S et al.
Circulation
Multicenter double-blind RCT in 365 elderly men with significant aortic valve calcification found that 720 µg MK-7 plus 25 µg vitamin D daily for 24 months did not reduce aortic valve calcification progression versus placebo, though dp-ucMGP was meaningfully reduced, confirming biological activity.
The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial
S H Rønn, T Harsløf, L Oei et al.
Osteoporosis International
Three-year double-blind RCT in postmenopausal women with osteopenia found MK-7 supplementation successfully increased osteocalcin carboxylation but did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture when added to standard calcium and vitamin D therapy.
Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in women with osteoporosis
Tusar K Giri, David Newton, Opal Chaudhary et al.
International Journal of Vitamin and Nutrition Research
Nine-week escalating-dose study in 29 postmenopausal women with fractures showed that both 5 mg and 45 mg/day MK-4 reduced undercarboxylated osteocalcin to levels typical of healthy pre-menopausal women. No additional benefit was observed at the 45 mg dose compared to 5 mg.
Vitamin K–Dependent Matrix Gla Protein as Multifaceted Protector of Vascular and Tissue Integrity
Fang-Fei Wei, Sander Trenson, Peter Verhamme et al.
Hypertension
Narrative review summarising mechanistic and clinical evidence that active MGP locally inhibits arterial calcification. Elevated dp-ucMGP (inactive MGP) correlates with vascular calcification risk across multiple populations. Warfarin use accelerates coronary calcification, confirming that vitamin K-dependent MGP activation is essential for vascular protection.
Dietary reference values for vitamin K
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)
EFSA Journal
EFSA scientific opinion setting Adequate Intakes for phylloquinone only, concluding that available evidence on menaquinone intake, absorption, function, and body content is insufficient to set separate dietary reference values for vitamin K2 forms. Adult AI is 70 µg/day phylloquinone equivalents.
The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review
Adriana J van Ballegooijen, Stefan Pilz, Andreas Tomaschitz et al.
International Journal of Endocrinology
Narrative review concluding that optimal concentrations of both vitamin D and vitamin K are beneficial for bone and cardiovascular health via complementary mechanisms. Vitamin D induces production of vitamin K-dependent proteins; vitamin K activates them. Co-supplementation may be more effective than either alone.
Low-Dose Daily Intake of Vitamin K2 (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trial
Naoko Inaba, Toshiro Sato, Takatoshi Yamashita
Journal of Nutritional Science and Vitaminology
Double-blind RCT demonstrated that daily MK-7 intake of 100 µg or more significantly improves osteocalcin γ-carboxylation, indicating effective activation of the bone protein osteocalcin at nutritional doses well below the pharmacological 45 mg/day used in Japanese MK-4 trials.
Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial
Marjo H J Knapen, Lavienja A J L M Braam, Nadja E Drummen et al.
Thrombosis and Haemostasis
Three-year double-blind RCT in 244 postmenopausal women found that 180 µg/day MK-7 significantly improved arterial stiffness as measured by carotid-femoral pulse wave velocity and stiffness index, particularly in women with high baseline arterial stiffness, suggesting vascular benefit beyond bone health.
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women
M H J Knapen, N E Drummen, E Smit et al.
Osteoporosis International
Landmark 3-year double-blind RCT in 244 healthy postmenopausal women showed 180 µg/day MK-7 significantly decreased the age-related decline in bone mineral content and BMD at the lumbar spine and femoral neck, and reduced bone strength loss, compared to placebo.
Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women
Toshiro Sato, Leon J Schurgers, Kazuhiro Uenishi
Nutrition Journal
Two-part RCT in healthy women demonstrated that MK-7 is well absorbed, reaching peak serum levels at 6 hours and detectable for 48 hours, while MK-4 was undetectable in serum at any time point after nutritional doses. MK-7 has markedly superior bioavailability for extrahepatic tissue support.
Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study
Johanna M Geleijnse, Cees Vermeer, Diederick E Grobbee et al.
Journal of Nutrition
Prospective cohort study in 4,807 adults followed for ~7 years found dietary menaquinone intake inversely associated with coronary heart disease mortality (RR 0.43 highest vs lowest tertile), all-cause mortality, and severe aortic calcification. Phylloquinone intake showed no cardiovascular association.
Evidence Database
Click any row to explore the studies behind each health outcome. Grades reflect the volume and quality of published research, not a recommendation.
| Grade | Health Outcome | |
|---|---|---|
| A | Osteocalcin Carboxylation (Mechanistic Marker)12 studies | |
| B | Bone Health & Fracture Risk19 studies | |
| B | Arterial Calcification & Cardiovascular Risk8 studies | |
| C | Insulin Sensitivity & Glucose Metabolism4 studies |
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General Information
Dosage (Evidence-Reported)
These figures reflect what clinical studies used — not personalised recommendations.
Safety Notes
- CLINICALLY SIGNIFICANT INTERACTION WITH WARFARIN (and all vitamin K antagonist anticoagulants): vitamin K2 directly opposes warfarin's mechanism — do not take without explicit medical guidance if prescribed anticoagulants
- Also interacts with acenocoumarol and phenprocoumon — the same contraindication applies
- Japanese MK-4 fracture trial data used 45 mg/day (45,000 mcg) — a pharmacological dose irrelevant to typical food supplements
- Fat-soluble: requires dietary fat for absorption — taking on an empty stomach reduces bioavailability
- Cardiovascular evidence is largely observational — no large RCT has confirmed fracture or CVD mortality reduction in European general populations
Key Benefits
- Activates osteocalcin, the primary bone protein responsible for calcium binding and mineralisation
- Activates matrix Gla-protein (MGP), a potent inhibitor of arterial calcification
- 180 mcg/day MK-7 for 3 years significantly reduced bone loss in postmenopausal women (PMID: 23525894)
- Higher dietary menaquinone intake associated with 41% lower coronary heart disease mortality in prospective cohort (PMID: 15514282)
- MK-7 produces sustained 24 h plasma K2 elevation — superior pharmacokinetics to MK-4 at supplement doses
- Works synergistically with vitamin D3 to support calcium metabolism
Quick Facts
Legal food supplement (UK). No prescription required. No EFSA-approved health claim specifically for vitamin K2 (menaquinone); EFSA has approved health claims for vitamin K in general for normal blood coagulation and for bone maintenance. MK-4 is licensed as a drug for osteoporosis in Japan at 45 mg/day — this is a pharmacological classification, not applicable to UK food supplements.
Frequently Asked Questions
Nutripedia is an educational resource. Content is sourced from peer-reviewed studies and does not constitute medical advice. Consult a healthcare professional before starting any supplement.