{"@context":"https://schema.org","@type":"DietarySupplement","id":"https://nutripedia.co.uk/items/vitamin-k2","url":"https://nutripedia.co.uk/items/vitamin-k2","name":"Vitamin K2","category":"Vitamins","tagline":"TL;DR — Research shows MK-7 at 180 mcg/day for 3 years reduces bone loss in postmenopausal women and improves arterial stiffness; observational data link higher menaquinone intake to lower coronary heart disease mortality. Directs calcium to bones and away from arteries.","verdict":"promising","evidenceRating":3,"verdictSummary":"Emerging evidence for cardiovascular and bone health benefits. Often paired with vitamin D3 for optimal calcium metabolism.","dosage":{"recommended":"100–200","unit":"mcg (MK-7)","timing":"With a fat-containing meal","notes":"MK-7 form has longer half-life than MK-4. Best taken alongside vitamin D3."},"keyBenefits":["Supports bone mineralisation by activating osteocalcin","May reduce arterial calcification","Synergistic with vitamin D3 supplementation"],"warnings":["May interact with blood-thinning medications (warfarin)","Consult a doctor if on anticoagulant therapy"],"evidenceSummary":null,"dosing":null,"safety":null,"whoMightBenefit":[],"whoShouldAvoid":[],"regulatoryNotes":null,"faqs":[{"question":"What is the difference between MK-4 and MK-7?","answer":"MK-4 (menaquinone-4) and MK-7 (menaquinone-7) differ in side-chain length, which affects pharmacokinetics. A pharmacokinetic crossover study (Sato et al., 2012, PMID: 23140417) found MK-7 at 180 mcg/day produced sustained plasma K2 elevations over 24 h, while MK-4 at the same molar dose produced only transient peaks. The serum half-life of MK-7 is estimated at ~72 hours vs 1–2 hours for MK-4. Japanese clinical trials of MK-4 used pharmacological doses of 45 mg/day — approximately 250 times the MK-7 doses used in European supplement trials. Both forms activate Gla-proteins (osteocalcin, MGP), but MK-7 is considered more suitable for once-daily food supplementation at microgram doses."},{"question":"Can vitamin K2 be taken by people on warfarin (anticoagulants)?","answer":"Vitamin K2 has a well-established and clinically significant interaction with warfarin. Warfarin works by antagonising vitamin K–dependent clotting factor activation; supplementing with any form of vitamin K counteracts this mechanism and reduces warfarin's anticoagulant effect, increasing the risk of blood clots. Some specialised protocols have explored stable low-dose vitamin K to reduce INR variability, but this must only be done under medical supervision. Anyone prescribed warfarin or any vitamin K antagonist anticoagulant (acenocoumarol, phenprocoumon) should not take vitamin K2 supplements without explicit guidance from their prescribing physician."},{"question":"What does the Rotterdam Study tell us about vitamin K2 and heart disease?","answer":"The Rotterdam Study (Geleijnse et al., 2004, PMID: 15514282) is a prospective cohort study of 4,807 adults followed for 10 years. It found that the highest tertile of dietary menaquinone (vitamin K2) intake was associated with a 41% lower risk of fatal coronary heart disease and significantly less aortic calcification, compared with the lowest tertile. Importantly, this is observational data and does not establish causation. People with higher K2 intake may differ in other dietary or lifestyle factors. No large RCT has yet confirmed that K2 supplementation reduces cardiovascular mortality in a general population."},{"question":"What doses have been used in vitamin K2 clinical trials?","answer":"Trials have used widely varying doses depending on form and outcome. For MK-7 in bone and cardiovascular studies, 90–360 mcg/day has been most common. The 3-year Knapen RCT (PMID: 23525894) used 180 mcg/day of MK-7 in postmenopausal women and reported reduced bone loss and arterial stiffness. For MK-4, Japanese pharmaceutical trials have used 45 mg/day (45,000 mcg) — this is a pharmacological dose used in osteoporosis treatment in Japan and is not equivalent to typical food supplement doses. European supplement guidelines typically position MK-7 at 75–200 mcg/day."},{"question":"Does vitamin K2 work synergistically with vitamin D3?","answer":"The proposed synergy between K2 and D3 is mechanistically plausible: vitamin D3 promotes intestinal calcium absorption, while vitamin K2 activates osteocalcin and matrix Gla-protein (MGP), directing that calcium toward bone mineralisation and away from arterial walls. Several trials have co-administered D3 and K2 and reported superior outcomes for bone markers vs D3 alone. However, no large RCT has been designed with sufficient statistical power to prove that the combination is superior for fracture or CVD endpoints. The synergy hypothesis is mechanistically supported but not definitively proven at the clinical outcomes level."},{"question":"What is matrix Gla-protein (MGP) and why does it matter for arteries?","answer":"Matrix Gla-protein (MGP) is a vitamin K–dependent protein expressed in vascular smooth muscle cells and cartilage. In its carboxylated (activated) form, MGP potently inhibits arterial calcification. In trials using the biomarker dephosphorylated uncarboxylated MGP (dp-ucMGP), populations consuming more dietary vitamin K2 have significantly lower dp-ucMGP levels, indicating more activated MGP. In one 3-year RCT (PMID: 25694037), 180 mcg/day of MK-7 significantly reduced dp-ucMGP and improved arterial stiffness, suggesting improved arterial MGP activation. This biomarker relationship is established; the clinical endpoint evidence in general populations remains less conclusive."},{"question":"Are there reported adverse events from vitamin K2 supplementation?","answer":"Controlled trials at supplement doses (up to 360 mcg/day MK-7) have not reported serious adverse events in individuals not taking anticoagulants. No tolerable upper limit has been set by EFSA for vitamin K2, as toxicity has not been observed at supplement doses. The primary safety concern is the interaction with vitamin K antagonist anticoagulants (warfarin, acenocoumarol), which is clinically significant and well-documented. In one crossover trial, even 90 mcg/day of MK-7 was sufficient to meaningfully alter INR in individuals on warfarin therapy."}],"research":{"totalCount":16,"papers":[{"title":"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","year":2024,"journal":"Bone & Joint Research","doi":"10.1302/2046-3758.1312.BJR-2024-0053.R1","pmid":"39657786","url":"https://doi.org/10.1302/2046-3758.1312.BJR-2024-0053.R1","studyDesign":"meta-analysis","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Vitamin K – a scoping review for Nordic Nutrition Recommendations 2023","year":2023,"journal":"Food & Nutrition Research","doi":"10.29219/fnr.v67.10260","pmid":"37920674","url":"https://doi.org/10.29219/fnr.v67.10260","studyDesign":"systematic-review","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials","year":2023,"journal":"Frontiers in Nutrition","doi":"10.3389/fnut.2023.1115069","pmid":"37252246","url":"https://doi.org/10.3389/fnut.2023.1115069","studyDesign":"meta-analysis","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials","year":2022,"journal":"Frontiers in Public Health","doi":"10.3389/fpubh.2022.979649","pmid":"36033779","url":"https://doi.org/10.3389/fpubh.2022.979649","studyDesign":"meta-analysis","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adults: Systematic Review and Meta-Analysis","year":2022,"journal":"Biomedicines","doi":"10.3390/biomedicines10051048","pmid":"35625785","url":"https://doi.org/10.3390/biomedicines10051048","studyDesign":"meta-analysis","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial","year":2022,"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.121.057008","pmid":"35465686","url":"https://doi.org/10.1161/CIRCULATIONAHA.121.057008","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"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","year":2021,"journal":"Osteoporosis International","doi":"10.1007/s00198-020-05638-z","pmid":"33030563","url":"https://doi.org/10.1007/s00198-020-05638-z","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in women with osteoporosis","year":2020,"journal":"International Journal of Vitamin and Nutrition Research","doi":"10.1024/0300-9831/a000554","pmid":"30816822","url":"https://doi.org/10.1024/0300-9831/a000554","studyDesign":"cohort","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Vitamin K–Dependent Matrix Gla Protein as Multifaceted Protector of Vascular and Tissue Integrity","year":2019,"journal":"Hypertension","doi":"10.1161/HYPERTENSIONAHA.119.12412","pmid":"31006332","url":"https://doi.org/10.1161/HYPERTENSIONAHA.119.12412","studyDesign":"systematic-review","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Dietary reference values for vitamin K","year":2017,"journal":"EFSA Journal","doi":"10.2903/j.efsa.2017.4780","pmid":"32625486","url":"https://doi.org/10.2903/j.efsa.2017.4780","studyDesign":"regulatory","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review","year":2017,"journal":"International Journal of Endocrinology","doi":"10.1155/2017/7454376","pmid":"29138634","url":"https://doi.org/10.1155/2017/7454376","studyDesign":"systematic-review","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Low-Dose Daily Intake of Vitamin K2 (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trial","year":2015,"journal":"Journal of Nutritional Science and Vitaminology","doi":"10.3177/jnsv.61.471","pmid":"26875489","url":"https://doi.org/10.3177/jnsv.61.471","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial","year":2015,"journal":"Thrombosis and Haemostasis","doi":"10.1160/TH14-08-0675","pmid":"25694037","url":"https://doi.org/10.1160/TH14-08-0675","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women","year":2013,"journal":"Osteoporosis International","doi":"10.1007/s00198-013-2325-6","pmid":"23525894","url":"https://doi.org/10.1007/s00198-013-2325-6","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women","year":2012,"journal":"Nutrition Journal","doi":"10.1186/1475-2891-11-93","pmid":"23140417","url":"https://doi.org/10.1186/1475-2891-11-93","studyDesign":"rct","fields":[],"conclusion":"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.","abstract":"","citationCount":0},{"title":"Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study","year":2004,"journal":"Journal of Nutrition","doi":"10.1093/jn/134.11.3100","pmid":"15514282","url":"https://doi.org/10.1093/jn/134.11.3100","studyDesign":"cohort","fields":[],"conclusion":"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.","abstract":"","citationCount":0}]},"machineReadable":{"markdownUrl":"https://nutripedia.co.uk/items/vitamin-k2/markdown","jsonUrl":"https://nutripedia.co.uk/items/vitamin-k2/json","llmsTxt":"https://nutripedia.co.uk/llms.txt"},"disclaimer":"Informational supplement research only. Not medical advice. Consult a qualified healthcare professional before taking supplements.","lastReviewed":"2026-04-01T00:00:00.000Z","updatedAt":"2026-04-20T00:00:00.000Z"}