Vitamin K2
Menaquinone
TL;DR
Vitamin K2 activates the proteins that put calcium into bone and keep it out of arteries. MK-7 at 100-200 mcg/day is the practical form thanks to its long half-life, and it belongs alongside vitamin D — but anyone on warfarin must not take it without medical supervision.
Ideal For
- Postmenopausal women and older adults concerned with bone density
- Anyone supplementing vitamin D at meaningful doses
- People taking calcium supplements, to direct calcium toward bone
- Those with a family history of vascular calcification
- People who eat little fermented food or organ meat
Avoid If
- You take warfarin or another vitamin K antagonist, without clinic supervision
- You have had a recent thrombotic event and are on anticoagulation
- You have significant liver disease affecting clotting
- You are on dialysis, without nephrology advice
Frequently Asked Questions
Do I need K2 if I eat lots of greens?
MK-4 or MK-7?
Can I take it with warfarin?
Should I take K2 with vitamin D?
Overview
Vitamin K exists as K1 (phylloquinone) from green leaves, which the liver preferentially uses for clotting factors, and K2 (menaquinones) from fermented foods and animal products, which reaches extrahepatic tissues including bone and arterial wall. That tissue distribution is the entire case for supplementing K2 separately: a diet rich in kale can leave bone and vascular vitamin K-dependent proteins undercarboxylated even while clotting is perfectly adequate.
The mechanism is elegant and specific. Vitamin K is the cofactor for gamma-glutamyl carboxylase, which carboxylates glutamate residues on a family of Gla proteins. Osteocalcin, once carboxylated, binds calcium into the bone hydroxyapatite matrix. Matrix Gla protein, once carboxylated, is the body's most potent inhibitor of vascular calcification. Undercarboxylated forms of both circulate in a large fraction of adults and predict fracture risk and arterial stiffness respectively — this is the so-called calcium paradox, where calcium ends up in the wrong tissue.
Human trials support the bone side reasonably well: three years of MK-7 at 180 mcg/day in postmenopausal women reduced bone loss at the lumbar spine and femoral neck and decreased vertebral height loss. Japanese trials of high-dose MK-4 at 45 mg/day show fracture reduction, though those results have not replicated well outside Japan. The vascular data are promising but less settled, with the Rotterdam cohort linking higher K2 intake to lower coronary calcification and a three-year MK-7 trial showing reduced arterial stiffness in the stiffest subjects.
Practically, MK-7 has a three-day half-life versus MK-4's few hours, so 100-200 mcg once daily works where MK-4 requires large divided doses. Take it with fat and with vitamin D, since D increases production of the very Gla proteins that K2 must activate. The single serious caution is warfarin, whose entire mechanism is vitamin K antagonism.
How It Works
- Cofactor for gamma-glutamyl carboxylase, which activates vitamin K-dependent Gla proteins
- Carboxylates osteocalcin, enabling it to bind calcium into bone hydroxyapatite
- Carboxylates matrix Gla protein, the strongest known inhibitor of vascular calcification
- Activates Gas6, involved in cell survival and vascular smooth muscle regulation
- Menaquinones reach extrahepatic tissues that preferentially retain K1 in the liver
- Supports the vitamin D axis by activating the Gla proteins vitamin D upregulates
Quick Facts
- Supports bone health
- May benefit heart health
- Works with vitamin D
- Helps calcium utilization
Benefits & Outcomes
Arterial Flexibility
MK-7 slows arterial calcification and improved stiffness in a three-year trial.
Bone Mineral Density
Japanese MK-4 trials show fracture reduction; MK-7 evidence is positive but thinner.
Bone Health Support
Vitamin K2 improves bone quality markers and has Japanese fracture data, but Western trials have been largely null.
Heart Health Support
Observational data linking K2 to less arterial calcification is promising, but randomised trials have not confirmed clinical benefit.
Cellular Health
Beyond its coagulation and calcium-handling roles, broader cellular benefits of K2 are speculative.
Health Concerns Addressed
Atherosclerosis
Mixed: one positive coronary calcium trial against several null ones, and no trial designed to test heart attacks or strokes.
Osteoporosis
Mixed: small open-label trials suggested fewer fractures, but larger trials and a 2019 review that tested results against risk of bias found no clear benefit.
Vitamin D Deficiency
K2 does nothing to raise vitamin D status. Its bone and vascular claims remain unproven in people with adequate K intake.
Supporting Research37 studies
Vitamin K2 and bone health: a systematic review
Iwamoto, I., Kosha, S., Noguchi, S.
Review of vitamin K2 (menaquinone) trials, dominated by Japanese studies of high-dose MK-4 (45 mg/day), reported improved bone mineral density maintenance and reduced vertebral and non-vertebral fracture rates in postmenopausal and osteoporotic women, with effects on bone quality via osteocalcin carboxylation rather than density alone.
Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial
Diederichsen ACP, Lindholt JS, Möller S +4 more
2 years MK-7 plus vitamin D supplementation did not influence AVC progression
The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials
Su S, He N, Men P +2 more
its benefit in fracture risk control was uncertain
Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules
Inoue T, Fujita T, Kishimoto H +4 more
menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set
Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03
Tanaka S, Miyazaki T, Uemura Y +4 more
concurrent treatment with vitamin K2 and risedronate was not efficacious
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
Rønn SH, Harsløf T, Oei L +2 more
did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture
Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women
Binkley N, Harke J, Krueger D +4 more
No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD
Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial
Vossen LM, de Leeuw PW, Schurgers LJ +4 more
supplementation with MK-7 for 2 years may slow calcification in noncalcified plaques
Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers
Theuwissen E, Teunissen KJ, Spronk HM +4 more
the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy
Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis
Shiraki M, Shiraki Y, Aoki C +1 more
vitamin K2 treatment effectively prevents the occurrence of new fractures
Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women
Knapen MH, Schurgers LJ, Vermeer C
K(2) did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo
The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial
Moore AE, Dulnoan D, Voong K +4 more
did not differ significantly following either K1 or MK-4 supplementation compared to placebo
Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials
Cockayne S, Adamson J, Lanham-New S +3 more
there is a strong effect on incident fractures among Japanese patients
Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials
Huang ZB, Wan SL, Lu YJ +3 more
vitamin K2 might play a role in maintaining the bone mineral density
Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT
Hasific S, Oevrehus KA, Lindholt JS +4 more
had no significant reduction in mean CAC progression over a 2-year follow-up
Effect of Vitamin K on Vascular Health and Physical Function in Older People with Vascular Disease--A Randomised Controlled Trial
Fulton RL, McMurdo ME, Hill A +4 more
Six months of vitamin K2 supplementation did not improve markers of vascular health
Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)
Haroon S, Davenport A, Ling LH +4 more
did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC
Vitamin K supplementation and arterial calcification in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial
Levy-Schousboe K, Frimodt-Møller M, Hansen D +4 more
did not hinder or modify the progression of arterial calcification in dialysis patients
Doppler Ultrasound Monitoring of Echogenicity in Asymptomatic Subcritical Carotid Stenosis and Assessment of Response to Oral Supplementation of Vitamin K2 (PLAK2 Randomized Controlled Trial)
Tshomba Y, Baccellieri D, Carta N +4 more
vitamin K2 beyond standard therapy did not determine a significant change in plaque composition
Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials
Ma ML, Ma ZJ, He YL +4 more
no significant difference in fracture incidence between the two groups
Vitamin K to prevent fractures in older women: systematic review and economic evaluation
Stevenson M, Lloyd-Jones M, Papaioannou D
found no evidence of a reduction in vertebral fracture risk
Vitamin K for the primary prevention of cardiovascular disease
Hartley L, Clar C, Ghannam O +3 more
We included only one small trial (60 participants randomised)
Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women
Rønn SH, Harsløf T, Pedersen SB +1 more
vitamin MK-7 preserves trabecular bone structure at the tibia
Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5
Kurnatowska I, Grzelak P, Masajtis-Zagajewska A +4 more
may reduce the progression of atherosclerosis, but does not significantly affect the progression of calcification
Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review
Zhou M, Han S, Zhang W +1 more
no serious adverse events related to vitamin K2 supplementation
Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials
Li T, Wang Y, Tu WP
VK supplementation has a significant effect on CAC scores, slowing down the progression of CAC
Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis
Lees JS, Chapman FA, Witham MD +2 more
Supplementation with vitamin K significantly reduced VC, but not VS, compared with control
Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis
Chen HG, Sheng LT, Zhang YB +4 more
higher dietary vitamin K consumption was associated with a moderately lower risk of CHD
High dietary menaquinone intake is associated with reduced coronary calcification
Beulens JW, Bots ML, Atsma F +4 more
Menaquinone intake was associated with decreased coronary calcification
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women
Knapen MH, Drummen NE, Smit E +2 more
MK-7 180 mcg/day decreased the age-related decline in lumbar spine and femoral neck bone mineral density.
Evaluation of the clinical efficacy and safety of an eye counter pad containing caffeine and vitamin K in emulsified Emu oil triglycerides
Ahmadraji F, Shatalebi MA
An eye pad containing caffeine and vitamin K significantly reduced infraorbital pigmentation after four weeks of twice-daily use.
Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: a double-blind randomised clinical trial
Knapen MH, Braam LA, Drummen NE +3 more
Carotid artery stiffness and pulse wave velocity decreased significantly after three years of MK-7.
Daily vitamin K supplementation improves anticoagulant stability
Rombouts EK, Rosendaal FR, van der Meer FJ
Consistent daily vitamin K intake improved anticoagulation stability rather than simply antagonising vitamin K antagonist therapy.
Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials
Mott A, Bradley T, Wright K +5 more
Apparent fracture benefits of vitamin K disappeared when analysis was restricted to higher-quality trials.
Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial
Emaus N, Gjesdal CG, Almås B +5 more
Vitamin K2 supplementation did not influence bone loss in early menopausal women over 12 months.
The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial
Zwakenberg SR, de Jong PA, Bartstra JW +3 more
Six months of MK-7 did not reduce femoral or coronary artery calcification despite improved vitamin K status.
Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study
Geleijnse JM, Vermeer C, Grobbee DE +5 more
High dietary menaquinone intake was associated with reduced coronary heart disease mortality and aortic calcification.
Safety Information
Potential Side Effects
Very safe with no known upper limit. May interact with blood-thinning medications
Contraindications
Warfarin and other vitamin K antagonist therapy without medical supervision. Caution in significant hepatic impairment and in dialysis patients.
Drug Interactions
- Warfarin and coumarin anticoagulants — direct antagonism, requires clinic management
- Orlistat and bile acid sequestrants — reduced fat-soluble vitamin absorption
- Broad-spectrum antibiotics — reduce gut bacterial menaquinone production
- Anticonvulsants — may increase vitamin K turnover
- Direct oral anticoagulants such as apixaban — no interaction, unlike warfarin
Pregnancy & Breastfeeding
Pregnancy: Likely safe
Breastfeeding: Likely safe
Dosage Guidelines
Dosage Used in Studies
100-200 mcg
Best Time to Take
Once daily with the largest fat-containing meal
Best Form
MK-7 at 100-200 mcg/day, taken with fat and alongside vitamin D3
Bioavailability
MK-7 is efficiently absorbed with fat and has a serum half-life of around three days, producing stable steady-state levels on once-daily dosing. MK-4 has a half-life of only a few hours and requires divided high doses.
Dosing by Goal
| Goal | Dose | Notes |
|---|---|---|
| High-dose MK-4 | 45 mg/day in three divided doses, as used in Japanese osteoporosis protocols | |
| With vitamin D | Pair with 1000-4000 IU vitamin D3 and adequate magnesium | |
| Postmenopausal bone loss | 180 mcg/day MK-7, the dose used in the three-year Dutch trial | |
| General bone and vascular | 100-200 mcg/day of MK-7, taken with a fat-containing meal | |
| Notes | Absolutely contraindicated with warfarin unless your anticoagulation clinic manages it |
Forms Compared
MK-7 (menaquinone-7)
Three-day half-life; 100-200 mcg once daily is the practical standard
MK-4 (menatetrenone)
Short half-life; Japanese fracture trials used 45 mg/day in divided doses
MK-7 with vitamin D3
The most sensible pairing — D raises Gla protein production, K2 activates it
Natto
The richest food source of MK-7, at roughly 900 mcg per 100 g
K1 (phylloquinone)
From leafy greens; supports clotting but reaches bone and artery poorly
Food & Timing
With a meal containing fat — vitamin K is fat-soluble and absorption is poor when fasted
Articles on Vitamin K2
All articlesVitamin D3 and K2 Supplements: Take Them Together?
Vitamin D3 and K2 can be taken together with a meal that contains fat. What trials of the pair show, doses used, timing, and who should avoid K2.
13 min readFat-Soluble vs Water-Soluble Vitamins Explained
Vitamins A, D, E and K dissolve in fat and are stored; C and the B vitamins are not. See how fat affects absorption and where the limits sit.
16 min readBlood Thinners and Supplements: What to Avoid
Which supplements to avoid with warfarin, Eliquis or Xarelto, why vitamin K matters only for warfarin, and what the trials show for fish oil and turmeric.
13 min read
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