Vitamin K2
Vitamin K is the cofactor for gamma-glutamyl carboxylase, which activates clotting factors in the liver and, outside it, proteins such as osteocalcin in bone and matrix Gla protein in artery walls. K1 from leafy greens is largely kept by the liver; menaquinones (K2), especially long-chain MK-7, circulate for days and reach other tissues. The mechanism behind the bone and artery claims for K2 is sound. The outcome trials are mostly negative or small.
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What It Does
Carboxylation adds a second carboxyl group to glutamate residues, which lets these proteins bind calcium. Matrix Gla protein is a local inhibitor of vascular calcification; mice that lack it calcify their arteries and die young, and people with low vitamin K status have more circulating uncarboxylated MGP. The "calcium paradox," osteoporosis alongside calcified arteries in the same patient, is the clinical picture K2 marketing is built on.
The observational data are encouraging. In the Rotterdam Study, people in the top third of dietary menaquinone intake had about half the coronary death rate of those in the bottom third, while K1 intake showed no link (Geleijnse 2004). Randomized trials are less so. Three years of 180 mcg MK-7 slowed bone mineral density loss at the spine and femoral neck in 244 postmenopausal women, without fracture data (Knapen 2013). Japanese trials of 45 mg a day of MK-4, a prescription osteoporosis drug there, reduced fractures in a meta-analysis, but all seven fracture trials were Japanese and most were small (Cockayne 2006). For arteries, 720 mcg MK-7 plus vitamin D for two years did not slow aortic valve calcification in 365 men (Diederichsen 2022).
The D3 pairing follows from biochemistry: vitamin D increases production of osteocalcin and MGP, and vitamin K activates them. No trial has shown that adding K2 to ordinary vitamin D doses improves bone or vascular outcomes, and the claim that vitamin D alone causes arterial calcification at usual doses is unsupported.
Warfarin is the real safety issue. In anticoagulated volunteers, MK-7 at 10-20 mcg a day produced clinically relevant drops in INR in some people, and 45 mcg lowered INR by about 40% (Theuwissen 2013). Direct oral anticoagulants such as apixaban do not depend on vitamin K and are not affected.
Forms and Bioavailability
Absorption ratings are broad tiers. Head-to-head human trials rarely support a finer ranking among well-absorbed forms.
| Form | Absorption | Typical dose | Cost | Labels |
|---|---|---|---|---|
| Vitamin K1 (Phylloquinone)phylloquinone, phytonadione | ModerateFat-soluble, absorbed with dietary fat. Taken up mainly by the liver for clotting factor carboxylation; short plasma half-life of a few hours. | 90-120 mcg daily (AI for total vitamin K) | Low | 19 |
| Vitamin K2 as MK-4 (Menatetrenone)menatetrenone, MK-4 | LowShort-chain menaquinone with a half-life of hours. A 420 mcg oral dose was not detectable in serum in Sato 2012, so it requires milligram doses taken several times daily. | 45 mg daily in divided doses (Japanese osteoporosis regimen) | Moderate | 97 |
| Vitamin K2 as MK-7menaquinone-7, MenaQ7 | HighLong-chain menaquinone, well absorbed with fat and carried in LDL. Half-life of about 3 days (Schurgers 2007) produces stable blood levels with once-daily microgram doses. | 90-180 mcg daily | Moderate | 734 |
Labels column: number of labels named as vitamin K2 products that list this form. A product can list more than one form, and some labels do not state a form at all.
MK-7's half-life is about three days, and daily dosing builds steady blood levels several times higher than K1 achieves (Schurgers 2007). MK-4 behaves differently: a single 420 mcg dose was undetectable in serum, and a week of 60 mcg daily raised MK-7 levels but not MK-4 (Sato 2012). Microgram doses of MK-4 do very little; the Japanese trials used milligrams. MK-7 comes from natto fermentation or synthesis, and only the all-trans isomer is active.
Typical Dosing
| Group | Adequate Intake (AI) |
|---|---|
| Men 19+ (total vitamin K) | 120 mcg |
| Women 19+ (total vitamin K) | 90 mcg |
| Upper limit (UL) | None established |
MK-7 supplements commonly provide 90-180 mcg daily. The AI covers all forms of vitamin K; there is no separate K2 recommendation.
Food sources: natto, hard and soft cheeses, egg yolk, chicken, pork.
What to Look For
The panel should name the menaquinone (MK-7 or MK-4) and the dose in mcg. A label that says only "vitamin K2" is incomplete. For MK-7, look for "all-trans" on the label or the manufacturer's documentation; MenaQ7 is the raw material used in the Dutch trials.
Typical MK-7 doses are 90-180 mcg. Anyone on warfarin or another vitamin K antagonist should not start, stop, or change a K2 supplement without the prescriber, and many D3 combination products contain K2, so check the panel.
Red flags: marketing that says D3 is dangerous without K2, unspecified "K2," and low-dose MK-4 products.
Vitamin K2 as MK-7
Long half-life, and the form used in the Dutch bone and artery-stiffness trials. Fracture benefit is unproven.
What to look for: 90-180 mcg all-trans MK-7 (MenaQ7 is the trial raw material). Not with warfarin unless the prescriber agrees.
Find on iHerb Affiliate linkVitamin K2 as MK-4 (Menatetrenone)
At microgram doses it barely registers in serum. At the 45 mg Japanese dose it is a drug, not a supplement.
What to look for: Skip low-dose MK-4 products. The milligram regimen belongs under medical supervision.
Find on iHerb Affiliate linkProducts on Titrate
9,882 of the 214,745 labels in the NIH Dietary Supplement Label Database list vitamin K2 as an active ingredient (4,728 on market). 959 are sold as vitamin K2 products by name.
Top on-market labels, ranked by label completeness and simplicity:
- D3 5000 IU K2 200 mcg
- Vitamin K2 + D3
- Vitamin D + K2
- Vitamin D-3 with Vitamin K-2 MenaQ7
- Vitamin D3 & K2 Drops
Vitamin K2 does not have its own search category yet. Each product above links to its full label in the NIH database.
Related Tools
References
NIH Office of Dietary Supplements. Vitamin K: Fact Sheet for Health Professionals.
Geleijnse JM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004;134(11):3100-3105.
Cockayne S, et al. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166(12):1256-1261.
Schurgers LJ, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109(8):3279-3283.
Sato T, et al. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012;11:93.
Theuwissen E, et al. Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. J Thromb Haemost. 2013;11(6):1085-1092.
Knapen MH, et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013;24(9):2499-2507.
Diederichsen ACP, et al. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022;145(18):1387-1397.
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