Evidence explainerVitamin K2 (MK-7 vs MK-4)
MK-7 vs MK-4: The Two Kinds of Vitamin K2, and Why Their Doses Differ a Thousandfold
One K2 label says 100 mcg, another says 45 mg. They are not typos. The two forms behave so differently in the body that they were studied at completely different amounts.
Key takeaways
- MK-7 stays in the blood for a long time and builds up 7 to 8-fold with daily intake [1].
- MK-4 at food-level amounts (a single 420 mcg dose, or 60 mcg/day for 7 days) was not detectable in blood, while MK-7 was [2].
- The bone trials used very different amounts: 180 mcg/day of MK-7 versus 45 mg/day of MK-4, and no trial has compared them head to head on bone outcomes [3][4].
- Neither form has an upper limit; the adequate intake for all vitamin K is 120 mcg/day for men and 90 mcg/day for women [5].
Safety at a glance
From our Vitamin K2 (MK-7 vs MK-4) monograph. Published interactions and cautions only, each with its source.
Interactions
- Warfarin and similar anticoagulants. Serious, potentially dangerous interaction: vitamin K counteracts these drugs, so sudden changes in vitamin K intake can change their effect. A study of MK-7 warned that 50 mcg/day or more may interfere with oral anticoagulant treatment in a clinically relevant way.[1][7]
- Antibiotics. Can destroy vitamin K-producing gut bacteria and may lower vitamin K status, especially with prolonged use and poor intake.[1]
- Bile acid sequestrants. Can reduce absorption of vitamin K and other fat-soluble vitamins.[1]
- Orlistat. Reduces absorption of fat-soluble vitamins including vitamin K; orlistat with warfarin might markedly raise prothrombin time.[1]
Who should be careful
- People on warfarin or similar anticoagulants. Do not start, stop or change a vitamin K2 supplement without your prescriber. Even 50 mcg/day of MK-7 may affect anticoagulation.[1][7]
- Pregnancy and breastfeeding. The AI is 90 mcg/day for adults 19+ in pregnancy and breastfeeding; no UL is set. Pregnancy-specific trial data for K2 supplements are not in our sources.[1]
- Malabsorption or bariatric surgery. People with malabsorption conditions or after bariatric surgery may have low vitamin K status and may need clinician monitoring.[1]
- Before you start. Talk to your pharmacist or clinician before adding this supplement, especially if you take prescription medicines, are pregnant or breastfeeding, or have a chronic health condition.[1]
The evidence, graded
Pulled from our monograph evidence tables. Grades follow our evidence-grading policy.
- Grade CImprovedAge-related bone density loss with MK-7MK-7 improved vitamin K status and reduced the decline in bone mineral content and density at the lumbar spine and femoral neck, but not the total hip; bone strength indices and vertebral height loss in the lower thoracic spine also favored MK-7.
- No effectNo effectBone density with high-dose MK-4 (or K1)Both forms lowered undercarboxylated osteocalcin but did not change bone turnover markers, lumbar spine or hip bone density, or hip geometry.
- Grade CImprovedArterial stiffness with MK-7Carotid-femoral pulse wave velocity and stiffness index β decreased versus placebo; more local stiffness measures improved in women with higher baseline stiffness. dp-ucMGP fell 50% versus placebo; inflammation and endothelial markers did not change.
What MK-7 and MK-4 are
Vitamin K2 is a family of compounds called menaquinones. Supplements mostly contain MK-7 (menaquinone-7, often from fermented natto) or MK-4 (menatetrenone) [5]. Vitamin K1 (phylloquinone) is the form in leafy greens [5].
How differently they behave
In a 2007 study comparing natto-derived MK-7 with synthetic K1, MK-7 had a very long half-life and accumulated 7 to 8-fold with daily intake, giving more stable blood levels [1].
A 2012 study in healthy women went further: a single 420 mcg dose of MK-7 was still detectable for up to 48 hours, while the same dose of MK-4 was not detectable at all; with 60 mcg/day for 7 days, MK-7 was detectable in blood and MK-4 was not [2]. That is why MK-4 has been studied at pharmacological amounts, in milligrams, rather than micrograms [4].
What each did for bone
MK-7: in a 3-year trial of 244 healthy postmenopausal women, 180 mcg/day slowed bone density loss at the lumbar spine and femoral neck (but not the total hip) compared with placebo [3]. "Slowed loss" is the honest phrasing; bones did not get denser [3].
MK-4: in a 12-month trial of 381 healthy postmenopausal North American women, 45 mg/day lowered undercarboxylated osteocalcin but did not change bone turnover, bone density or hip geometry [4]. A 2019 meta-analysis across all vitamin K trials found no effect on bone density [6].
The same MK-7 cohort also showed lower arterial stiffness after 3 years; see vitamin K2 and your arteries [7].
Reading a K2 label
Because the two forms were studied at amounts roughly a thousand times apart, micrograms on an MK-7 label and milligrams on an MK-4 label are not interchangeable [3][4]. If a product does not say which menaquinone it contains, you cannot match it to the research.
The one safety rule applies to both: vitamin K counteracts warfarin, and an MK-7 study warned that 50 mcg/day or more may interfere with anticoagulation [5][1]. Talk to your prescriber first if you take warfarin. For the popular pairing with vitamin D, read D3 and K2 together; full details are on the vitamin K2 monograph.
Keep reading
Full monographs
Related articles
- Can Vitamin K2 Keep Calcium Out of Your Arteries? What 14 Trials Actually Show
- Vitamin D3 and K2 Together: Smart Pairing or Marketing? What the Research Actually Shows
- 400 IU of Vitamin E Is Either 268 mg or 180 mg. The "d" or "dl" on the Label Decides
- B12 After 50 and on Metformin: Why Levels Drop, and What the Trials Say About Fixing Them
Browse the full Supplement & Nutrient Encyclopedia or all supplement articles.
References
- [1]Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 2007.
- [2]Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J, 2012.
- [3]Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int, 2013.
- [4]Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res, 2009.
- [5]Vitamin K: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements, 2021.
- [6]Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int, 2019.
- [7]Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost, 2015.