Vitamin K2 Food Sources and MK-4 vs MK-7

Vitamin K2 Food Sources and MK-4 vs MK-7 — scientific infographic poster

Vitamin K2 (the menaquinones) comes mainly from animal and fermented foods. Natto, the sticky fermented soybean dish, is the richest measured food source of the long-chain menaquinone MK-7, at 939 mcg per 100 g in one Japanese analysis. Full-fat cheeses carry mostly the longer menaquinones MK-9 to MK-11, and egg yolk, meat and dairy carry MK-4. This page sets out what food analyses have measured, how MK-4 and MK-7 differ in half-life and absorption, the doses the trials used, and what the research reports about the interaction with warfarin and other vitamin-K-antagonist anticoagulants, which work by limiting vitamin K.


Table of Contents

  1. Food Sources: Where K2 Comes From
  2. Natto: The Richest Measured Source of MK-7
  3. Cheese, Dairy, and Fermented Foods
  4. Egg Yolk, Meat, and Animal MK-4
  5. MK-4 vs MK-7: Two Very Different Molecules
  6. Pharmacokinetics: Half-Life and Absorption
  7. Doses Used in the Research
  8. Warfarin and Vitamin K Antagonists
  9. Sources and Forms: A Summary of the Findings
  10. Key Research Papers
  11. External Resources
  12. Connections
  13. Featured Videos

Food Sources: Where K2 Comes From

Unlike vitamin K1, which is abundant in green plants, vitamin K2 is found mainly in animal products and bacterially fermented foods (Schurgers & Vermeer 2000 list K2 in meat, liver, butter, egg yolk, natto, cheese and curd cheese). The menaquinones in food fall into two practical groups: short-chain MK-4, the only menaquinone not made by bacteria, which occurs in animal tissues (animals make it from the menadione in feed and from other dietary forms of vitamin K), and the longer-chain menaquinones (MK-7 and up), which are produced by bacteria during fermentation. Measured amounts from published food analyses:

A bar chart of measured vitamin K per 100 g of food on one linear scale: natto, 939 mcg of MK-7 (Kamao 2007, Japan); soft cheese 506, blue cheese 440, semi-soft cheese 289 and hard cheese 282 mcg of total vitamin K, mostly MK-9 to MK-11 (Fu 2017, US); eggs and meat carry MK-4 without a single figure given here. A side column contrasts MK-7, with a half-life of about three days, against MK-4, about one to two hours. NATTO LEADS ON MK-7 measured vitamin K per 100 g of food, and the menaquinone each one carries FOOD · FORM MCG PER 100 G Natto Soft cheese Blue cheese Semi-soft cheese Hard cheese Eggs, meat, butter MK-7 · Kamao 2007, Japan mostly MK-9 to MK-11 · Fu 2017, US mostly MK-9 to MK-11 · Fu 2017, US mostly MK-9 to MK-11 · Fu 2017, US mostly MK-9 to MK-11 · Fu 2017, US MK-4 · animal tissue 939 506 total K 440 total K 289 total K 282 total K MK-4 present · no single figure given one linear scale for every row → the cheese figures are total vitamin K, mostly MK-9 to MK-11 Fu 2017 found little MK-5 to MK-7 in most dairy products TWO DIFFERENT MOLECULES MK-7 lasts, MK-4 is gone in hours MK-7 half-life is about three days; MK-4 about 1–2 hours (Knapen 2007) the trial doses differ MK-7 bone and arterial trials: 180 mcg a day; MK-4 bone trials: 45 mg a day, given as three 15 mg doses nutritional MK-4 not seen in serum a single 420 mcg MK-4 dose was not detectable in serum (Sato 2012) with a vitamin K antagonist, 10–45 mcg a day of MK-7 lowered the INR in volunteers (Theuwissen 2013) two analyses from two countries · fermentation, cheese type and animal feed cause wide variation

Outside Japan, where natto is rarely eaten, dietary K2 comes mostly from cheese, egg yolk, and meat — the profile seen in the European cohort studies discussed on the heart page, where cheese was a major dietary K2 contributor.

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Natto: The Richest Measured Source of MK-7

Natto is fermented soybeans, traditionally made by fermenting cooked soybeans with the bacterium Bacillus subtilis var. natto, which produces MK-7. In a Japanese food analysis natto contained 939 mcg MK-7 per 100 g, and MK-7 from pulses (including fermented soybean foods) was one of the major contributors to vitamin K intake in young women in eastern Japan, supplying 24.9% of their total vitamin K (Kamao 2007). In a feeding study in six healthy men, circulating K2 concentrations after a natto meal were about 10 times higher than K1 concentrations after a spinach meal (Schurgers & Vermeer 2000).

Kaneki and colleagues (2001) measured serum MK-7 of 5.26 ng/mL in postmenopausal women in Tokyo, where natto is eaten frequently, 1.22 in Hiroshima, where it is seldom eaten, and 0.37 in British women. Frequent natto eaters had significantly higher serum MK-7, and across Japan's prefectures hip-fracture incidence in women was inversely correlated with natto consumption. The authors suggest that higher MK-7 from natto may contribute to a lower fracture risk; this is an ecological correlation, not proof that natto prevents fractures. Natto has a sticky, stringy texture and a strong aroma, and it is a soy food, which matters for people with soy allergy. See Natto.

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Cheese, Dairy, and Fermented Foods

In Western diets fermented dairy is the main other source of menaquinones. A US analysis found appreciable menaquinones in full-fat dairy, mainly as MK-9, MK-10 and MK-11, with modest amounts of MK-4, MK-8 and MK-12 and little MK-5 to MK-7 in most products. Fermented cheeses carried the most (282–506 mcg total vitamin K per 100 g by cheese type), non-fermented processed cheese much less (98 mcg), and the vitamin K content of dairy foods was proportional to their fat content (Fu 2017).

Other traditionally fermented foods can contribute variable amounts depending on the microbes involved. In the same analysis, reduced-fat and fat-free dairy products contained about 5–22% of the vitamin K of their full-fat equivalents. For related foods, see Eggs, Milk, and Yogurt.

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Egg Yolk, Meat, and Animal MK-4

MK-4 is the only menaquinone not produced by bacteria. Animals and humans make it in their tissues, from the synthetic menadione (vitamin K3) used in animal feed and from other dietary forms of vitamin K, including K1. That is why MK-4 appears in animal foods: egg yolk, meat, poultry and dairy. Feed matters: in a hen-feeding trial, MK-4 made up 91–98% of the vitamin K in eggs, and more vitamin K3 in the feed raised the eggs' MK-4 content (O'Sullivan 2020).

The amounts are modest: a US analysis of 128 meat, 24 dairy-and-egg and 169 fast-food samples found that no single item was a rich source of any one form of vitamin K, though these foods may matter because they are eaten in large quantities (Elder 2006). And in a bioavailability study in healthy Japanese women, a single 420 mcg dose of MK-4 was not detectable in serum at any time point, leading the authors to conclude that “MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels” (Sato 2012). See Organ Meats, Beef, and Pork.

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MK-4 vs MK-7: Two Very Different Molecules

MK-4 and MK-7 are both vitamin K2, but the research describes them as behaving very differently. The differences reported:

The trials cited on this page did not compare the two forms head to head on bone or vascular outcomes. At nutritional doses, the absorption data favour MK-7; the bone data for MK-4 come from the 45 mg pharmacologic dose, which Japan uses as a prescription osteoporosis drug (menatetrenone). The 2019 updated meta-analysis of vitamin K and fractures, and the later questions about some of the Japanese evidence, are covered on the MK-7 vs MK-4 page.

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Pharmacokinetics: Half-Life and Absorption

Schurgers and colleagues (2007) compared synthetic vitamin K1 with natto-derived MK-7 in healthy volunteers. Both were absorbed well, with peak serum concentrations 4 hours after intake. The major difference was MK-7's very long half-life, which produced much more stable serum levels and accumulation to 7- to 8-fold higher levels during prolonged intake, and MK-7 induced more complete carboxylation of osteocalcin (the bone protein). MK-4 was not part of that study; its short half-life is described by Knapen 2007.

The same paper draws the safety consequence: the authors write that “preparations supplying 50 mug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.” Vitamin K is fat-soluble, and the absorption studies above gave their doses with a meal (Sato 2012: a standardized breakfast); in Schurgers & Vermeer 2000, pure K1 was absorbed faster than food-bound vitamin K (serum peaks at 4 vs 6 hours).

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Doses Used in the Research

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Warfarin and Vitamin K Antagonists

The interaction with vitamin K antagonist anticoagulants is the main safety finding in the vitamin K2 research.

Warfarin and the other vitamin-K-antagonist anticoagulants — acenocoumarol, phenprocoumon — work by limiting vitamin K. They block the enzyme (VKORC1) that recycles vitamin K, which reduces the carboxylation of clotting factors. Added vitamin K — K1 or K2, from a supplement or a large dietary change — opposes the drug: the INR falls and anticoagulation weakens. Fluctuations in INR are often ascribed to changes in dietary vitamin K intake (Schurgers & Vermeer 2000), and the Linus Pauling Institute reports that experts now advise a reasonably constant dietary vitamin K intake for patients taking vitamin K antagonists.

The research on MK-7 specifically:

Decisions about vitamin K supplements, especially alongside anticoagulants, belong with a clinician.

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Sources and Forms: A Summary of the Findings

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Key Research Papers

  1. Schurgers LJ et al. (2007). Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood — PubMed PMID: 17158229
  2. Sato T et al. (2012). Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutrition Journal — PubMed PMID: 23140417
  3. Kaneki M et al. (2001). Japanese fermented soybean food (natto) as the major determinant of the large geographic difference in circulating vitamin K2. Nutrition — PubMed PMID: 11369171
  4. Knapen MHJ et al. (2015). Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. Thromb Haemost — PubMed PMID: 25694037
  5. Knapen MHJ et al. (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int — PubMed PMID: 23525894
  6. Shiraki M et al. (2000). Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res — PubMed PMID: 10750566
  7. Iwamoto J, Takeda T, Sato Y (2006). Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis. Nutrition Reviews 64(12): 509–517 [expression of concern 2020, Nutr Rev 78(7): 612] — PubMed PMID: 17274493
  8. Schurgers LJ et al. (2007). Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood — PubMed PMID: 17138823
  9. Rennenberg RJMW et al. (2010). Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood — PubMed PMID: 20354170
  10. Schurgers LJ, Cranenburg ECM, Vermeer C (2008). Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost — PubMed PMID: 18841280
  11. Vermeer C (2012). Vitamin K: the effect on health beyond coagulation — an overview. Food & Nutrition Research — PubMed PMID: 22489224
  12. Knapen MHJ, Schurgers LJ, Vermeer C (2007). Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporosis International 18(7): 963–972 — PubMed PMID: 17287908
  13. Theuwissen E, Teunissen KJ, Spronk HM, Hamulyák K, Ten Cate H, Shearer MJ, Vermeer C, Schurgers LJ (2013). Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. Journal of Thrombosis and Haemostasis 11(6): 1085–1092 — PubMed PMID: 23530987
  14. Kamao M, Suhara Y, Tsugawa N, Uwano M, Yamaguchi N, Uenishi K, Ishida H, Sasaki S, Okano T (2007). Vitamin K content of foods and dietary vitamin K intake in Japanese young women. Journal of Nutritional Science and Vitaminology 53(6): 464–470 — PubMed PMID: 18202532
  15. Fu X, Harshman SG, Shen X, Haytowitz DB, Karl JP, Wolfe BE, Booth SL (2017). Multiple vitamin K forms exist in dairy foods. Current Developments in Nutrition 1(6): e000638 — PubMed PMID: 29955705
  16. Schurgers LJ, Vermeer C (2000). Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30(6): 298–307 — PubMed PMID: 11356998
  17. Elder SJ, Haytowitz DB, Howe J, Peterson JW, Booth SL (2006). Vitamin K contents of meat, dairy, and fast food in the U.S. diet. Journal of Agricultural and Food Chemistry 54(2): 463–467 — PubMed PMID: 16417305
  18. O'Sullivan SM, E Ball ME, McDonald E, Hull GLJ, Danaher M, Cashman KD (2020). Biofortification of chicken eggs with vitamin K — nutritional and quality improvements. Foods 9(11): 1619 — PubMed PMID: 33172200

PubMed Topic Searches

  1. PubMed: natto & MK-7 content
  2. PubMed: MK-4 vs MK-7 pharmacokinetics
  3. PubMed: K2 in foods
  4. PubMed: warfarin & vitamin K interaction
  5. PubMed: MK-7 dosing & carboxylation

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External Resources

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Connections

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