Vitamin K2 MK-7 and Cardiovascular Calcification

Published: 4-Dec-2018

Prevention and reversal (part II

Several studies demonstrate that K2 can reduce CVD risk by preventing arterial calcification and hardening.

The Rotterdam study of nearly 5000 Dutch men and women provides some of the strongest evidence for the CVD prevention role of vitamin K2. Participants aged 55 and older took part in the study for 8–11 years.

The study showed that diets high in vitamin K2 reduced cardiovascular disease risk and mortality. The study reported that arterial calcification and cardiovascular-related death were both reduced by 50%, and that all-cause mortality was reduced by 25%.14

Another study, the Prospect study of 16,000 women aged 40–79, reported similar results. This study demonstrated an inverse correlation between dietary K2 levels and coronary heart disease, and specifically that each additional 10 µg/day of K2 intake was associated with a 9% risk reduction in CVD mortality.15

The pivotal 2015 Knapen study provides solid evidence that, in addition to prevention, vitamin K2 can reverse existing levels of calcification and restore arterial flexibility.

Among participants with an elevated arterial stiffness at baseline, this study demonstrated a significant decrease in stiffness among the MK-7 test group after 3 years (at doses of 180 µg/day), compared with a slight increase in stiffness for the control group.

The MK-7 group demonstrated a restoration of vessel elasticity and flexibility — essentially the return of the circularity system to a previous state or degree of health.16

Vitamin K2: diet or supplementation?

Western diets are generally viewed as K2 deficient.17 Studies measuring non-activated MGP levels demonstrate that 10–40% of total MGP is typically not activated among the general population.18 However, an increase in vitamin K2 intake decreases the amount of inactive MGP enzymes.16,19,20

Vitamin K2 (menaquinone [MK]) is different from vitamin K1 (phylloquinone), which primarily contributes to blood coagulation. K2 is further divided into a subfamily of 10 molecules that share a molecular quinone ring, but have isoprenoid side-chains of different lengths (MK-4 to MK-13).

EFSA K2 approval, however, is limited to the MK-7 forms. Studies also demonstrate that MK-7 is best for supplementation because it is better absorbed and is most bioactive.17,21–24 The presence of any other MK-form in an MK-7 supplement product is essentially a contamination.

Securing adequate K2 from food sources alone would require an extreme diet. Some K2 is converted from K1 in the gut, but not enough.

Natto, the fermented dish from Japan, is high in MK-7, as are some fermented cheeses and liver pâtés. K2 is also present in low concentrations in milk, cheeses and other dairy products, but these are primarily less efficient MK-forms (MK-4, MK-8, MK-9). A daily diet would require many litres of milk or kilos of dairy products to meet K2 requirements.

Changes in food preservation and storage that reduce natural fermentation in foods is a possible explanation for K2 deficiency, as is a shift to grain-fed livestock.

These might explain how humans evolved to require a nutrient not common in today’s diet. K2 supplementation is an effective option to address deficiency, and MK-7 is the best, most bioactive K2 form.

An all-trans MK-7, such as K2VITAL K2 MK-7, is required because only the trans form provides K2 health benefits (compared with the biologically inactive cis form).

Vitamin K2, heart-healthy coingredients and stability

Vitamin K2 protects the heart by balancing calcium … but the body requires other important nutrients for optimal cardiovascular health. Multi-ingredient heart health formulations leverage the synergistic health effects of ingredients to reduce CVD risk.

L-arginine, for example, is an amino acid that relaxes the blood vessels and lowers blood pressure. Magnesium regulates cardiac function, rhythm and vascular muscle tone. B-complex vitamins also contribute to normal heart function.

Omega-3 fatty acids are also important to heart health. The body needs both omega-3 and omega-6 fatty acids for good health. Western diets are high in omega-6 (from vegetable and soybean oils) and low in omega-3 (from fish).

K2 plus omega-3 is a winning heart health product combination. In fact, vitamin K2 offers many existing product opportunities in terms of upgrades and differentiation.

Consumer data demonstrates that products that contain K2 perform better in markets than similar products that do not, and consumers rate concept products that include K2 higher for uniqueness and purchase intent compared with products that do not.

Unprotected K2 MK-7, however, is not compatible in formulations with minerals such as magnesium or highly alkaline L-arginine and will degrade rapidly. A 2017 market study demonstrated that most unprotected K2-plus-mineral products tested missed label claim, the majority by a wide margin.25

MK-7 in solution is also very sensitive to light exposure and will fully degrade in a matter of hours. This makes standard MK-7 unsuitable for use in translucent dosage forms.

Innovative coingredient combinations and dosage forms will accelerate K2 use in the heart health and other market categories, but only if brands and manufacturers correctly factor for the inherent properties of the MK-7 molecule.

Use of protected, microencapsulated K2 MK-7 such as K2VITAL DELTA for mineral formulations, and innovations such as light-stable ProVitamin MK-7, ensure that consumers receive the K2 that’s promised and deliver the healthy future development of the K2 market.


  • 14. J.M. Geleijnse, et al., “Dietary Intake of Menaquinone is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study,” J. Nutr. 134(11), 3100–3105 (2004).
  • 15. G.C. Gast, et al., “A High Menaquinone Intake Reduces the Incidence of Coronary Heart Disease,” Nutr. Metab. Cardiovasc. Dis. 19(7), 504–510 (2009).
  • 16. M.H. Knapen, et al., “Menaquinone-7 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women: A Double-Blind Randomised Clinical Trial,” Thromb. Haemost. 113(5), 1135–1144 (2015).
  • 17. L.J. Schurgers and C. Vermeer, “Determination of Phylloquinone and Menaquinones in Food. Effect of Food Matrix on Circulating Vitamin K Concentrations,” Haemostasis 30(6), 298–307 (2000).
  • 18. E. Theuwissen, E. Smit and C. Vermeer, “The Role of Vitamin K in Soft-Tissue Calcification,” Adv. Nutr. 3(2), 166–173 (2012).
  • 19. R. Caluwe, et al., “Vitamin K2 Supplementation in Haemodialysis Patients: A Randomized Dose-Finding Study,” Nephrol. Dial. Transplant. 29(7), 1385–1390 (2014).
  • 20. G.W. Dalmeijer, et al., “The Effect of Menaquinone-7 Supplementation on Circulating Species of Matrix Gla Protein,” Atherosclerosis 225(2), 397–402 (2012).
  • 21. B.L. Gijsbers, K.S. Jie and C. Vermeer, “Effect of Food Composition on Vitamin K Absorption in Human Volunteers,” Br. J. Nutr. 76(2), 223–229 (1996).
  • 22. T. Sato, L.J. Schurgers and K. Uenishi, “Comparison of Menaquinone-4 and Menaquinone-7 Bioavailability in Healthy Women,” Nutr. J. 11, 93 (2012).
  • 23. L.J. Schurgers, et al., “Vitamin K-Containing Dietary Supplements: Comparison of Synthetic Vitamin K1 and Natto-Derived Menaquinone-7,” Blood 109(8), 3279–3283 (2007).
  • 24. L.J. Schurgers and C. Vermeer, “Differential Lipoprotein Transport Pathways of K-Vitamins in Healthy Subjects,” Biochim. Biophys. Acta 1570(1), 27–32 (2002).
  • 25. Kappa Bioscience AS, Market Study: K2 Stability 2016 (2017).

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