Vitamin K is a member of fat soluble vitamins, existing in two forms: vitamin K1 (phylloquinone) and vitamin K2 (menaquinones). While vitamin K1 plays an important role in blood clotting, vitamin K2 acts more on extra-hepatic tissues (such as bone, brain, heart, kidneys, and lungs) where it activates proteins such as osteocalcin and matrix gla protein. Menaquinones can be synthesized by gut bacteria and they are present in fermented foods such as dairy products, as well as in animal products (liver, egg yolk, meat).
Osteoporosis/ bone health
A meta-analysis was conducted to test the hypothesis that vitamin K2 could play important role in the prevention/treatment of osteoporosis in postmenopausal females. 19 randomized, controlled trials were included in an analysis with more than 6500 participants. Results indicated that vitamin K2 could significantly improve vertebral bone mineral density and prevent fractures in women with osteoporosis. Also, as this meta-analyses indicated, vitamin K2 caused increment in osteocalcin with reduction in undercarboxylated osteocalcin, which might explain favorable effects on bone mineral density.
Another study reviewed the effects of vitamin K2 therapy in postmenopausal women. This review indentified 8 randomized controlled clinical trials which investigated the effects of vitamin K2 supplementation on bone density in postmenopausal women with osteoporosis. Based on available studies, it presented positive evidence that vitamin K2 monotherapy might reduce incidence of fractures in postmenopausal women with reduction in levels of undercarboxylated osteoacalcin (as a marker of risk of fractures).
- Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26(3):1175-86.
- Iwamoto J. Vitamin K₂ therapy for postmenopausal osteoporosis. Nutrients. 2014;6(5):1971-80.
According to the observational study there is positive association between menaquinone (vitamin K2) and cardiovascular health. This association was investigated in some intervention studies as well. For instance, one study questioned impact of three years long supplementation with vitamin K2 on arterial stiffness in health postmenopausal women. In double blind randomized manner, 120 participants received vitamin K2, while 124 received placebo. Comparing with the placebo, vitamin K2 significantly improved arterial stiffness in treated subjects and decreased the levels of uncarboxylated matrix Gla-protein. Matrix Gla protein is a calcification inhibitor of the arterial wall and its activity depends on vitamin K-dependent carboxylation. One study investigated the impact of vitamin K2 intake on coronary artery calcification and arterial stiffness. It was designed as open label single arm study in which 26 participants received vitamin K2 for 1 year. The benefits of vitamin K2 were observed only in subjects with K2 insufficiency at the beginning of the study.
Further on, one trial analyzed data form168 countries to elucidate the association of vitamin K2 deficiency, among other factors, with early deaths of cardiovascular disease. As this study showed, countries with intake of vitamin K2 < 5µg per 2000 kcal/day per capita had 2.2 times higher the rate of early cardiovascular deaths comparing with the countries with > 24 µg/day of vitamin K2 per 2000 kcal/day per capita. This, the conclusion was that intake of vitamin K2-containing foods (fermented plant foods- sauerkraut, miso, and natto) should be increased in order to decrease incidence of early cardiovascular deaths (before the age of 65).
- Knapen MH, Braam LA, Drummen NE, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015;113(5):1135-44.
- Ikari Y, Torii S, Shioi A, Okano T. Impact of menaquinone-4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study. Nutr J;15(1):53.
- Cundiff DK, Agutter PS. Cardiovascular Disease Death Before Age 65 in 168 Countries Correlated Statistically with Biometrics, Socioeconomic Status, Tobacco, Gender, Exercise, Macronutrients, and Vitamin K. Cureus. 2016;8(8):e748.