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Conly JM, Stein K, Worobetz L, Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am J Gastroenterol 1994;89:915-23. [ PubMed abstract] Ebina K, Shi K, Hirao M, et al. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod Rheumatol. 2013;23(5):1001-1007. Caraballo PJ, Gabriel SE, Castro MR, Atkinson EJ, Melton LJ (1999). "Changes in bone density after exposure to oral anticoagulants: a meta-analysis". Osteoporosis International. 9 (5): 441–8. doi: 10.1007/s001980050169. PMID 10550464. S2CID 12494428.
The mechanism of action of vitamin K 2 is similar to vitamin K 1. K vitamins were first recognized as a factor required for coagulation, but the functions performed by this vitamin group were revealed to be much more complex. K vitamins play an essential role as cofactor for the enzyme γ-glutamyl carboxylase, which is involved in vitamin K-dependent carboxylation of the gla domain in "Gla proteins" (i.e., in conversion of peptide-bound glutamic acid (Glu) to γ-carboxy glutamic acid (Gla) in these proteins). [10] Carboxylation reaction – the Vitamin K cycle In an observational study conducted in the Netherlands in 564 postmenopausal women, dietary menaquinone (but not phylloquinone) intake was inversely associated with coronary calcification [ 42]. Menaquinone intake was also inversely associated with severe aortic calcification in a prospective, population-based cohort study involving 4,807 men and women age 55 years and older from the Netherlands [ 41]. Participants in this study who had dietary menaquinone intakes in the mid tertile (21.6–32.7 mcg/day) and upper tertile (>32.7 mcg/day) also had a 27% and 57% lower risk of coronary heart disease mortality, respectively, than those in the lower tertile of intake (<21.6 mcg/day). Phylloquinone intake had no effect on any outcome. supplementation suppresses bone turnover in young adult males. J Clin Endocrinol Metab. 1998 Aug;83(8):2742-8.to the current enrichment program for cereal-grain products? Am J Clin Nutr. 2004 Aug;80(2):264-70. https://www.osteoporosis.foundation/facts-statistics/epidemiology-of-osteoporosis-and-fragility-fractures.
Raggi P, Shaw LJ, Berman DS, Callister TQ (May 2004). "Prognostic value of coronary artery calcium screening in subjects with and without diabetes". Journal of the American College of Cardiology. 43 (9): 1663–9. doi: 10.1016/j.jacc.2003.09.068. PMID 15120828. In addition to its positive effects on blood clotting and strong bones, vitamin K helps keeps your heart healthy. That’s because of the way it acts to clear out calcium from your blood vessels.Vitamin K is a cofactor for the gamma-carboxylation of many proteins, including osteocalcin, one of the main proteins in bone [ 28]. Some research indicates that high serum levels of undercarboxylated osteocalcin are associated with lower bone mineral density [ 5, 28]. Some, but not all, studies also link higher vitamin K intakes with higher bone mineral density and/or lower hip fracture incidence [ 29-34]. Menadione, which is sometimes called vitamin K3, is another synthetic form of vitamin K. It was shown to damage hepatic cells in laboratory studies conducted during the 1980s and 1990s, so it is no longer used in dietary supplements or fortified foods [ 3]. Vitamin K Intakes and Status While much is still to be learned about vitamin K2, the signs so far point to an underutilized and underappreciated powerhouse for our bodies.
Most U.S. diets contain an adequate amount of vitamin K [ 7]. Data from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) show that among children and teens age 2–19 years, the average daily vitamin K intake from foods is 66 mcg [ 20]. In adults age 20 and older, the average daily vitamin K intake from foods is 122 mcg for women and 138 mcg for men. When both foods and supplements are considered, the average daily vitamin K intake increases to 164 mcg for women and 182 mcg for men.Vitamin K2 has several subtypes. Vitamin K2 homologs or Menaquinones (MK) are characterized by isoprenoids (sometimes called terpenoids, naturally occurring organic compounds) residues in their side chains. MK-n is an abbreviated form of menaquinones, n stands for the number of terpenoids side chain residues. For example, MK-7 (abbreviation of Menaquinone-7) has seven terpenoids side chain residues. Menaquinone have several forms but two subtypes menaquinone-4 (MK4) and menaquinone-7 (MK7) are studied extensively. Biochemical studies have shown that MK-7 is not produced by human tissues, so it is different from MK-4 in that sense. Insufficient data were available to establish an EAR for vitamin K, so the FNB established AIs for all ages that are based on vitamin K intakes in healthy population groups [ 3]. Table 1 lists the current AIs for vitamin K in micrograms (mcg). The AIs for infants are based on the calculated mean vitamin K intake of healthy breastfed infants and the assumption that infants receive prophylactic vitamin K at birth as recommended by American and Canadian pediatric societies [ 3]. Table 1: Adequate Intakes (AIs) for Vitamin K [ 3] Age This section focuses on two conditions in which vitamin K might play a role: osteoporosis and coronary heart disease. Osteoporosis
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