MK-7 Bioavailability Increases Extrahepatic Tissue Utilization
Schurgers et al conducted human studies to compare the in vivo properties of orally administered K1 and MK-7. The results supported better bioavailability and utilization of MK-7. Expressed as AUC96, MK-7 demonstrated a six-fold better half-life, a seven- to eight-fold higher dose-response level, and a three times
higher carboxylated to uncarboxylated osteocalcin ratio (cOC:ucOC†). Furthermore, on a molar basis, MK-7 is a three-to-four times more potent antidote for oral anticoagulation than is K1. Researchers note that, aside from sensitive individuals, “MK-7 supplements containing more than 50 mcg/d may interfere with oral
anticoagulant treatment, whereas doses of at least 50 mcg are not likely to affect the INR value in a relevant way.”[2] Nonetheless, practitioners should closely monitor patients taking anticoagulants.

While studies on the absorption and bioavailability of MK-4 at nutritional levels (i.e., doses of 500 mcg/d or lower) suggest less efficacy compared to longer-chain menaquinones at similar doses,[4] this remains subject to debate. It is possible that rapid uptake of MK-4 could account for its observed lack of detection in serum
after oral administration,[5] but more studies are needed for clarification.

Bone Benefits
Among the dietary factors critical to bone health, vitamin K has emerged as a key player. Vitamin K is believed to be necessary for bone mineralization. Through carboxylation, vitamin K activates osteocalcin, the protein needed to bind calcium to the mineral matrix in bone.[6] Several studies have demonstrated the efficacy
of MK-7 (e.g., doses of 45-90 mcg/d) to increase osteocalcin carboxylation and to increase the cOC:ucOC ratio. A high cOC:ucOC ratio is associated with bone health.[1,2,4] A recent in vitro study also showed an osteogenic effect of MK-7 administration on human mesenchymal cell differentiation.[6] In addition, the
vitamin may protect bone integrity by reducing the synthesis of prostaglandin E2 or interleukin-6 by osteoclasts.[7] Animal and human studies have demonstrated a significant beneficial effect of MK-7 supplementation on bone health.[8-10] Vitamin K and vitamin D share some similar characteristics and are believed to act synergistically.*[11]

Cardiovascular and Other Health Benefits
Vitamin K benefits cardiovascular health by participating in the carboxylation of matrix GLA protein (MGP), a protein regarded to be the most potent inhibitor of arterial calcification. Researchers have demonstrated that supplementation with vitamin K reduces arterial calcium deposits[1,3,12] and that long-term intake of long-chain menaquinones is inversely correlated with calcium accumulation in arteries.*[5]

Vitamin K has specific receptor binding sites that allow it to regulate gene activity.[13] Besides its gene-mediating effects upon critical proteins, the vitamin can also bind with the steroid and xenobiotic receptors and influence their expression.[14] In addition, vitamin K also demonstrates antioxidant activity[15]; reduces levels of certain markers, such as acute phase reactants (e.g., C-reactive protein)[16]; and participates in the induction of apoptosis.*[17]

Vitamin D (as D3)
Although vitamin D3 (cholecalciferol) is made in the skin when 7-dehydrocholesterol reacts with sunlight, many things affect the degree to which this biosynthesis occurs, including time of day, seasons, location, smog/
pollution, clothing, shade of skin (darker skin requires more sun), and sunscreen use. Low-cholesterol diets and certain cholesterol therapies can also affect vitamin D formation. By some estimates, one billion people worldwide have vitamin D deficiency or insufficiency.[18] The body needs vitamin D to absorb calcium, and the
importance of vitamin D in skeletal health and bone density is well-established. Without adequate absorption, the body must take calcium from its stores in the skeleton, which weakens existing bone and prevents the formation of strong, new bone. Researchers suggest that vitamin D supplementation may decrease bone turnover and increase bone mineral density.[19] A pooled analysis evaluating 11 randomized, double-blind, placebo-controlled trials supported this analysis. It concluded that vitamin D supplementation (> 800 IU daily) was favorable in maintaining hip and nonvertebral bone integrity in individuals aged 65 and older.*[20]

Although D2 and D3 are similar biochemically, one study demonstrated D3 to be approximately 87% more potent in raising and maintaining serum calcidiol (the body’s storage form) concentrations and in producing two- to threefold greater storage of vitamin D than did equimolar D2.*[21]

†The cOC:ucOC ratio can be used as a determinant of vitamin K status.

References
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2. Schurgers LJ, Teunissen KJ, Hamulyák K, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83. [PMID: 17158229]
3. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93. [PMID: 18722618]
4. Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012 Nov 12;11:93. [PMID: 23140417]
5. Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002 Feb 15;1570(1):27- 32. [PMID: 11960685]
6. Gigante A, Brugè F, Cecconi S, et al. Vitamin MK-7 enhances vitamin D3- induced osteogenesis in hMSCs: modulation of key effectors in mineralization and vascularization. J Tissue Eng Regen Med. 2012 Oct 29. [PMID: 23109511]
7. Weber P. Management of osteoporosis: is there a role for vitamin K? Int J Vitam Nutr Res. 1997;67(5):350-56. [PMID: 9350477]
8. Yamaguchi M, Taguchi H, Gao YH, et al. Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. J Bone Miner Metab. 1999;17(1):23-29. [PMID: 10084398]
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10. Kanellakis S, Moschonis G, Tenta R, et al. Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II. Calcif Tissue Int. 2012 Apr;90(4):251-62. [PMID: 2239252]
11. Bolton-Smith C, McMurdo ME, Paterson CR, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007 Apr;22(4):509-19. [PMID: 17243866]
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