Low Vitamin K2 Linked to Calcified Arteries and Weak Bones

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By James J. Kenney, ?PhD, FACN

Vitamin K is composed of a group of compounds, but the one found in plants is Vitamin K1 (phylloquinone). Vitamin K2 is the main storage form of vitamin K in humans and animals and it has several subtypes, which differ in their isoprenoid chain length. These vitamin K2 homologues are called menaquinones. Menaquinones are often abbreviated MK-n, with the “n” representing the number of isoprenoid side chain residues. For example, menaquinone-4 (abbreviated MK-4) has four isoprene residues in its side chain. Menaquinone-4 is the most common type of vitamin K2 in animal products, since MK-4 can be synthesized from vitamin K1 in certain animal tissues (e.g. arterial walls, pancreas, and testes). Vitamin K2 is also produced from Vitamin K1 by gut bacteria. Vitamin K2 has some enzyme functions distinct from those of vitamin K1, so the ability to convert some K1 into K2 may be important.

Vitamin K2 Helps Strengthen Bones

A study of the incidence of hip fractures in Japanese women found that those with the lowest vitamin K2 intake had a greater risk of fracture. In Tokyo, the regular consumption of natto, a fermented soy food that is naturally high in vitamin K2, is associated with a significantly lower risk of hip fractures compared with data from western Japan, where natto isn’t frequently consumed (1). Vitamin K2 activates osteocalcin via carboxylation and this protein is involved in moving calcium into bones, so it is possible that vitamin K2 has some unique benefits for improving bone metabolism (2).

Vitamin K2 May Help Reduce Heart Disease

Vitamin K2 also activates another protein called matrix gal protein (MGP) via carboxylation. Once activated by vitamin K2, MGP helps remove excess calcium from soft tissues and so may help prevent calcium accumulation in arteries. This role takes on significant importance, considering that about 20% of advanced atherosclerotic plaques are comprised of calcium and more calcified plaques are associated with increased risk of heart attacks. More calcified arteries may also contribute to stiffer arteries and may increase the risk of aortic rupture, and possibly heart valve damage and heart failure (3). Patients taking the anti-vitamin K drug coumadin have long been known to be at increased risk of developing more calcified arteries and osteoporotic fractures. Research suggests Vitamin K2-activated MGP may be an important factor for preventing this artery calcification seen in late stage atherosclerosis (4). A cohort study investigating vitamin K insufficiency and cardiovascular disease (CVD) found that low circulating dephosphorylated-uncarboxylated MGP (ucMGP) levels of less than 400 pmol/L were significantly associated with a greater risk of both fatal and non-fatal CVD in 577 healthy men and women aged 55-65 years old (5). So if vascular calcification (VC) can be prevented or reduced by menaquinones (vitamin K homouloges), then it is plausible that this may be how vitamin K2 may reduce the risk for CVD events. Future strategies to reduce the risk of VC and CVD may one day encourage people to increase dietary menaquinone or more likely take a supplement of vitamin K2.

An analysis of data from the long-running Rotterdam Study followed more than 4,800 subjects aged 55 and older for up to 10 years. Dr. Geleijnse and colleagues found that a lower vitamin K2 intake was associated with more aortic calcification. They noted that subjects diagnosed with severe aortic calcification tended to have a lower intake of vitamin K2 compared with subjects with mild to moderate aortic calcification (6).

Is Calcium Supplementation With K2 Deficiency Dangerous?

Many physicians recommend calcium supplements to postmenopausal women to help prevent or treat osteoporosis. However, if these women are deficient in vitamin K2, the extra calcium may end up in their arteries rather than their bones, putting them at risk of developing cardiovascular events. Further study is needed to answer questions about the efficacy and safety of calcium supplementation in postmenopausal woman who may be deficient in vitamin K2. There is growing evidence that calcium supplements are likely to do more harm than benefit in people who are deficient in vitamin K and/or vitamin D. Data from the Women’s Heath Initiative Study noted that women taking calcium supplements, even with vitamin D, had a modest increased risk of CVD (7). Might a lack of vitamin K and particularly insufficient vitamin K2 be responsible?

Most Food Sources of Vitamin K2 Are Not So Healthy

Plant foods generally supply little or no vitamin K2. Natto is by far the best vegetarian source of vitamin K2. The intestinal bacteria in human intestines do synthesize some vitamin K2 from vitamin K1, but this might not be sufficient for preventing vitamin K2 deficiency in some people. People taking antibiotics and/or coumadin may not have sufficient vitamin K2 levels to maintain proper calcium metabolism. The more complex guts of some animals allow many of them to synthesize much more vitamin K2 from the vitamin K1 they obtain from the grass and other plant food than do people eating a largely plant-based diet. This is why some meats, eggs, and fatty dairy products tend to be good dietary sources of vitamin K2. Unfortunately, this means that many of the best food sources of vitamin K2 are animal products that are high in saturated fat and/or cholesterol, so they would be poor choices for people with CVD or hoping to avoid CVD in their lifetimes. Although serum vitamin K2 levels aren’t very reliable, the measurement of undercarboxylated or ucOsteocalcin represents an indirect marker for vitamin K2 status that could become more available in the future, providing a useful assessment tool for the diagnosis of possible vitamin K2 deficiency. Supplements of MK-4, a synthetic version produced from an extract of the plant Nicotiana tabacum, and MK-7, a more natural form sourced from natto, are available and may help clients/patients who have calcified arteries and/or thinning weal bones.

Bottom Line: Currently the Dietary Reference Intake for vitamin K doesn’t differentiate between the two main types of this fat-soluble vitamin. However, this may need to change if people consuming plenty of vitamin K1 still end up having elevated levels of ucMGP and/or ucOsteocalcin. In the meantime, knowing that food sources of vitamins K1 and K2 are different and that vitamin K2 deficiency may be more common than had been thought, it may be prudent to increase dietary sources of vitamin K2 or start taking a supplement of vitamin K2 to ensure proper calcium utilization. Until more definitive data become available, there is no risk of taking a supplement containing 30 to 100mcg of MK-4 or MK-7. They might be worth trying in people with evidence of VC and/or osteoporosis.

References:

  1. Vermeer C, Shearer MJ, Zittermann A, et al. Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. Eur J Nutr. 2004;43(6):325-335.
  2. Plaza SM, Lamson DW. Vitamin K2 in bone metabolism and osteoporosis. Altern Med Rev. 2005;10(1):24-35.
  3. Rheaume-Bleue K. Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life. 1st ed. Ontario, Canada; Wiley: 2011.
  4. Schurgers LJ, Cranenberg EC, Vermeer C. Matrix Gla protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008:100;593-603.
  5. van den Heuvel, E. G. H . M, van Scoor, N. M., Lips. P., Magdeleyns, E. J. P., Deeg, D. J. H., Vermeer, C., and den Heijer, M. (2014). “Circulating uncarboxylated matrix gal protein, a marker of vitamin k status, as a risk factor of cardiovascular disease.” Maturitas.77: 137–141. doi:10.1016/j.maturitas.2013.10.008.
  6. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004;134(11):3100-3105.
  7. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.
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