The Neglected Vitamin K2 and its Critical Role in Bone and Cardiovascular Health

By: Roya Riazi Ph.D, RD
Consulting Dietitian and Part-Time Professor at Seneca College
and Canadian Memorial College of Chiropractic

Vitamin K (VK) is a fat-soluble vitamin that was discovered in the early 1930s by the Danish biochemist, Henrik Dam. K stands for the Danish word “Koagulation” or “Clotting (1). Most of the attention on VK so far has been on its role in coagulation. However, VK has two forms: K1 (also referred to as phylloquinone), which is found in plant sources and green leafy vegetables and K2 (also referred to as menaquinone), which is found in dairy products from grass fed animals, and fermented soy products. While VK1’s critical role is in blood coagulation, the distinct role of VK2 in bone and cardiovascular health was only recently discovered. VK1 deficiency is rare and almost non-existent (1, 2). However it is possible to have VK2 deficiency with no sign of bleeding or bruising (1) but significant chronic disease. Therefore it is important to know about the role and impact of VK2 deficiency on health as it is less widely known by the public (including many clinicians) and most people do not get sufficient VK2 from the normal North American diet.

Bone Health
Bone health is widely known to be affected by dietary intake of calcium, vitamin D, and magnesium. However, VK2 plays a critical role in metabolism of calcium (1,2). Normal bones go through a continuous process of remodelling, a balance between bone building and bone breakdown (resorption). VK2 activates the calcium-binding actions of a protein called osteocalcin, which plays an important role in balancing of these two processes (1,3). Osteocalcin is secreted by osteoblasts, the body’s bone-building cells. When Osteocalcin is activated (carboxylated) in presence of VK2, it facilitates incorporation of calcium into the bone matrix (2). In addition, VK2, when combined with vitamin D3, helps to reduce bone breakdown by down-regulating osteoclasts which are responsible for bone resorption (4). A study in postmenopausal women supplemented with MK-7 (a dietary form of VK2 from fermented food sources) for 3 years found improvement in age-related decrease in bone mineral density (5). Similarly, another Japanese study reported reduced incidence of hip fractures in Japanese women with VK2 intake (1). Several trials with VK2 found reduction in spinal fractures, hip fractures and non-spinal fractures (1, 4, 6). In line with these findings, VK2 supplements have been recommended for prevention and treatment of osteoporosis in Japan (1).

Cardiovascular Health
Calcium buildup in arteries around heart and major arteries (atherosclerosis) are important risk factor for heart disease (1). Twenty percent of atherosclerotic plaques are comprised of calcium. Therefore anything that can reduce calcium accumulation in vascular tissue will be important in reducing the risk of cardiovascular disease (2).

Physicians recommend calcium supplements to postmenopausal women in order to prevent or treat osteoporosis. Although calcium is the main mineral present in the bone matrix, supplementation may not necessarily result in stronger bones if it accumulates in arteries instead, a scenario which exists when there is a deficiency of VK2.

VK2 is believed to prevent calcium being deposited in the arteries through activating osteocalcin which in turn activates another protein called matrix GLA protein (MGP). MGP is responsible for removing excess calcium accumulated in soft tissues such as arteries (2, 9). In a number of large observational studies such as the Rotterdam Study, which followed more than 4,800 subjects aged 55 and older for up to 10 years, there was an association between VK2 intake and aortic calcification. In this study, people with the highest intake of VK2 were 52% less likely to develop artery calcification and had a 57% lower risk of dying from heart disease. In the same study, subjects diagnosed with severe aortic calcification had a lower intake of VK2 compared with subjects with mild to moderate aortic calcification (10).

A large-scale meta-analysis published in the American Journal of Clinical Nutrition in 2007 found that calcium supplementation did not lower the risk of hip fracture in men or women (7). Another meta- analysis published in the British Medical Journal in 2011 showed that calcium supplementation with or without vitamin D significantly increased the risk of myocardial infarction or stroke in postmenopausal women (8). Based on the current literature, calcium supplementation alone is not recommended for the treatment or prevention of osteoprosis. Additional studies are needed to determine if supplementation with VK2 alone or in combination with calcium and vitamin D can produce better outcomes for bone and heart health.

Cancer
Cancer is a common cause of death in western societies. Therefore, finding effective prevention strategies is of great importance. Several studies have been done on VK2 and certain types of cancer. Two clinical studies suggest that VK2 reduces recurrence of liver cancer and increases survival times (12). An observational study has found that a high VK2, but not VK1, intake was linked to a lower risk of prostate cancer (13). More studies are needed here before drawing more definitive conclusions.

Food Sources of Vitamin K2
While VK1 mostly is found in leafy greens, animal products are good sources of VK2. These include meat, especially liver, from grass fed animals such as chicken and beef, as well as bacon and ham. Egg yolks (from chickens that are fed diverse diet, including grass), but not egg whites, also provide high amounts of VK2 as do high-fat dairy products from grass fed animals, especially cheeses made with whole milk (1,3, 14). Natto is the only vegetarian source of vitamin K2 because of a specific strain of bacteria used in its fermentation (4). Although intestinal bacterial synthesize small amounts of VK2, this does not appear to be sufficient in preventing vitamin K2 deficiency in most people (4).

Dietitian’s Perspective
Although serum VK2 levels is not a reliable method to detect VK2 deficiency, undercarboxylated (inactive) osteocalcin is an indirect marker for VK2 status and provides useful assessment tool (15, 4). Given food rich in VK2 may not be part of regular intake of most of the population in North America, many people are thought to be deficient in this vitamin. Unfortunately, the current Dietary Reference Intake for VK doesn’t differentiate between the types of this fat-soluble vitamin at this time (1, 4,15). But it is important to know that food sources of VK1 and VK2 are different and prevalence of VK2 deficiency is likely high in the population. Given VK2 deficiency in the North American population may, at least in part, explain the high rates of osteoporosis and heart disease here, health care providers should be aware of the importance of VK2 in the diet and inform clients of food sources to ensure optimum calcium utilization and health benefits of this lesser known vitamin.

References
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3. Hauschka, P.V. Osteocalcin: the Vitamin K-dependent Ca2+-binding protein of bone matrix. Homastasis, 1986: 16 (3-4):258-272.
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10. 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.
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13. Nimptsch, K. Rohrmann, S., Linseisen, J. Dietary intake of vitamin K and risk of prostate cancer in Heidelberg cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am. J. Clin. Nutr. 2008: 87(4): 985-992.
14. Booth, S.L. Vitamin K: food composition and dietary intake. Food and Nutrition Research. 2012: 56:5505.
15. Jacob, A. Vitamin K2- A little known nutrient can make a big difference in heart and bone health. Today’s Dietitian. June 2013: 15 (6): 54.