Vitamin K2: Powerful Bone-Building, Heart-Protecting Nutrient

by VRP Staff

Vitamin K was first recognized in 1929 for its vital role in the healthy blood-clotting process. Since that time, this multifaceted coenzyme has been shown to be effective in bone, heart, liver and prostate health. Recent findings have added to our accumulating database of vitamin K’s biological functions and health applications.

The vitamin occurs naturally in two forms. K1, or phylloquinone, is found in green leafy vegetables. K2, comprised of a group of compounds known as menaquinones, is synthesized by intestinal microflora and also obtained from dietary sources including organ meats, egg yolks, fermented dairy products, and the Japanese fermented soybean dish, natto (the richest food source).

Although vitamin K2 occurs in much smaller amounts in the diet than K1, scientific findings suggest that the menaquinone form confers most of the benefits in regard to heart and bone health and promoting overall tissue health. Vitamin K1, meanwhile, has been studied for its beneficial effects in supporting healthy insulin levels.¹

Heart and Bone Health: The Common Denominator

Although not at first apparent, research has established a connection between two seemingly diverse aspects of health: bone integrity and cardiovascular health. The common link is faulty calcium metabolism caused by an insufficiency of vitamin K2.

Vitamin K2 plays a vital role in ensuring that calcium stays in the bones (maintaining adequate bone mineral density) and out of the arteries (supporting normal calcium homeostasis and vascular flexibility). It is an essential cofactor for a chemical process known as carboxylation, which enables calcium-regulating proteins to perform their functions. One of these proteins, osteocalcin, binds calcium to the bone matrix. However, without sufficient K2, the carboxylation reaction that activates osteocalcin cannot proceed, resulting in the loss of calcium from bone tissue.^2-3 Another protein, matrix GLA-protein, is a calcification-inhibitor; that is, it prevents the deposition of excess calcium in arteries and promotes calcium deposition in bone and related tissue. Similarly, this protein’s precursor must undergo carboxylation, mediated by K2, to convert to its active form. In the absence of vitamin K2, this conversion to matrix GLA-protein is hindered, resulting in an imbalance in calcium ions in the vascular system.^4-5 Adequate levels of calcium-regulating menaquinones are vital, since insufficiencies are associated with a greater risk of suboptimal bone integrity^3,6,15 and cardiovascular concerns.^4,7

Vitamin K2 and Heart Health

In 2004, the results of a ground-breaking seven-year study of 4,800 subjects (known as the Rotterdam Study) linking menaquinone intake with enhanced heart health were published. Participants in the Netherlands were tracked for seven years for dietary intake of vitamins K1 and K2 and concomitant levels of calcium ions in the arteries and coronary heart health. Researchers found that those with the higher levels of vitamin K2 in their diets (greater than 32.7 mcg a day) experienced better heart health and less deposition of calcium in the aorta compared with subjects with minimal K2 intake. K1 did not confer this benefit. The researchers concluded, “Our findings suggest a protective effect of menaquinone intake…”⁴

In the past few years, other studies have confirmed that vitamin K2 supports cardiovascular health. In humans, higher intake was associated with better coronary health as a result of improved calcium homeostasis in the coronary artery⁷ and in vitro, vitamin K2 helps maintain normal levels of calcium in smooth muscle cells, like those in the arteries.^8-9

Healthy Bones

Suboptimal bone health occurs when resorption of calcium and other minerals from bones outpaces formation, causing unwanted effects to structure and integrity, a potentially dangerous situation, especially for the elderly.

Much of the research on vitamin K2 has been performed in Japan, where researchers discovered that people who regularly consume the soybean dish, natto, have significantly enhanced bone structural integrity compared with less frequent consumers.^10-11 The efficacious ingredient in natto responsible for these bone-supporting qualities is vitamin K2.

The connection between menaquinone intake and bone health is supported by a slew of other research which confirms that vitamin K2 supports bone integrity and maintains bone mineral density (BMD).^6,12-14 In addition, it has been shown to benefit people already using standard options to enhance and maintain bone health.^6,14-15 For example, in a 1-year randomized trial of 44 women, those who received vitamin K2 (45 mg/day) in addition to their normal regimen had enhanced osteocalcin carboxylation. This led to a better supported hip bone mineral density compared to the standard regimen alone.¹⁵

Cellular Health

MK-4, a vitamin K2 analog, has demonstrated beneficial effects on cells and also has been shown to be involved in hematological and liver health^16-17 most likely by inducing processes involved in healthy cell turnover.¹⁷ In a study originally intended to examine the efficacy of MK-4 in bone health in 40 women with liver concerns, researchers observed that subjects receiving the 45 mg dose had markedly enhanced liver health. Two of the 21 women experienced suboptimal liver health in the supplemented group compared with nine of the 19 subjects in the control group. Researchers concluded that there is a possible role for vitamin K2 in supporting liver health in women with suboptimal liver health.¹⁸

Vitamin K2 has also been found to support continued, long-term liver health.^16-17,19 In one study of 61 people, those receiving 45 mg of MK-4 were significantly healthier than subjects in the control group.¹⁹

In the first epidemiologic study linking insufficient dietary intake of vitamins K1 and K2 with suboptimal prostate health, over 11,000 men were tracked for over 8.5 years with respect to dietary intake and prostate health. Researchers observed an inverse relationship between the incidence of suboptimal prostate health and total menaquinone intake. K1 intake was unrelated to the incidence of suboptimal prostate health.²⁰

Dosage and Safety

The Food and Nutrition Board of the Institute of Medicine recommendation for adequate vitamin K intake is 120 mcg/day for men and 90 mcg/day for women.²¹ Although these levels may be sufficient to ensure healthy blood clotting, research indicates that they may not be optimal for cardiovascular and bone health.³ Consider that menaquinone intake is 10 percent of total vitamin K intake;⁴ based on the daily recommendation, this translates to 9 and 12 mcg/day of vitamin K2—extremely low values! What is a suitable dose? As we have seen, benefits were obtained over a vast range—greater than 32.7 mcg per day (which resulted in optimal cardiovascular health in the Rotterdam study) to as high as 45 mg per day (the recommended dose of MK-4 used for optimal bone health).

Vitamin K2 appears to have a wide safety margin. According to the Food and Nutrition Board, “No adverse effects associated with vitamin K consumption from food or supplements have been reported in humans or animals.”²¹ This is supported by a large body of research, which draws conclusions such as: “the safety, relatively low cost and ease of use of vitamin K2 have led to good compliance.”¹⁷

One caution to keep in mind is that individuals taking warfarin should only take vitamin K or K2 under the guidance of a physician.

Conclusion

With its record as a safe and effective way to support optimal heart and bone health, vitamin K2 is a valuable addition to a comprehensive supplement program. However, the menaquinones’ full health potential is yet to be realized, as research continually reveals new applications for this unique class of compounds.

References

1. Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg C, Dawson-Hughes B, Dallal G, Booth SL. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care. 2008 Aug 12. Published Online Ahead of Print.

2. Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner. Metab.2008;26(3):260-4.

3. Bügel S. Vitamin K and bone health in adult humans.Vitam Horm. 2008;78:393-416.

4. 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 Nov;134(11):3100-5.

5. Schurgers LJ, Teunissen KJ, Knapen MH, et al. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1629-33.

6. Iwamoto J, Takeda T, Sato Y. Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Curr Drug Saf. 2006 Jan;1(1):87-97.

7. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008 Jul 19.

8. Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res. 2008;122(3):411-7.

9. Saito E, Wachi H, Sato F, Sugitani H, Seyama Y. Treatment with vitamin k(2) combined with bisphosphonates synergistically inhibits calcification in cultured smooth muscle cells. J Atheroscler Thromb. 2007 Dec;14(6):317-24.

10. Kaneki M, Hodges SJ, Hosoi T, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition. 2001 Apr;17(4):315-21.

11. Ikeda Y, Iki M, Morita A, et al. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J Nutr. 2006 May;136(5):1323-8.

12. Ishida Y. Treatment of osteoporosis and evidence-based medicine. Vitamin k(2). Clin Calcium. 2008 Oct;18(10):1476-82.

13. Tanaka I, Oshima H. Vitamin K2 as a potential therapeutic agent for glucocorticoid-induced osteoporosis. Clin Calcium. 2007 Nov;17(11):1738-44.

14. Hara K, Akiyama Y. Vitamin K and bone quality. Clin Calcium. 2007 Nov;17(11):1678-84.

15. Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H. Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab. 2008;26(3):260-4.

16. Mizuta T, Ozaki I. Hepatocellular carcinoma and vitamin K. Vitam Horm. 2008;78:435-42.

17. Tamori A, Habu D, Shiomi S, Kubo S, Nishiguchi S. Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res. 2007 Sep;37 Suppl 2:S303-7.

18. Habu D, Shiomi S, Tamori A, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004 Jul 21;292(3):358-61.

19. Mizuta T, Ozaki I, Eguchi Y, et al. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study. Cancer. 2006 Feb 5;106(4):867-72.

20. Nimptsch K, Rohrmann S, Linseisen. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008 Apr;87(4):985-92.

21. http://www.iom.edu/Object.File/Master/54/411/DRIs.Vitamins.pdf.