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All about vitamin K and how supplementation can benefit at many stages of life

What is vitamin K?

Vitamin K is a collective term for a group of fat-soluble compounds. Discovered in 1929 by a Danish nutritional biochemist (and later, Nobel prize recipient) Dr. Henrik Dam, the name vitamin K reflects the compound’s ability to support Koagulation (coagulation)1. Vitamin K has traditionally been understood to aid in blood clotting, preventing hemorrhage, and promoting wound healing. While these functions still hold true, this group of compounds has more recently been found to have other key responsibilities in how we function.

There are two natural kinds of vitamin K: vitamin K1 (phylloquinone or phytonadione) and vitamin K2 (menaquinone) which has many forms, including menaquinone 7 (MK-7).

What are the differences between vitamins K1 and K2?

Vitamin K1 is a single compound found in green cruciferous vegetables3,4 as well as certain vegetable oils such as soybean and rapeseed oils.5,6 Primarily, it plays a role in the carboxylation of the natural vitamin K clotting factors.

Vitamin K2 is made by bacteria and performs numerous functions throughout the body. K2 is essential for the function of several binding calcium proteins.7 K2 also works in the bloodstream to help place calcium in bones where it belongs, rather than in the arteries where calcium can be a risk factor for cardiovascular complications. Populations across the world overwhelmingly consume more K1 than K2, other than the population in Eastern Japan where regular consumption of natto (fermented soybean) is common.8

Vitamin K2, also known as menaquinone, includes a range of related forms that differ mainly in the number of isoprenyl groups in the side chains of the molecule. If there are four such groups, it is called K2-4 (or MK-4, for menaquinone K-4). If there are seven, it is called K2-7 (or MK-7).

Vitamin K2-4 is a short-chain menaquinone that is found in meat and chicken, egg yolks, some cheeses, and butter made from the milk of grass-fed cattle. You can also buy K2-4 in a synthetic form. However, this form of vitamin K2 has a short half-life and remains in the blood for no more than a few hours. To maintain levels of synthetic MK-4 in the blood, one would need to ensure adequate intake every few hours.9

Figure 2: Vitamin K molecular structures. The difference between the three molecule is the length of the carbon chain and the number of carbon double-bonds: Vitamin K1 has one carbon double bond, vitamin K2-4 has same carbon chain length as vitamin K1 but four carbon double bonds, and Vitamin K2-7 has a longer carbon chain and seven carbon double bonds. While all three molecules function as coenzymes in various processes (modifying protein structure) such as carboxylations, the activity and half-life vary depending on type.6

The K2-7 advantage

Vitamin K2-7 is a long-chain menaquinone. The best dietary source is the superfood natto, a food traditional to the Japanese diet.10,11 It can also be found in certain types of natural (non-processed) cheese and butter. Studies have shown that K2-7 has better bioavailability than other forms of vitamin K212 – that is, it is absorbed more easily by the body. It also has a longer half-life,13,14 which results in more stable serum concentrations.

MenaquinGold® is a natural source of vitamin K2 (MK-7). It is produced via a deep tank fermentation process with the strain Bacillus licheniformis NAT, a non-GMO, GRAS organism. This is essentially the same vitamin K2 found in high concentrations in natto, which has been consumed for over 2000 years. However, unlike the K2 found in natto, MenaquinGold® is fermented from chickpeas and the production process is completely soy-free.

The physiological functions of vitamin K

Recent studies have shown that in addition to their role in the carboxylation of coagulation factors, vitamin K dependent proteins (VKDP) are involved in bone metabolism and the inhibition of arterial calcification.15 The two VKDPs extensively studied in this regard are osteocalcin and matrix Gla Protein (MGP)16; both of which are present outside the liver.

Osteocalcin is synthesized mainly by osteoblasts (bone cells), and when carboxylated, they enable calcium absorption onto the bone, thus promoting mineralization. MGP is synthesized primarily by chondrocytes and vascular smooth muscle cells and is found in the cartilage, bone, and vasculature. MGPs, when carboxylated, play a key role in the inhibition of arterial calcification, becoming a very critical factor in preventing plaque formation.17

Primary transport and uptake of vitamin K1 occurs in the liver.18 The liver takes the amount of vitamin K1 it needs, and the remaining vitamin K1 is used by other tissues. This is why vitamin K1 insufficiency mainly occurs in extra-hepatic tissues (that is non-liver tissue), increasing the risk of weakening the bones, or calcium buildup on the blood vessels.19

Vitamin K2 is redistributed by the liver and transported to the extra-hepatic tissues where insufficiency is more typically found.20 When compared with K1, vitamin K2 exerts a more powerful influence on bone, and has been found to be more effective in decreasing bone turnover. In addition, vitamin K2 has been linked to health benefits within heart health.21

Why supplement with vitamin K2?

Vitamin K2 is a vitamin for the whole body. Further market expansion is almost inevitable given the convergence of the following factors:

  • A growing aging population22.
  • Significant increase in the incidence and prevalence of health challenges associated with bone health, heart health, and sugar metabolism.23,24
  • Increasing interest in non-traditional intervention in the prevention and management of health challenges.25
  • Growing awareness and documentation of the effects of vitamin K2 supplementation in supporting specific body systems.
  • Supplementing with vitamin K2 supports bone mineralization by helping to activate osteoblasts and works synergistically with vitamin D to maintain osteocalcin. Vitamin K2-7 is uniquely positioned to support the aging demographic who are experiencing bone density loss, particularly post-menopausal women with reduced bone strength.26

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References

  1. Ferland, G. (2012). The Discovery of Vitamin K and Its Clinical Applications. Annals of Nutrition & Metabolism, 61(3), 213–218. https://www.jstor.org/stable/48508233

  2. Schurgers, L. J., K. J. Teunissen, K. Hamulyk, M. H. Knapen, H. Vik, and C. Vermeer. 2007. “Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7.” Blood no. 109 (8):3279-83. doi: 10.1182/blood-2006-08-040709.

  3. Beulens, J., Booth, S., Van den Heuvel, E., Stoecklin, E., Baka, A., & Vermeer, C. (2013). The role of menaquinones (vitamin K2) in human health. British Journal of Nutrition, 110(8), 1357-1368. doi:10.1017/S0007114513001013

  4. Bolton-Smith, C., Price, R. J., Fenton, S. T., Harrington, D. J., & Shearer, M. J. (2000). Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. British Journal of Nutrition, 83(4), 389-399.

  5. Schwalfenberg G. K. (2017). Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health. Journal of nutrition and metabolism, 2017, 6254836. https://doi.org/10.1155/2017/6254836

  6. Přemysl Mladěnka, Kateřina Macáková, Lenka Kujovská Krčmová, Lenka Javorská, Kristýna Mrštná, Alejandro Carazo, Michele Protti, Fernando Remião, Lucie Nováková, the OEMONOM researchers and collaborators, Vitamin K – sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity, Nutrition Reviews, Volume 80, Issue 4, April 2022, Pages 677–698, https://doi.org/10.1093/nutrit nutrit/nuab061

  7. Rishavy MA & Berkner KL (2012) Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase. Adv Nutr 3, 135–148. 15. 3

  8. Kaneki, M., Hodges, S. J., Hosoi, T., Fujiwara, S., Lyons, A., Crean, S. J., Ishida, N., Nakagawa, M., Takechi, M., Sano, Y., Mizuno, Y., Hoshino, S., Miyao, M., Inoue, S., Horiki, K., Shiraki, M., Ouchi, Y., & Orimo, H. (2001). 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 (Burbank, Los Angeles County, Calif.), 17(4), 315–321. https://doi.org/10.1016/s0899-9007(00)00554-2

  9. Sato, T., L. J. Schurgers, and K. Uenishi. 2012. “Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.” Nutr J no. 11:93. doi: 10.1186/1475-2891-11-93.

  10. Schurgers L, J, Vermeer C: Determination of Phylloquinone and Menaquinones in Food. Haemostasis 2000;30:298-307. doi: 10.1159/000054147

  11. Kaneki, M., Hodges, S. J., Hosoi, T., Fujiwara, S., Lyons, A., Crean, S. J., Ishida, N., Nakagawa, M., Takechi, M., Sano, Y., Mizuno, Y., Hoshino, S., Miyao, M., Inoue, S., Horiki, K., Shiraki, M., Ouchi, Y., & Orimo, H. (2001). 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 (Burbank, Los Angeles County, Calif.), 17(4), 315–321. https://doi.org/10.1016/s0899-9007(00)00554-2

  12. Schurgers, L. J., Teunissen, K. J., Hamulyák, K., Knapen, M. H., Vik, H., & Vermeer, C. (2007). Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 109(8), 3279–3283. https://doi.org/10.1182/blood-2006-08-040709

  13. Sato, T., L. J. Schurgers, and K. Uenishi. 2012. “Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.” Nutr J no. 11:93. doi: 10.1186/1475-2891-11-93.

  14. Schurgers, L. J., Teunissen, K. J., Hamulyák, K., Knapen, M. H., Vik, H., & Vermeer, C. (2007). Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 109(8), 3279–3283. https://doi.org/10.1182/blood-2006-08-040709

  15. The Medical Benefits of Vitamin K2 on Calcium-Related Disorders – PMC (nih.gov)

  16. https://doi.org/10.1007/s00223-022-00955-3

  17. Vik, H. 2019. “Highlighting The Substantial Body Of Evidence Confirming The Importance Of Vitamin K(2) As A Cardio-Support Nutrient, And How The Right K(2) Makes All The Difference.” Integr Med (Encinitas) no. 18 (6):24-28.

  18. doi:10.1017/S0007114513001013

  19. Halder, M., P. Petsophonsakul, A. C. Akbulut, A. Pavlic, F. Bohan, E. Anderson, K. Maresz, R. Kramann, and L. Schurgers. 2019. “Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.” Int J Mol Sci no. 20 (4). doi: 10.3390/ijms20040896.

  20. doi:10.1017/S0007114513001013

  21. Hariri, E., N. Kassis, J. P. Iskandar, L. J. Schurgers, A. Saad, O. Abdelfattah, A. Bansal, T. Isogai, S. C. Harb, and S. Kapadia. 2021. “Vitamin K(2)-a neglected player in cardiovascular health: a narrative review.” Open Heart no. 8 (2). doi: 10.1136/openhrt-2021-001715.

  22. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health

  23. Roth, Gregory A., et al. “Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019.” Journal of the American College of Cardiology, vol. 76, no. 25, Dec. 2020, pp. 2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010.

  24. Saklayen M. G. (2018). The Global Epidemic of the Metabolic Syndrome. Current hypertension reports, 20(2), 12. https://doi.org/10.1007/s11906-018-0812-z

  25. https://www.pwc.com/gx/en/industries/healthcare/emerging-trends-pwc-healthcare/diy-non-traditional-healthcare.html

  26. Sato, T., L. J. Schurgers, and K. Uenishi. 2012. “Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.” Nutr J no. 11:93. doi: 10.1186/1475-2891-11-93.

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