Vitamin K

Vitamin K The wellness vitamin

Vitamin K2 is an essential fat-soluble vitamin that directs calcium to the right places in the body. K2VITAL® K2 MK-7, the superior form of K2, activates the osteocalcin proteins that incorporate calcium to bones, and the matrix-Gla proteins (MGP) that bind calcium to prevent deposits in arteries and smooth muscle walls. K2VITAL® is offered in a range of formulations, including microencapsulated K2VITAL® DELTA for excellent K2 stability in mineral formulations.

Ahhealthy cardiovascular system affects personal well-being far beyond the prevention of serious cardiovascular disease. Clean, flexible arteries and blood vessels that can deliver nutrient-rich blood whenever and wherever it’s needed are the cornerstone of health and well-being. Whether you’re participating in a fun run, playing with the kids or just carrying the groceries into the house, our bodies make certain demands in response to physical activity. Soft, flexible arteries that expand during exercise improve blood flow and increase oxygenation for sustained energy. This not only helps us perform the activity, but also affects how we feel while doing it.

AUTHOR: Mathilde Pinon, Marketing Manager, Kappa Bioscience If some degree of hardening is normal and affects the body’s response to physical activity, what does this say about the potential benefits of vitamin K2 MK-7? Can vitamin K2 have a decisive effect on the vitality and well-being of otherwise healthy individuals?

Heart & Blood - Engine and Fuel of our Life

Oxygen is a nutrient. It supplies the muscles and tissues with energy. During physical exertion - whether climbing stairs or crossing the finish line - more oxygen is needed. A healthy heart and a clean, flexible circulatory system can meet these intermittent demands placed by increased physical activity. They provide the body with oxygenated blood where and when it is needed. However, the mineral calcium can disrupt this system. While calcium determines the health of bones and teeth, it also has a drawback. When there is too much calcium in the body, it can build up in the form of calcium plaques in the arteries and blood vessels. However, according to studies, calcifications and vascular hardening develop gradually in a process measured over several decades. Initial signs of arterial calcification have been noted in otherwise healthy children. Studies have shown that nearly 30 percent of the U.S. population over the age of 452 suffers from calcium deposits on arterial walls. This condition typically worsens with aging3 . What does it mean? That there is a realistic likelihood that individuals who are actually far from being in the risk group for CVD, or who have not yet reached the age of risk for

CVD, may suffer some degree of arterial stiffness and loss of flexibility. Arteries and blood vessels may lose their stretching ability. This results in decreased blood flow when the body needs to supply more oxygen to the tissues. In this case, not only is there too little oxygen available, but the heart must work harder to pump blood through the blood vessels, which are stiff and reduced in diameter. In purely unscientific terms, we would describe or perceive this condition as “weak endurance.” It can prevent us from pursuing desired activities at the desired time and also affect how we feel about those activities. Calcium and age-related hardening of the arteries would therefore affect our own well-being in accomplishing or perceiving our everyday tasks and opportunities.

K2: The wellness vitamin

The role K2 plays in promoting wellness starts early and is not limited to benefits for our heart. K2 activates osteocalcin. This protein ensures that calcium reaches the bones. K2 ensures healthy bone growth in our childhood. This begins in the womb. Throughout our lives, K2 helps maintain strong bones. It keeps our bodies robust and resilient while protecting us from diseases such as osteoporosis.

But what happens when we consume too much calcium due to our diet, dietary supplements or environmental factors (e.g. due to elevated calcium levels in drinking water)? How does Vitamin K2 restore the “calcium balance” to ensure that we can reap its benefits for good bone health while avoiding its negative effects on the cardiovascular system? Vitamin K2 MK-7 activates another protein that plays a crucial role in a healthy cardiovascular system. Vitamin K2 is indispensable for the activation of the calcium-binding protein matrix Gla protein (MGP)4. After activation of MGP by K2, MGP binds the excess calcium floating freely in the blood, preventing it from being deposited in the circulatory system5. Calcium-free arteries and vessels remain soft and flexible. They are ready to adapt to the demands of increased oxygen supply and increased blood flow due to physical activity.

The science of K2 and a healthy circulatory system

Various studies show a clear link between K2 and arteriosclerosis. High levels of unactivated MGP in the blood are associated with vitamin K deficiency and also with arterial calcification. In healthy adults, levels of unactivated MGP are related to age5, with people at increased risk for arterial calcification having greater amounts of unactivated MGP in their blood. Non-activated MGP inversely correlates with dietary low intake of vitamin K. Correlations between non-activated MGP and (lower) survival from HKL disease highlight the importance of MGP activation6. In a stud y of 577 elderly subjects, nonactivated MGP was associated with an increased risk of cardiovascular disease, and this risk was again attributed to low vitamin K levels7. Taken together, these studies show that high levels of unactivated MGP (with K2-dependent activation) are associated with vascular calcification. However, further studies show that K2 supplements cause a significant decrease in unactivated MGP in healthy individuals8-10. In addition, vitamin K2 provides significant enhancement of carboxylation (activation) of MGP in healthy adults at doses of 90µg and above. Finally, one study showed that the level of activated MGP increased significantly after taking vitamin K2 MK-7 at doses close to the recommended daily allowance (RDA 90µg and above)11 .

Prevent calcification? Yes. But how can it be reversed?

K2VITAL® vitamin K2 MK-7 activates matrix Gla protein, which prevents calcification by binding excess calcium. But can it also reverse them? Can K2 restore flexibility to vessels and arteries, restoring them to their previous state of health and thus improving the body’s ability to carry blood and oxygen optimally? If so, surely vitamin K2 could actually “turn back time” by restoring the body’s ability to respond to physical activity. The role that vitamin K2 plays in prevention is supported by two large studies. Through the study conducted with more than 4,800 men and women in Rotterdam, it is shown that the risk of HKL disease and mortality risk are dramatically reduced with a diet rich in vitamin K2 . A study of more than 16,000 subjects has shown an inverse correlation between K2 intake and risk of coronary heart disease, with mortality risk reduced by 9% with each additional 10µg/day intake13 . However, the Knapen study conducted in 2015 most clearly proves that calcification can be reversed. It has shown that a high intake of vitamin K2 MK-7 is related to the reduction of arterial calcification. It has further shown that existing arterial stiffness decreased (was reversed) within the test group over a 3-year period, while it increased in the placebo group14. The vitamin K2 used in the Knapen study is equivalent to K2VITAL®15 . While many K2 studies have been conducted with average healthy, elderly or sick individuals, studies with healthier individuals have just begun. A study conducted in 2017 with highly trained athletes showed a 12% increase in performance, as measured by cardiac output, after taking the K2 MK-7 supplement for a period of just 8 weeks16. This increase is impressive considering that the basis of measurement is likely higher in trained athletes compared to average individuals, making it more difficult to determine the differences. Although the exact mechanisms of the results obtained with K2 need to be further explored, this study provides good evidence that vitamin K2 can impact the factors that ultimately influence our personal well-being.

An enormous market opportunity

K2 is one of only a few essential vitamins, and they are not discovered every day. Although K2 was discovered several decades ago, its importance to bone and heart health has only recently been understood. While K2 is found in some meats and cheeses, as well as certain fermented foods, most Western diets are considered to be low in K217. However, the greatest commercial advantage of K2 is its applicability across many different consumer and market catego-

ries. Both men and women need vitamin K2 at all ages, from childhood through the teenage and adult years and into old age. In children, K2 is important for the development of strong bones. Teenagers need it during their growth spurts. And for women, it’s (especially) important so they can build strong, maximum bone density to prevent future bone disease. Both sexes benefit from the cardiovascular benefits K2 provides. While this article focuses more on K2 in the area of wellness products, equally strong, if not stronger, arguments can be made for “healthy aging,” “women’s health,” “sports nutrition,” and other areas. From the general nutritional deficiency and the wide range of applications in diverse product and consumer categories, the market potential is enormous. Vitamin K2 provides additional health benefits when combined with four of the five key ingredients in dietary supplements - calcium, magnesium, omega-3 and multivitamin blends. Innovative dosage forms extend the reach of K2 beyond traditional tablets and capsules. Since K2 holds great promise for the “sports nutrition” and “active lifestyle” categories, it will most likely make a breakthrough here by being used as a fortifier in dairy products such as milk, yogurt, probiotic drinks, and sports drinks and bars. The development of light-strength provitamin K2 will only increase the use and acceptance of K2 in active lifestyle products.

Arguments in favor of K2 as a wellness vitamin

The benefits that K2 provides to the cardiovascular system through the activation of MGP are very promising for improving the overall health and well-being of healthy, active people. K2 prevents and reverses calcification in the circulatory system. This allows the body to meet the increased oxygen demands associated with physical activity. The increased endurance experienced during athletic or everyday physical activities can lead to an improved perception of overall well-being in healthy individuals. The market potential for K2 is enormous, whether it is used in the consumer segment, in the market category, or as an additional ingredient in formulations.

References:

1 Greenland, P., et al, ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/

AHA Writing Committee to Update the 2000 Expert Consensus

Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and

Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol, 2007. 49(3): p. 378-402. 2 Image, D.E., et al, Ethnic differences in coronary calcification: the

Multi-Ethnic Study of Atherosclerosis (MESA). Circulation, 2005. 111(10): p. 1313-20. 3 IIribarren, C., et al, Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA, 2000. 283(21): p. 2810-5. 4 Dalmeijer, G.W., et al, Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care, 2013. 36(11): p. 3766-71.

Haemost, 2010. 104(4): p. 811-22. 6 Ueland, T., et al, Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med, 2010. 268(5): p. 483-92. 7 van den Heuvel, E.G., et al, Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas, 2014. 77(2): p. 137-41. 8 Cranenburg, E.C., L.J. Schurgers, and C. Vermeer, Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost, 2007. 98(1): p. 120-5. 9 Schurgers, L.J., et al, Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 2007. 109(8): p. 3279-83. 10 Theuwissen, E., et al, Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr, 2012. 108(9): p. 1652-7.

11 Theuwissen, E., et al, Vitamin K status in healthy volunteers. Food

Funct, 2014. 5(2): p. 229-34. 12 Geleijnse, J.M., et al, Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam

Study. J Nutr, 2004. 134(11): p. 3100-5. 13 Gast, G.C., et al, A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis, 2009. 19(7): p. 504-10. 14 Knapen, M.H., et al, Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost, 2015. 113(5): p. 1135-44. 15 Moller, M., et al, Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised

Controlled Trials. Int J Vitam Nutr Res, 2016: p. 1-15. 16 McFarlin, B.K., A.L. Henning, and A.S. Venable, Oral Consumption of

Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise. Altern Ther Health Med, 2017. 23(4): p. 26-32. 17 Vermeer, C., Vitamin K: the effect on health beyond coagulation - an overview. Food Nutr Res, 2012. 56.

Kappa Bioscience AS is the pioneer in development and production of biologically active all-trans menaquinone-7 (vitamin K2 MK-7), marketed under the K2VITAL® brand name. Kappa’s innovation of MK-7 synthesis marks the commercial milestone to attain widespread consumer adoption. Effective synthesis production drives scalability, price reduction and a secure supply chain - with unmatched ingredient purity and documentation. Combined with other Kappa innovations such as the patented K2VITAL® DELTA microencapsulation process, which provides K2 stability in mineral formulations, K2VITAL® offers brands and manufacturers a path to broader market segments.

www.kappabio.com

Vita Nova is the official representative of renowned foreign producers of the highest quality raw materials for the pharmaceutical and food industry, with a special focus on raw materials for food supplements. The offer includes minerals and mineral salts, vitamins and vitamin mixtures, plant extracts, emulsifiers and stabilizers, produced using the latest technologies throughout Europe. Vita Nova also offers its customers cooperation in the field of new product development and knowledge of the application of raw materials in production processes. www.vitanova.com.mk