When form meets function:

delivering proven bone and cardiovascular support

Every hour in South Africa, five people have heart attacks and ten people have strokes, leading to ten fatalities. This is according to the Heart and Stroke Foundation South Africa1 .

The National Osteoporosis Foundation of South Africa also estimates that one in three South African women and one in five South African men could develop osteoporosis in their lifetime. This means that potentially between 4 and 6 million South Africans suffer from compromised bone health.2

What would happen if we could promote bone health while simultaneously protecting our cardiovascular health simply by taking a vitamin?

Vitamin K2 as MK-7 (menaquinone-7) is a newly-recognised vitamin shown in clinical studies to support bone and cardiovascular health by activating proteins that help the body properly utilise calcium. Unfortunately, it is nearly impossible to obtain this vital nutrient from diet alone, leaving 97% of the Western population deficient3, making supplementation a viable alternative.

WHAT IS VITAMIN K2?

The supplement consists of a family of vitamins comprised of vitamin K1 (phylloquinone) and vitamin K2 (menaquinone). Phylloquinone and menaquinone share similarities, such as working in the liver for blood clotting; and chemically share a quinone ring called menadione. This is, however, where similarities end.

Vitamin K2 has several molecules, called menaquinones, which are available beyond the liver for other systems such as bones and heart. There are actually multiple forms of K2, but the two most common forms as dietary supplements are K2 as MK-4 (menaquinone-4) and K2 as MK-7 (menaquinone-7). Vitamin K2 as MK-7 is superior since it requires a single daily microgram dose and works for 72 hours compared to K2 as MK-4 that requires multiple daily milligram intakes and works for only 90 minutes.4,5

THE K2 MECHANISM

Vitamin K2 activates vitamin K-dependent proteins (VKDP) already present in the body. Most of the research focuses on two VKDPs: • Matrix Gla Protein (MGP) inhibits calcium from depositing in arteries and soft tissues; • Osteocalcin (OC) binds calcium to the bone mineral matrix for a stronger skeleton and dentin.

For these proteins to do their jobs, they must first be activated by Vitamin K2. The more incoming calcium, with no or not enough vitamin K2, the more likely it will be deposited into arterial blood vessels, increasing cardiovascular risks. When the body has enough K2, it accelerates MGP’s activity of transporting incoming calcium out of arteries and boosting OC’s bone remodeling activity.6,7

FOOD SOURCES

The body cannot synthesise K vitamins (just small levels in the intestine), so people are mainly dependent on regular food intake.

Vitamin K1 is found in leafy green vegetables such as spinach and kale. However, K1 from food is very poorly absorbed – only about 10% of it reaches the circulation, meaning a small amount can reach peripheral parts of the body. Moreover, the liver takes what it needs of K1 with little left for other tissues.

Add to this a common misconception that if one eats plenty of green leafy vegetables, they are getting plenty of vitamin K2.

Natural vitamin K2 is produced during bacterial fermentation and is present in food such as cheese (the most popular Western source). These products contain relatively small levels, which would require consuming large amounts. The best source of natural vitamin K2 as MK-7 is the traditional Japanese dish natto. Several studies link natto consumption in Japan to significant improvement in K vitamins status and bone health8,9. But the dish is rarely consumed outside of Japan, and there are clear indications that Western populations have insufficient intake of vitamin K2 from their regular diets; hence supplementation is a viable alternative.

PROVEN BONE BENEFITS

Vitamin K2 supports bone health due to its activation of OC. This has been established in a raft of studies, highlighted by a breakthrough double-blind, randomised clinical trial published in Osteoporosis International using a specific K2 as MK-7 called MenaQ7.

The study demonstrated for the first time clinically statistically significant protection of the vertebrae and the hip (femoral neck) against bone loss. This was attained with a nutritional dose (180mcg) of K2 as MK-7 taken daily for three years.

In this study of 244 healthy postmenopausal women, the K2 group showed significantly decreased circulating uncarboxylated OC (ucOC). After three years, both bone mineral content and bone mineral density and bone strength were statistically significantly better for the MK-7 group than the placebo group.10

Vitamin K2’s importance in impacting bone health is not limited to adult populations. In fact, it is a noteworthy bone support nutrient for children due to their bones taking shape: • 2009: Healthy children aged 6 to 10 years who took 45mcg of K2 (as MenaQ7) a day resulted in more active OC, leading to stronger, denser bones.11 • 2012: Children and adults over the age of 40 express the greatest K deficiency and had the strongest response to K2 supplementation (45mcg for children; 90mcg for adults; both as MenaQ7).12 • 2013: Children and teens given MenaQ7

K2 (50mcg) and vitamin D (5mcg calcitriol) daily showed improvements in bone mineral density.13

A NEWLY-ESTABLISHED CARDIOPROTECTIVE NUTRIENT

The most substantial body of growing evidence shows vitamin K2’s positive impact on and support for cardiovascular health.

Previous population-based studies have shown an association between K2 intake and cardiovascular risk14,15. Validation for its cardiovascular benefits culminated with the publication of another three-year study using MenaQ7, the first intervention trial focused on K2 as MK-7 supplementation with cardiovascular endpoints.

Using the same cohort as the threeyear bone study, researchers monitored subjects using pulse wave velocity (PWV) and ultrasound techniques. The participants were randomly assigned to take 180mcg of K2 daily for three years or placebo capsules. Results confirmed that K2 as MK-7 inhibited age-related stiffening of the artery walls and made an unprecedented statistically significant vascular elasticity improvement.16

These results were corroborated recently in a separate one-year placebocontrolled randomised clinical trial that showed that 180mcg/day of K2 (MenaQ7) improved vascular health in male and female participants with poor K status, as measured by dp-ucMGP (inactive MGP). Regardless of the participants’ gender, the K2 group maintained arterial flexibility and the stiffness did not increase, whereas the placebo group became stiffer and less flexible.17

Vitamin K2 as MK-7 is the only compound to date shown to impact arterial calcification through its activation of MGP. Thus, the medical community is beginning to explore it as a potential therapy for patients whose conditions present symptoms of intense calcification.

CONCLUSION

Vitamin K2 as MK-7 is the superior vitamin K, safely and effectively delivering benefits for children and adults, serving as an essential companion for calcium supplementation. By implementing this simple nutritional strategy, the population can simultaneously support their bone health while protecting themselves from cardiovascular risks. And the only vitamin K2 as MK-7 proven to deliver bone and heart support is MenaQ7. •

References:

1 https://www.heartfoundation.co.za/ wp-content/uploads/2017/10/CVD-StatsReference-Document-2016-FOR-MEDIA-1.pdf 2 https://osteoporosis.org.za 3 Shea MK, et al. Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery Calcium, in older adults. J Nutr. 2011 Aug;141(8):1529-34. 4 Rheaume-Bleue, Kate. 2013. Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life. Harper; Reprint edition. 5 Howard, Larry M, Payne, Anthony G. 2006. Health Benefits of Vitamin K2: A Revolutionary Natural Treatment for Heart Disease and Bone Loss. 1st edition. Basic Health Publications, Inc. 6 Schurgers LJ, Cranenburg EC, Vermeer C. 2008. Matrix gla-protein: the calcification inhibitor in need of vitamin K. Thrombosis and Haemostasis, 100(4): 593-603. 7 Tsugawa N, et al. 2006. Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am J Clin Nutr, 83(2): 380-86. 8 Kaneki M, 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. 17 (4), 315–321 (2001). 9 Ikeda Y, et al. Intake of Fermented Soybeans, Natto, Is Associated with Reduced Bone Loss in Postmenopausal Women: Japanese Population-Based Osteoporosis (JPOS) Study. J. Nutr. 136 (5), 1323–1328 (2006). 10 Knapen MHJ, et al. Three-Year LowDose Menaquinone-7 Supplementation Helps Decrease Bone Loss in Healthy Postmenopausal Women. Osteoporosis Int. 24 (9), 2499–2507 (2013). 11 van Summeren, et al. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br J Nutr (2009) 102(8): 1171-8. 12 Theuwissen E, et al. Vitamin K Status in Healthy Volunteers. Food Funct.5 (2), 229–234 (2014). 13 Ozdemir MA, et al. The Efficacy of Vitamin K2 and Calcitriol Combination on Thalassemic Osteopathy. J. Pediatr. Hematol. Oncol. 35 (8), 623–627 (2013). 14 Geleijnse JM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004, 134(11):3100-5. 15 Gast GC, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009, 19:504-10. 16 Knapen MHJ, et al. 2015. Menaquinone-7 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women: DoubleBlind Randomised Clinical Trial, Thrombosis and Haemostasis, 113(5): 1135-1144. 17 Vermeer C and Vik H. Effect of Menaquinone-7 (vitamin K2) on vascular elasticity in healthy subjects: results from a one-year study. 2020 Vascul Dis Ther, 5: doi: 10.15761/VDT.1000179.

About the author: Dr. Hogne Vik is the chief medical officer of NattoPharma ASA, Norway.

Brentag – www.brenntag.com/en-za/