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Bone Health

Having strong healthy bones is important throughout all stages of life. Insufficient dietary intake of vitamins and minerals may impact on bone quality. Adequate calcium is essential through life and is crucial for strong healthy bones. Inadequate calcium leads to osteopenia or osteoporosis.1 More than 66% of Australians over the age of 50 have poor bone health.2

  • Calcium combines with other minerals to form hard crystals that give bones their strength and structure.3
  • Vitamin D is required for absorption of calcium and phosphorous from the small intestine, extracellular calcium homeostasis and mineralisation of the skeleton.4
  • Vitamin K acts as a coenzyme to the enzyme glutamate carboxylase. This enzyme mediates the conversion of glutamate to gamma carboxyglutamate (Gla-protein). Gla-protein attracts calcium and enhances its incorporation into the hydroxyapatite crystals of the bones. When insufficient vitamin K is available for this process, Gla-protein cannot be carboxylated and has limited ability to bind calcium and aid in bone metabolism.5

Calcium Balance in the Body

Just as insufficient dietary calcium may lead to weak, brittle bones, excess calcium in the body may contribute to cardiovascular conditions.

Some questions have been raised over a possible connection between calcium supplementation and increased cardiovascular risk due to vascular calcification.6 The body contains many proteins including osteocalcin and matrix Gla-protein (gamma carboxyglutamate), which regulate calcium balance.78 Both calcification activity and MGP (matrix Gla Protein) activity are correlated with vitamin K2 intake.9

The Role of Vitamin K

Vitamin K is a fat-soluble vitamin that the body stores in the liver and fat cells. It is available in three forms:10

  • Vitamin K1, phylloquinone is produced by green vegetables such as broccoli, kale, spinach, cabbage, dark green lettuce and asparagus.
  • Vitamin K2, menaquinone (MK-7) may be produced in the intestines by bacteria and also found in some foods - cheese, natto, liver. Vitamin K2 is generally absent from the western diet. 11
  • Vitamin K3, menaphthone or menadione a synthetic form.12

All three forms are metabolically activated in the liver to become co-factors in the activation of vitamin K-dependent proteins that are important for normal blood coagulation, and normality of bones and arteries (Gla-proteins).12 The only structural difference between vitamin K1 and K2 is the side chain. Vitamin K2 has side chain of repeating isoprenoid units (phytyl side-chain). The common bioactive region (menadione comprising a methylated naphthoquinone ring) of both K1 and K2 molecules is identical. It is understood that vitamin K2 is more resistant to hepatic metabolism allowing vitamin K2 to travel systemically in the body to other tissues.1314

Vitamin K114

Vitamin K114

Vitamin K1 Phylloquinone

Vitamin K was first identified as an essential vitamin required for blood clotting through acting as a cofactor in the normal biosynthesis of several plasma blood clotting factors (factors II, VII, IX and X).15 Vitamin K1 appears to have a short half-life of one-two hours,15 needing to be replaced through the diet regularly.15

Vitamin K2 Menaquinone-7 (MK-7)

Vitamin K supports the body’s calcium balance for strong bones and is thought to play an integral role in calcium absorption into the bone.161718 Vitamin K2 optimises the calcium balance by activating osteocalcin and matrix Glaprotein.171819 When vitamin K status is inadequate, these two proteins are not carboxylated as they would normally be, and therefore, have limited ability to bind to calcium and aid in bone mineralisation.19

People at risk for developing vitamin K deficiency include those with chronic malnutrition (including those with alcohol dependency) or conditions that limit absorption of dietary vitamins, such as various gut issues.20

Who benefits from Vitamin K2

Vitamin K2 (MK-7) is well-absorbed and has a longer half-life than vitamin K1, remaining in the body for approximately 72 hours.12 Both calcification activity and MGP (matrix Gla Protein) activity are correlated with vitamin K2 intake8, however larger interventions with longer follow-up will further clarify the role of vitamin K2 in optimising calcium balance.

In young healthy people (20 to 40 years old) and older people (60 to 80 years old) an increase in daily intake of vitamin K for 5 days from 100 to 420 μg, reduced the undercarboxylated fraction of ostecalcin by 40%.21

Studies of postmenopausal women who have taken vitamin K2, show beneficial effects on bone health. One placebocontrolled study examined the effect of fortified dairy products on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Each intervention group provided 800mg calcium, and 10μg of vitamin D while two were also enriched with 100μg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). This study showed more favourable changes on bone metabolism and bone mass indices for the CaDK2 (as well as CaDK1) supplemented group compared to the group receiving calcium and vitamin D only.22

Another placebo-controlled study conducted over a three year period resulted in a decrease in age-related decline in bone mineral content and density at the lumbar spine and femoral neck with MK-7 intake. Bone strength was also favourably affected and there was a significant decrease in the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.23

Cautions

Changes to vitamin K intake (from diet and/or supplementation) may interfere with the action of warfarin and other vitamin K antagonists.24

Recommended Adult Daily Dose

  • General bone health: 90mcg
  • To reduces bone loss in postmenopausal women: 180mcg

Summary

  • More than 66% of Australians over the age of 50 have poor bone health
  • The presence of Vitamin K2 is generally absent from the western diet
  • Vitamin K2 is more bio available than Vitamin K1
  • Vitamin K2 helps to support/maintain:
    • calcium balance in the body
    • activate osteocalcin, a protein which regulates calcium in bone turnover
    • bone strength by transferring calcium to where it is needed most
    • optimise delivery of calcium into the bones

References

  1. Osteoporosis Australia. Statement on Calcium Supplements. 2013
  2. Watts J.J. et al. Osteoporosis Australia. Osteoporosis costing all Australians, A new burden of disease analysis. 2012: 1-80
  3. Osteoporosis Australia. Calcium Consumer Handout. 2013;1-4
  4. Australian Council for Responsible Nutrition (ACRN). Vitamin & Minerals: Functions & Safety. 1998. pp.11-12.
  5. Bugel S. Vitamin K and bone health. Proceedings of the Nutritional Society. 2003;62:839-843
  6. Reid I. Cardiovascular Effects of Calcium SupplementsNutrients 2013;5:2522-29
  7. Flore R et al. Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis. Eur Rev Med Phamacol Sci. 2013; 17: 2433-2440
  8. Booth S L et al. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat. Rev. Endocrinol. 2013; 9: 43–55
  9. Schurgers L.J. et al. Matrix Gla-protein: The calcification inhibitor in need of vitamin K. 2008: 100: 593–603
  10. University of Maryland Medical Centre. Vitamin K. 2013, URL access: http://umm.edu/health/medical/altmed/supplement/vitamin-k
  11. MenaQ7. URL access: http://menaq7.com/index.php?page=sources
  12. European Food Safety Authority. Scientific Opinion on the safety and efficacy of vitamin K3 (menadione sodium bisulphite and menadione nicotinamide bisulphite) as a feed additive for all animal species. Journal; 2014; 12(1) 1-29
  13. Schurgers et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone. 2007; 109(8): 3279-3283
  14. Goodman and Gilman’s Pharmacological Basis of Therapeutics (1993) p. 1563.
  15. 15 FAO. Agriculture and Consumer Protection. 2014 URL access: http:// www.fao.org/docrep/004/Y2809E/y2809e0g.htm
  16. 16 Dalmeijer et al. The effect of menaquinone-7 supplementation on circulating species of matrix Gla Protein 2012; 225(2): 397-402.
  17. Dalmeijer et al. Circulating desphospho-uncarboxylated matrix c-carboxyglutamate protein and the risk of coronary heart disease and strokeJ Nutr Biochem 2014; 24(4): 624-8.
  18. Theuwissen et al. The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Br J Nutr 2012;108(9):1652-7.
  19. Linus Pauling Institute. Vitamin K. Oregan State University. 2014;
  20. Natural Standard Database. Vitamin K. 2014
  21. Schaafsma, et al. Delay of Natural Bone Loss of Higher Intakes of Specific Minerals and Vitamins. Critical Reviews in Food Science and Nutrition. 2001; 41(3):225-249
  22. Kanellakis et al. Changes in Parameters of Bone Metabolism in Postmenopausal Women Following a 12-Month Intervention Period Using Dairy Products Enriched with Calcium, Vitamin D, and Phylloquinone (Vitamin K1) or Menaquinone-7 (Vitamin K2): The Postmenopausal Health Study II Calcif Tissue Int 2012; 90:251-62.2.
  23. Knapen et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis Int 2013;24(9): 2499-507
  24. National Institues of Health. Important drug and food information: Warfarin and Vitamin K. URL access: http://www.cc.nih.gov/ccc/patient_ education/drug_nutrient/coumadin1.pdf.
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