Doctor's Formulas Vitamin K2 120caps - For bone strength & density

Bones consist of living tissue, just as the kidneys, the heart, and other organs of the body are. They are made up of a hard outer layer and inner spongy layer tissue, which continuously remodels and redevelops.

Throughout the duration of our life, bones continuously go through a process of deconstruction and reconstruction so as to adjust to new mechanical conditions that are created over time.This continuous reconstruction is two-fold i) aims at the restoration and preservation of the anatomical and functional integrity of the bones, repairing any damage that has occurred – damage which is very frequent and ii) aims towards the maintenance of maximum bone density.  Therefore, in a period of 9 to 10 years, a complete replacement of all bone tissue may have taken place. This process of restoration of deteriorated bone mass with new bone is referred to as "reconstruction".

The bones are never found in metabolic inertia. A condition of bad bone metabolism is a condition characterized by the loss of bone density and leads to weaker bones and bones that are more prone to fractures. This metabolic process is largely regulated by osteoblasts (cells that synthesize bone tissue) and osteoclasts (cells that breakdown bone tissue).

Osteoblasts produce a protein called Osteocalcin. This is a Vitamin K - dependent protein which binds the calciumto the bonematrix and builds healthy bones. Osteocalcin though also needs adequate amounts of vitamin K2 to be enabled. When the analogy of the bone constructing process is greater than the bone deconstruction process then the maintenance of healthy bones is kept under control.However, when this delicate process is disturbed, bones become weak and brittle. The strong connection between vitamin K2 deficiency and impaired bone health has been proven both in laboratory and clinical studies. It has been found out that a vitamin K2 deficiency leads to a decreased level of activated osteocalcin which in turn increases the risk of brittle bones.

K2 is a cofactor for an enzyme called γ - glutamyl carboxylase.  In cases where there is an insufficient supply of K2, the enzyme is not triggered for the biochemical reaction of carboxylation. Carboxylation triggers a number of proteins that are essential for healthy bones. If Vitamin K2 doesn’t activate the enzyme that activates the proteins that regulate where calcium will be deposited, the proteins don't function properly. This results in calcium being deposited inthe arteries, kidneys, heart, etc. and not in the bones.These proteins are called gamma-carboxyglutamic acid containing proteins or Gla-proteins. One of these is osteocalcin whose purpose is to attract the calcium ions that are circulated and then deposit them in the bones ashydroxyapatite minerals. If a small amount of osteocalcin is activated, then only a very little amount of the available calcium in circulation will result in it being deposited inthe bones.

K2 is also responsible for the activation of another basic protein called matrix gla - protein which prevents the deposition of calcium in soft tissues. When K2 is very low, this protein remains inactive.Therefore, the calcium that we consume and need for it to be deposited in the bones oppositely ends up being deposited in unwanted places in the body. Subsequently, it becomes calcified and isn’t recycled.  Bones store calcium and release it for the body’s needs, contain bone marrow tissue and along with the liver and spleen is the main organ for red and white cell formation.

Calcium,hematopoietic tissue and energy are all stored in bone tissue hence making the bones essential organs for the survival and functionality of individual.

VITAMIN K2 Formula is a nutritional supplement containing both vitamin K2 and vitamin C.

Vitamin K2 contributes to the maintenance of normal bone density, while Vitamin C contributes to the normal collagen formulation, the normal functioning of blood vessels, bone and cartilage.

Bibliography: 1. Knapen, M.H.J., Schurgers, L.J., Vermeer, C. Vitamin K2 supplementation improves bone geometry and bone strength indices in postmenopausal women. Osteoporosis Int. 18 (2007) 963-972. 2. Vitamin K2: a novel therapy for osteoporosis. 3. Prabhoo R, Prabhoo TR.J Indian Med Assoc. 2010 Apr;108(4):253-4, 256-8. 4. Effect of vitamin K in bone metabolism and vascular calcification: a review of mechanisms of action and evidences. 5. Villa JK, Diaz MA, Pizziolo VR, Martino HS. 6. Crit Rev Food Sci Nutr. 2016 Jul 20:0. 7. Plantalech L, Guillaumont M, Vergnaud P, Leclercq M,Delmas PD. Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women. J Bone Miner Res. 1991;6(11):1211-6. 8. Van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C. Pronounced elevation of undercarboxylated osteocalcin in healthy children. 9. Pediatr Res.2007;61(3):366-70. 10. [ Prynne CJ, Thane CW, Prentice A, Wadsworth ME. Intake and sources of phyllo-quinone (vitamin K(1)) in 4-year-old British children: comparison between 1950 and the 1990s. 11. Public Health Nutr. 2005 Apr;8(2):171-80. 12. Suttie JW. The importance of menaquinones in human nutrition. Annu Rev Nutr. 1995;15:399-417. 13. Booth SL, Suttie JW. Dietary intake and adequacy of K vitamins. J Nutr. 1998;128(5):785-8. 14. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. 15. Maresz K. Integr Med (Encinitas). 2015 Feb;14(1):34-9. 16.Review. 15. Comparison of the effects of 12 months of monthly minodronate monotherapy and monthly minodronate combination therapy with vitamin K2 or eldecalcitol in patients with primaryosteoporosis. 16. Ebina K, Noguchi T, Hirao M, Kaneshiro S, Tsukamoto Y, Yoshikawa H. J Bone Miner Metab. 2016 May;34(3):243-50. doi: 10.1007/s00774-015-0710-2. Epub 2015 Aug 25. 17. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausalwomen: a meta-analysis of randomized controlled trials. 18. Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. 19.Osteoporos Int. 2015 Mar;26(3):1175-86. doi: 10.1007/s00198-014-2989-6. Epub 2014 Dec 17. 20. Assessment of vitamin K2 levels in osteoporotic patients: a case control study. 21. Noori A, Lashkari M, Oveisi S, Khair Khah MR, Zargar A. 22. Glob J Health Sci. 2014 Jul 14;6(6):82-7. doi: 10.5539/gjhs.v6n6p82. 23. Vitamin K₂therapy for postmenopausal osteoporosis. 24. Iwamoto J. Nutrients. 2014 May 16;6(5):1971 80. doi: 10.3390/nu6051971. Review. 25. Effects of gamma-glutamyl carboxylase gene polymorphism (R325Q) on the association between dietary vitamin K intake and gammacarboxylation of osteocalcin in young adults. 25. Haraikawa M, Tsugawa N, Sogabe N, Tanabe R, Kawamura Y, Okano T, Hosoi T, Goseki-Sone M.Asia Pac J Clin Nutr. 2013;22(4):646-54. doi: 10.6133/apjcn.2013.22.4.01. 25. Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis. 26. Flore R, Ponziani FR, Di Rienzo TA, Zocco MA, Flex A, Gerardino L, Lupascu A, Santoro L, Santoliquido A, Di Stasio E, Chierici E, Lanti A, Tondi P, Gasbarrini A. 27. ur Rev Med Pharmacol Sci. 2013 Sep;17(18):2433-40. Review. 28. Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis. 29. Kasukawa Y, Miyakoshi N, Ebina T, Aizawa T, Hongo M, Nozaka K, Ishikawa Y, Saito H, Chida S, Shimada Y. 30. J Bone Miner Metab. 2014 May;32(3):290-7.doi: 10.1007/s00774-013-0490-5. Epub 2013 Jul 12. 31. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. 32. Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y.J Bone Miner Metab. 33. 2014 Mar;32(2):142-50. doi: 10.1007/s00774-013-0472-7. Epub 2013 May 24. 34. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthypostmenopausal women. 35.Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23. 36. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. 37. Ebina K, Shi K, Hirao M, Kaneshiro S, Morimoto T, Koizumi K, Yoshikawa H, Hashimoto J.Mod Rheumatol. 2013 Sep;23(5):1001-7. doi: 10.1007/s10165-012-0789-4. Epub 2012 Nov 6. 38. [Vitamin K2]. Ishida Y. 39. Clin Calcium. 2008 Oct;18(10):1476-82. doi: CliCa081014761482. Review. Japanese. Update on the role of vitamin K in skeletal health. 40. Shea MK, Booth SL. 41. Nutr Rev. 2008 Oct;66(10):549-57. doi:10.1111/j.1753-4887.2008.00106.x. Review. 42. Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Iwamoto J, Takeda T, Sato Y. 43. Curr Drug Saf. 2006 Jan;1(1):87-97. Review 44. Osteoclast inhibitory effects of vitamin K2 alone or in combination with etidronate or risedronate in patients with rheumatoid arthritis: 2-year results. Morishita M, Nagashima M, Wauke K, Takahashi H, Takenouchi K. 45. J Rheumatol. 2008 Mar;35(3):407-13. Epub 2008 Feb 1. 46. Vitamin K2 supplementation improves hip bone geometry and bone strength indices inpostmenopausal women. Knapen MH, Schurgers LJ, Vermeer C. 47. Osteoporos Int. 2007 Jul;18(7):963-72. Epub 2007 Feb 8. 48. Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women. 49. Yasui T, Miyatani Y, Tomita J, Yamada M, Uemura H, Miura M, Irahara M. 50. Gynecol Endocrinol. 2006 Aug;22(8):455-9. 51. Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. 52. Purwosunu Y, Muharram, Rachman IA, Reksoprodjo S, Sekizawa A. J Obstet Gynaecol Res. 2006 Apr;32(2):230-4. 53. Vitamin K in the treatment and prevention of osteoporosis and arterial calcification. 54. Adams J, Pepping J. Am J Health Syst Pharm. 2005 Aug 1;62(15):1574-81. 55. Review [Vitamin K2 and bone quality]. Kobayashi M, Hara K, Akiyama Y. Clin Calcium. 2005 Jul;15(7):49-55. Review.Japanese Vitamin K2 in bone metabolism and osteoporosis. 56. Plaza SM, Lamson DW. Altern Med Rev. 2005 Mar;10(1):24-35. Review Effects of vitamin K2 on osteoporosis. 57. Iwamoto J, Takeda T, Sato Y. Curr Pharm Des. 2004;10(21):2557-76. 59. Review Vergnaud P, Garnero P, Meunier PJ, Bréart G, Kamihagi K, Delmas PD. 60. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. J Clin Endocrinol Metab. 1997;82(3):719-24. [17] Booth SL, Broe KE, Peterson JW, Cheng DM, Dawson-Hughes B, Gundberg CM, Cupples LA, Wilson PW, Kiel DP. Associations between K vitamins biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab. 61. 2004;89(10):4904-9. [18] Knapen MH, Nieuwenhuijzen Kruseman AC, Wouters RS, Vermeer C. Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. 62. Calcif Tissue Int. 1998;63(5):375-9. [19] Schurgers LJ,Knapen MH, Vermeer C. K vitamins2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Int. Congr.Series 2007; 179-187. 63. [20] Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. 64. Osteoporos Int. 2007;18(7):963-72. [21] Knapen M. H. J., N. E. Drummen, E. Smit, C. Vermeer, E. Theuwissen. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507.

Notification number of the European Medicines Agency (EMEA): 50992 / 23-06-2016. The notification number in the European Medicines Agency (EMEA) does not serve as a distribution permit from the European Medicines Agency (EMEA).