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Vitamin K-2 (180 ug MK-7) helped both bone density and strength – RCT March 2013

Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women

Osteoporosis International March 2013
M. H. J. Knapen, N. E. Drummen, E. Smit, C. Vermeer, E. Theuwissen

We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.

Introduction: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K’s role in maintenance of normal bone. In line with EFSA’s opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health.

Methods Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment.

Results: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.

Conclusions: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.

From Press Release

The MenaQ7 supplementation group significantly increased the circulating active Osteocalcin (cOC), a well-established biomarker for bone and vitamin K status. The inactive protein, Undercarboxylated Osteocalcin (ucOC), in the MenaQ7 group, decreased with 51% +/- 21 % as compared to the placebo group (+4 % +/- 49%). This is pointing to the positive MenaQ7 bone effect. After three years of supplementation, improvements in both bone mineral content (BMC) and bone mineral density (BMD) were statistically significant in the MenaQ7 group. Moreover bone strength (BS) was statistically improved, demonstrating therapeutic benefits for the MenaQ7 group as compared to the placebo group.

“These demonstrated improvements in clinical outcomes are extremely important”, says Dr. Cees Vermeer, Principal Investigator for the study at VitaK laboratory at Maastricht University. “Despite reports on small or insignificant effects on bone health after clinical interventional studies on vitamin K2 – lasting up to one year - we have documented that MenaQ7 supplementation over three years prevents bone loss in postmenopausal women, confirming that bone health benefits of vitamin K2 is best demonstrated over longer periods than previously thought. The dose of 180 mcg of MenaQ7 per day significantly decreases age-related loss in bone mass and thereby exerts improvements in bone strength.”


See also VitmainDWiki


References in the study

  1. McCann JC, Ames BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 90:889–907
  2. Shearer MJ, Newman P (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100:530–47
  3. Theuwissen E, Smit E, Vermeer C (2012) The role of vitamin K in soft-tissue calcification. Adv Nutr 3:166–73
  4. Price PA, Toroian D, Lim JE (2009) Mineralization by inhibitor exclusion: the calcification of collagen with fetuin. J Biol Chem 284:17092–101
  5. Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1996) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone 18:487–8
  6. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PW, Ordovas J, Schaefer EJ, Dawson-Hughes B, Kiel DP (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 71:1201–8
  7. Luukinen H, Kakonen SM, Pettersson K, Koski K, Laippala P, Lovgren T, Kivela SL, Vaananen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15:2473–8
  8. Knapen MH, Nieuwenhuijzen Kruseman AC, Wouters RS, Vermeer C (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int 63:375–9
  9. Apalset EM, Gjesdal CG, Eide GE, Tell GS (2011) Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone 49:990–5
  10. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R (2008) Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS medicine 5:e196
  11. Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD, Shearer MJ (2007) Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res 22:509–19
  12. Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963–72
  13. Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–23
  14. Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr 108:1652–7
  15. (2009) Scientific Opinion on the substantiation of health claims related to vitamin K and maintenance of bone pursuant to Article 13(1) of Regulation (EC) No 1924/20061. The EFSA Journal 7:1128.
  16. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–61
  17. Fang Y, Hu C, Tao X, Wan Y, Tao F (2012) Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Miner Metab 30:60–8
  18. Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O'Donnell CJ, Gundberg CM, Peterson JW, Booth SL (2008) Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 88:356–63
  19. Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2009) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–40
  20. Forli L, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O (2010) Dietary vitamin K2 supplement improves bone status after lung and heart transplantation. Transplantation 89:458–64
  21. Gundberg CM, Lian JB, Booth SL (2012) Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr 3:149–57
  22. Yamaguchi M, Weitzmann MN (2011) Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-kappaB activation. Int J Mol Med 27:3–14
  23. Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–83
  24. Sato T, Schurgers LJ, Uenishi K (2012) Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J 11:93
  25. Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, 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 17:315–21
  26. Ikeda Y, Iki M, Morita A, Kajita E, Kagamimori S, Kagawa Y, Yoneshima H (2006) Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J Nutr 136:1323–8
  27. Karlamangla AS, Barrett-Connor E, Young J, Greendale GA (2004) Hip fracture risk assessment using composite indices of femoral neck strength: the Rancho Bernardo study. Osteoporos Int 15:62–70
  28. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48
  29. Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y (2012) 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 K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II. Calcif Tissue Int 90:251–62
  30. Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73:21–6
  31. Bugel S, Sorensen AD, Hels O, Kristensen M, Vermeer C, Jakobsen J, Flynn A, Molgaard C, Cashman KD (2007) Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Br J Nutr 97:373–80
  32. Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res 24:983–91
  33. Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. The British journal of nutrition 1–6
  34. Bazzocchi A, Spinnato P, Fuzzi F, Diano D, Morselli-Labate AM, Sassi C, Salizzoni E, Battista G, Guglielmi G (2012) Vertebral fracture assessment by new dual-energy X-ray absorptiometry. Bone 50:836–41
  35. Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BH, Slart RH (2011) Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int 22:1059–68