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Vitamin K2: Evidence-based Support of Bones & Joints

Aging healthily is integrally linked to maintaining one’s mobility. Yet compromised bone health impacts most adults worldwide. Gnosis by Lesaffre asserts that this is attributable to a vitamin K2 deficiency.

Xavier Berger., Global Market Manager

November 18, 2022

6 Min Read
Vitamin K2: Evidence based support of bones & joints
© iStock/Geber86 | Copyrights held by Gnosis by Lesaffre

A substantial body of research has demonstrated vitamin K2’s impact on bone health for adults, and evidence is increasing, demonstrating that K2 has excellent potential for impacting joint health through its bone support mechanism and anti-inflammatory action. Learn more about the secret to encouraging a more mobile and vibrant customer base with the inclusion of clinically validated MenaQ7 vitamin K2 as MK-7.

Aging healthily is integrally linked to maintaining one’s mobility. Yet compromised bone health impacts most middle-aged adults worldwide, with osteoporosis causing millions of fractures annually. Further, a systematic analysis published in the Annals of Rheumatic Diseases shows an increase in global age-standardized prevalence and incidence rates of rheumatoid arthritis (RA).[1]

A substantial body of evidence shows that vitamin K2 is an essential calcium companion, ensuring peak calcium utilization for the skeleton and the highest possible protection from calcium accumulation in arterial walls.

At the same time, low vitamin K status has been associated with joint problems.[2] Evidence is increasing, demonstrating that K2 has excellent potential for impacting joint health through its bone support mechanism and anti-inflammatory action.

K2 Mechanism of Action

Vitamin K2 activates osteocalcin (OC), a vitamin K-dependent protein (VKDP) synthesized by osteoblasts and has been demonstrated to be related to bone mineralization. Vitamin K2 may also decrease bone resorption by reducing prostaglandin E2 synthesis in osteoclasts (cells responsible for the dissolution and absorption of bone).[3]

In addition to OC carboxylation, which modulates calcium deposition in bone, vitamin K2 increases collagen synthesis and accumulation[4] and production by osteoblasts.[5] Collagen is essential for bone flexibility and elasticity, occupying more than half the volume of bones. It is responsible for matrix production, the material on which calcium and other minerals accumulate. Therefore, collagen accumulation and bone minerals are critical for high-quality bone formation.

Further, through its anti-inflammatory action and activation of VKDPs, K2 may contribute to decreased articular cartilage calcification, joint pain, and inflammation.[6]

K2 & Bone Mineralization

Vitamin K2 as MK-7 has been shown to have the highest bioavailability and the most significant effect on OC carboxylation in humans among vitamin K homologs. At the current recommended daily intake (RDI) for vitamin K, vitamin K1 and K2 as MK-4 are insufficient to activate OC. Therefore, it is expected that MK-7 may be the best option for promoting bone health.[7]

Various clinical trials in adults have reported that daily supplementation with vitamin K2 improved bone mineral density (BMD), significantly reduced bone loss, and improved bone strength measures, which may contribute to reduced fracture risks.[8-13]

Most notable is a three-year study of 244 healthy postmenopausal women. The subjects were randomly assigned to take 180 mcg of MenaQ7® daily for three years or placebo capsules. After supplementation, maintenance in both bone mineral content and bone mineral density was statistically significant in the MenaQ7® group. Moreover, bone strength was statistically improved, demonstrating therapeutic benefits for the MenaQ7® group compared to the placebo group. This was the first clinically statistically significant protection of the vertebrae and the hip (femoral neck) against bone loss with a nutritional dose of vitamin K2. [14]

K2 for Joint Health

Low vitamin K status has been associated with joint problems.[15] In recent years, researchers tried to address the therapeutic benefits of MK-7 in managing patients with rheumatoid arthritis (RA) as menaquinones (MKs) have been reported to induce apoptosis in RA synovial cells. As RA progresses, the synovium, which produces synovial fluid, swells and thickens, producing an excess of synovial fluid. This, in turn, leads to further swelling and inflammation, which causes pain and stiffness in the joint.

A study in 2015 was designed to clarify the therapeutic role of vitamin K2 as MK-7 added to the standard therapeutic regimen of RA in patients with different stages of the disease with a clinical follow-up through a randomized clinical trial. Eighty-four RA patients were divided into MK-7 treated group (n=42) and MK-7 naïve group (n=42). MK-7 capsules were administered at a dose of 100 µg/day for three months in the first group without changing other medications. In the MK-7 group, a significant decrease in the levels of undercarboxylated osteocalcin (ucOC), erythrocyte sedimentation rate (ESR), disease activity score assessing 28 joints with ESR (DAS28-ESR), C-reactive protein (CRP), and matrix metalloproteinase (MMP-3) was found, and a marked decrease in RA clinical and biochemical markers for moderate and good response compared to non-responders was observed in ucOC, ESR and DAS28-ESR. The results suggest that MK-7 represents a new promising agent for RA in combination therapy with other disease-modifying antirheumatic drugs.[16]

A similar 2013 cross-sectional study gave comparable results. Namely, the vitamin K2-treated group showed lower serum CRP, MMP-3, and DAS28-CRP. In the longitudinal study, patients who were additionally treated with vitamin K2 without changing their medications for three months demonstrated significant decreases in serum CRP, MMP-3, and DAS28-CRP. For this reason, vitamin K2 may be used to improve disease activity besides osteoporosis in RA.[17]

Conclusion

Evidence has linked one’s K2 status to the state of bone health, and joint health is a burgeoning new area that researchers continue to explore. Because of its high bioavailability and clinically validated impact on osteocalcin activation, MenaQ7® Vitamin K2 as MK-7 remains the optimal choice.

References

  1. Safiri S, Kolahi AA, Hoy D, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis. 2019;78:1463-1471.

  2. Neogi T, et al. Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum. 2006 Apr;54(4):1255-61.

  3. Koshihara Y, Hoshi K, Shiraki M. Vitamin K2 (menatetrone) inhibits prostaglandin synthesis in cultured human osteoblast-like periosteal cells by inhibiting prostaglandin H synthase activity. Biochem Pharmacol. 1993 Oct 19;46(8):1355-62.

  4. Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 2006;281(25):16927-16934. doi:10.1074/jbc.M600896200

  5. Sato T. Vitamin K2 and Bone Quality. Vitam. Trace Elem. 2012:S6. doi: 10.4172/2167-0390.S6-001

  6. Chin KY. The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence. Nutrients. 2020 May; 12(5): 1208.

  7. Sato T, Inaba N, Yamashita T. MK-7 and Its Effects on Bone Quality and Strength. Nutrients. 2020;12(4):965. Published 2020 Mar 31. doi:10.3390/nu12040965

  8. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000;15:515-21.

  9. Iwamoto I, Kosha S, Noguchi S, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas. 1999;31:161-4.

  10. Yonemura K, Kimura M, Miyaji T, Hishida A. Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis. Calcif Tissue Int. 2000;66:123-8.

  11. Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18(7):963-972.

  12. Cockayne S, Adamson J, Lanham-New S, et al. Vitamin K and the prevention of fractures. systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:1256-61.

  13. Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507.

  14. Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep; 24(9):2499-507.

  15. Neogi T, et al. Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum. 2006 Apr;54(4):1255-61.

  16. Abdel-Rahman MS, et al. Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. Eur J Pharmacol. 2015 Aug 15;761:273-8. doi: 10.1016/j.ejphar.2015.06.014. Epub 2015 Jun 11.

  17. Ebina K, Shi K, Hirao M, et al. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod Rheumatol. 2013;23(5):1001-1007. doi:10.1007/s10165-012-0789-4.

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About the Author

Xavier Berger.

Global Market Manager, Gnosis by Lesaffre

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