Should we Supplement with Vitamin K2?

W E ALL LEARNED ABOUT VITAMIN K. 1 WHEN WE WERE in school. It is called phylloquinone, we get it in green leafy vegetables, and we recognize it as the vitamin needed for clotting. The recommended intake ranges from 90 and 120 meg per day of vitamin K. for females and males aged 19 and older.1 While we all likely struggled to memorize the many fac­ets of the clotting cascade, it turns out that vitamin K. has a single major function. It serves as the cofactor for one enzyme known as gamma-glutamylcarboxylase, which is located in the endoplasmic reticulum within cells of certain tissues.1 The carboxylation process functions to activate key proteins, such as prothrombin, which then allows for normal clotting, the best known function of vitamin K. Vitamin K.2 is called menaquinone and it also functions to car-boxylate prothrombin and other proteins. Unlike K. I, however, vitamin K2 is not is derived from green vegetables. Multiple subtypes of K2 have been identified, which are found in various foods and designated as MK.-4 through MK-14. The most nutritionally relevant menaquinones are MK.-4 and MK-7,8,9.2 MK-4 is found in meat, while MK-7. MK-8, and MK.-9 are found in fermented foods such as cheese and curds. MK.-7 is also found abundantly in a fermented soybean product called natto.u If you google "natto," you can get a visual image. It is an unusual looking food and reportedly the texture and flavor are unique and take some getting used to. Experts suggest that most people get adequate vitamin K. for maintaining normal hemostasis, however, the current level of intake and current recommended intakes may not be adequate to support other vitamin K-dependent proteins,'-2 such as os­teocalcin and vascular matrix Gla protein. Without adequate vitamin K, osteocalcin and matrix Gla protein will be under-carboxylated and less active. In this regard, McCann and Ames1 state in a recent review that, "the most important outcome of this part of the analysis is that genetic impairment in osteocalcin or matrix Gla protein in both mice and humans, limited vitamin K. availability, and chronic warfarin therapy are all variously linked to the same set of age-associated conditions (bone de­terioration and fragility late in life and arterial calcification or other cardiovascular conditions)." The consideration for supplementation with vitamin K.2 is thus based on its relationship to the support of bone and cardio­vascular health.: The same can be said of other more common supplements, such as magnesium, omega-3 fatty acids, and vitamin D.3'5 We should also remember that both osteoporosis and cardiovascular disease are driven by a low-grade chronic inflammatory state, which means that it is important for patients to adopt an anti-inflammatory diet.'6 Vitamin K and Bone Interestingly, osteocalcin requires both vitamin K and vitamin D for activation.:-7 Carboxylated osteocalcin has a greater affin­ity for both calcium and hydroxyapatite,7 which is why patients with elevated blood levels of under-caboxylated osteocalcin tend to have reduced bone mass.2 In Japan, those sectors of the population that consume natto tend to have higher levels of carboxylated osteocalcin, better bone density, and less os­teoporosis.8 Such findings have led to supplementation trials with MK.-7 ranging from 180-360 meg per day, which led to an increase in the desired carboxylated calcitonin. Bone mass increase was evident in one ot the three studies.9'" Experts argue that longer-term stud­ies are needed when MK.-7 is used as a monotherapy, and this makes sense, considering that bone loss and reduced bone health develop over decades. It is also possible that MK-7 exerts bone-strengthening effects that are not dependent on bone mass. Vitamin K and Vascular Health In arterial walls, matrix gamma-carboxyglutamate (Gla) protein (MGP) is produced in vascular smooth muscle cells when adequate vitamin K. is present. Vascular MGP is a strong inhibitor of vascular calcification.12 so it is not surprising that significantly increased levels ofunder-carboxylatcd MGPhave been identified in atherosclerotic vessels.13 Interestingly, vitamin Kl intake has not been correlated to coronary heart disease, while MK-7, MK.-8, and MK.-9 appear to be protective.14 Research suggests that MK-7 is the preferred cofactor for the vascular carboxylation enzyme and animal studies suggest that vitamin K.2 supplementation can lead to a regression of arterial calcification.15 It is known that most subjects in the healthy population are not optimally protected against vascular calcification due to the presence of uncarboxy-alted MGP, suggesting that MK-7 supplementation may be an effective preventive strategy.15 Supplementation with MK-7 as a preventive strategy may be beneficial for certain back pain patients. Consider that a subgroup within the prospective Framingham Study underwent lumbar spine X-rays between 1967 and 1968 and were X-rayed again 25 years later. Individuals with aortic wall calcification at baseline were more likely to have degenerative changes in their lumbar spines at follow-up, and were also more likely to report low back pain."' Summary As the health care expen­ditures related to declining bone and vascular health are substantial, it seems that supplementation with vitamin K2 is a reasonable practice, in addition to the other discussed measures. Only patients taking Cou- madin or other blood thinning agents should avoid vitamin K2 supplementation. Dr. David Seaman ix an Adjunct Axxociate Professor at Palmer College of Chiropractic Florida, has a part-time practice in Onnond Beach, and is the Clinical Educa­tion Director for Anabolic Laboratories. He has written numerous articles on the treatment options for chronic pain patients, with a focus on nutritional management, lie can be reached at [email protected]. i References /. McCaim JC, Ames BN. Vitamin K. an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nulr 2009:9():HS9-90 7. Vermeer C. Shearer MJ, Zittermann A, etui. Bevond deficiency: potential benefits of increased intakes of vitamin K for bone and vas­ cular health. EurJNutr. 2004:43:325-335. Seaman DR. Health care for our bones: A practical nutritional approach to preventing osteo­porosis. .1 Manip Physiol Then 2004; 27:591-95. 4. Siinoponlos A P. The importance of the oniega-6/ omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med. 2008:233:674-88. 5. Holick ME. Deficiency of sunlight and vitamin D. Brit Med.l. 2008:336:1318-19. O'KeefeJH. Gheewala NM. O'KeefeJO. Dietaty strategies for improving post-prandial glucose, lipids. inflammation, and cardiovas­ cular health. JAm Coll Cardiol. 2008: 51(3):249-55. Lee AJ. Hodges S, Eastell R. Measurement of osteocalcin. Ann Clin Biochem. 2000:37:432-46. (Osteocalcin is vitamin Kami vitamin D dependent) Ikeda Y, Iki M. Morita A. et al. Intake of fermented soybeans, natto, is associated with reduced hone loss in postmenopausal women: Japanese Population-Based Osteoporosis I.JPOS) Study .1 Nun: 2006; 136:1323-28. Emaus N, Gjesdal CG, Almas B et al. Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int. 2009 Nov 25. [Epub ahead of printJ. van Suinmeren MJ. Brawn LA. Lilien MR el al. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxvlation in healthy prepubertal children. Brit J Null: 2009; I02(8):117l-78. Forli L, Bollerslev J, Simonsen S. et al. Dietary vitamin K2 supplement improves bone status after lung and heart Iran s - plantation. Transplantation. 2010:89:458-64. Cranenhurg EC, VermeerC. Koos R et al. The circulating inac­ tive form of matrix Gla protein (ucMGP) as a hiomarker for cardiovascular calcification. J Vase Res. 2008:45:427-36. Schurgers LJ, Teunissen KJ, Knapen Mil el al. Novel confor­ mation-specific antibodies against matrix gamma-carboxvglutamic acid (Gla) protein: undercarboxvlaled matrix Gla protein as marker for vascular calcification. Aterioscler Thromh Vase Biol. 2 0 0 5 ; 25(8): 1629-33. 14. Gast GC. de Roos NM, Sluijs I el al. A high menaquinone intake reduces incidence of coronary heart disease in women. Nutr Met ah Cardiovas Dis. 2009:19:504-10. 15. Schurgers L.I, Cranenburg EC. Vermeer C. Ma­ trix Gla-protein: the calcification inhibitor in need of vitamin K. Thromh Haemost. 2008; 100:593- 603. 16. Kauppila LI. McAlindon T. Evans S. el al. Disc degen­ eration/hack pain and calcification of the abdominal aorta: a 25-year follow- up study in Frainingham. Spine 1997,22:1642- 47.' Ezxa