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Deficiency of K2 in both mice and humans is associated with coronary calcification; low vitamin K2 levels are associated with increased activity of Gla matrix protein, an enzyme that causes calcium deposition in artery walls. People who take warfarin (Coumadin®), a potent blocker of vitamin K2, experience more arterial and heart valve calcification. The 2004 Rotterdam Heart Study was the experience that really brought this concept closer to our interests. This well-conducted study of 4800 Dutch demonstrated an association of vitamin K2 intake with 57% reduction in cardiovascular events and lesser degrees of aortic calcification (another surrogate for atherosclerosis). Benefit appeared to be associated with a daily K2 intake of 32.7 micrograms per day (Geleijnse JM et al 2004). An important corollary of this study is that it suggests that a vitamin K2-mediated reduction in coronary calcification is accompanied by reduced likelihood of heart attack and other events.

Arterial calcification, a process of hardening of the arteries, may be inhibited and even reversed with supplementation with high-dose vitamin K, suggests an animal study.

Research has uncovered the fact that vitamin K also plays a crucial role in maintaining bone health. It was found that the amount of vitamin K required to halt bone absorption leading to osteoporosis requires much greater intakes than that required for blood clot regulation. Further, it appears that bone and vascular tissue (like coronary arteries) maintain a preference for a different form of vitamin K than that required for blood clotting regulation. Rather than vitamin K1 needed for clotting, vitamin K2 is the form preferred by bones and arteries (Schurgers LJ et al 2001). It appears that much of the information generated over the years for vitamin K focused on the K1 form, ignoring the K2 form necessary for bone and vascular health. Normal deposition of calcium occurs only in bone and in teeth. Abnormal deposition of calcium in the body occurs in three places: the inner lining of the arteries of the body (the intima) that causes atherosclerotic plaque; the muscle layer of arteries ("medial calcification"); and heart valves. K2 appears to be the form of vitamin K responsible for controlling these phenomena.

Vitamin K in the treatment and prevention of osteoporosis and arterial calcification.\nAdams J, Pepping J.\nAm J Health Syst Pharm. 2005 Aug 1;62(15):1574-81. Review.\nPMID: 16030366

Vitamin K epoxide reductase complex and vascular calcification: is this the important link between vitamin K and the arterial vessel wall? Spronk HM. Circulation. 2006 Mar 28;113(12):1550-2. Review. PMID: 16567578

25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS. J Am Soc Nephrol. 2009 Aug;20(8):1805-12. Epub 2009 May 14. PMID: 19443637 doi: 10.1681/ASN.2008111157 "In conclusion, lower 25-hydroxyvitamin D concentrations associate with increased risk for incident CAC. Accelerated development of atherosclerosis may underlie, in part, the increased cardiovascular risk associated with vitamin D deficiency."

Zittermann A, Schleithoff SS, Koerfer R. \nVitamin D and vascular calcification.\nCurr Opin Lipidol. 2007 Feb;18(1):41-6. Review.\nPMID: 17218831 [PubMed - indexed for MEDLINE

July 29, 2008 - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, known as Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World War II Birth Cohort (ERA JUMP) included 868 randomly selected men aged 40 to 49. Of these, 281 were Japanese men living in Japan; 306 were white men living in the US, and 281 were third- or fourth-generation Japanese American men from Hawaii. All study participants had a physical examination, completed a lifestyle questionnaire, and had blood tests to measure cholesterol levels and levels of omega-3 fatty acids. Atherosclerosis was assessed by measuring carotid intima-medial thickness (IMT) and coronary artery calcification (CAC). Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids - a finding that was independently linked to low levels of atherosclerosis.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C. Blood. 2007 Apr 1;109(7):2823-31. PMID: 17138823 DOI 10.1182/blood-2006-07-035345. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one is considered a likely predictor of the other. This relationship has led to the hypothesis that these conditions share core pathophysiological mechanisms. Recent advances in our understanding of the complimentary roles played by vitamin D3 and vitamin K2 in vascular and bone health provide support for this hypothesis, along with insight into key metabolic dysfunctions underlying cardiovascular disease and osteoporosis. Part II, The Vitamin K Connection to Cardiovascular Health, reviews the ways in which vitamin K regulates calcium utlization, preventing vascular and soft tissue calcification while complimenting the bone-building actions of vitamin D, and also discusses vitamin K safety and dosage issues, and the necessity of providing vitamin K and vitamin A along with vitamin D to preclude adverse effects associated with hypervitaminosis D.

Vitamin K has been known as the coagulation vitamin, because of its role in the blood-clotting process. However, research over the last few decades has shown that the role of K Vitamins - and natural Vitamin K2, the menaquinones, in particular - has been greatly expanded. Of note, K Vitamins activity outside the liver is required for calcium utilization, the key factor in maintaining both bone and cardiovascular health.\n\nVitamin K2 helps to activate vitamin K-dependent proteins responsible for healthy tissues. In bone, it activates osteocalcin, a protein required to bind calcium to the mineral matrix, thus strengthening the skeleton. In circulation, Vitamin K2 participates in carboxylation of Matrix Gla Protein (MGP), the most potent inhibitor of arterial calcification known, lowering the risk of vascular damage.

Vitamin K2 is produced by animal tissues, including the mammary glands, from vitamin K1, which occurs in rapidly growing green plants. A growing body of published research confirms Dr. Price's discoveries, namely that vitamin K2 is important for the utilization of minerals, protects against tooth decay, supports growth and development, is involved in normal reproduction, protects against calcification of the arteries leading to heart disease, and is a major component of the brain. Vitamin K2 works synergistically with the two other "fat-soluble activators" that Price studied, vitamins A and D. Vitamins A and D signal to the cells to produce certain proteins and vitamin K then activates these proteins. Vitamin K2 plays a crucial role in the development of the facial bones, and its presence in the diets of nonindustrialized peoples explains the wide facial structure and freedom from dental deformities that Weston Price observe

In 1945, Dr. Weston Price described "a new vitamin-like activator" that played an influential role in the utilization of minerals, protection from tooth decay, growth and development, reproduction, protection against heart disease and the function of the brain. Using a chemical test, he determined that this compound-which he called Activator X-occurred in the butterfat, organs and fat of animals consuming rapidly growing green grass, and also in certain sea foods such as fish eggs. Vitamin K2 is produced by animal tissues, including the mammary glands, from vitamin K1, which occurs in rapidly growing green plants. A growing body of published research confirms Dr. Price's discoveries, namely that vitamin K2 is important for the utilization of minerals, protects against tooth decay, supports growth and development, is involved in normal reproduction, protects against calcification of the arteries leading to heart disease, and is a major component of the brain

Dietary linolenic acid is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Djoussé L, Arnett DK, Carr JJ, Eckfeldt JH, Hopkins PN, Province MA, Ellison RC; Investigators of the NHLBI FHS. Circulation. 2005 Jun 7;111(22):2921-6. Epub 2005 May 31. PMID: 15927976 doi: 10.1161/CIRCULATIONAHA.104.489534

Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. Sekikawa A, Curb JD, Ueshima H, El-Saed A, Kadowaki T, Abbott RD, Evans RW, Rodriguez BL, Okamura T, Sutton-Tyrrell K, Nakamura Y, Masaki K, Edmundowicz D, Kashiwagi A, Willcox BJ, Takamiya T, Mitsunami K, Seto TB, Murata K, White RL, Kuller LH; ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort) Study Group. J Am Coll Cardiol. 2008 Aug 5;52(6):417-24. PMID: 18672160 Conclusions Very high levels of marine-derived n-3 FAs have anti-atherogenic properties independent of traditional cardiovascular risk factors and may contribute to lower burden of atherosclerosis in Japanese in Japan, which is unlikely due to genetic factors.

Pittsburgh, PA and Shiga, Japan - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids-a finding that was independently linked to low levels of atherosclerosis. "The death rate from coronary heart disease in Japan has always been puzzlingly low. Our study suggests that the very low rates of coronary heart disease among Japanese living in Japan may be due to their lifelong high consumption of fish," Sekikawa said." Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. In addition, the significant differences between Japanese and American men in multivariable-adjusted IMT and CAC prevalence became nonsignificant after adjustment further for marine-derived omega-3 fatty acids.