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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.

High dietary menaquinone intake is associated with reduced coronary calcification.\nBeulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT.\nAtherosclerosis. 2008 Jul 19. [Epub ahead of print]\nPMID: 18722618 \ndoi:10.1016/j.atherosclerosis.2008.07.010 \n

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

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.

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."

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one type of pathology is considered a likely predictor of the other. This potentially causal relationship has led to the hypothesis that these conditions share core 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 I of this review summarizes current research linking vitamin D deficiency to cardiovascular disease, the physiological mechanisms underlying vitamin D's cardiovascular effects, and leading vitamin D researchers' recommendations for significantly higher supplemental doses of the pro-hormone. Part II reviews the vitamin K connection to cardiovascular disease; the ways in which vitamin D and vitamin K pair up to prevent inflammation, vascular calcification and osteoporosis; and the necessity of providing vitamin K along with vitamin D to preclude adverse effects associated with hypervitaminosis D, which include vascular and other soft tissue calcification.

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

If you've been following the Track Your Plaque conversation, you know that, contrary to prevailing opinion among many cardiologists, there is an emerging notion that coronary calcification is an active process, a true part of the disease. Vitamin D3 is an important aspect of this question. So is vitamin K2. Not to be confused with K1 that plays a role in blood coagulation, K2 has an important role in calcium metabolism. Thus, vitmain K2 deficiency is related to osteoporosis and to coronary calcification.

Serum vitamin D level after an annual intramuscular injection of ergocalciferol. Heikinheimo RJ, Haavisto MV, Harju EJ, Inkovaara JA, Kaarela RH, Kolho LA, Rajala SA. Calcif Tissue Int. 1991;49 Suppl:S87. PMID: 1933611 An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels.

Annual injection of vitamin D and fractures of aged bones. Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, Kokko AM, Kolho LA, Rajala SA. Calcif Tissue Int. 1992 Aug;51(2):105-10. PMID: 1422948

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.

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.

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.

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.

Marangella M, Di Stefano M, Casalis S, Berutti S, D'Amelio P, Isaia GC. Effects of potassium citrate supplementation on bone metabolism. Calcif Tissue Int. 2004 Apr;74(4):330-5. PMID: 15255069 [PubMed - indexed for MEDLINE]

Tufts University Confirms That Vitamin A Protects Against Vitamin D Toxicity by Curbing Excess Production of Vitamin K-Dependent Proteins Tufts University confirmed my hypothesis that vitamin A protects against vitamin D's induction of renal calcification (kidney stones) by normalizing the production of vitamin K-dependent proteins in December, 2008, without citing my hypothesis or telling me they had confirmed it. I am, of course, very grateful that they thought it significant enough to investigate.

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

Calcium and vitamin D intakes may be positively associated with brain lesions in depressed and nondepressed elders. Payne ME, Anderson JJ, Steffens DC. Nutr Res. 2008 May;28(5):285-92. PMID: 19083421 doi: 10.1016/j.nutres.2008.02.013 In conclusion, calcium and vitamin D consumption were associated with brain lesions in elderly subjects even after controlling for potentially explanatory variables. These associations may be due to vascular calcification or other mechanism. The possibility of adverse effects of high intakes of calcium and vitamin D needs to be further explored in longitudinal studies of elderly subjects.