MONACOLIN K-FREE RED YEAST RICE Dr. Tzu-Ming Pan is an Emeritus Professor of Biotechnology at the National Taiwan University in Taipei. His research over many years focused on beneficial molecules produced by Monascus and many other plants and bacteria. His lab identified a strain of Monascus that did not make monacolin K, yet surprisingly was able to reduce LDL cholesterol in animal models. After several years of work, Dr. Pan and his group isolated two molecules from red yeast rice that were responsible for this cholesterol lowering effect. These molecules, named monascin and ankaflavin, are chemically very similar (see Figure 4),
Having healthy arteries certainly has something in common with having healthy bones; both organs depend on vitamin K2 to regulate the deposition of calcium in them. Relatively recent research has revealed more about how vitamin K2 level can be an indicator of the health of both your arteries and bones. Clinical studies have demonstrated that low levels of vitamin K2 are associated with an increased risk of having heart disease and atherosclerotic plaque development.1
Vitamin K Basics
Vitamin K1 (phylloquinone) is found in plants including green leafy vegetables; it has less bioavailability than vitamin K2. Vitamin K2 (menaquinone) is present in dairy, egg yolks, and organ meats. In supplements, the most commonly used forms are MK-4 (menatetrenone/menaquinone-4) which is synthetic and is also produced by bacteria in the human body, and MK-7 (menaquinone-7) which is found in the fermented soy food natto. Vitamin K1 is metabolized to MK-4 inside the body, suggesting that this is the form that the body actually uses. The liver requires vitamin K in order to make blood clotting proteins, and as this article discusses, for the regulation of calcium deposition. The vitamin K2 menaquinones comprise approximately 10% of vitamin K; menaquinone exists naturally in the body in several different forms ranging from MK-3 to MK-13.
How Can Calcium Accumulate in the Arteries?
When calcium is lacking in the bone, it is frequently observed in excess in the arteries and vice versa, this has been established for quite some time in the medical community. However, earlier on it was not fully understood what processes were at work to cause abnormal calcium deposition in the arterial system, or a lack of normal calcium deposition where it should be occurring, in the bones. A lack of calcium in the bones leads to osteoporosis, a condition where the bones become porous and brittle; whereas coronary heart disease can result from calcium deposition in the arteries and reduce the ability of blood to flow. Vitamin K has already received plenty of attention for its role in promoting healthy blood clotting; however, there is not enough awareness of the amount of vitamin K2 needed to maintain healthy arteries and bones. Many people are not getting the amount of vitamin K necessary to support a healthy cardiovascular system, which is believed to be greater than 32 mcg per day according to a clinical study.1
The Discovery of Arterial Plaque
In the 19th century, an unknown material resembling bone was discovered in the linings of diseased arteries. Abnormal calcium deposits are found in the lining of the arteries (the intima), the arterial muscle layers, and also the in the heart valves. Scientists questioned what was controlling the deposition of this material in the body. Later on, a protein was found by Dr. Linda Demur (at the University of California in Los Angeles) in human arterial tissue that was previously thought to only have existed in bone tissue; this protein called morphogenetic protein-2 has an important function in influencing the formation of bone.2 Since that time, a number of bone calcium regulators have been found in atherosclerotic plaque tissues, such as osteopontin and matrix GLA-protein, proving that both arterial and bone health are related, and interestingly they are both regulated by similar influences.3
What Do Bones and Arteries Have in Common?
Although patients with vascular disease and osteoporosis may share many characteristics in common such as a sedentary lifestyle, smoking, diabetes and high cholesterol, abnormal calcium deposition in the arteries has been observed even in apparently healthy people.3 Both the bones and the arterial system have their own regulation mechanisms, therefore it is clear that there are other processes occurring to cause abnormal calcium deposition in the arteries in the case of diseased arteries. Prescription drugs such as alendronate (Fossimax) and raloxifene (Evista) are able to increase calcium deposition in the bones, however they do not stop the formation of calcium plaques in the arteries. Research is continuing to demonstrate that vitamin K is able to influence calcium metabolism in the body by promoting deposition in the bone and at the same time prevent it from accumulating in the arteries. A Japanese study conducted over a two year period investigated vitamin K2’s ability to improve bone health in osteoporosis patients. It found that vitamin K2 supplements reduced spine fractures by 52% in these patients as compared to those that did not get the treatment of 45mg/day.4 Although this dose which is typical for osteoporosis treatments is relatively high, lower dosages have also proven to provide substantial benefits.
Clinical Studies Prove the Vitamin K Connection to Arterial Health
A large scale clinical trial carried out in Holland starting in 2004, the Rotterdam Heart Study, proved that vitamin K2 levels are intimately related to heart disease. A total of 4800 participants were tracked for seven years to determine the effect that vitamin K2 had on their cardiovascular health. Both MK-4 and MK-7 were used in the study, but not analyzed separately. The study concluded that those who had the highest intakes of vitamin K2 had a reduced risk of death from heart disease by 57%, over those that had the lowest intake levels.1 It is important to note that this relationship was not observed with vitamin K1. The higher intakes of vitamin K2 corresponded
with a decreased amount of calcium in the aorta, this being an indirect measurement of atherosclerosis. Moderate to severe calcification was observed in those participants that had the least amounts of vitamin K intake. Heart attack and aortic calcification risk was lowest if an amount greater than 32.7 mcg per day of vitamin K2 was taken.1 Another Dutch cross-sectional study at the Julius center for Health Sciences involved 564 post menopausal women, 360 of whom already had coronary artery calcification. The effects of both vitamin K1 and vitamin K2 (mk-4-mk-10) were compared; it was determined that the vitamin K2 reduced levels of coronary artery calcification.5
Vitamin K2 is an Essential Heart Heath Nutrient
In conclusion, abnormal calcium signaling is therefore responsible for contributing to atherosclerotic plaque growth, and vitamin K deficiency is now believed to promote this occurrence. The present recommended dosages of 120 mcg/day for men and 90 mcg/day for women may not be high enough to ensure that optimal heart and bone health are maintained.6,7,8 Ensuring that you are receiving adequate levels of vitamin K may be one of the best things you can do for your heart!
1. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.
2. Bostrom K, Watson KE, Horn S, et al. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993 Apr;91(4):1800-9.
3. Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1161-70.
4. 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 Mar;15(3):515-21.
5. . Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93. Epub 2008 Jul 19.
6. Schurgers LJ, Dissel PE, Spronk HM, et al. Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90 Suppl 3:57-63.
7. Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Curr Pharm Des. 2004;10(21):2557-76.
8. Shoji S. Vitamin K and vascular calcification. Clin Calcium. 2002 Aug;12(8):1123-8
Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Curr Pharm Des. 2004;10(21):2557-76.