Vitamin K2: Bones, Cardiovascular Health, Blood Sugar Control & Cancer Prevention

Thursday, May 19, 2011
By: Byron J. Richards,
Board Certified Clinical Nutritionist
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Vitamin K is an important antioxidant nutrient well known for its important assistance in clotting blood.  It is also the target of the commonly overly prescribed Coumadin, adding to society wide problems of vitamin K deficiency. Ironically, such deficiency causes hardening of the arteries via increased calcification of arterial walls.  Importantly, the lack of vitamin K is a major factor in poor bone health and new science shows it is also important for blood sugar regulation. Once again, the symptom suppressing, drug pushing medical profession needs to get its head out of the sand and quit harming people under the false pretense of pretended help.

Vitamin K1 (phylloquinone) in your diet comes primarily from green leafy vegetables. Vitamin K2 (menaquinone) is naturally produced by bacteria in your large intestine. Its highest dietary source is cheese (also in milk, yogurt, eggs, and beef).  Typical dietary intake is 90 percent K1 and 10 percent K2 (with additional intestinal production of K2).  While both forms of vitamin K are important, it does appear that vitamin K2 has a longer half-life in your blood, thus potentially providing enhanced vitamin K status.

Vitamin K1 and K2 act to modify a number of proteins so that they become biologically active. Vitamin K does this via a process known as carboxylation (converting glutamate in proteins to gamma-carboxyglutamate). This process is required for the proteins involved with blood clotting to work correctly. In an attempt to reduce the theoretical risk of stroke in an ever-expanding list of potential target patients, warfarin (Coumadin) is given, which directly blocks the carboxylation activity of vitamin K everywhere in the body. It also disrupts the vital antioxidant function of vitamin K1

This sledgehammer approach disrupts normal blood clotting, resulting in warfarin causing bleeding and increased risk for hemorrhage fueled stroke. This is why warfarin is the number one cause of trips to the emergency room. Heaven forbid if you get in car accident and need your blood to clot. Former Israeli Prime Minister Arial Sharon is an example of someone reduced to a comatose state as a result of a warfarin-induced hemorrhage stroke.

Blocking vitamin K activity on blood clotting cells does not address the source of a “sticky blood” problem. Rather it ignores the source of the problem, while seeking to block the last step of the problem. The logic is similar to stopping an ocean floor oil spill by standing on the beach with a mop. Even more ironic, new science shows that sticky blood may be a protective adaptation to excessive plaque  - while warfarin may actually produce smaller plaques that are more harmful and pose more risk to health.

Furthermore, relatively little vitamin K is needed for clotting enzymes to function. There are only so many receptors for vitamin K on these clotting cells. Once they are loaded with vitamin K they have the potential to clot. In health, that means clot when needed. In inflammatory disease states, that means clot unpredictably with the potential for stroke. However, there is no such thing as higher levels of vitamin K intake promoting excessive clotting. To the contrary, higher levels of vitamin K intake are highly protective of cardiovascular health.

In comparison to the relatively small amount of vitamin K needed for clotting, a far larger amount is needed for bone health and other healthy vitamin K functions. New science shows that your liver prioritizes which of the 16 vitamin K proteins will receive the available vitamin K first. As it turns out, it feeds the five clotting proteins first. This means that using enough warfarin to suppress vitamin K clotting activity causes a significant shortage of vitamin K for other healthy functions. It is also now known that adequate vitamin K is needed to protect your liver against inflammation.

In a 2006 study a comparison was made between elderly Medicare patients with atrial fibrilation who were taking warfarin (4,461) and those who weren’t (7,587).  The study showed an alarming 25 percent increased rate of fracture2 with a very high rate of consequent mortality.  Other information clearly shows that both vitamin K1 and vitamin K23 increase bone strength and reduce the risk of fractures.  It is proven in hip fracture patients that they have low levels of vitamin D, vitamin K1, and vitamin K2.  Invariably doctors, in typical MDiety fashion, claim that their drug dispensing benefits outweigh the risks. How can they say that in the case of warfarin?

Vitamin K2 and Bone Health

Vitamin K works in harmony with the bone building carpenter cells called osteoblasts. These cells produce a protein called osteocalcin. To become biologically active osteocalcin must be carboxylated by vitamin K.  Once this happens then osteocalcin can “glue” calcium into its correct three dimensional structure within the bone tissue matrix. Without adequate vitamin K calcium cannot be properly attached to bone. There is no way around this important step in bone formation. This means that vitamin K adequacy is needed for bone strength.

In participants of the Framingham Heart Study4 it was found that those with the highest level of vitamin K dietary intake had a 35 percent lower risk of hip fracture.

Vitamin K2 has been proven to activate osteocalcin5.  A study with postmenopausal women6 showed that vitamin K2 maintained the proper bone geometry of the hip resulting in better strength of the bone (preventing the loss of bone strength).  A study in patients with osteoporosis7 showed that supplemental vitamin K2 prevented new fractures; even though there was still a lack of bone density there was better bone strength.  Interestingly, in addition to enhancing the function of bone building osteocalcin, vitamin K2 has also been shown to turn down inflammation at the gene level, regulating NF-kappaB8 in macrophages.  It is excessive inflammatory macrophage activity within bone that leads to excessive bone loss. 

A potent extract of vitamin K2 called MenaQ7 (menaquinone-7) is now available as a dietary supplement.  MenaQ7 is an extract of natto, the traditional fermented soy Japanese dish that is rich in natural menaquinone-7 (Mk-7), and is the most bioavailable and bioactive form of supplemental vitamin K2.  Only non GMO soy is used in this combination of a traditional yet high tech process of making a dietary supplement ingredient.  This form of vitamin K29 has demonstrated high absorption, a longer life in the blood, and an excellent boosting of biologically active osteocalcin, making it an excellent form of vitamin K for dietary supplementation.  It requires only microgram doses to be effective.

Part of how vitamin K2 helps bones is by regulating the key inflammatory gene signal NF-kappaB in osteoblasts and osteoclasts.  By regulating this signal in bone building osteoblasts it helps activate them. By regulating this signal in the potentially overly active bone reducing osteoclasts it helps calm them down. The researchers called this “an effective mechanism for ameliorating pathological bone loss and for promoting bone health.”

Animal studies with vitamin K210 as menaquinone-7 show a dramatic prevention of typical bone-loss biochemistry that is associated with the aging process. It also normalized the function of parathyroid hormone, an important regulator of vitamin D and calcium balance.  It offset inflammation that provokes bone loss.  It improved glucose metabolism in bone tissue – indicating better bone tissue energetic metabolism.  It boosted osteocalcin concentration even in ovariectomized rats.  The authors concluded that menaquinone-7 “may play an important role in the prevention of age-related bone loss.”

A human study recently showed that vitamin K2 as menaquinone-7 boosted the bone status11 in patients following transplant surgery, which is a highly metabolically stressful event. 

A study with children12 showed that this form of vitamin K2 (at a dose of 45 microgram per day) was able to significantly increase the amount of biologically active osteocalcin. This is important as maximizing bone health during bone growth years can have long-term bone benefits. It is also important for blood sugar metabolism, as will be discussed shortly.

Vitamin K2:  Cardiovascular Health, Diabetes Reeducation & Cancer Prevention

Matrix Gla Protein is another key protein in your body that must be carboxylated (activated) by vitamin K. This is the protein in your circulation that prevents calcium from accumulating in your arteries and hardening them. When there is a dietary deficiency or a warfarin induced deficiency of vitamin K carboxylation activity then the inactive form of Matrix Gla Protein builds up in your blood and calcification of your arteries begins to occur.  The build up of the inactive form of Matrix Gla Proteins13 is highly predictive of cardiovascular disease risk.

An analysis of 4,807 participants of the population-based Rotterdam Study showed that high dietary intake of vitamin K2 (menaquinone), but not vitamin K1, reduced the rate of mortality from coronary artery disease14.  In fact, the level of vitamin K2 was inversely related to the risk of death from any cause.  The authors concluded that vitamin K2 “could be important for coronary heart disease prevention.”

Scientists are now sounding alarm bells15 on the fact that warfarin causes calcification of arteries and heart valves (not that the medical profession is listening).  The latest study16 documents the facts of the issue. The problem has been explained in medical literature for the past five years17.

As I have previously explained in my recent article on another bone building nutrient, Cissus quadrangularis, and in my earlier article, The New World of Bones – Thyroid, Leptin, Blood Sugar, and Bone Strength, biologically active osteocalcin not only acts to build bone but also acts as a hormone that travels to fat and boosts the production of the blood sugar regulating hormone known as adiponectin.

A recently published study of 38,094 Dutch men and women ages 20 – 70 found that vitamin K2 intake had a statistically significant inverse relationship to the risk of developing type 2 diabetes18.  Vitamin K1 intake also trended in the preventive direction, though the benefit was not enough to be statistically significant. This finding corresponds to the science showing that vitamin K2 is a more potent activator of osteocalcin than vitamin K1 (although both help).

The link between osteocalcin, type 2 diabetes, and the full metabolic syndrome19 has just been confirmed in the medical literature. It will only be a matter of time before research shows that disrupting osteocalcin activity with warfarin either causes type 2 diabetes and metabolic syndrome or makes it worse.

The results have just been published on the European Prospective Investigation into Cancer and Nutrition - Heidelberg cohort study20 involving 24,340 participants aged 35 – 64.  They were free of cancer at enrollment (1994-1998) and actively followed up for cancer incidence and mortality through 2008.  Their vitamin K1 and K2 dietary intake was tracked over these years and compared to cancer incidence and mortality. Vitamin K2, but not vitamin K1, was inversely associated with the risk of cancer and cancer mortality. The benefit of vitamin K2 was greatest for men, with a notable reduction in prostate and lung cancer.  The researchers concluded that the “intake of menaquinones, which is highly determined by the consumption of cheese, is associated with a reduced risk of incident and fatal cancer.”

Researchers at Minnesota’s Mayo Clinic have found that people who have higher intakes of vitamin K have a lower risk of developing Non-Hodgkin lymphoma.  Those in the top quarter of vitamin K1, from diet and dietary supplements, had a 45 percent less risk for developing this cancer of immune cells.  As I mentioned earlier, warfarin disables a cell’s vitamin K activity in the fat-soluble antioxidant network, which by definition exposes cells to higher amounts of free radical damage and potential mutation. 

A new study evaluated warfarin21 use in men showing up with prostate cancer. Two years or less of warfarin use did not pose a problem in terms of prostate cancer severity.  However, men taking warfarin for four or more years had a 220 percent increased risk of having advanced prostate cancer.  This finding is consistent with having long-term depletion of antioxidants. 

Collectively all these studies show that vitamin K2 is a potent health boosting nutrient.  Its primary function is to make various key proteins biologically active so that they can perform bone building, enhance cardiovascular fitness, improve blood sugar metabolism, carry on normal blood clotting, and help protect against cancer.  That is quite an array of powerful functions to attribute to one nutrient.  Sadly, the biological activity of this important nutrient is routinely blocked by the ridiculous and paranoid overuse of warfarin – a crime against elderly Americans and a testament to the lack of understanding of the medical profession on how to actually improve cardiovascular health for patients in need. 

Article originally published on July 8, 2010.  Updated on May 19, 2011.


Referenced Studies:
  1. ^ Vitamin K as an Antioxidant  Biochem Pharmacol.   Vervoort LM, Ronden JE, Thijssen HH.
  2. ^ Warfarin Use and the Risk of Bone Fractures  Arch Intern Med.  Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF.
  3. ^ Vitamin K Reduces Fracture Risk  Nutr Res.  Iwamoto J, Sato Y, Takeda T, Matsumoto H.
  4. ^ Vitamin k Levels and Hip Fracture Risk  American Journal of Clinical Nutrition  Sarah L Booth, Katherine L Tucker, Honglei Chen, Marian T Hannan, David R Gagnon, L Adrienne Cupples, Peter WF Wilson, Jose Ordovas, Ernst J Schaefer, Bess Dawson-Hughes and Douglas P Kiel
  5. ^ Vitamin K2 Boosts Osteocalcin Function  Clin Calcium.  Amizuka N, Li M, Guo Y, Liu Z, Suzuki R, Yamamoto T.
  6. ^ Vitamin K2 Promotes Hip Bone Strength  Osteoporosis  Knapen MH, Schurgers LJ, Vermeer C.
  7. ^ Vitamin K2 Prevents Fractures in Osteoporosis Patients  J Bone Miner Res.  Shiraki M, Shiraki Y, Aoki C, Miura M.
  8. ^ Vitamin K2 Lowers NF-KappaB  J Nutr Biochem.  Ohsaki Y, Shirakawa H, Miura A, Giriwono PE, Sato S, Ohashi A, Iribe M, Goto T, Komai M.
  9. ^ This form of vitamin K2    
  10. ^ Animal studies with vitamin K2    
  11. ^ Vitamin K2 Preserves Bone Health in Transplant Patients  Transplantation.  Forli L, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O.
  12. ^ Vitamin K2 as Menaquinone-7 Boosts Bone Health in Children  Br J Nutr.  van Summeren MJ, Braam LA, Lilien MR, Schurgers LJ, Kuis W, Vermeer C.
  13. ^ Lack of Vitamin K Leads to Cardiovascular Calcification  Journal of Vascular Research  Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC.
  14. ^ Vitamin K2 Reduces Cardiovascular Disease and All-Cause Mortality  J Nutr.  Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.
  15. ^ Vitamin K-dependent Proteins, Warfarin, and Vascular Calcification  Clin J Am Soc Nephrol.  Danziger J.
  16. ^ How Warfarin Causes Vascular Calcification  Thromb Haemost.   Koos R, Krueger T, Westenfeld R, Kühl HP, Brandenburg V, Mahnken AH, Stanzel S, Vermeer C, Cranenburg EC, Floege J, Kelm M, Schurgers LJ.
  17. ^ Proof Warfarin Causes Increases Heart Valve and Arterial Calcification  Am J Cardiol.   Koos R, Mahnken AH, Mühlenbruch G, Brandenburg V, Pflueger B, Wildberger JE, Kühl HP.
  18. ^ Vitamin K2 is Inversely Associated with Diabetes Risk  Diabetes Care.  Beulens JW, van der A DL, Grobbee DE, Sluijs I, Spijkerman AM, van der Schouw YT.
  19. ^ Osteocalcin is Needed to Protect Against Metabolic Syndrome  Eur J Endocrinol.   Yeap B, Chubb SA, Flicker L, McCaul K, Ebeling P, Beilby J, Norman PE.
  20. ^ Vitamin K2 Reduces Cancer Rate and Mortality  Am J Clin Nutr.   Nimptsch K, Rohrmann S, Kaaks R, Linseisen J.
  21. ^ Warfarin and Advanced Prostate Cancer  Pharmacoepidemiol Drug Saf.  Tagalakis V, Tamim H.

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