First discovered in 1929, vitamin K has long been recognized as necessary for healthy blood clotting. This, of course, is a critical function—without sufficient vitamin K, we would bleed to death from even a minor wound. But in the past decade, vitamin K has been shown to play a much greater role in health than was previously recognized.
Research shows that vitamin K, in synergy with vitamin D, is an essential nutrient for building strong bones. Vitamin K also supports cardiovascular health, promotes an appropriate inflammatory response, ensures healthy cellular function, and provides redox/antioxidant activity.
What Exactly Does Vitamin K Do?
When talking about vitamin K, it’s important to understand that there are two main forms to consider. Vitamin K1, or phylloquinone, is found in green leafy vegetables such as broccoli, kale, and spinach. K1 goes directly to the liver and helps to maintain healthy blood clotting. Vitamin K2, or menaquinone, is made by microflora in the gastrointestinal tract. K2 bypasses the liver and goes directly to the bones, blood vessels, and other tissues.
Menaquinones can also be found in foods, but are not abundant in the typical Western diet. For example, small amounts of MK4 can be found in eggs, butter, and meat from pastured animals; MK7, MK8, and MK9 are found in fermented food products, including kefir, brie, and sauerkraut. The Japanese delicacy natto (a fermented soybean product) is by far the richest source of MK-7, but it is an acquired taste, and not one that many Westerners enjoy.
Vitamin K1 makes up about 90% of the vitamin K in a typical Western diet, whereas Vitamin K2 makes up only about 10%. In general, we’re not getting enough Vitamin K2, and this deficiency is creating a plethora of health problems.
One of the primary functions of K2 is to regulate calcium metabolism. K2 acts like a traffic cop, ensuring that calcium is delivered into the bones and teeth (where it belongs), while staying out of soft tissues (where it doesn’t belong). As we age, our bodies are less efficient at regulating calcium balance. This, in combination with insufficient dietary intake of vitamin K, causes calcium to accumulate in soft tissues throughout the body. Diseases of aging such as arthritis, bone spurs, cataracts, kidney stones, and coronary artery disease are the result.
Ensuring optimal vitamin K levels may help to protect against these diseases by restoring proper calcium metabolism. Studies show that higher levels of vitamin K benefit vitamin K-dependent proteins, including the bone protein osteocalcin. For this reason, vitamin K2 is widely used in treating osteoporosis. Clinical studies have shown that vitamin K not only increases bone density in osteoporosis, but also reduces fracture rates.1
The wider benefits of vitamin K were highlighted in a 2009 study, which demonstrated that vitamin K deficiency induced by chronic anticoagulant (warfarin) therapy is a causal factor in age-associated conditions including bone fragility and arterial calcification linked to cardiovascular disease.2
Intriguing research also indicates that vitamin K may be beneficial for inhibiting unhealthy cell growth and regulating apoptosis, which makes it a promising adjunct to cancer therapies.3
Vitamin K and Cardiovascular Health
Calcification of the arteries—which of course, are soft tissues—is a huge risk factor for cardiovascular disease. In fact, research shows that the calcium score test, which measures artery calcification, is a much more accurate indicator of future heart disease than cholesterol levels. Vitamin K appears to be one of the most powerful agents known for protecting the arteries from calcification.
Calcification of the arteries can begin as early as the second decade of life, and it’s pretty much universal by age 65 (of course, there are great variances among individuals). Calcification occurs in the cardiovascular system in two places: the tunica media (the middle layer of the artery) and the tunica intima (the innermost layer of the artery). The tunica media contains elastic fibers that allow the artery to stretch and accommodate changes in blood pressure. The tunica intima is where atherosclerosis develops. Keeping calcium out of these tissues maintains the elasticity of arteries, and allows for unimpeded blood flow.
In addition to preventing calcification of the arteries, vitamin K2 also appears to protect against atherosclerosis by inhibiting inflammation and the accumulation of lipids and white blood cells that cause plaque formation.
The potential heart health benefits of vitamin K are supported by findings from both observational and intervention trials. Data from the European Prospective Investigation into Cancer and Nutrition (EPICNL) cohort, published last year in Clinical Nutrition, indicated that increased intakes of long chain menaquinones (vitamin K2) might reduce the risk of mortality from coronary heart disease (CHD). More support comes from data from a long-term intervention study using NattoPharma’s MenaQ7 vitamin K2, which showed that a daily dose of 180 micrograms per day for three years inhibited agerelated stiffening of the artery walls and improved vascular elasticity.4
Other studies show that an overall higher intake of vitamin K is associated with decreased serum levels of the inflammatory marker CRP (C-reactive protein). Laboratory research suggests that high doses of vitamin K2 (100mg/kg/body weight daily) may inhibit arterial calcification and reduce coronary calcification, as well as lowering total cholesterol and decreasing lipid peroxidation.5
How Vitamin K2 Inhibits Arterial Calcification
Vitamin K has been shown to reduce arterial stiffness, and it does so in a complex metabolic process that begins in the liver. Through an activity called carboxylation, vitamin K activates proteins that have widespread effects throughout the body, including regulating blood clotting and the movement of calcium. The liver uses K1 to carboxylate clotting factors, while K2 is the preferred form to carboxylate other vitamin K-dependent proteins, including osteocalcin, which is essential for bone health, and matrix-Gla protein (MGP), which prevents calcification of blood vessels, organs, and other soft tissues. This includes moving osteocalcin into bones, and shuttling matrix Gla-protein (MGP) out of blood vessels.
It is generally accepted that MGP is a potent inhibitor of arterial calcification, and MGP is dependent upon sufficient levels of vitamin K2. Obviously, maintaining an optimal vitamin K intake is essential to keep the risk and rate of calcification as low as possible. In a study published in the American Journal of Hypertension, researchers looked at data from 66 diabetics (type 2) and found that levels of inactive MGP (matrix GLAprotein) correlated with artery stiffness.6
Similar correlations were reported in the journal Nephron for a study of 83 people with chronic kidney disease. This study was conducted to explore the correlations of plasma dp-ucMGP with vascular calcification and vascular stiffness in chronic kidney disease (CKD) patients. The researchers determined that plasma dp-ucMGP was positively associated with vascular calcification and might be utilized as an early marker for vascular calcification in CKD patients.7
Vitamin K and Warfarin: Why The Conventional Medical Protocol Is Wrong
The drug warfarin and other vitamin K antagonists (VKA’s) are commonly used to prevent blood clots that can cause heart attacks and strokes. These drugs are prescribed for people with atrial fibrillation, pulmonary embolism, artificial heart valve, or hip surgery. One of the side effects of warfarin and other VKA’s is that they inhibit the normal function of vitamin K in the body by blocking the carboxylation of MGP and other important inhibitors of mineralization. Research shows that patients who take warfarin are at especially high risk of developing aortal stenosis and excessive arterial calcification, resulting in a greatly increased risk of heart disease and stroke.8
Studies show that large doses of vitamin K (especially K2) prevent warfarin-induced vascular calcification. MGP appears to block calcium deposition via two mechanisms—directly by forming a complex with fetuin-A; and indirectly, blocking BMP-2 osteogenic differentiation.8 Unfortunately, it has been common practice to discourage patients taking warfarin from eating vitamin-K-rich foods, such as green leafy vegetables. The reasoning is that dietary vitamin K intake could counteract the anticoagulant effect of the drugs. This conclusion is not only wrong; it is dangerous to the long-term health of those who take warfarin.
Based on a summary of all the data to date, evidence of the effects of dietary intake of vitamin K on coagulation response appears to have both positive effects on mitigating side effects relating to arterial stiffness/calcification, while assisting better control of INR. Some studies found a negative correlation between vitamin K intake and INR changes (a measure of how long it takes blood to clot), while others suggested that a minimum amount of vitamin K is required to maintain adequate anticoagulation.
The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. In fact, restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habits, avoiding wide changes in the intake of vitamin K.10
More supportive research comes from a recent multi-center, placebo-controlled, randomized trial conducted at four university-affiliated hospitals in Canada. In the study, patients on chronic warfarin therapy received oral vitamin K (150 mcg daily) or a placebo for a total of six months. The researchers observed that daily supplementation with low-dose oral vitamin K (LDVK) and warfarin improved INR stability.11
As a clinical herbalist, I also believe that it’s important to note that herbs (including St John’s wort, Asian ginseng, Ginkgo biloba, and ginger) 12 or specific foods (such as those rich in vitamin K) have little to do with people having difficulty regulating their warfarin dosage. What matters most is pharmacokinetics—the movement of a drug within the body, including the absorption, bioavailability, distribution, metabolism, and excretion of the drug. There is currently a wealth of data surrounding genetic polymorphisms in two genes, CYP2C9 and VKORC1, and how these specific polymorphisms affect variation in warfarin dose requirements.13
How To Insure That You’re Getting Enough Vitamin K
It’s obvious that vitamin K is essential for optimal health, and for protecting against cardiovascular disease and other diseases associated with aging. It’s easy to get enough vitamin K1 from dark leafy greens. But modern life and agricultural practices have left most of us deficient in vitamin K2.
Studies show significant benefits from supplementing with vitamin K2. The Vitamin K I recommend is vitamin K1 and K2 in combination with vitamins D and A. Vitamin D, vitamin K and the carotenoid complex are known for their beneficial pleiotropic influence on healthy immune response, cell-cycle functions, bone, and cardiovascular health. These vitamins also promote a healthy inflammatory response and provide antioxidant activity. The vitamin A I recommend is derived from whole red palm oil, which provides a diversity of naturally occurring highly bioavailable carotenoids within a fatty emulsion. Red palm oil is also one of the richest sources of tocotrienols.14
As almost always holds true, I find that combining nutrients delivers far greater results than taking isolated nutrients. In addition, there are numerous benefits to using highly bioavailable, food-based forms of nutrients. (For an in-depth discussion of quality nutritional supplements, see my blog “Do You Know What’s In Your Supplements?”)
- Booth S. Vitamin K and the skeleton. Proceedings of the 4th International Symposium on Nutritional Aspects of Osteoporosis. May 17-20, 2000; Lausanne, Switzerland. In: Burckhardt P, Dawson-Hughes B, Heaney RP, eds. Nutritional Aspects of Osteoporosis. A Serono Symposia S.A. Publication. New York, NY: Springer-Verlag New York, Inc. 2000.
- McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009 Oct; 90(4):889-907. doi: 10.3945/ajcn.2009.27930. Review.
- Tamori A, Habu D, et al. Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res. 2007 Sep. 37 Supp (2):S303-307.
- Thamratnopkoon et al. “Correlations of Plasma Desphosphorylated Uncarboxylated Matrix Gla Protein with Vascular Calcification and Vascular Stiffness in Chronic Kidney Disease.” Thrombosis and Haemostasis. 2015 Vol. 113, No. 5, pp. 911–1157.
- Schurgers LJ, Dissel PE, et al. Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001. 90 Suppl(3):57-63.
- Sardana M. et al. “Inactive Matrix GlaProtein and Arterial Stiffness, in Type 2 Diabetes Mellitus” American Journal of Hypertension, December 7, 2016, doi: 10.1093/ajh/hpw146Published online ahead of print, doi: 10.1159/000453368.
- Thamratnopkoon S, Susantitaphong P, Tumkosit M, Katavetin P, Tiranathanagul K, Praditpornsilpa K, Eiam-Ong S. Correlations of Plasma Desphosphorylated Uncarboxylated Matrix Gla Protein with Vascular Calcification and Vascular Stiffness in Chronic Kidney Disease; Nephron.2016 Dec 13.
- Howe & Webster, Warfarin exposure and calcification of the arterial system in the rat, International Journal of Experimental Pathology, Volume 81 Issue 1, Pages 51 – 56, Published Online: 25 Dec 2001, Department of Anatomy, University of Sydney, Sydney, NSW, Australia
- Karwowski W, Naumnik B, Szczepański M, Myśliwiec M. The mechanism of vascular calcification – a systematic review, Med Sci Monit.2012 Jan;18(1):RA1-11.
- Violi F1, Lip GY, Pignatelli P, Pastori D. Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review. Medicine (Baltimore).2016 Mar;95(10):e2895.
- Boonyawat K, Wang L, Lazo-Langner A, Kovacs MJ, Yeo E, Schnurr T, Schulman S, Crowther MA. The effect of low-dose oralvitamin K supplementation on INR stability in patients receivingwarfarin. A randomised trial. Thromb Haemost. 2016 Aug 30;116(3):480-5. doi: 10.1160/TH16-04-0320.
- Jiang X., Blair EY., McLachlan AJÆ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokineticpharmacodynamic modeling approach, J Clin Pharmacol. 2006 Nov;46(11):13708.
- Shah SH, Voora D. Warfarin dosing and VKORC1/CYP2C9. Available at: http://emedicine.medscape.com/article/1733331-overview Accessed May 30, 2011. Anderson JL, Horne BD, Stevens SM, et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation. 2007;116:2563-2570.
- Oguntibeju OO, Esterhuyse AJ, Truter EJ. Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life. Br J Biomed Sci. 2009;66(4):216-22.