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Thursday, January 20, 2011

Amazing Vitamin K


The Amazing Vitamin K Story

by JP Saleeby, MD

In very recent years, the medical and scientific communities have begun to focus their attention on the benefits of Vitamin K.  While not as popular as its big brother, Vitamin D, Vitamin K will no doubt come to the attention of mainstream media as soon as its many benefits are realized by the public.   In the last five years, primary care physicians and specialists are testing Vitamin D levels on almost every patient.  As research has poured in on the many health benefits in multiple arenas, from bone health to immune function, Vitamin D therapy is now considered standard of care.  Likewise, Vitamin K is slowly gaining momentum in the public eye and in doctor’s offices. 

Of historical interest, Vitamin K was first discovered as a compound in the 1930's.  It was reported in a German science journal as koagulationvitamin for its control over coagulation, hence the letter designation “K” for koagulation.  Newsworthy in the mid-20th century, Vitamin K made headlines when the 1943 Nobel Prize in Medicine was shared by American Dr. Edward A. Doisy and German Dr. Henrik Dam for their work with this vitamin.  As early as 1938, the first report of using Vitamin K to treat a life threatening case of hemorrhage due to liver disease was documented.  Its use as a therapeutic saved the patient from certain death.

Vitamin K is a lipophilic vitamin (meaning it is fat soluble) and is required chiefly for blood coagulation and metabolism of bone and other tissues.  There are two natural forms of this vitamin and several synthetic versions.  Vitamin K1, also known as phytomenadione, and Vitamin K2, menaquinone, are the two natural forms.  Vitamin K2 is produced chiefly by bacteria in our large intestines. Vitamin K1 is found in green leafy vegetables such as spinach, turnip greens, Swiss chard, and the brassica vegetables like cabbage, broccoli, Brussels sprouts, and kale.  Fruits like kiwifruit and avocado, as well as soybean oil are other food sources of Vitamin K.

The chief utilization of Vitamin K in medicine as a "therapeutic" is in its role with the coagulation of blood.  It plays a key role in factors II, VII, IX and X as well as in protein-C and protein-S.  All of these blood factors and proteins are linked to the clotting cascade that prevents us from hemorrhaging in the event of a severe traumatic injury.  Additionally, Vitamin K has a significant role in bone metabolism with a relation to osteocalcin.  It acts as a bone building hormone in a way, much like Vitamin D.    Osteocalcin is synthesized by Vitamin K and is the "matrix" in bone that holds the calcium molecules together.  Without Vitamin K, hip bone fracture rates increase despite adequate Vitamin D and calcium intake.  In the 1998 Nurse’s Health Study, oral administrations of 110 micrograms per day of Vitamin K proved to decrease hip fractures when compared to control subjects. 

Vitamin K is important in vascular biology as well, especially in the realm of artery plaque formation (calcification).  There are Vitamin K dependent proteins involved in atherosclerosis or hardening of the arteries.   The process of calcium plaque formation is hindered with adequate Vitamin K levels in circulation.  Warfarin (Coumadin ®) is a drug often used to treat folks with coronary artery disease (CAD) and to prevent blood from clotting in heart chambers and deep veins where severe compilations may arise.  However, while treating certain medical conditions with these blood thinners, which inactivate Vitamin K, we create other problems.  Chief among these problems are an increase in our risk for developing arterial plaques, the possibility of affecting our immune system, and the likely impediment of bone mineralization.

Vitamin K's effect on coronary arteries goes like this.  With low levels of circulating Vitamin K in the serum, there is an impact on the function of a protein within the endothelial lining of the arteries called the Matrix Gla protein (MGP).  The effect of low Vitamin K on this protein is that it allows for an increase deposition of calcium in arteries.  Drugs that lower Vitamin K's effect in a sense raise the risk for coronary artery disease.  Vitamin K facilitates our immune system with positive links to phagocytosis and chemotaxis (the process by which “microorganism attacking cells" in our body find and eliminate infectious organisms).  Furthermore, Vitamin K appears to have a role in apoptosis, the process of natural and desirable cell death.  Apoptosis is the process by which our bodies can eliminate damaged, old or mutated cells thus reducing many forms of cancers.

Because Vitamin K2 is produced by bacteria in the human alimentary tract, the overuse of broad-spectrum antibiotics can wipe out this good type of bacteria in our intestines and may cause a relative deficiency.  Poor nutrition with inadequate consumption of greens and fruit is another way to attain deficiency.  Both means of deficiency can lead to clotting dysfunction, immune disruption, bone loss, and coronary disease.  With a look at the latest research, it appears that Vitamin K2 is longer acting, has better bioavailability, and provides better bone strength when compared to Vitamin K1 supplementation.  A subset of Vitamin K2 known as menaquinone–7, or MK–7 shows promise in current research as even a more potent form of Vitamin K.  In the future, we may learn the better Vitamin K supplement to take is in fact MK-7.

There is no known upper limit or toxic level of the natural Vitamin K1 & K2, however, scientists show toxicity with the synthetic forms and that they should be avoided as a source of supplementation.  This fact was demonstrated in a recent ban on synthetic Vitamin K3 due to the occurrence of hemolytic anemia and cytotoxicity.  This is yet another example of how natural compounds often trump synthetics in nutritional medicine.  It appears Mother Nature can rarely be outperformed in the lab.

How to get the most Vitamin K out of your veggies?  Well, cooking them in water will yield less concentration due to the hydrophobic properties of this vitamin.  You will probably throw out much of the Vitamin K in your vegetables when you pour off the cooking water.  Cooking them in oil (sautéing in olive oil, for example) will retain the bioavailability of this vitamin three-fold.  Eating meat, eggs, and dairy is another source of providing Vitamin K2 in addition to that produced by E. coli in our gut.  But it is with a healthy gut microflora that we acquire most of our Vitamin K2.

Deficiencies can occur with Inflammatory Bowel Syndrome (IBS), cystic fibrosis, alcoholism, liver disease, in bulimics, and those taking chronic anticoagulants, antibiotic therapy, and salicylates.  Bleeding and bruising disorders are signs of deficiency; osteoporosis and coronary artery disease (CAD) are also associated, but realized over the course of many years.  Unlike many other vitamins, Vitamin K is recycled in our bodies, thus reducing the threat of deficiency, provided both enzymes responsible for this process in our bodies are working well.  Warfarin (Coumadin ®) blocks Vitamin K epoxide reductase (VKOR), one of the two enzymes responsible for Vitamin K recycling and maintaining healthy levels.  Interesting to note, long term use of aspirin (ASA) and
cephalosporins (an antibiotic class) can lead to K1 deficiencies by interference with enzyme function.  Furthermore, the drugs cholestyramine, cholestipol, orlistat, and the fat substitute, olestra, have been noted to decrease Vitamin K absorption, in all probability leading to a drop in serum Vitamin K levels that can affect health. 
Because newborns are susceptible to clotting abnormalities, due to immature livers and sterile guts (inability to have E. coli produce Vitamin K2), they are usually born deficient in varying degrees.  There is a 1.5% incidence of unexpected bleeding in newborns due to low levels of Vitamin K.  Mothers on anticonvulsants, rifampin and isoniazid (both antibiotics) while pregnant tend to have offspring with sterile guts and an even higher incidence of Vitamin K deficiency.  Therefore, the American Academy of Pediatrics recommends about 1.0 milligram of Vitamin K1 be administered to each newborn. 

There is a connection in theory with Alzheimer’s disease.  The APOE4 gene that has been implicated in Alzheimer's disease seems to be responsible for low Vitamin K levels in this subset of patients.  It is surmised that supplementation with Vitamin K may reduce the occurrence of Alzheimer's disease, but more research is needed.  There also appears to be a connection with some types of cancers.  Interestingly, there are two Japanese studies showing females with liver disease with a high risk for liver cancer, having a 90% reduction in development of liver malignancy if they were supplemented with Vitamin K.  In a 2008 published German study of male subjects, there was a drop in prostate cancer risk with Vitamin K supplementation.

Vitamin K must be rather important to our body as there are at least three ways in which it is maintained; by diet (eating greens), by production in our gut (bacterial), and by enzymatic recycling.  Sometimes the importance of a particular substance can be found in the redundancies our body creates to conserve it, such is the case with Vitamin K.


Pearls from Dr. Saleeby:
  • Vitamin D dependent osteoblasts effect production of osteocalcin, a Vitamin K dependent protein, leading to good bone health, as long as both vitamins are in adequate and balanced supply.
  • Growth arrest specific gene 6 protein (Gas6) a Vitamin K dependent protein is responsible for cellular growth regulation factor found in nerve tissue, heart, lung, kidney and cartilage.
  • Good idea to supplement with between 10 - 120 mcg/d of Vitamin K2 (providing Coumadin users are monitored closely under physician supervision).
  • Large Vitamin A doses have been noted to affect absorption of Vitamin K, while large doses of Vitamin E can affect and antagonize Vitamin K enzymatic activity.  We see a rise in bleeding risk with large doses of Vitamin E intake.  There is a balance between the fat soluble vitamins that needs to be adhered to.  It is unwise to guess and gamble with what you take and supplement.
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JP Saleeby, MD is an integrative and nutritional medicine practitioner.  He has been the chief formulator for a number of independent nutraceutical companies.  He is a medical writer / blogger and offers telemedicine consultations to his patients.

(c) 2011

References:

Berkner, K. L. and Runge, K. W. (2004), “The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis”. Journal of Thrombosis and Haemostasis, 2: 2118–2132.

Neil C Binkley, Diane C Krueger, Tisha N Kawahara, Jean A Engelke, Richard J Chappell and John W Suttie. (2002) "A high phylloquinone intake is required to achieve maximal osteocalcin {gamma}-carboxylation". American Journal of Clinical Nutrition 76 (5).

Higdon (2008).
"Vitamin K". Linus Pauling Institute, Oregon State University. http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/. Retrieved 01-10-2011.

Warner, E.D.; Brinkhous, K. M.; Smith, H. P. (1938). Proceedings of the Society of Experimental Biology and Medicine 37: 628.

Stafford, D.W. (2005), “The vitamin K cycle.”. Journal of Thrombosis and Haemostasis, 3: 1873–1878.

Saxena S.P.; Israels, E.D.; Israels L.G. (2001). "Novel vitamin K-dependent pathways regulating cell survival.". Apoptosis 6 (1-2): 57–68.

Nimptsch K, Rohrmann S, Linseisen J (2008). "Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. (EPIC-Heidelberg)". Am. J. Clin. Nutr. 87 (4): 985–92.

Brown, S.E.,
"Key vitamins for bone health — vitamins K1 and K2". www.womentowomen.com. http://www.womentowomen.com/bonehealth/keynutrients-vitamink.aspx. Retrieved Jan., 10 2011.

Nimptsch K, Rohrmann S, Linseisen J (2008).
"Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. (EPIC-Heidelberg)". Am. J. Clin. Nutr. 87 (4): 985–92.

Allison (2001). "The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease.". Medical hypotheses  57 (2): 151–5.

Habu, D., (2004) "Role of Vitamin K2 in the Development of Hepatocellular Carcinoma in Women With Viral Cirrhosis of the Liver.". JAMA, 292 (3): 358-361.

Bellido-Martin, L. (2008) "Vitamin K-dependent actions of Gas6.". Vitam. Horm. 78:185-209.

Hendler S.S., Rorvik D.R., eds. (2001) “PDR for Nutritional Supplements.”. Montvale: Medical Economics Company.

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