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Integrative Medicine and Wellness

with Joe Pizzorno, Jr., ND

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Thursday, November 29, 2007

Vitamin K – Keeping Calcium in Your Bones and Out of Your Blood Vessels

You may have thought vitamin K was all about blood clotting – the necessary kind that prevents you from bleeding to death when you get cut or injured – but this nutrient plays other roles just as essential to your health. New research reveals that vitamin K controls calcium, keeping it in your bones and out of your blood vessels.

In nature, vitamin K is found in primarily in two forms – K1 (phylloquinone) and K2 (menaquinone).

K1 is the form in which vitamin K produces clotting factors. Produced by plants and algae, K1 is found in green leafy vegetables such as broccoli, kale and Swiss chard, and in plant oils, such as canola and soybean oil.

K2 is more potent and has the widest range of activity. Far more active than K1 in both bone formation and reduction of bone loss, K2 is also the form in which vitamin K has been found to protect against arterial calcification and the oxidation (free radical damage) of LDL cholesterol. (Schurgers LJ, Dissel PE, et al. Z Kardiol 2001; Jono S, Ikari Y, et al. Thromb Haemost 2004)

Produced by bacteria and also via the conversion of K1 to K2 by beneficial bacteria in the intestines of animals, including humans, K2 is better absorbed than K1 and remains active far longer; K1 is cleared by the liver within 8 hours, but measurable levels of K2 have been detected 72 hours after ingestion. (Schurgers LJ, Teunissen KJ Blood 2007)

Natto (fermented soybeans) is the richest dietary source of vitamin K2. Dairy products (milk, butter, cottage cheese, cheese) and egg yolk also provide small amounts.

How Does Vitamin K Work in the Body?

Vitamin K carboxylates Gla-proteins. Carboxylation activates these proteins, which have widespread effects throughout the body, including regulating blood clotting and calcium. Fifteen Gla-proteins have been identified, but researchers think up to 100 may yet be discovered. (Uotila L, Scand J Clin Lab Invest Suppl 1990)

K1 is the preferred form used in the liver to carboxylate clotting factors, while K2 is preferentially used in the rest of the body to carboxylate the other vitamin K-dependent Gla-proteins, including osteocalcin, which is essential for bone health, and matrix-Gla protein, which prevents calcification of soft tissue, i.e., blood vessels and organs.

Vitamin K aids bone health in a number of ways:

  • After it’s carboxylated by vitamin K2, osteocalcin can latch on to calcium and bind it to hydroxyapatite crystals forming the bone matrix. (Think of carboxylation as adding a trailer hitch to calcium, allowing it to be towed into and attached to bone.) (Bügel S, Proc Nutr Soc 2003)
  • Vitamin K2 also teams up with vitamin D3 to increase the production of Gla-proteins, including osteocalcin in osteoblasts (the cells that build bone), while also inhibiting the production of osteoclasts (the cells that break down bone). (Plaza S, Lamson D. Alt Med Rev 2005, Masterjohn C. Med Hypotheses 2007; Yamaguchi M, Sugimoto E, et al. Mol Cell Biochem 2001; Yamaguchi M, Uchiyama S, et al. Mol Cell Biochem 2003)
  • K2 works synergistically with bisphosphonate drugs, such as Fosamax, which lessen bone loss by poisoning osteoclasts (the cells that break down old bone). In a study of postmenopausal women with osteoporosis, fractures were experienced by 2 out of 25 women taking a bisphosphonate, 6 of 24 women taking calcium lactate, and only 1 of 26 women taking vitamin K and a bisphosphonate. (Iwamoto J, Takeda T, et al. Yonsei Med J 2003)

Research has linked osteoporotic fracture with vitamin K insufficiency for more than 20 years. A study published in 1984 found that patients who suffered fractures caused by osteoporosis had vitamin K levels 70% lower than age-matched controls. This association has been repeatedly confirmed with one recent trial involving almost 900 men and women finding those with the lowest blood levels of vitamin K had a 65% greater risk of hip fracture compared to those with the highest levels of the nutrient. (Hart JP, Lancet 1984; Bitensky L, Hart JP et al, J Bone Surg Br 1988; Hodges SJ, Pilkington MJ, et al. Bone 1991; Booth SL, Tucker KL, et al. AJCN 2000 )

Supplementation with vitamin K2 has been shown to be an effective treatment against osteoporosis. A review study of randomized controlled human trials of at least 6 months duration that assessed the use of vitamin K1 or K2 to lower fracture risk identified 13 trials. In all but one, vitamin K reduced bone loss with K2 being most effective, reducing risk of vertebral fracture by 60%, hip fracture by 77%, and all non-vertebral fractures by 81%. (Cockayne S, Adamson J, et al. Arch Intern Med 2006)

Vitamin K Combats Cardiovascular Disease

When levels of vitamin K are insufficient, high levels of uncarboxylated (inactive) osteocalcin float around in the bloodstream. Not only is calcium not delivered to the bones, which become porous, but it’s deposited in the arteries, which become calcified. (Bitensky L, Hart JP, et al. J Bone Joint Surg Br 1988; Schurgers LJ, Dissel PE, et al, Z Cardiol 2001; Demer LL, Tintut Y, et al. Curr Opin Nephrol Hypertens 2002; Berkner KL, Rune KW, J Thromb Haemost 2004; Braam LA, Hoeks, AP, et al. Thromb Haemost 2004; Adams J, Pepping J. Am J Health Syst Pharm 2005; Purwosunu Y, Muharran, et al. J Obstet Gynaecol Res 2006; Cranenburg EC, Schurgers LJ, et al. Thromb Haemost 2007)

Cardiovascular disease is not just about cholesterol, which, if oxidized, can cause atherosclerosis, the formation of plaques on the innermost wall of the arteries. Just as lethal is arteriosclerosis, hardening of the arteries due to calcium deposits in their muscular midsection. Arteriosclerosis is the major culprit behind those surprising sudden deaths that occur in young men whose cholesterol levels are just fine.

Sudden death from heart attack is much more highly correlated with calcification of the aorta than cholesterol. In Framingham study research, aortic calcification was associated with double the risk of death from cardiovascular disease in men and women younger than 65, even after other risk factors (e.g., cholesterol) were taken into account. In men younger than 35, calcification of the aorta increased risk of sudden coronary death 7-fold. (Witteman JC, Kannel WB et al. Am J Cardiol 1990; Pohle K, Ropers D, et al. Heart 2003; Iribarren C, Sidney
S et al. JAMA 2000)

In other research involving more than 100,000 men and women in California, aortic calcification increased risk of coronary heart disease 127% in men and 122% in women. Among women, it also increased risk of stroke 146%. (Iribarren C, Sidney S. JAMA 2000)

Fortunately, one of the vitamin K2-dependent proteins, matrix Gla-protein (MGP) is the strongest inhibitor of tissue calcification presently known. MGP is produced by small muscle cells in the vasculature where – once carboxylated by vitamin K2 – it binds to and inhibits a protein called bone morphological protein-2 (BMP-2). BMP-2 causes calcium deposition in blood vessels. (Kaneki M, Takayuki H, et al., Nutrition 2006; Demer LL, Tintut Y et al, Curr Opin Nephrol Hypertens 2002)

K2 also helps promote blood vessel elasticity by safeguarding elastin, the core protein in the muscle fibers primarily responsible for the elasticity of the arterial wall. Existing elastin is damaged and new production is inhibited by calcium deposition. (Seyama Y, Wachi H. J Athero Thromb)

In the Rotterdam study, a major European clinical trial following 4,807 subjects aged at least 55 over a 7-10 year period, researchers found that K2, but not K1, significantly reduced risk of cardiovascular disease by 57%, death from all causes by 26%, and severe aortic calcification by 52%. K1 had no beneficial effects. (Geleijnse JM, Vermeer C, et al. J Nutr 2004)

Special K Benefits for Postmenopausal Women: Combating the Calcification Paradox

As women enter menopause, they simultaneously lose calcium from bone and increase its deposition in arteries – a negative double whammy called the “calcification paradox,” which greatly increases risk of both osteoporosis and cardiovascular disease. (Adams J, Pepping J, Am J Health Syst Pharm 2005) The drop in estrogen causes both problems, but vitamin K can help rectify them.

A 3-year study of 325 postmenopausal women receiving either K2 or placebo found that supplementation with K2 can prevent bone loss associated with estrogen decline. In the women given K2, bone mineral content increased, and hip and bone strength remained unchanged, whereas in the placebo group, bone mineral content and bone strength decreased significantly. (Booth SL, Broe KE, J Clin Endocrinol Metab; Knapen MH, Schurgers LJ, Osteoporos Int. 2007)

Plus, the vitamin K-dependent matrix-Gla protein that inhibits vascular calcification helps maintain the elasticity of postmenopausal women’s blood vessels. In a 3-year study of 181 postmenopausal women, one-third were given a supplement containing vitamin D, one-third got a supplement providing both vitamin K1 and D, and one-third were given a placebo. In both the vitamin D and the placebo group, the elasticity of the common carotid artery decreased, while in those given K along with D, elasticity was maintained. (Braam LA, Hoeks AP, Thromb Haemost 2004)

Should You Supplement with Vitamin K?

While it is unlikely that your vitamin K levels are insufficient to meet clotting needs, levels of vitamin K necessary for clotting are much lower than those needed for bone and arterial protection. Studies of healthy adults have found high levels of uncarboxylated osteocalcin and matrix Gla-protein (MGP) in all subjects tested. (Cranenburg EC, Schurgers LJ et al. Thromb Haemost 2007)

Deficiency is more likely in people with digestive problems such as celiac disease, irritable bowel disease, or who have had intestinal bypass surgery, since vitamin K is a fat-soluble nutrient, and these conditions increase the likelihood of fat malabsorption.

Our vitamin K needs also increase with age. Older individuals (over age 70) require higher levels of vitamin K. (Tsugawa N, Shiraki M, et al. Am J Clin Nutr 2006)

Bile acid sequestrants (e.g., Cholestyramine, Colestipol), a class of drugs used to lower cholesterol levels, also bind and carry out fat-soluble vitamins, including vitamin K.

Anticoagulant medications, such as Coumadin, decrease clotting by interfering with vitamin K and may actually cause arterial calcification by preventing vitamin K from activating matrix Gla-protein. (Uotila L, Scand J Clin Lab Invest Suppl 1990; Schurgers LJ, Aebert H, et al. Blood 2004) Two recent studies involving more than 100 subjects have shown that patients treated with oral anticoagulants have double the calcification of patients not on these vitamin K-blocking drugs. (Schurgers LJ, Aebert H, Blood 2004; Koos R, Mahnken AH, Am J Cardiol 2005).

People taking these medications should discuss their vitamin K needs with their physician and NOT experiment with vitamin K foods or supplements on their own.

Want to Check Your Vitamin K Status?

A normal prothrombin time (the test for clotting activity that has been the standard used to check vitamin K sufficiency) is not sufficient indication that enough vitamin K is present to maintain vascular matrix-Gla protein activity or bone osteocalcin activity. Request an osteocalcin test; it measures how much uncarboxylated osteocalcin is present in the blood. High levels of uncarboxylated osteocalin indicate insufficient vitamin K is present to promote optimal bone health. Similarly, high levels of undercarboxylated matrix-Gla protein (MGP) indicate that insufficient vitamin K is present to protect against vascular calcification. (Berkner KL, Rune KW, J Thromb Haemost 2004; Cranenburg EC, Schurgers LJ et al. Thromb Haemost 2007; Bugel S. Proc Nutr Soc 2003)

~Lara Pizzorno, MDiv, MA, LMT

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Posted by: Joe Pizzorno, Jr., ND at 11:32 am