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Weak Bones Cause Heart Attack and Stroke

November 2002

By Melissa Block


News stories about nutrition research tend to give the impression that certain nutrients have only one function in the body, or that they can act as "magic bullets" to prevent or cure diseases. While this approach makes for striking headlines, it often causes nutrients to get noticed only when news is overwhelmingly good or bad. The diverse biological roles played by nutrients are too often overlooked.

Take vitamin K, for example. Most of what has been written about this vitamin has to do with its participation in the clotting of blood. People taking anti-coagulant drugs to prevent abnormal blood clots are warned to avoid foods containing vitamin K for fear that the nutrient will counteract the blood thinner's effects. The association between vitamin K and blood clotting has become this vitamin's most newsworthy characteristic.

However, the facts show that vitamin K has other important roles in the body such as building bone and maintaining blood vessel integrity. For at least four years, compelling evidence has existed that most people don't get enough vitamin K to protect their health. Despite this documentation, the vast majority of multivitamins do not contain any vitamin K, and few health conscious consumers understand the importance of supplementing with it.

The tide is about to turn. Research supporting vitamin K's usefulness against osteoporosis and heart disease is becoming too abundant to overlook. Here's what you need to know about the next big news story in nutritional medicine.

The recommended daily allowance (RDA) for vitamin K is currently 65 micrograms for adult females and 80 micrograms for adult males. Human clinical studies have used as much as 45 milligrams per day without problems, thus showing that ingesting more than 450 times the RDA of vitamin K is safe. Unlike other fat-soluble nutrients, vitamin K does not build up in the body.

Vitamin K deficiency was, until recently, considered a rarity in adults. A healthful diet was thought to provide plenty of this nutrient for children and adults. The problem is that the consumption of K-rich dark leafy greens is at an all-time low in the U.S., having been supplanted by processed foods, french fries and iceberg lettuce. Deficiency of vitamin K can also be produced by the use of cholesterol-lowering drugs (which decrease the amount of lipoprotein complexes on which fat-soluble K can "hitch a ride" for transport to where it's needed), antibiotics (which kill off K2-making bacteria in the GI tract), and synthetic estrogens. (In healthy people, vitamin K1 is converted into K2 in the body.) People with gallstones, liver disease or gastrointestinal disease are also subject to vitamin K deficiency.1,2

Vitamin K and calcium regulation

Image with Caption
Vitamin K's actions on bone and
the circulatory system arise from
its effects on the utilization of
calcium in the body. Calcium is
generally thought of as a bone-
building mineral, but the buildup
of this mineral isn't always a
good thing.

Vitamin K's actions on bone and the circulatory system arise from its effects on the utilization of calcium in the body. Calcium is generally thought of as a bone-building mineral, but the buildup of this mineral isn't always a good thing. When calcium deposits form in blood vessel walls, those vessels become stiff and noncompliant-a process known as arteriosclerosis or, in the vernacular, "hardening of the arteries." Arteriosclerosis isn't always caused by atherosclerosis, where cholesterol-filled lesions build up and obscure blood flow through the coronary arteries; atherosclerosis is only one type of arteriosclerosis.

Calcium deposition in the artery walls increases heart attack risk.3 In the world-famous Framingham study, subjects with detectable arterial calcification at the age of 35 were seven times more likely to have a heart attack during the course of the study.4 A recent study by researchers in Oakland and San Francisco, California, found that women whose mammograms showed arterial calcification in their breasts had significantly increased risk of stroke.5 Calcification can also occur in the kidneys, lungs and brain, and wherever it happens, it disrupts the normal function of those organs. Understanding the actions of vitamin K may be the key to understanding and reversing harmful calcium deposition in blood vessels.

Vitamin K "turns on" proteins that regulate the deposition of calcium during a process called carboxylation. When these proteins have insufficient vitamin K supplies, they are not able to fully carboxylate these calcium-controlling proteins. Their state of undercarboxylation prompts them to allow calcium to drift from bone into arteries and other soft tissues.6 Gamma-carboxyglutamic acid (Gla) is the name of one group of these calcium-controlling proteins. Fifteen of these proteins have been discovered, and all of them are dependent upon vitamin K for their activity. Properly carboxylated Gla strongly inhibits calcium deposition in the walls of blood vessels, while incomplete carboxylation handicaps this process. Lab mice bred to lack the gene for one type of Gla develop severe vascular calcification.7 When the drug warfarin-which prevents blood clot formation by inhibiting the vitamin K-dependent process that creates Gla-is given, an increase in arterial calcification is likely to result.

Research on vitamin K and cardiovascular disease

Supplemental doses of vitamin K are gaining recognition as valuable helpmates in the prevention of cardiovascular disease.8 In one study, rats were fed a diet designed to cause calcium buildup in their blood vessels. Some of the rats were given vitamin K, while others got vitamin E. The ratio of arterial calcification between animals receiving supplemental vitamin K or no K was an astonishing 1 to 17.5.9 Vitamin E had an even greater inhibitory effect on calcium buildup, and both K and E were found to reverse heart valve damage incurred by the diet.

In a more recent study, researchers in the Netherlands lent support to the theory that arterial vessel walls have a high preference for accumulating and utilizing vitamin K2 over K1. In rats treated with blood thinners (anticoagulant drugs), it was found that high Gla concentrations exist around calcium deposits within blood vessel walls.10 This finding led the research team to conclude that undercarboxylated Gla is indeed a risk factor for vascular calcium deposition, and that the present RDA for vitamin K does not supply enough vitamin K2 to prevent these deposits from forming.

Another study, performed by a team at Wake Forest University in North Carolina, provides a review of current knowledge about bone-related proteins in the regulation of arterial calcification.11 They describe studies that identify undercarboxylated Gla as an inhibitor of the principal osteogenic (bone-building) growth factor. When Gla is not properly modified with the aid of vitamin K, this growth factor induces the deposition of calcium in soft tissues.

An Australian research group administered warfarin to rats from birth until up to 12 weeks of age. They gave the rats K1 to counteract warfarin's effects on blood clotting factors made in the liver, allowing only K2 to become deficient. (Both are depleted by warfarin.) All of the treated animals were found to have extensive arterial calcification at the experiment's end. This study is of major importance in highlighting the essential nature of K2 for the prevention of calcification.11

Three Different Forms of Vitamin

Vitamin K1 (phylloquinone) is found in chlorophyll-rich plant foods, especially dark green leafy vegetables. Vitamin K2 (menaquinone) is made by the probiotic bacteria that reside in the intestinal tract, and vitamin K3 (dihydrophylloquinone) is produced during the hydrogenation of oils. Vitamin K2 can be made from K1, but the efficiency of this conversion is not always adequate to provide enough K2. Both K1 and K2 are essential for different aspects of good health; K3 is a free radical producer that doesn't act like real vitamin K in the body, and should not be considered a good source of vitamin K.* Vitamin K3 may, however, prove to be useful in the treatment of certain cancers.

* Blackwell GJ, et al, Inhibition of human platelet aggregation by vitamin K. Thromb Res 1985; 37:103-14.

Lipsky JJ, Nutritional sources of vitamin K. Mayo Clin Proc 1994;69:462-66.

Vitamin K and osteoporosis

The flip side of vitamin K's role in arterial health is its role in the prevention of osteoporosis. (In fact, this nutrient has been used as an osteoporosis therapy in Japan since 1995.) Osteoporosis and artery disease have long been known to be epidemiologically related; patients with osteoporosis have a significantly greater chance of dying from stroke and heart disease-and even cancer-than age-matched counterparts without thinning bones.12-15 New research shows that osteoporosis may well be a warning that calcium that ought to be going into the bones is ending up in the arteries.

When calcium isn't directed into bone and tooth, as it should be, it means these tissues aren't being built up as they need to be to prevent the thinning of bones that eventually leads to fractures. One side effect of the blood thinner warfarin, which works by blocking the activity of vitamin K in the clotting cascade, is increased calcium excretion and increased risk of osteoporosis.16 In the Nurses' Health Study, women with high intake of vitamin K were found to have 1/3 less likelihood of ending up with a hip fracture.17 Other research has indicated that those at risk for calcium loss- including men who are being treated for prostate cancer with androgen-blocking medications-benefit from supplemental vitamin K, which slows the loss of calcium through the urine.

In a Japanese study of 94 postmenopausal women, researchers administered hormone replacement therapy (HRT) and vitamin K2 to women who, despite the use of HRT, were losing bone mass. (HRT usually causes slight increases in bone mass for two to three years, and maintains it thereafter.) The women who added vitamin K to their HRT regimen showed a significant improvement in bone mineral density during the three-year study.18 In fact, the Nurses' Health Study-mentioned earlier-demonstrated that high vitamin K intake via green vegetables was more effective at preserving bone mass than HRT. This is a good thing, considering that mainstream HRT has been found to have significant risks in recent studies.