Vitamin K2

Keeps Calcium Out of Your Arteries and In Your Bones

Smart Publications

Vitamin K has recently received a lot of attention from health and nutrition researchers. A long forgotten and misunderstood nutrient, vitamin K is making a comeback and its importance to human health is rapidly being unveiled.

From assisting the development of bone, to preventing arterial calcification, to fighting off cancer and inflammation, vitamin K is the new hot nutrient and for good reason.

What is vitamin K?

Originally identified as a fat-soluble nutrient required for normal blood coagulation, vitamin K is actually a family of similar compounds, which recent research reveals are also necessary for integrating calcium into bone and preventing its deposit within blood vessels. The latest research also indicates vitamin K possesses significant anti-cancer and anti-inflammatory actions.

In nature, vitamin K is found in the forms of vitamin K1 (phylloquinone) and several different types of vitamin K2 (menaquinones):

K1, which is involved in photosynthesis, is produced by plants and algae, its highest concentrations found in green leafy vegetables. Primary dietary sources of K1 are leafy greens, such as broccoli, kale, and Swiss chard, and plant oils, such as canola and soybean oil.

K2 is produced by bacteria and also via the conversion of K1 to K2 by beneficial bacteria in the intestines of animals, including humans. 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.

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 a 15-fold more powerful antioxidant than K1, and 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.123


 


Finally, K2 occurs in numerous forms that vary in their activity. Vitamin K2 can have a side chain between 4 and 9 units long. This side chain has a great effect on the bioavailability of vitamin K. Shorter chain length results in shorter half-life within the body, thus limiting our body’s ability to utilize vitamin K. Both vitamin K1 and vitamin K2 in the form of menaquinone-4 have very short half-lives in the body, while longer chain forms of vitamin K2, such as menaquinone-7, have dramatically longer half-lives and much higher bioactivity. Because recent research has shown that vitamin K2, in the form of menaquinone-7, is the most potent and longest acting form of vitamin K2, many researchers now consider it to be the most important dietary form of vitamin K for protecting the cardiovascular system and promoting bone health.4

What are the mechanisms behind vitamin K’s functions in the body?

Vitamin K is needed for the “carboxylation” of Gla-proteins. Carboxylation activates these proteins, which perform a number of essential activities throughout the body, including regulating blood clotting and calcium.5

K1 is the form used in the liver to activate clotting factors, while K2 is the form used in the rest of the body to activate other vitamin K-dependent Gla-proteins, including osteocalcin, which is essential for bone health, and matrix-Gla protein, which prevents calcification of blood vessels and organs, including the heart and kidneys.

Vitamin K2 is also found in high concentrations in the brain, where it contributes to the production of myelin (a fatty substance that covers and protects nerves), protects brain cells against free radical injury, and is thought to play a role in the development of the central nervous system.67

K2 also activates a number of other proteins that regulate bone metabolism and inhibit the growth of cancer cells.89

Balancing blood clotting

Blood must flow freely through our cardiovascular system, unless injury causes a breach in a blood vessel, in which case, blood must clot rapidly to prevent excessive, potentially fatal blood loss. If clots form too readily, however, blood vessels can become blocked, cutting off the delivery of oxygen and nutrients, which rapidly results in tissue and organ death.

Vitamin K-dependent Gla-proteins are responsible for maintaining the delicate balance needed between coagulation and anticoagulation. In a system called the “coagulation cascade,” procoagulant vitamin K-dependent proteins (including prothrombin and the coagulation factors) create a dense mesh of fibrin that traps platelets and stops the loss of blood. At the same time, their anti-coagulant partners inhibit the process, preventing excessive clotting and rapidly clearing clots once they are no longer necessary.

Keeping calcium out of arteries

Cardiovascular disease is not just about cholesterol, which, if oxidized, can form visible plaques on the innermost wall of the arteries, a condition called atherosclerosis. Just as lethal is arteriosclerosis; hardening of the arteries due to calcium deposits.

The elasticity that characterizes a healthy artery is what enables it to accommodate increases in blood flow. Add enough calcium and that pliability is lost; the artery can’t expand and contract, so blood pressure rises.

Sudden death from heart attack is even 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.1011

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%.12

A high coronary artery calcium score on electron beam tomography has been found to be a better predictor of mortality than age. A calcium score of less than 10 confers a reduction in functional age by 10 years in subjects older than 70, while a calcium score of >400 adds as much as 30 years of functional aging to younger patients.131415

Fortunately, vitamin K-dependent proteins have been shown to inhibit calcification in the heart and arteries, and also in the kidneys, where K2 prevents the calcification that typically accompanies dialysis and diabetes. In women whose diets provide the most vitamin K2 have significantly less breast calcification compared to those whose diets provide the least.16

How does vitamin K prevent arterial calcification and promote blood vessel elasticity?

One of the vitamin K-dependent proteins, matrix Gla-protein (MGP) is the strongest inhibitor of tissue calcification presently known. MGP’s importance for blood vessel health was first demonstrated in animals bred to be MGP-deficient, all of which died of massive arterial calcification within 6–8 weeks after birth.17 MGP is produced by small muscle cells in our blood vessels where—once activated by vitamin K—it prevents calcium deposits.18

K2 also helps promote blood vessel elasticity by safeguarding elastin, the protein primarily responsible for the elasticity of the arterial wall. Existing elastin is damaged and new production is inhibited by calcium deposition.19

In the Rotterdam study, a massive 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 provided no significant cardiovascular protection.20

Controlling calcium: mineralizing bone not blood vessels

How does vitamin K strengthen bones?

Osteocalcin, the protein responsible for anchoring calcium within bone, is a vitamin K-dependent Gla-protein. Only after its carboxylation by vitamin K is osteocalcin able to latch on to calcium forming the bone matrix. (Think of carboxylation as adding a trailer hitch to calcium, allowing it to be towed into and attached to bone.) Without enough vitamin K, osteocalcin remains uncarboxylated, so calcium cannot deposit in bone.21


Vitamin K aids bone health in a number of other ways. Vitamin K2 teams up with vitamin D3 to increase production of osteocalcin in osteoblasts (the cells that build bone), while also inhibiting the production of osteoclasts (the cells that break down bone).2223

A deficiency of vitamin K results in high levels of uncarboxylated (inactive) osteocalcin 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.2425262728

Studies confirm K2’s bone-protective effects

In animal studies, vitamin K2 has been shown to prevent bone loss associated with the use of corticosteroids and the anti-epileptic drug phenytoin, immobilization (such as would occur during extended illness or hospitalization), testosterone deficiency (as might occur with treatment for prostate cancer or aging), menopause (estrogen deficiency) and weightlessness (as occurs during space flight).

Each of these is known to reduce bone formation while increasing bone turnover, leading to bone loss and increased fracture risk. Vitamin K2 greatly lessens or completely reverses this trend.

Even calcium-deficient animals are protected from bone loss by vitamin K2 in rat models of postmenopausal osteoporosis and testosterone deficiency.7

In human studies, 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.29

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.3031

In other human research, vitamin K2 has been shown to be an effective treatment against osteoporosis:

A review study of all randomized controlled human trials of at least 6 months duration that assessed the use of vitamin K1 or K2 to lessen fracture risk identified 13 trials. All but one showed 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%.32

In a 2-year study of 241 women with osteoporosis, subjects were given either K2 plus calcium or calcium alone. At the end of the study, women receiving only calcium had lost an average of 3.3% of their lumbar bone mineral density (BMD), while those receiving vitamin K2 lost just 0.5%. Women taking K2 plus calcium had one-third the fracture risk of those receiving calcium only.33

K2 teams up with vitamin D to more effectively prevent bone loss and protect blood vessels

Vitamin D increases the production of Gla-proteins, whose activation depends on vitamin K. Vitamin D thus increases both the demand for vitamin K and the potential for benefit from K-dependent proteins, such as matrix Gla- protein in blood vessels and osteocalcin in bone.34

A number of trials have shown that the combination of K2 and vitamin D3 is more effective in preventing bone loss than either nutrient alone.353637

In one two year study, 92 postmenopausal women were assigned to one of four groups: K2, D3, a combination of K2 and D3, or calcium lactate. In the women receiving only calcium, lumbar BMD (lower spine bone mineral density) decreased. Those given either D3 or K2 experienced a slight increase in BMD, while those taking both K2 and D3 group fared much better, increasing their lumbar BMD by 1.35%.36

K2 improves the efficacy of bisphosphonate drugs, e.g., Fosamax®

K2 not only does not interfere with, but 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 K2 and a bisphosphonate.38

Vitamin K’s special benefits for 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 the risk of both osteoporosis and cardiovascular disease.39 The drop in estrogen causes both problems, but vitamin K can help rectify them.

Among postmenopausal women not using estrogen replacement, low levels of vitamin K or high levels of uncarboxylated (vitamin K-dependent) osteocalcin are associated with low spine BMD, but a 3-year study of 325 postmenopausal women, receiving either K2 or placebo, shows 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.4041

Vitamin K, specifically the vitamin K-dependent matrix Gla-protein that inhibits vascular calcification, also 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, but in those given K along with D, elasticity was maintained.26

Cancer

Researchers are just beginning to identify K-dependent proteins that are important in a number of cell signaling processes including cellular survival, transformation and replication.

One example is 17β-HSD4, a key enzyme in the conversion of estradiol to estrone. Estradiol is a much more potent form of estrogen than estrone, and is often elevated in cancerous liver tissue. By promoting the conversion of estradiol to less active estrone, K2 helps inhibit the development of liver cancer.8

Another K-dependent protein, growth-arrest-specific gene-6 (Gas6) increases in neurons under attack by free radicals and helps them to survive, in part by acting as an anti-inflammatory. Gas6 also signals damaged cells that might otherwise multiply into a tumor to begin apoptosis (the process of cellular suicide that removes damaged or malignant cells).42

In humans, studies suggest that K2 helps prevent progression to liver cancer from cirrhosis and also inhibits disease recurrence in patients with liver cancer, a form of cancer for which the rate of recurrence is especially high.43

K2 greatly lessened risk of progression to liver cancer in a study of 40 postmenopausal women with cirrhosis due to hepatitis. After 8 years, risk of having developed liver cancer was 80% lower in the women given K2.44

In a trial of 121 patients with liver cancer, the addition of K2 to conventional therapy significantly improved survival. After 12 months, cancer had progressed to the portal vein in only 2% of those receiving K2 compared to 23% of the control group. After 2 years, cancer had invaded the portal vein of 47% of controls, but only 23% of those taking K2.9

Brain cell protection / antioxidant effects

During the process of carboxylating proteins, vitamin K is also changed. This altered vitamin K is then regenerated and reused continuously in what is called the vitamin K cycle. During this cycle, vitamin K functions as an antioxidant, inactivating free radicals that would otherwise damage cholesterol and the delicate fats that are primary constituents of our brain cells, spinal cord, and the membranes surrounding each of our cells.45

In addition, intriguing lab research has shown that vitamin K specifically protects brain cells against free radical damage. Oxidative stress (free radical damage) is a central factor in damage caused by many brain disorders, including Alzheimer’s disease and stroke. In studies conducted jointly by Harvard Medical School and Tufts University, vitamin K, in both its K1 and K2 forms, completely prevented free radical accumulation, and therefore, death, in brain cells.46

Are you likely to be deficient in 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.17

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 (>70) require higher levels of vitamin K.47

Anticoagulant medications such as Coumadin®, decrease clotting by interfering with vitamin K, seen in studies as a direct cause of arterial calcification by preventing vitamin K from activating matrix Gla-protein.48 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.49 People taking these medications should discuss their vitamin K needs with their physician and not experiment with vitamin K on their own.

A normal prothrombin time (the test for clotting activity that has been the standard used to check vitamin K sufficiency) is not an indication that enough vitamin K is present to maintain vascular matrix Gla-protein activity or bone osteocalcin activity.26

If you want to check your vitamin K levels, request an osteocalcin test; it measures how much uncarboxylated osteocalcin is present in the blood. High levels of uncarboxylated osteocalin, abbreviated as “ucOC,” indicate insufficient vitamin K is present to activate it, so it can deposit calcium in bone. Similarly, high levels of undercarboxylated matrix Gla-protein (MGP) indicate that insufficient vitamin K is present to protect against vascular calcification.17

Is vitamin K supplementation safe?

Even in high doses, K1 and K2, the natural forms of vitamin K, have produced no adverse effects. For this reason, the Institute of Medicine at the National Academy of Sciences chose not to set a Tolerable Upper Limit (UL) for vitamin K when it revised its public health recommendations for this vitamin in 2000.

If you are taking Warfarin (Coumadin), vitamin K can interfere with its anti-clotting activity. Discuss vitamin K supplementation with your physician. Do not increase your intake of vitamin K without your physician’s assistance.

What should I look for in a vitamin K supplement?

The majority of studies evaluating the effectiveness of vitamin K for the prevention of osteoporosis have used one type of vitamin K2 (MK-4 menaquinone-4) at a dosage of 45 milligrams/day. This is an extremely large amount of vitamin K, since the Recommended Daily Intake of vitamin K is 80 micrograms daily. However, epidemiological studies on cardiovascular disease have shown protective effects from vitamin K2 intake of only 45 micrograms a day (this is 1,000 times less than 45 milligrams). Importantly, this protective effect came from the long-chain menaquinones such as MK-7. Vitamin K1 and menaquinone-4 (MK-4) did not provide any significant protection.

This has caused quite a bit of confusion among consumers. Vitamin K1 is the form of vitamin K found in the largest amount in our diets. It can also be converted to vitamin K2, in the form of menaquinone-4, within our bodies. Unfortunately, vitamin K1 is not converted to the more potent, long-chain menaquinone forms of vitamin K2, such as menaquinone-7. Current research is focusing on the beneficial health effects of these long-chain, extremely potent forms of vitamin K2, such as menaquinone-7, because it appears to be much more effective than any of the other forms of vitamin K. This is due to the fact that its effects last for days within the body, unlike other forms of vitamin K which only are effective for a few hours.

Thus, to obtain all the health benefits of vitamin K, we should look for a supplement that contains high dietary amounts of vitamin K1 (at least several hundred micrograms), along with at least 45 micrograms a day of the more potent, long-chain form of vitamin K2, menaquinone-7. Additionally, since menaquinone-7 is extracted from natto, an ideal product will also be labeled to show its nattokinase activity. Nattokinase, a natural enzyme found in natto, has been shown to promote proper blood flow and protect cardiovascular health. This will ensure your body receives adequate amounts of all the important forms of vitamin K, which work together to promote optimum health, along with natto’s two cardiovascular protectors, vitamin K2 as menaquinone-7 and nattokinase.

Other Articles of Interest from
Smart Publications Health & Wellness Update

Exciting New Research Shows Vitamin K2 is Vital to Bone Health 


This article is not intended to diagnose, treat, cure, or prevent any disease.
Always consult with a physician before embarking on a dietary supplement program.
 

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