Super K with Advanced K2 Complex

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Super K with Advanced K2 Complex 90 softgels

Item Catalog Number: 01724

An abundance of human clinical data reveals that vitamin K plays a critical role in maintaining healthy bone density by facilitating the transport of calcium from the bloodstream into the bone.6-10 Vitamin K is also required by calcium-regulating proteins in the arteries. Matrix Gla-protein (MGP) is a vitamin K-dependent protein, and it must be carboxylated to function properly. Poor vitamin K status leads to inactive uncarboxylated MGP (ucMGP), which accumulates at sites of arterial calcification.11,12 Since MGP is a potent local inhibitor of arterial calcification, MGP is important in relation to the health of the entire cardiovascular system. Without adequate vitamin K, calcium in the blood can bind to the arterial wall resulting in calcification.13,14 As people age, even a subclinical vitamin K deficiency can pose risks to the vascular system. Poor vitamin K status also results in increased circulating levels of undercarboxylated osteocalcin that is shown to be associated with increased bone loss in postmenopausal women.15,16

Humans get most of their vitamin K from green vegetables in the form of vitamin K1. The problem is that K1 is tightly bound to plant fiber and only a small fraction absorbs into the bloodstream.17-19

Vitamin K2 (menaquinones) is found in meat, eggs, and dairy products and is also made by bacteria in the human gut, which provides a certain amount of the human vitamin K requirement.20 Human studies show that vitamin K2 is up to ten times more bioavailable than K1. Vitamin K2 remains biologically active in the body far longer than K1. For instance, K1 is rapidly cleared by the liver within eight hours, whereas measurable levels of K2 (MK-7) have been detected 72 hours after ingestion.10

The Rotterdam Heart Study, a large-scale, well-controlled clinical trial that tracked 4,800 participants for seven years, revealed that participants who ingested the greatest quantities of vitamin K2 in their diet experienced a better cardiovascular condition than people who ingested the least.21 High intakes of vitamin K2 also corresponded to less calcium deposition in the aorta, whereas participants who ingested less K2 were more likely to show moderate or severe calcification. Animal studies suggest vitamin K intake not only blocks the progress of further calcium accumulation, but also induces 37% regression of preformed arterial calcification.22,23

Ideal Forms of Vitamin K2
In recent years, two forms of vitamin K2 have been extensively researched and the findings reveal vastly improved effects compared to K1. The MK-4 form of vitamin K2 is the most rapidly absorbed and is now routinely used in Japan to maintain healthy bone density. MK-4, however, only remains active in the blood for a few hours. The MK-7 form of K2, on the other hand, remains bioavailable to the human body over a sustained 24-hour period24 and to higher levels (seven- to eightfold) during prolonged intake.10 Both MK-4 and MK-7 have demonstrated remarkable health benefits when studied in human populations.

The Most Complete Vitamin K Formula
Vitamin K1 is the form found in plants and vegetables and should be part of most people’s daily supplement regimen. Even more important is inclusion of the MK-4 and MK-7 forms of vitamin K2.

Based on data substantiating the long-acting effects of MK-7, it is now possible to ingest fewer total micrograms of vitamin K but achieve far higher sustained blood levels of this critical nutrient.

The latest Super K with Advanced K2 Complex formula provides vitamin K1 and the MK-4 and MK-7 forms of vitamin K2 in just one daily softgel. The virtue of this formula is that it provides the precise amount of the long-acting MK-7 form of vitamin K2 that recent human studies have shown provides optimal K2 levels over a 24-hour period. The MK-4 is included to provide the rapid increase in vitamin K blood levels that may account for its beneficial effects in certain studies.

 

Details

Supplement Facts

Serving Size 1 softgel

Amount Per Serving

Vitamin C (as Ascorbyl palmitate)

10 mg

Vitamin K activity

2200 mcg

From:

 

Vitamin K1 (as phytonadione)

1000 mcg

Vitamin K2 (as menaquinone-4)

1000 mcg

Vitamin K2 (as menaquinone-7)

200 mcg

Other ingredients: extra virgin olive oil, gelatin, glycerin, beeswax, purified water, carob color.

Dosage and Use
  • Take one (1) softgel daily with food, or as recommended by a healthcare practitioner.
Caution

If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult with your healthcare provider before taking this product.

Warnings
  • KEEP OUT OF REACH OF CHILDREN
  • DO NOT EXCEED RECOMMENDED DOSE
  • Do not purchase if outer seal is broken or damaged.
  • When using nutritional supplements, please consult with your physician if you are undergoing treatment for a medical condition or if you are pregnant or lactating.

The Surprising Longevity Benefits of Vitamin K

By Judy Ramirez

The Surprising Longevity Benefits of Vitamin K  

Dr. Bruce Ames is one of the world’s leading authorities on aging and nutrition. Four years ago, Dr. Ames published research indicating that optimum intake ofvitamin K plays an important role in longevity.1

A new 2014 study on vitamin K confirms that ample vitamin K intake can indeed help you live longer.2 In a group of more than 7,000 people at high risk for cardiovascular disease, people with the highest intake of vitamin K were36% less likely to die from any cause at all, compared with those having the lowest intake.

This protection even extended to those with initially low vitamin K intake who boosted their consumption during the course of the study—demonstrating that it’s never too late to start gaining the benefits of vitamin K supplementation. Increasing intake conferred protection against cardiovascular death as well.2

Vitamin K is capable of opposing many of the leading causes of death in modern-day Americans—including atherosclerosis,3 osteoporosis,4 diabetes,5,6 and cancer2,7—because it has the unique ability to activate proteins involved in these conditions.

In this article, we will review a host of new studies that detail the impact of vitamin K supplementation on preventing these and other major age-related diseases.

 

Risk Reduction By Increased Vitamin K Intake

Condition

Vitamin K Form

Risk Reduction

All-Cause
Mortality

K2

26% (Highest vs. Lowest Intake)3

All-Cause 
Mortality

K1

36% (Highest vs. Lowest Intake)2

Cancer

K1

46% (Highest vs. Lowest Intake)2

Cancer, Advanced 
Prostate

K2

63% (Highest vs. Lowest Intake)7

Cancer 
Death

K2

28% (Highest vs. Lowest Intake)54

Coronary 
Artery Calcification

K2

20% (Highest vs. Lowest Intake)30

Coronary Heart Disease

K1

21% (Highest vs. Lowest Intake)66

Coronary Heart Disease

K2

9% lower risk for each 10 microgram/d increased intake67

Coronary Heart Disease Mortality

K2

57% (Highest vs. Lowest Intake)3

Metabolic Syndrome

K1

27% for having low HDL-cholesterol* 
49% for having elevated triglycerides* 
82% for having high blood sugar*
(All Highest vs. Lowest Intake)68

Type II 
Diabetes

K2

7% lower risk for each 10 microgram/d increased intake5

Type II 
Diabetes

K1

17% reduction for each 100 microgram/d increased intake6

Type II Diabetes

K1

51% with increased K1 intake vs. decreased or no change in intake6

*Based off of odds ratios

The Many Benefits Of Vitamin K

Vitamin K was first discovered in 1935, when it was found to be an essential nutrient to prevent abnormal bleeding in chickens.8 For decades thereafter, vitamin K was identified as the “coagulation vitamin” (in fact, the initial “K” comes from the German spelling, koagulation). During that time, it was established that vitamin K worked by activating certain proteins made in the liver that are required for normal blood clotting. Without sufficient vitamin K, blood would not clot, and severe bleeding would ensue.9,10

Vitamin K activates those blood-clotting proteins by making a small but vital chemical change in the proteins’ structure, specifically on the protein building block called glutamic acid.11

By the turn of the 21st century, scientists had learned that vitamin K produces similar changes to glutamic acid molecules to activate a handful of other vital proteins in the body, with the collective name of Gla-proteins.12-16According to 2014 research, 16 different vitamin K-dependent Gla-proteins have been identified.17 This means that they depend on vitamin K to activate them in order to carry out their intended role.

With the discovery of the Gla-proteins, scientists learned that vitamin K is vital for much more than the healthy clotting of blood. For example, the Gla-protein in bone, called osteocalcin, is responsible for making sure calcium is deposited in bones, while the Gla-protein in arterial walls, called matrix Gla protein, prevents calcium from being deposited in arteries.18

Insufficient blood clotting was thought to be the main sign of vitamin K deficiency. However, scientists have since learned that you can have enough vitamin K to promote healthy blood clotting, yet still not have enough vitamin K for it to activate the Gla-proteins necessary to help prevent cardiovascular disease, osteoporosis, diabetes, and cancer, all conditions in which vitamin K-dependent proteins are known to be factors.13,14,19 Fortunately, studies show that vitamin K supplementation can significantly increase the amount of activated Gla-proteins in tissues—without over-activating the clotting proteins.18

Vitamin K And Atherosclerosis

As we age, calcium that belongs in our bones begins to make its appearance in other unwanted areas, including inside the linings of major arteries.20 Over time, normal smooth muscle cells in artery walls transform into bone-like cells through the deposition of calcium, essentially turning sections of artery into bony tissue that is not resilient and flexible, and does not have the ability to effectively regulate blood flow.19,21 This process lends literal reality to the term “hardening of the arteries,” which we now know as late-stage atherosclerosis.

Nature has provided a powerful inhibitor of arterial calcification in the form of matrix Gla protein, one of the 16 Gla-proteins activated by vitamin K. This specific Gla-protein is produced in arterial walls, but is only activated when sufficient vitamin K is present.3,14,15,19,22-24 In the absence of sufficient vitamin K, arterial calcification is able to continue unopposed, leading to advanced atherosclerosis and its deadly consequences, heart attacks and strokes.14,16 Indeed, in older men and women who had the highest levels of inactive matrix Gla protein (indicating low vitamin K levels), there was a nearly 3-fold increased risk of cardiovascular disease compared to those with the lowest levels.23

Researchers have known for nearly 20 years that insufficient vitamin K intake in the diet is related to atherosclerosis in the aorta, the body’s largest blood vessel.16 Since that time, a host of basic science and laboratory studies have indicated that higher vitamin K intake is essential for preventing atherosclerosis in major vessels of all kinds. Animal studies even show that vitamin K can “rescue” calcified arteries that occur as a result of the overuse of drugs that inhibit vitamin K, such as certain blood thinners.25,26

Another way matrix Gla proteins help protect against atherosclerosis is by inhibiting the production of inflammatory signaling molecules (cytokines), which contribute to plaque formation and calcification.27 People with the highest dietary intake of vitamin K have significantly lower levels of those inflammatory markers, and also of substances involved in appetite generation and insulin resistance, both of which are important in preventing atherosclerosis.28 (Some of these effects may be related to increased levels of another vitamin K-dependent Gla-protein that suppresses inflammation and promotes glucose tolerance.) 29

WHAT YOU NEED TO KNOW
Vitamin K Promotes Longevity

Vitamin K Promotes Longevity

  • Once thought to be exclusively concerned with blood coagulation, vitamin K is now known to affect at least 16 Gla-proteins in the body.
  • These include proteins involved in protecting arteries from calcification, those protecting bones from losing calcium, and ones that help prevent against diabetes and cancer.
  • A new study demonstrated that people with higher vitamin K intakes are less likely to die from all causes, lending new urgency to the issue of supplementation.
  • A multitude of studies now point to the fact that adequate vitamin K intake, including supplementation, can offer prevention against atherosclerosis, osteoporosis, diabetes, and cancer.
  • Assure that your vitamin K intake is adequate by adopting a daily vitamin K supplement that provides both K1 and Kfor optimum coverage.

Human Studies On Vitamin K

Human Studies On Vitamin K  

Human studies on dietary vitamin K intake have been somewhat inconsistent, probably because of confusion about which form of the vitamin is most important.30

Vitamin K1 (phylloquinone) is the main dietary form of the vitamin, but vitamin K2(menaquinone) has a stronger relationship to arterial calcification.15

In one study, people with the highest intake of vitamin K2 were 57% less likely to die of coronary heart disease compared with those with the lowest intake.3 In another study, women with the highest intake of vitamin K2 were found to be at a 20% lower risk for coronary artery calcification compared with women with the lowest intake levels, while the same study found that vitamin K1 had no significant impact.30

Vitamin K supplementation studies suggest that both forms of the vitamin contribute to protection from arterial calcification in atherosclerosis, with a slight edge for vitamin K2. For example, when healthy men and postmenopausal women supplemented with 500 micrograms of vitamin K1 per day, they experienced a modest6% reduction in the progression of arterial calcification, but only in subjects with the most advanced disease at baseline.22 And a study using vitamin K1 in combination with vitamin D and minerals demonstrated that the combined supplement could slow the loss of arterial suppleness and promote elasticity.14

Similarly, supplementation with both 180 and 360 micrograms of vitamin K2 significantly reduced the amounts of inactivated matrix Gla protein, thereby lowering the risk of atherosclerosis with calcification; placebo recipients in that study showed no effect.31 In another study, a group of kidney disease patients on hemodialysis (who have a very high risk for advanced atherosclerosis with calcification) took either 135 or 360 micrograms of vitamin K2.Supplementation dramatically decreased the amount of inactivated matrix Gla protein by 77% at the lower dose, and 93% at the higher dose.32

Intriguingly, it is now apparent that women with atherosclerosis are more likely to have lower bone mass than women without atherosclerosis. They’re also more likely to have lower circulating vitamin K levels, highlighting the age-related trade-off between calcium in bones (which is desirable) and calcium in arterial walls (which is undesirable).20

Vitamin K And Osteoporosis

Sufficient vitamin K is also required in order to activate the Gla-protein osteocalcin, which binds tightly to bone minerals to create strong bones.33 With inadequate vitamin K, bones can’t hold on to vital calcium, which leads to osteoporosis.34 To make matters worse, the calcium has to go somewhere, so it enters the bloodstream, where it contributes to stiffening arteries.33

Fortunately, supplementation with vitamin K is an effective means of protecting your bones from osteoporosis.

A study of healthy postmenopausal women between 50 and 60 years old demonstrated that three years of supplementation with 1 mg/day of vitamin K1, plus 8 micrograms (320 IU)/day of vitamin D together with minerals, reduced the loss of bone in the hip and spine compared both to placebo recipients and to those supplemented with vitamin D and minerals alone.35

In another study, postmenopausal women with pre-existing osteoporosis took 1,500 mg of calcium carbonate and45 mg of vitamin K2 or placebo each day for 48 weeks. Compared to baseline values, the women experienced an increase in spinal bone mineral density and a 55.9% reduction in inactive osteocalcin levels, while a 9.3% reduction occurred in the group taking only the calcium supplement.36 The same dose of K2 was later shown to maintain hip bone strength and improve the overall geometry of the femoral neck over a three-year period, while placebo recipients lost hip bone strength during that time.37

Even lower doses of 180 micrograms/day of vitamin K(especially in the form of longer-lasting MK-7, which is derived from natto or fermented soybeans), when given for three years, increased the amount of activated osteocalcin and produced significant improvements in bone mineral content and density in the lower spine and femoral neck, while also increasing bone strength and preventing loss of height in spinal vertebrae.38

Vitamin K2 has recently been recognized by the European Food Safety Authority as having an important role in maintaining normal bone health.38 When added to alendronate, a common anti-osteoporosis drug, vitamin K2significantly increased bone mineral density in the femoral neck compared with alendronate alone.39

Vitamin K And Diabetes

Type II diabetics have an increased risk of bone fracture. This is likely due in part to the incomplete activation of the Gla-protein osteocalcin (caused by lack of vitamin K), and the decrease of calcium being deposited in bone that occurs as a result.40 Conversely, people with the highest vitamin K1 intakes have reductions in inflammatory markers related to diabetes.28

Vitamin K has also been found to have a direct impact on the diabetic state itself. In a group of healthy volunteers between 26 and 81 years old, higher dietary vitamin K1 intake was associated with greater insulin sensitivity and lower post-meal glucose levels.41 And in a study of older adults at high risk for cardiovascular disease, the risk of developing type II diabetes was reduced by 17% per 100 micrograms of K1 intake per day.6

Another study demonstrated that both vitamins K1 and K2 reduced the risk of developing diabetes. However, the stronger and more significant association occurred with K2, which reduced the risk of type II diabetes by 7% for each 10-microgram increase in intake.5

In addition to reducing the risk of diabetes, vitamin K has been shown to reduce the effects of diabetes as well.

Supplementation studies in animals show that diabetic rats, like diabetic humans, develop bone mineral loss. However, when diabetic rats were supplemented with vitamin K2, not only was osteopenia prevented, hyperglycemia was prevented as well.42

Human supplementation studies demonstrate that both K1 and K2 are effective in combating the effects of diabetes. In older, non diabetic men, three years of supplementation with 500 micrograms/day of vitamin K1produced a significant reduction in insulin resistance compared with controls.43 And in a study of healthy young men, just four weeks of supplementation with 30 mg of K2 three times daily improved insulin sensitivity.44 This may have occurred as a result of an increase in the vitamin K-dependent Gla-protein osteocalcin, which has been shown in animal studies to increase insulin secretion and sensitivity.45

TYPES OF VITAMIN K
Types Of Vitamin K

It is clear that vitamin K affects specific and vital proteins throughout the body, well beyond the blood-clotting functions originally described for the vitamin. Less clear, at least for now, are differences in impact on the human body of several different types of vitamin K.

Phylloquinone, or K1, is the predominant source of vitamin K in the diet,55 but it becomes converted to menaquinone, or K2 , in animals, including humans.56 Vitamin K2 itself has several different subtypes, based on molecular structure variations. The subtype MK-4, or menaquinone-4, predominates in animal tissues; it is the natural product of K1 modification in the gastrointestinal tract.57

It is likely that both K1 and K2 are necessary for overall normal vitamin K function, and it appears that supplementation with both is useful, especially for the mounting number of biological tissues other than blood clotting that rely upon adequate vitamin K. The subtype of K2 called MK-7, menaquinone-7 has recently been shown to be more bioavailable than MK-4.58

Vitamin K And Cancer

Studies of vitamin K intake reveal potent preventive properties against several types of cancer, including prostate, colon, and liver cancers.46

When prostate cancer cells in culture are treated with vitamin K2, both those sensitive to male hormones (androgens) and those resistant to male hormones are unable to reproduce, and eventually die.47 Vitamin K2 has been associated with a 63% lower risk of advanced prostate cancer in men with the highest intake of the nutrient.7Similarly, a higher ratio of vitamin K-activated osteocalcin versus inactive osteocalcin correlates closely with reduced prostate cancer risk, demonstrating the molecular connection.48

In human colon cancer cells, vitamin K2 has been shown to induce cancer cell death by several different mechanisms and to suppress the growth of colon tumors implanted into mice.49,50

Supplementation studies also reveal vitamin K’s powerful effect on the most common kind of liver cancer, calledhepatocellular carcinoma. This cancer is almost always associated with alcoholism or hepatitis B or C infection.51Although surgical or radiation treatment can destroy the primary tumor, recurrence is common and typically determines the long-term prognosis.52,53 Several human studies show that vitamin K2 supplementation can dramatically reduce the recurrence rate in hepatocellular carcinoma and may impact the survival rate as well.52,53

As with most nutrients, vitamin K is not the single answer to cancer prevention, but it shows tremendous promise, which highlights the importance of maintaining adequate levels through boosting your intake. A large European study showed that cancer death was 28% less likely overall in those with the highest versus lowest intakes of vitamin K2.54

 

Impact Of Vitamin K2 Supplement On Liver Cancer Patients53

 

Recurrence Rate, %

Survival Rate, %

12 mo

24 mo

36 mo

12 mo

24 mo

36 mo

Vitamin K2 45 mg/day

12.5

39.0

64.3

100

96.6

87.0

Controls

55.2

83.2

91.6

96.4

80.9

64.0

Summary

A recent large study confirms that people with the highest vitamin K intakes are significantly less likely to die from any cause, compared with those having the lowest intakes.

Because of its unique ability to activate proteins involved in atherosclerosis, osteoporosis, diabetes, and cancer, vitamin K is capable of opposing many of the leading causes of death in modern-day Americans. A host of new studies details the impact of vitamin K supplementation on preventing these, and possibly other, major age-related diseases.

Once considered just a blood coagulation vitamin, vitamin K2 has now achieved the status of a multi-function vitamin. If you are interested in a longer and healthier life, consider supplementing with this often- overlooked nutrient.

If you are taking a blood-thinning drug, check first with your doctor to coordinate doses and follow-up testing.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at1-866-864-3027.

THE DANGERS OF BLOOD THINNERS
Tart Cherry Juice Versus Extract

People at risk for dangerous blood clots include those with various heart rhythm abnormalities (e.g., atrial fibrillation),59 as well as those with artificial heart valves,60 stents, and other hardware, and those at risk for certain kinds of strokes. For these people, blood-thinning drugs known as anticoagulants offer significant protection.26

But many traditional blood thinners, such as Coumadin® (warfarin), act specifically by inhibiting the action of vitamin K to produce clotting proteins. The emerging science of vitamin K is revealing a disturbing fact: While inhibiting vitamin K action on blood clotting proteins, these drugs also inhibit other vitamin K-dependent proteins, including the matrix Gla protein that naturally prevents arterial calcification.26

Studies in both animals and humans now show that the use of anticoagulant drugs such as Coumadin (warfarin), while effective at clot prevention, do indeed accelerate arterial calcification, placing patients at increased risk for cardiovascular disasters.61,62 The good news is that by supplementing with low-dose vitamin K, you may help rescue arteries from calcification induced by warfarin.63

However, if you are taking a blood-thinning drug, DO NOT stop using it and DO NOT begin any vitamin K supplementation on your own. Instead, speak with your doctor about starting a vitamin K supplement at a proper dose. With careful monitoring of coagulation tests, you are likely to find a balance between the benefits and the risks of anticoagulant use.64,65

Newer blood-thinning drugs such as Pradaxa® (dabigatran) and Eliquis® (apixaban) are not affected by vitamin K intake, meaning you can take full-dose vitamin K and not comprise the desired anticoagulant effects.

References

  1. Ames BN. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake. J Nucleic Acids. 2010 Sep 22;2010.
  2. Juanola-Falgarona M, Salas-Salvado J, Martinez-Gonzalez MA, et al. Dietary Intake of Vitamin K Is Inversely Associated with Mortality Risk. J Nutr. 2014 May;144(5):743-50.
  3. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.
  4. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med.2006;166(12):1256-61.
  5. Beulens JW, van der AD, Grobbee DE, Sluijs I, Spijkerman AM, van der Schouw YT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care. 2010 Aug;33(8):1699-705.
  6. Ibarrola-Jurado N, Salas-Salvado J, Martinez-Gonzalez MA, Bullo M. Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease. Am J Clin Nutr. 2012 Nov;96(5):1113-8.
  7. Nimptsch K, Rohrmann S, Linseisen J. 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.2008 Apr;87(4):985-92.
  8. Carpenter, KJ. A short history of nutritional science: part 3 (1912–1944). J Nutr. 2003;133(10):3023-32.
  9. Mammen EF. Coagulation abnormalities in liver disease. Hematol Oncol Clin North Am. 1992 Dec;6(6):1247-57.
  10. Mammen EF. Coagulation defects in liver disease. Med Clin North Am. 1994 May;78(3):545-54.
  11. Stanley TB, Wu SM, Houben RJ, Mutucumarana VP, Stafford DW. Role of the propeptide and gamma-glutamic acid domain of factor IX for in vitro carboxylation by the vitamin K-dependent carboxylase. Biochemistry. 1998 Sep 22;37(38):13262-8.
  12. Willems BA, Vermeer C, Reutelingsperger CP, Schurgers LJ. The realm of vitamin K dependent proteins: Shifting from coagulation toward calcification. Mol Nutr Food Res. 2014 Feb 17.
  13. Kaneki M. Genomic approaches to bone and joint diseases. New insights into molecular mechanisms underlying protective effects of vitamin K on bone health. Clin Calcium. 2008 Feb;18(2):224-32.
  14. Braam LA, Hoeks AP, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C. Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost.2004 Feb;91(2):373-80.
  15. Shea MK, Holden RM. Vitamin K status and vascular calcification: evidence from observational and clinical studies. Adv Nutr. 2012 Mar;3(2):158-65.
  16. Jie KS, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis. 1995 Jul;116(1):117-23.
  17. Okano T. Gla-containing proteins. Clin Calcium. 2014 Feb; 24(2):241-8.
  18. Theuwissen E, Cranenburg EC, Knapen MH, et al. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr. 2012 Nov 14;108(9):1652-7.
  19. Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res. 2008;122(3):411-7.
  20. Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int. 1996 Nov;59(5):352-6.
  21. Weaver J. Insights into how calcium forms plaques in arteries pave the way for new treatments for heart disease. PLoS Biol. 2013; 11(4): e1001533.
  22. Shea MK, O’Donnell CJ, Hoffmann U, et al. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr. 2009 Jun;89(6):1799-807.
  23. van den Heuvel EG, van Schoor NM, Lips P, et al. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas. 2014 Feb;77(2):137-41.
  24. Vermeer C, Theuwissen E. Vitamin K, osteoporosis and degenerative diseases of ageing. Menopause Int. 2011 Mar;17(1):19-23.
  25. Erkkila AT, Booth SL. Vitamin K intake and atherosclerosis. Curr Opin Lipidol. 2008 Feb;19(1):39-42.
  26. Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012 Jul;26(4):155-66.
  27. Clauser S, Meilhac O, Bieche I, et al. Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques. Thromb Haemost. 2012 Jan;107(1):140-9.
  28. Juanola-Falgarona M, Salas-Salvado J, Estruch R, et al. Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovasc Diabetol. 2013;12:7.
  29. Kuo FC, Hung YJ, Shieh YS, Hsieh CH, Hsiao FC, Lee CH. The levels of plasma growth arrest-specific protein 6 is associated with insulin sensitivity and inflammation in women. Diabetes Res Clin Pract. 2014 Feb;103(2):304-9.
  30. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93.
  31. Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JW. The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis. 2012 Dec;225(2):397-402.
  32. Westenfeld R, Krueger T, Schlieper G, et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95.
  33. Bentkowski W, Kuzniewski M, Fedak D, et al. Undercarboxylated osteocalcin (Glu-OC) bone metabolism and vascular calcification in hemodialyzed patients. Przegl Lek. 2013;70(9):703-6.
  34. Zittermann A. Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):483-7.
  35. Braam LA, Knapen MH, Geusens P, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003 Jul;73(1):21-6.
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