We highlight the significant body of evidence supporting the importance of vitamin K2 as a cardio-supporting nutrient and how the right K2 makes all the difference (2024)

In an ideal world, vitamin K is₂is said to have the same link to cardiovascular health as folic acid does to pregnancy. Optimal vitamin K₂intake is essential to prevent the build-up of calcium plaque due to atherosclerosis, thereby minimizing the risk and rate of calcification.^1-3

Matrix GLA protein (MGP) – found in tissues of the heart, kidneys and lungs – plays a dominant role in vascular calcium metabolism. Its production is stimulated by vitamin D₃, but it does require sufficient vitamin K₂to activate intake (corresponding to the bone-building protein osteocalcin). Once activated by vitamin K₂MGP can bind calcium and escort it out of the areas where this mineral is destructive, namely arteries and soft tissue.^1,4

No other productive mechanism for maintaining flexible blood vessel walls has been discovered, making MGP the only known and most potent existing inhibitor of cardiovascular calcification.

So it's vitamin K₂is essential as a nutrient for cardiovascular health. Here we will try to clear up the significant confusion surrounding vitamin K₂, ensuring the correct form is identified, as well as providing the significant body of evidence supporting its role as a cardiovascular supporting nutrient.

Why vitamin K?₂I am MK-7 is the most important

Vitamin K is a family of vitamins, of which the K vitamins are the most important₁(phylloquinon) en K₂(menaquinones). Think of them as fraternal twins. They have similarities, such as their action in the liver to detect blood clots, and chemically they share a quinone ring called menadione.

But this is where their similarities end.

Vitamin K₂has several molecules called menaquinones that K₂available outside the liver to other systems. Vitamin K₁is the most important source of vitamin K in the diet and is necessary for proper blood clotting. Meanwhile, vitamin K₂is essential to prevent calcium deposits in the arteries and build and maintain strong bones. (A more detailed breakdown of vitamin K₁and vitamin K₂, states the review article, “Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K₁a K₂in health and disease,” udgivet iInternational Journal of Molecular Sciences.⁵)

Not all forms of vitamin K₂is created equal. The two most commercialized forms of vitamin K₂are MK-4 and MK-7. Because of its side chain, MK-7 has a much longer half-life in the body than MK-4, giving it better access to tissues outside the liver.

In addition, the serum half-life of MK-4 has been shown to be several hours, compared to a half-life of more than 3 days for MK-7.

Although they have the same molecular mechanism of action, MK-7 is therefore more bioavailable than MK-4. And because of MK-4's short half-life and low bioavailability, multiple doses are required per daymilligramlevels - vs. MK-7smicrogramlevels – for measurable efficiency.

How vitamin K₂“Engages” MGP

So how does the MK-7 allow the MGP to reach its full potential?

Vitamin K₂, especially MK-7, activates special proteins, allowing the body to use calcium properly. Two of these proteins are osteocalcin (OC) and MGP. The first attracts calcium to where it is locatedis most needed, namely in bones and teeth; the latter keeps calcium away from where it residesIs not necessary, namely soft tissue.

Proteins already present in the body depend on cofactors. Vitamin K₂is the cofactor for an enzyme called vitamin K-dependent carboxylase. The vitamin K-dependent proteins are activated by gamma carboxylation, which alters the structures of OC and MGP by adding another carboxyl group so that these proteins can bind calcium. In the case of vitamin K₂deficiency, they remain "undercarboxylated" or inactive.¹

What MK-7 does better than any form of vitamin K is activate proteins made in various organs of the body, including MGP in the circulatory system. MGP is the most powerful modulator of vascular calcification known, provided the body has sufficient vitamin K₂to activate it.

The collateral damage of a budget deficit is tragic. A five-year study of 10,000 asymptomatic individuals published inAtherosclerosisfound that survival rates were related to the amount of calcium in the blood vessels. The differences were large: “A calcium score of less than 10 correlated with biological age that was 10 years younger than the 'real age' in individuals over 70 years of age. A calcium score above 400 – on the other hand – correlated with biological age up to 30 years older than the actual age of younger patients.”⁶

It is important to note that recent evidence highlights the benefits of active MGP beyond the heart and bones. At the end of 2018, DeJournal of Alzheimer's DiseaseInScientific reportspublished articles examining the role of aortic stiffness due to calcification as a contributing factor to dementia and retinal arteriolar health, respectively. Both conditions are affected by active MGP status.

According to “Aortic Stiffness Linked to Increased Risk of Dementia in Older Adults,”⁷Risk factors for cardiovascular disease – including age, hypertension and diabetes – contribute to aortic stiffness and subclinical cardiovascular and cerebrovascular disease, increasing the risk of dementia.

In "Inactive matrix gla protein is a novel circulating biomarker that predicts retinal arteriolar constriction in humans",⁸researchers studied a randomly recruited Flemish population. Conclusion: Circulating inactive MGP (dp-ucMGP) is a long-term predictor of smaller retinal arteriolar diameter in the general population.

“Our observations highlight the possibility that vitamin K supplementation may promote retinal health,” the researchers said.

Furthermore, a 2019 study was published inArteriosclerosis, thrombosis in vascular biologynoted that based on the activation of MGP vitamin K₂has the ability to scavenge free radicals and reduce oxidative stress.⁹

Vitamin K₂'s cardiovascular connection

Evidence linking vitamin K₂Intake for cardiovascular benefits really started to take off in 2004. NattoPharma ASA saw this early observational evidence and went even further, sponsoring interventional studies that confirmed this link and elucidated the actual mechanism. There is now a significant research base and the majority of the research used NattoPharma's MenaQ7® Vitamin K₂such as MK-7 as the source material itself.

The heart-healthy relationship between vitamin K₂and MGP first appeared in the groundbreaking Rotterdam study, which showed that high dietary intake of vitamin K₂– but no vitamin K₁-has a strong protective effect on cardiovascular health.

The results of this 10-year population study indicated that eating foods rich in natural vitamin K₂(at least 32 mcg/day) resulted in a 50 percent reduction in arterial calcification, a 50 percent reduction in cardiovascular risk, and a 25 percent reduction in all-cause mortality.¹⁰In 2009, these findings were confirmed by another population study with 16,000 subjects (49 to 70 years old) from the Prospect-EPIC cohort population. After following female participants for eight years, researchers found that for every 10 mcg of vitamin K₂(MK-7, MK-8 and MK-9) ingested - again, no vitamin K₁- the risk of coronary heart disease was reduced by 9 percent. Vitamin K₁swallowing had no effect.¹¹

The Rotterdam Study (2004) and the Prospect-EPIC Study (2008) were the first population-based evidence that high dietary vitamin K intake₂– but no vitamin K₁-offered a strong positive reduction in cardiovascular risk.

These important observational data highlighted the need for further research. That's why NattoPharma sponsored a landmark cardiovascular endpoint intervention study in which MenaQ7^®Vitamin K₂since MK-7 was the source material.

Researchers conducted a double-blind, randomized intervention study in 244 postmenopausal women who received 180 mcg of vitamin K₂I'm MK-7 (I'm MenaQ7^®by NattoPharma) or placebo daily for 3 years.

This first interventional study of MK-7 nutritional supplementation and cardiovascular endpoints demonstrated that 3-year supplementation with a daily nutritional dose of MenaQ7^®was sufficient to actually reduce arterial stiffness in healthy postmenopausal women.

Using ultrasound and pulse wave velocity measurements (recognized as standard measures of cardiovascular health), researchers found that carotid artery distensibility was significantly improved over a three-year period in MenaQ7^®compared with a placebo group, especially in women with high arterial stiffness. Furthermore, pulse wave velocity showed a statistically significant decrease for vitamin K after three years₂(MK-7) group, but not for the placebo group, showing an increase in elasticity and a reduction in age-related arterial stiffness, again especially in women with high arterial stiffness.

This study had historical impact. It was the first intervention trial in which the results confirmed the link from previous population studies: vitamin K₂intake is associated with cardiovascular risk. A nutritional dose of vitamin K₂, Actually,promotescardiovascular health. No other compound has yet been shown to provide the same cardiovascular protection as vitamin K₂I'm MK-7.¹²

Two 2019 studies further strengthened (and confirmed) the relationship between vitamin K.₂and cardiovascular disease.

First, researchers examined the causal link between genetically predicted K concentrations and the risk of coronary heart disease in more than 103,000 cases in Europe. They found that K₁had no effect on MGP, but that vitamin K₂had a positive impact on cardiovascular health.¹³

Second, the American Health Association's "Central Hemodynamics in Relation to Circulating Desphospho-uncarboxylated Matrix Gla Protein: A Population Study" evaluated vitamin K status (dp-ucMGP) in 835 randomly recruited Flemish people. Researchers noted that higher inactive vitamin K was associated with greater pulse wave velocity, central pressure, forward pulse wave, and reverse pulse wave.

“Strengthening and calcification of the large arteries are precursors to cardiovascular complications,” the authors said. “MGP, which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that its central hemodynamic properties may be associated with inactive desphosphouncarboxylated MGP (dp-ucMGP).¹⁴

A silver lining to an eternally dark prognosis

Despite all the illuminating research, the news about cardiovascular health remains sickening.

What the consistent, grim statistics tend to hide is that poor cardiovascular health is not a problem reserved for the middle-aged or elderly. A 2019 study of 22,346 young adults ages 30 to 49 who underwent coronary artery calcium (CAC) testing for clinical indications found that 34.4% had CAC, and those with elevated CAC scores had significantly higher rates of coronary artery disease and coronary artery disease had. mortality due to disease.¹⁵

Traditional prescriptions for cardiovascular disease include anticoagulants and statins, both of which have an important relationship with vitamin K₂it must be considered.

AnticoagulantThe most common treatment for poor blood flow is to prescribe a vitamin K antagonist, such as coumarin or warfarin. These prescription medications disrupt vitamin K activity in the liver by inhibiting enzymes, preventing the blood from forming an unwanted clot. However, recent studies have found an association between long-term anticoagulant treatment and reduced bone quality due to the reduction of active osteocalcin, as well as twice as much arterial calcification compared to patients who did not receive vitamin K antagonists.

Fortunately, the standard of care has improved with the emergence of a new class of oral anticoagulantsdoesn'tvitamin K antagonists and relatively without major safety concerns.

Statins.Statins are a common recommendation to lower LDL-C (cholesterol) levels, and their use has increased in recent decades. However, a 2015 article stated that statins can act as 'mitochondrial toxins' with negative effects on the heart and blood vessels via the depletion of coenzyme Q.₁₀(CoQ₁₀) and by inhibiting vitamin K₂synthesis.¹⁶

This new article speaks directly to statins interrupting the mechanism of action by which vitamin K₂inhibits calcification. But while CoQ₁₀and vitamin K₂Both are affected by statins, there is currently no recommendation for supplemental vitamin K₂should be given to statin patients.

Vitamin K₂can be an excellent opportunity to maintain the benefits of these medications while mitigating their harmful effects. This means more treatment options for patients who can continue to support their cardiovascular health with vitamin K₂subsidy.

K₂because MK-7 is a complementary cardio nutrient

It is also important to note that vitamin K₂works in combination with other nutrients that may already be part of a person's cardiovascular regimen.

A 2013 study looked at vitamin K₂'s influence on vascular calcification in stage 3-5 patients with chronic kidney disease over six months. This prospective, randomized clinical trial in humans evaluated the cardiovascular effects of oral vitamin K administration₂(I'm MenaQ7^®) plus vitamin D or vitamin D alone.

The progression of coronary artery calcification index (CAC) and common carotid artery intima media thickness (CCA-IMT) – both markers of calcium deposits in arteries detected by computed tomography – showed slower progression of calcification in MenaQ7^®/vitamin D group than in the D-only group, an encouraging sign to use this potentially powerful duo.¹⁷

Additionally, Omega-3 has been recognized for cardiovascular support, with qualified health claims for reducing the risk of coronary heart disease in the United States. Although Omega-3's mechanism of action is related to supporting healthy inflammation, triglycerides, blood pressure and promoting arterial health, it is not recognized that it affects vascular calcification. That's what vitamin K does₂a perfect complementary nutrient – ​​providing the final piece of the heart health puzzle.

NattoPharma ASA has been awarded a Canadian patent (No. 2,657,748) for pharmaceutical and nutraceutical products that provide vitamin K₂in combination with one or more polyunsaturated fatty acids, including fish and/or krill oil, for benefits related to bones, cartilage and the cardiovascular system.

Proven bone benefits of K₂sum MK-7: Simultaneous support

In addition to coexisting peacefully with other nutrients, patients receiving vitamin K₂also receives the powerful bone health benefits that come from its action on osteocalcin. This has been established in a number of studies, highlighted by a groundbreaking, double-blind, randomized clinical trial published in 2013 inOsteoporosis International.

The study demonstrated for the first time clinically statistically significant protection of the vertebrae and the hip (femoral neck) against bone loss. This was achieved with a nutritional dose of vitamin K₂such as MK-7 (again MenaQ7^®of NattoPharma) taken daily for three years.

In this study of 244 healthy postmenopausal women, MenaQ7^®the group taking 180 mcg daily showed significantly reduced circulating non-carboxylated osteocalcin (ucOC). After three years, bone mineral content, bone mineral density and bone strength were statistically significantly better for the MK-7 group compared to the placebo group.¹⁸

Vitamin K₂The effect on bone health in children is particularly notable because childhood is the most important time for building healthy bones. Here are some highlights:

• 2009: Healthy children aged 6-10 years who took 45 mcg of MenaQ7^®K₂per day resulted in more active osteocalcin, leading to stronger, denser bones.¹⁹

• 2012: Children and adults over 40 show the greatest K deficiency and responded most strongly to MenaQ7^®K₂supplement (45 mcg for children; 90 mcg for adults).²⁰

• 2013: Children and teenagers receive MenaQ7^®K₂(50 mcg) and vitamin D (5 mcg calcitriol) showed improvements in bone mineral density daily.²¹

Conclusion

In less than 20 years, more than 19 clinical trials of vitamin K have been conducted in humans₂Publications have been published confirming the benefits for bone and cardiovascular health in both healthy and patient populations, young and old. The research will only grow. MenaQ7 from NattoPharma was used in these studies^®as the source material itself, further reinforcing the need to use MenaQ7^®asyour sourceof vitamin K₂such as MK-7, especially as cardiovascular health wreaks havoc on the world's population.

NattoPharma has taken the lead on a vitamin K₂RDI, but primary care physicians can play a more direct role in raising awareness about vitamin K₂like the MK-7. You can explain the power of vitamin K – and simplify it further₂for your patients and colleagues.

Biography

References