Vitamin K2 MK-7: Benefits and Dangers

Vitamin K2 is a rare nutrient in our diet. However, it plays an essential role in the body by fighting against vascular calcifications and preserving our bone balance. Supplementation with menaquinone-7 (MK-7), its most effective and non-toxic form, could protect us from a wide range of chronic diseases.

The different forms of Vitamin K
Vitamin K is a fat-soluble vitamin. It has several forms or vitamers, with slightly different chemical structures and specific properties.

Vitamin K1 and Vitamin K2
A distinction is made between vitamin K1 or phylloquinone and vitamin K2 or menaquinones (MK). Vitamin K1 is found in plant foods, especially green vegetables (cabbage, spinach).

Vitamin K2 is derived from bacterial fermentation and is found in animal products (meat, fish, eggs), dairy products, and fermented vegetables.

The bioavailability of vitamin K2 is higher than that of vitamin K1. There is also vitamin K3, a synthetic form called menadione, which has toxic effects.

Several forms of Vitamin K2
Vitamin K2 comes in a series of compounds, from menaquinone-1 (MK-1) to menaquinone-14 (MK-14). The most common is MK-4, also called menatetrenone, and MK-7. They have been the subject of the most significant number of scientific studies devoted to the benefits of vitamin K2 on our health. These two forms of vitamin K2 are not equivalent since our bodies more easily assimilate MK-7.

MK-7 vitamin K2 exerts its effects for a more extended period. Its half-life – the time it takes to lose half of its biological activity – is 70 hours, while that of vitamin K2 MK-4 is only one and a half hours.

Recommended intakes focused on Vitamin K1
EFSA has established adequate daily intake levels for vitamin K1 only, set at 70µg for adults.

They are based on our body’s needs to maintain good blood coagulation. Vitamin K is indeed involved in this phenomenon, which gets its name. The “K” comes from the Danish Coagulation, the language of Henrik Dam, the scientist who discovered this vitamin in the 1930s.

To fulfill this function, vitamin K1 acts at the level of the liver. Vitamin K2 is widely distributed throughout the body, where it plays multiple roles.

Effects of Vitamin K2 on bone metabolism
Vitamin K2 plays an essential role in bone balance. It promotes the formation of osteoblasts, the cells responsible for the production of bone tissue, and several proteins found in the bone that depend on vitamin K2.

The effects of Vitamin K on osteocalcin, an essential bone protein
Vitamin K conditions the functioning of a small protein, osteocalcin. Osteoblasts produce it under the effect of calcitriol, the active form of vitamin D, which is also crucial for bone health.

Most of the osteocalcin is incorporated into the bone to facilitate calcium binding. To be active, however, it must undergo a chemical transformation: an enzyme grafts three carboxyl groups onto it. The enzyme performing this carboxylation cannot do its job without vitamin K.

A vitamin K deficiency causes bone fragility
When vitamin K is lacking, osteocalcin cannot be carboxylated and remains inactive. The level of under-carboxylated osteocalcin in the body increases, and with it, the risk of fracture.

This protein increases bone strength during aging, notably by creating dilation spaces in the bones that attenuate the consequences of shocks and prevent fracture. It also plays a regulatory role by preventing excessive bone development.

MK-7 supplementation is the most effective way to activate osteocalcin
A clinical trial showed that active osteocalcin levels increased with the supplementation of 100μg or 200μg of vitamin K2 MK-7 per day for four weeks.

For other forms of vitamin K, the situation is very different. Supplementation of 250 to 1000µg per day of vitamin K1 or 600 to 1500µg of vitamin K2 MK-4 per day is required to activate osteocalcin.

Vitamin K acts on other bone proteins
Osteocalcin is not the only protein essential to bone health that depends on vitamin K. Matrix protein Gla (MGP), which promotes bone formation; protein S, whose deficiency is associated with low bone density, and periostin, which is involved in bone repair, are also dependent on vitamin K.

High intakes of Vitamin K2 MK-7 for stronger bones
The information of a high quantity of vitamin K2 MK-7, mainly through supplementation, could fight against bone loss and limit the fracture risk.

In Japan, natto consumption reduces the frequency of fractures
Natto is a Japanese specialty made from soybeans fermented by Bacillus subtilis bacteria. This food is the best source of vitamin K2 MK-7: it contains 200 to 400µg per 30 to 45g portion. Hip fractures in women are found to be less common in the regions of the country where it is consumed the most.

Vitamin K2 MK-7 supplementation improves bone density
However, natto is rarely included in our menus. MK-7 supplementation could replicate its benefits by increasing bone density at sensitive times. In postmenopausal women, supplementation with 180μg per day for three years leads to improved mineral density in the lumbar and femoral necks. The treatment also improves bone strength and reduces height loss in the spine.

Outside the context of menopause, bone loss is also common after major surgery. The same dose as in the previous study was given to organ transplant recipients (heart or lung) for one year after surgery. The loss of mineral density in the lumbar region was attenuated.

The benefits of menaquinone-7 for the joints
Vitamin K2 MK-7 also appears to improve the function of our joints.

A study in Egypt involved 84 people with rheumatoid arthritis, half of whom were given 100µg per day of MK-7 for three months, with the other half being a control group. The participants continued to take their usual medication.

Several blood parameters that are increased in rheumatoid arthritis were lowered after supplementation. Patients’ symptoms decreased.

However, 14% of the supplemented group did not respond to treatment, possibly due to a metabolic problem affecting vitamin K use.

The benefits of Vitamin K2 on cardiovascular health
In addition to its effects on blood clotting, vitamin K benefits cardiovascular health, particularly in the fight against arterial calcification.

Anti-calcifying effects of Vitamin K2 MK-7
The development of calcifications in the blood vessel wall is one of the phenomena involved in cardiovascular diseases. The calcium deposits that accumulate tend to stiffen them and thus disrupt the blood flow through them.

Vitamin K2 protects against this mechanism through the proteins it activates. This is particularly true of the matrix protein Gla, which plays a role in the bone. It also prevents the formation of hydroxyapatite crystals (made up of phosphate and calcium) and their deposition on blood vessel walls.

A diet rich in Vitamin K2 protects against vascular calcifications
High dietary intakes of vitamin K2 are thus associated with a reduced risk of calcifications in the arteries. They also protect against coronary artery disease, which deprives the heart of an optimal blood supply. This benefit is specific to this form of vitamin K and is not found with vitamin K1.

Vitamin K2 MK-7 and vascular calcifications in renal disease
People with kidney disease often have a vitamin K deficiency. Blood levels of the inactive form of matrix protein Gla rise, and veins and arteries gradually become calcified.

Administering a dose of 360, 720, or 1080µg of MK-7 three times a week for eight weeks to dialysis patients lowers these levels, and the more effectively the dose is high. This approach could therefore prevent the occurrence or worsening of vascular calcifications in patients with advanced renal disease. A clinical trial is currently underway to evaluate its effectiveness.

However, it is already known that this intervention can improve blood vessel function in kidney transplant patients. The administration of 360µg per day of menaquinone-7 for eight weeks improves arterial flexibility, an asset to preserve the fragile cardiovascular health of these people.

MK-7 improves arterial flexibility in postmenopausal women
The benefits of supplementation in this context have also been demonstrated in menopausal women. Daily intake of 180µg of MK-7 for three years reduced the amount of inactive matrix protein Gla by half and, consequently, arterial stiffness.

Vitamin K2 a guarantee of good metabolic health
Vitamin K appears to improve glucose metabolism and thus delay the risk of type 2 diabetes.

A diet rich in Vitamin K2 limits the risk of type 2 diabetes
The follow-up of 38094 adults living in the Netherlands over ten years showed the protective effect of vitamin K2 dietary intake against type 2 diabetes. The risk of developing this disorder is lowered by 7% for any increase in intake of 10µg.

Better control of the disease thanks to MK-7 supplementation
Supplementation can benefit people who have declared the disease, as shown by a clinical trial conducted with 45 people with type 2 diabetes. One group received 200µg per day of vitamin MK-7, the other a placebo, for 12 weeks. Fasting blood sugar, glycated hemoglobin (an indicator of blood sugar control), fasting insulin, and insulin resistance decreased.

The mechanism of action of Vitamin K on insulin
Vitamin K can improve the body’s sensitivity to insulin by acting on different levers.

It fights against oxidative stress and inflammation, both of which are involved in the resistance of cells to this hormone responsible for regulating blood sugar levels.

It also increases levels of adiponectin, which helps regulate glucose metabolism. Adiponectin is produced by fatty tissue and is not sufficiently concentrated in the blood in cases of obesity. Vitamin K also stimulates the production of other compounds, sirtuin, and AMPK, which are also involved in this phenomenon.

The beneficial influence of Vitamin K2 MK-7 on body composition
Excessive weight is a breeding ground for metabolic disorders, mainly when fat is concentrated in the belly.

Vitamin K2 MK-7 supplementation can favor this parameter, according to a study conducted with 214 postmenopausal women. It was based on administering a dose of 180µg per day for three years.

Some participants responded well to the treatment, as evidenced by an increase in the level of active osteocalcin in their bodies. In these women, fat in the abdomen and around the viscera decreased. This favorable development could counteract the body’s loss of sensitivity to insulin and thus delay the risk of diabetes.

The promising potential of Vitamin K2 in the fight against cancer
Laboratory experiments have shown that vitamin K2 has anti-cancer activity. Adding it to cultures of cells from different types of cancers (liver, leukemia, digestive tract, lung, prostate) leads to their destruction.

The protective effects of Vitamin K2 nutritional intake
The follow-up of nearly 25,000 people living in Europe for 10 to 14 years has shown that cancer mortality is lower in those with high vitamin K2 intakes. Vitamin K2 intakes are particularly protective against lung and prostate cancer.

These data confirm those obtained in a previous study for prostate cancer, which also stated that vitamin K1 intake had no influence on the risk of developing the disease, unlike K2 intake.

The benefits of Vitamin K2 supplementation
To date, the clinical trials conducted in this context concern vitamin K2 MK-4. They have focused on preventing and treating hepatocellular carcinoma, the most common liver cancer, with mixed results. A meta-analysis of 6 highlights benefits on the recurrence rate of the disease 2 and 3 years after diagnosis and the total survival of patients.

It would be interesting to evaluate whether supplementation with MK-7, which is more bioavailable, gives better results in humans. Encouraging data have already been obtained in animals. A Chinese research team has shown that the administration of this form of vitamin K allows the attenuation of tumor processes in mice used as a study model for colon cancer. This action is achieved through an increase in adiponectin level, which opposes the process of carcinogenesis at the digestive level.

Potential benefits for a large number of diseases
The benefits of vitamin K2 could extend far beyond the conditions previously mentioned.

The potential of Vitamin K2 for the nervous system
Vitamin K2 is active in the brain and has been shown to have protective effects on neurons in laboratory experiments. These elements suggest potential applications in the field of neurology.

Benefits are suspected in the context of multiple sclerosis, an autoimmune disease that affects the central nervous system. A study of 45 patients and 29 healthy people showed that the former had reduced levels of vitamin K2 compared to the latter. Low levels of vitamin K2 in the body of patients are associated with a higher number of MS attacks per year and more frequent optic nerve damage.

A beneficial immunosuppressive action in case of allergy
Vitamin K2 seems to be able to temper specific immune response surges. It could thus be helpful in case of eczema, for example. In this skin disease, specific white blood cells – T lymphocytes – cause inflammation of the skin and lead to the formation of fluid-filled blisters.

A study has shown that adding vitamin K2 to these immune cells collected from young patients modulates their action. Vitamin K1, on the other hand, has no such effect.

The role of Vitamin K2 in case of infection
Could vitamin K also protect us in case of viral infection? Dutch researchers have recently established a link between the vitamin K2 status of patients and the severity of Covid-19. Their preliminary results were published in a pre-publication.

The mortality rate was greater in patients with high levels of inactive matrix Gla protein, reflecting vitamin K2 deficiency. Calcification of lung tissue may be one reason for the increased risk of developing a severe form of the disease.

Side effects of Vitamin K
Vitamins K1 and K2 are not toxic when given orally, even at high doses. Therefore, no maximum intake has been defined. A very high dose (45 mg daily, whereas the usual dosages are in the microgram range) does not lead to excess blood coagulation.

Regarding the specific form of vitamin K2 MK-7, a review of the scientific literature concludes that supplementation does not pose a public health problem.

Vitamin K can interfere with warfarin, an anticoagulant drug that prevents blood clots from forming or increasing in size. In this case, discussing supplementation with your doctor is essential to determine the appropriate dosage.

Unlike vitamins K1 and K2, vitamin K3 is very toxic and is therefore not used in humans.

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