Vitamin K2

Vitamin K2 or menaquinone (MK) is one of three types of vitamin K, the other two being vitamin K1 (phylloquinone) and K3 (menadione). 

K2 is both a tissue and bacterial product, derived from vitamin K1 in both cases.

Vitamin K2 consists of various forms.

Vitamin K2 is a type of vitamin K that plays a crucial role in bone health and blood clotting. 

Vitamin K2, also known as menaquinone, is a fat-soluble vitamin that is similar in structure to Vitamin K1. 

Like vitamin K1, it is essential for blood clotting and bone metabolism, but it has some distinct roles and sources in the body.

One of the key differences between vitamin K2 and K1 is that K2 is produced by bacteria in the gut and is also found in certain animal products such as cheese, eggs, and liver. 

Vitamin K2 is known to facilitate the activation of osteocalcin, a protein that is important for bone health. 

It also plays a role in regulating calcium metabolism and helps to prevent the buildup of calcium in arterial walls, which can lower the risk of cardiovascular disease.

Vitamin K2 is generally considered safe, but excessive intake can interfere with the action of anticoagulants or blood-thinning medication.

It helps the body transport calcium to the bones, preventing it from accumulating in the arteries and soft tissues. 

Vitamin K2 can be found in some animal-based foods, such as dairy products, egg yolks, and meat, as well as in fermented foods like natto and cheese. 

It is also available in supplement form.

The most common in the human diet is the short-chain, water-soluble menatetrenone (MK-4), which is usually produced by tissue and/or bacterial conversion of vitamin K1, and is commonly found in animal products. 

Vitamin K2, the main storage form in animals, has several subtypes, which differ in isoprenoid chain length. 

Vitamin K2 homologues are called menaquinones, and are characterized by the number of isoprenoid residues in their side chains. 

MK-4 and MK-7 are both subtypes of K2.

The mechanism of action of vitamin K2 is similar to vitamin K1. 

K vitamins play an essential role as cofactor for the enzyme γ-glutamyl carboxylase, which is involved in vitamin K-dependent carboxylation of the gla domain in “Gla proteins”.

Carboxylation of these vitamin K-dependent Gla-proteins are essential for the function of the protein, and is important in a vitamin recovery mechanism since it serves as a recycling pathway to recover vitamin K from its epoxide metabolite for reuse in carboxylation.

There are several human Gla-containing proteins synthesized in several different types of tissues.’

These Gla-proteins are synthesized in the liver and play an important role in blood homeostasis.

Osteocalcin. This non-collagenous protein is secreted by osteoblasts and plays an essential role in the formation of mineral in bone.

Matrix gla protein (MGP). This calcification inhibitory protein who’s role is most pronounced in cartilage and in arterial vessel walls.

Growth arrest-specific protein 6 (GAS6) is secreted by leucocytes and endothelial cells in response to injury and helps in cell survival, proliferation, migration, and adhesion.

With regard to utilization, reports suggest that Vitamin K2 is preferred by the extrahepatic tissues of bone, cartilage, vasculature.

Vitamin K is absorbed along with dietary fat from the small intestine and transported by chylomicrons in the circulation.

There is insufficient evidence to publish a dietary reference value for vitamin K or for K2.

There is no known toxicity associated with high doses of menaquinones (vitamin K2). 

Unlike the other fat-soluble vitamins, vitamin K is not stored in any significant quantity in the liver. 

There is no evidence of toxicity associated with the intake of either K1 or K2.

Apart from animal livers, the richest dietary source of menaquinones are fermented foods, from bacteria.

Food sources include cheeses consumed in Western diets, containing MK-8 and MK-9 and fermented soybean products, containing MK-7.

MK-4 is synthesized by animal tissues and is found in meat, eggs, and dairy products.

Cheeses have been found to contain MK-8 at 10–20 μg per 100 g and MK-9 at 35–55 μg per 100 g.

In addition to its animal origins, menaquinones are synthesized by bacteria during fermentation and are found in most fermented cheese and soybean products.

Food frequency questionnaire about 90% of total vitamin K intakes are provided by K1, about 7.5% by MK-5 through MK-9 and about 2.5% by MK-4.

There is a clear association between long-term oral or intravenous anticoagulant treatment and reduced bone quality due to reduction of active osteocalcin. 

Oral anticoagulants might lead to an increased incidence of fractures, reduced bone mineral density or content, osteopenia, and increased serum levels of undercarboxylated osteocalcin.

Oral anticoagulants are often linked to undesired soft-tissue calcification in both children and adults, dependent upon the action of K vitamins. 

OAC treatment, two-fold more arterial calcification was found as compared to patients not receiving vitamin K antagonists.

Among consequences of anticoagulant treatment: increased aortic wall stiffness, coronary insufficiency, ischemia, and even heart failure. 

Arterial calcification might also contribute to systolic hypertension and ventricular hypertrophy.

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