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Vitamin K

Vitamin K is essential for normal blood coagulation.

Vitamin K functions as a co-enzyme during the synthesis of several proteins involved in the coagulation process. Importantly, these proteins include prothrombin. In individuals with vitamin K deficiency, the “prothrombin time” increases, and in severe cases can lead to haemorrhage. Vitamin K is also important for the and in the metabolism of bone. Date of preparation: February 2019

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Importance of vitamin K for health

Vitamin K is essential for normal blood coagulation; it functions as a co-enzyme during the synthesis of several proteins involved in coagulation. Importantly, these proteins include prothrombin (also known as coagulation Factor II). In individuals with vitamin K deficiency, the “prothrombin time” increases, and in severe cases can lead to haemorrhage (1). Vitamin K is also important for the and in bone metabolism.

Vitamin K occurs in several different forms, but all share the menadione ring structure (2-naphthoquinone). Phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone), known as vitamin K1, is found in all green vegetables such as spinach, broccoli, kale and Swiss Chard, which contain >200 μg/100 g (2, 3). Bioavailability in green vegetables is low (<10%). Some fat consumed concomitantly helps the absorption of the vitamin in the digestive tract. Soybean and canola oil are also sources of vitamin K (100 μg/ 100 g) with a higher bioavailability (2), though these oils are likely consumed in lesser quantities than green leafy vegetables, bringing the overall contribution relatively similar.

The second form of vitamin K, the menaquinones, collectively known as vitamin K2, have a long chain with 6 to 13 isoprenoid units in the 3-position, and are denoted by MK-n, where nsignifies the number of isoprenoid units (4-6). Menaquinones are produced by bacterial fermentation, either in the large intestine (mainly by Bacteriodes spp.), or in foods such as cheese, curd and natto, a Japanese food made of fermented soya beans (3-6). Menaquinones have a different bioavailability – almost 100% from dairy produce (6, 7). They also have different pharmacokinetics to phylloquinones, leading to variable plasma half-life times (4)and distrubution. Menaquinones produced by intestinal bacterial are, however, poorly available for intestinal absorption (8). The composition of menaquinone intake varies regionally, depending on the type of produce being consumed in the habitual diet (9)and may be a relatively small contributor to total vitamin K intake.

MK-4 is different to other menaquinones, in that it is not a major bacterial product, but is formed by the cellular alkylation of Vitamin K3 (menadione; 2-methoyl-1,4-naphthoquinine), which is a synthetic form of vitamin K found in animal feed and thus originates from animal products, or from phylloquinone, with menadione as intermediate (4).

Risk and consequences of vitamin K deficiency

Due to dietary ubiquity and recycling of the vitamin K molecule, vitamin K deficiency is rare in adults, and mainly limited to those with disorders of fat absorption and digestion (2). However, low vitamin K intakes are associated with an increased risk of osteoporotic fractures (2)and are associated with a higher risk of cardiovascular disease , though data from clinical trials on the beneficial role of vitamin K do not support supplementation(3).

Vitamin K deficiency is much more frequent in neonates than in adults, since infants are born vitamin K-deficient due to poor maternal-placental transfer (2), and a low endogenous production due to a sterile gut (8).

WHO recommendation (2018): All newborns should be given 1 mg of vitamin K intramuscularly after birth (i.e. after the first hour during which the infant should be in skin-to-skin contact with the mother and breastfeeding should be initiated). (Strong recommendation, moderate quality evidence.)

Risks of vitamin K excess

Vitamin K is not toxic, and there is no upper limit within current dietary reference intakes (2).

Keywords

clotting, pro-coagulant, osteoporosis, calcification, inflammation, oxidative stress, apoptosis

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