Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation and for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modificat
This article is about the family of vitamers. For vitamin K1, the form most commonly used as a dietary supplement or in a multi-vitamin, see Phytomenadione.
Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements.[1] The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ("K" from Danish koagulation, for "coagulation") and for controlling binding of calcium in bones and other tissues.[2] The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor.
Vitamin K is used in the liver as the intermediate VKH2 to deprotonate a glutamate residue and then is reprocessed into vitamin K through a vitamin K oxide intermediate.[3] The presence of uncarboxylated proteins indicates a vitamin K deficiency.[2] Carboxylation allows them to bind (chelate) calcium ions, which they cannot do otherwise.[4] Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. Research suggests that deficiency of vitamin K may also weaken bones, potentially contributing to osteoporosis, and may promote calcification of arteries and other soft tissues.[2][4][5]
Chemically, the vitamin K family comprises 2-methyl-1,4-naphthoquinone (3-) derivatives. Vitamin K includes two natural vitamers: vitamin K1 (phylloquinone) and vitamin K2 (menaquinone).[4] Vitamin K2, in turn, consists of several related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms. The two most studied are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).[2]
Vitamin K1 is made by plants, and is found in highest amounts in green leafy vegetables, being directly involved in photosynthesis.[1] It is active as a vitamin in animals and performs the classic functions of vitamin K, including its activity in the production of blood-clotting proteins.[1][2] Animals may also convert it to vitamin K2, variant MK-4. Bacteria in the gut flora can also convert K1 into K2. All forms of K2 other than MK-4 can only be produced by bacteria, which use these during anaerobic respiration. Vitamin K3 (menadione), a synthetic form of vitamin K, was used to treat vitamin K deficiency, but because it interferes with the function of glutathione, it is no longer used in this manner in human nutrition.[2]
Definition
Vitamin K refers to several structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. These are similar in structure in that they share a quinone ring, but differ in the length and degree of saturation of the carbon tail and the number of repeating isoprene units in the side chain (see figures in § Chemistry). Plant-sourced forms are primarily vitamin K1. Animal-sourced foods are primarily vitamin K2.[1][6] Vitamin K has several roles: an essential nutrient absorbed from food, a product synthesized and marketed as part of a multi-vitamin or as a single-vitamin dietary supplement, and a prescription medication for specific purposes.[1]
Dietary recommendations
The US National Academy of Medicine does not distinguish between K1 and K2 – both are counted as vitamin K. When recommendations were last updated, in 1998[update], sufficient information was not available to establish an estimated average requirement or recommended dietary allowance, terms that exist for most vitamins. In instances such as these, the academy defines adequate intakes (AIs) as amounts that appear to be sufficient to maintain good health, with the understanding that at some later date, AIs will be replaced by more exact information. The current AIs for adult women and men ages 19 and older are 90 and 120 μg/day, respectively, for pregnancy is 90 μg/day, and for lactation is 90 μg/day. For infants up to 12 months, the AI is 2.0–2.5 μg/day; for children ages 1–18 years the AI increases with age from 30 to 75 μg/day. As for safety, the academy sets tolerable upper intake levels (known as "upper limits") for vitamins and minerals when evidence is sufficient. Vitamin K has no upper limit, as human data for adverse effects from high doses are not sufficient.[5]
In the European Union, adequate intake is defined the same way as in the US. For women and men over age 18 the adequate intake is set at 70 μg/day, for pregnancy 70 μg/day, and for lactation 70 μg/day. For children ages 1–17 years, adequate intake values increase with age from 12 to 65 μg/day.[7] Japan set adequate intakes for adult women at 65 μg/day and for men at 75 μg/day.[8] The European Union and Japan also reviewed safety and concluded – as had the United States – that there was insufficient evidence to set an upper limit for vitamin K.[8][9]
For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percentage of daily value. For vitamin K labeling purposes, 100% of the daily value was 80 μg, but on 27 May 2016 it was revised upwards to 120 μg, to bring it into agreement with the highest value for adequate intake.[10][11] Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales.[12][13] A table of the old and new adult daily values is provided at Reference Daily Intake.
Fortification
According to the Global Fortification Data Exchange, vitamin K deficiency is so rare that no countries require that foods be fortified.[14] The World Health Organization does not have recommendations on vitamin K fortification.[15]
Sources
Vitamin K1 is primarily from plants, especially leafy green vegetables.[1][2] Small amounts are provided by animal-sourced foods. Vitamin K2 is primarily from animal-sourced foods, with poultry and eggs much better sources than beef, pork or fish.[6] One exception to the latter is nattō, which is made from bacteria-fermented soybeans.[2] It is a rich food source of vitamin K2 variant MK-7, made by the bacteria.[1][16]
Vitamin K1
Vitamin K2
See also: Vitamin K2 § Dietary sourcesAnimal-sourced foods are a source of vitamin K2.[17][19] The MK-4 form is from conversion of plant-sourced vitamin K1 in various tissues in the body.[20]
