Vitamin Ok refers to structurally comparable, fat-soluble vitamers present in meals and marketed as dietary dietary supplements.[1] The human physique requires vitamin Ok for post-synthesis modification of sure proteins which are required for blood coagulation (Ok from koagulation, Danish for “coagulation”) or for controlling binding of calcium in bones and different tissues.[2] The entire synthesis entails ultimate modification of those so-called “Gla proteins” by the enzyme gamma-glutamyl carboxylase that makes use of vitamin Ok as a cofactor. The presence of uncarboxylated proteins signifies a vitamin Ok deficiency. Carboxylation permits them to bind (chelate) calcium ions, which they can’t do in any other case.[3] With out vitamin Ok, blood coagulation is significantly impaired, and uncontrolled bleeding happens. Analysis means that deficiency of vitamin Ok may additionally weaken bones, doubtlessly contributing to osteoporosis, and should promote calcification of arteries and different comfortable tissues.[2][3][4]
Chemically, the vitamin Ok household includes 2-methyl-1,4-naphthoquinone (3-) derivatives. Vitamin Ok contains two pure vitamers: vitamin K1 (phylloquinone) and vitamin K2 (menaquinone).[3] Vitamin K2, in flip, consists of numerous associated chemical subtypes, with differing lengths of carbon aspect chains manufactured from isoprenoid teams of atoms. The 2 most studied ones are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).
Vitamin K1 is made by crops, and is present in highest quantities in inexperienced leafy greens, as a result of it’s immediately concerned in photosynthesis. It’s energetic as a vitamin in animals and performs the basic capabilities of vitamin Ok, together with its exercise within the manufacturing of blood-clotting proteins. Animals may additionally convert it to vitamin K2, variant MK-4. Micro organism within the intestine flora also can convert K1 into MK-4. All types of K2 apart from MK-4 can solely be produced by micro organism, which use these throughout anaerobic respiration. Vitamin K3 (menadione), an artificial type of vitamin Ok, was used to deal with vitamin Ok deficiency, however as a result of it interferes with the perform of glutathione, it’s now not used this fashion in human vitamin.[2]
Contents
Definition[edit]
Vitamin Ok refers to structurally comparable, fat-soluble vitamers present in meals and marketed as dietary dietary supplements. “Vitamin K” embody a number of chemical compounds. These are comparable in construction in that they share a quinone ring, however differ within the size and diploma of saturation of the carbon tail and the variety of repeating isoprene items within the aspect chain (see figures in Chemistry part). Plant-sourced kinds are primarily vitamin K1. Animal-sourced meals are primarily vitamin K2.[1][5][6] Vitamin Ok has a number of roles: a necessary nutrient absorbed from meals, a product synthesized and marketed as a part of a multi-vitamin or as a single-vitamin dietary complement, and a prescription treatment for particular functions.[1]
Dietary suggestions[edit]
The US Nationwide Academy of Drugs doesn’t distinguish between K1 and K2 – each are counted as vitamin Ok. When suggestions had been final up to date in 1998, enough data was not obtainable to ascertain an estimated common requirement or really helpful dietary allowance, phrases that exist for many nutritional vitamins. In situations comparable to these, the academy defines ample intakes (AIs) as quantities that seem like enough to keep up good well being, with the understanding that at some later date, AIs shall be changed by extra actual data. The present AIs for grownup men and women ages 19 and older are 90 and 120 μg/day, respectively, for being pregnant is 90 μg/day, and for lactation is 90 μg/day. For infants as much as 12 months, the AI is 2.0–2.5 μg/day; for kids ages 1–18 years the AI will increase with age from 30 to 75 μg/day. As for security, the academy units tolerable higher consumption ranges (often called “upper limits”) for nutritional vitamins and minerals when proof is enough. Vitamin Ok has no higher restrict, as human knowledge for hostile results from excessive doses should not enough.[4]
Within the European Union, ample consumption is outlined the identical approach as within the US. For men and women over age 18 the ample consumption is about at 70 μg/day, for being pregnant 70 μg/day, and for lactation 70 μg/day. For kids ages 1–17 years, ample consumption values enhance with age from 12 to 65 μg/day.[7] Japan set ample intakes for grownup ladies at 65 μg/day and for males at 75 μg/day.[8] The European Union and Japan additionally reviewed security and concluded – as had america – that there was inadequate proof to set an higher restrict for vitamin Ok.[8][9]
For US meals and dietary complement labeling functions, the quantity in a serving is expressed as a share of every day worth. For vitamin Ok labeling functions, 100% of the every day worth was 80 μg, however on 27 Could 2016 it was revised upwards to 120 μg, to convey it into settlement with the best worth for ample consumption.[10][11] Compliance with the up to date labeling laws was required by 1 January 2020 for producers with US$10 million or extra in annual meals gross sales, and by 1 January 2021 for producers with decrease quantity meals gross sales.[12][13] A desk of the previous and new grownup every day values is supplied at Reference Each day Consumption.
Fortification[edit]
In response to the World Fortification Knowledge Change, vitamin Ok deficiency is so uncommon that no international locations require that meals be fortified.[14] The World Well being Group doesn’t have suggestions on vitamin Ok fortification.[15]
Sources[edit]
Vitamin K1 is primarily from crops, particularly leafy inexperienced greens. Small quantities are supplied by animal-sourced meals. Vitamin K2 is primarily from animal-sourced meals, with poultry and eggs significantly better sources than beef, pork or fish.[6] One exception to the latter is nattō, which is constituted of bacteria-fermented soybeans. It’s a wealthy meals supply of vitamin K2 variant MK-7, made by the micro organism.[16]
Vitamin K1[edit]
Vitamin K2[edit]
Animal-sourced meals are a supply of vitamin K2[18][19] The MK-4 kind is from conversion of plant-sourced vitamin K1 in varied tissues within the physique.[20]
Vitamin deficiency[edit] – “vitamin k chemical name”
Vitamin Ok deficiency is assessed as a vitamin-responsive failure to transform glutamate amino acids to gamma-carboxyglutamate amino acids in prothrombin, the precursor protein to the enzyme thrombin, which has the useful consequence of accelerating prothrombin time – a measure of blood clotting exercise – and in extreme instances may end up in bleeding, both inside or exterior.[2][4] Regular diets are often not missing in vitamin Ok. Thus, main deficiency is rare in wholesome youngsters and adults.[3] One exception is infants, who’re at an elevated threat of deficiency whatever the vitamin standing of the mom throughout being pregnant and breast feeding due to poor switch of the vitamin to the placenta and low quantities of the vitamin in breast milk.[17]
Secondary deficiencies can happen in individuals who eat ample quantities however have a malabsorption situations comparable to cystic fibrosis, or power pancreatitis, and in individuals who have liver injury or illness, for instance because of alcoholic liver illness, because the liver is the first storage organ for the vitamin. Secondary vitamin Ok deficiency also can happen in individuals who have a prescription for a vitamin Ok antagonist drug comparable to warfarin.[2][3] A drug related to elevated threat of vitamin Ok deficiency is cefamandole, though the mechanism is unknown.[21]
Medical makes use of[edit]
Treating vitamin deficiency in newborns[edit]
Vitamin Ok is given as an injection to newborns to stop vitamin Ok deficiency bleeding.[17] The blood clotting components of new child infants are roughly 30–60% that of grownup values; this seems to be a consequence of poor switch of the vitamin throughout the placenta, and thus low fetal plasma vitamin Ok.[17] Incidence of vitamin Ok deficiency bleeding within the first week of the toddler’s life is estimated at 0.25–1.7%, with a prevalence of two–10 instances per 100,000 births. Human milk accommodates 0.85–9.2 μg/L (median 2.5 μg/L) of vitamin K1, whereas toddler components is formulated in vary of 24–175 μg/L.[17] Late onset bleeding, with onset 2 to 12 weeks after start, could be a consequence of unique breastfeeding, particularly if there was no preventive remedy.[17] Late onset prevalence reported at 35 instances per 100,000 stay births in infants who had not obtained prophylaxis at or shortly after start.[22] Vitamin Ok deficiency bleeding happens extra regularly within the Asian inhabitants in comparison with the Caucasian inhabitants.[17]
Bleeding in infants because of vitamin Ok deficiency will be extreme, resulting in hospitalization, mind injury, and demise. Intramuscular injection, sometimes given shortly after start, is more practical in stopping vitamin Ok deficiency bleeding than oral administration, which requires weekly dosing as much as three months of age.[17]
Managing warfarin remedy[edit]
Warfarin is an anticoagulant drug. It capabilities by inhibiting an enzyme that’s accountable for recycling vitamin Ok to a useful state. As a consequence, proteins that must be modified by vitamin Ok should not, together with proteins important to blood clotting, and are thus not useful.[23] The aim of the drug is to scale back threat of inappropriate blood clotting, which might have severe, doubtlessly deadly penalties.[2] The right anticoagulant motion of warfarin is a perform of vitamin Ok consumption and drug dose. On account of differing absorption of the drug and quantities of vitamin Ok within the weight loss plan, dosing should be monitored and individualized for every affected person.[24] Some meals are so excessive in vitamin K1 that medical recommendation is to keep away from these (examples: collard greens, spinach, turnip greens) completely, and for meals with a modestly excessive vitamin content material, preserve consumption as constant as potential, in order that the mixture of vitamin consumption and warfarin preserve the anti-clotting exercise within the therapeutic vary.[25]
Vitamin Ok is a remedy for bleeding occasions attributable to overdose of the drug.[26] The vitamin will be administered by mouth, intravenously or subcutaneously.[26] Oral vitamin Ok is utilized in conditions when an individual’s Worldwide normalised ratio is larger than 10 however there isn’t a energetic bleeding.[25][27] The newer anticoagulants apixaban, dabigatran and rivaroxaban should not vitamin Ok antagonists.[28]
Treating rodenticide poisoning[edit]
Coumarin is used within the pharmaceutical trade as a precursor reagent within the synthesis of numerous artificial anticoagulant prescribed drugs.[29] One subset, 4-hydroxycoumarins, act as vitamin Ok antagonists. They block the regeneration and recycling of vitamin Ok. A few of the 4-hydroxycoumarin anticoagulant class of chemical substances are designed to have excessive efficiency and lengthy residence occasions within the physique, and these are used particularly as second era rodenticides (“rat poison”). Demise happens after a interval of a number of days to 2 weeks, often from inside hemorrhaging.[29] For people, and for animals which have consumed both the rodenticide or rats poisoned by the rodenticide, remedy is extended administration of huge quantities of vitamin Ok.[30][31] This dosing should generally be continued for as much as 9 months in instances of poisoning by “superwarfarin” rodenticides comparable to brodifacoum. Oral vitamin K1 is most well-liked over different vitamin K1 routes of administration as a result of it has fewer negative effects.[32]
Strategies of evaluation[edit]
A rise in prothrombin time, a coagulation assay, has been used as an indicator of vitamin Ok standing, nevertheless it lacks enough sensitivity and specificity for this utility.[33] Serum phylloquinone is essentially the most generally used marker of vitamin Ok standing. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages embody exclusion of the opposite vitamin Ok vitamers and interference from latest dietary consumption.[33] Vitamin Ok is required for the gamma-carboxylation of particular glutamic acid residues throughout the Gla area of the 17 vitamin Ok–dependent proteins. Thus, an increase in uncarboxylated variations of those proteins is an oblique however delicate and particular marker for vitamin Ok deficiency. If uncarboxylated prothrombin is being measured, this "Protein induced by Vitamin K Absence/antagonism (PIVKA-II)" is elevated in vitamin Ok deficiency. The check is used to evaluate threat of vitamin Ok–poor bleeding in new child infants.[33] Osteocalcin is concerned in calcification of bone tissue. The ratio of uncarboxylated osteocalcin to carboxylated osteocalcin will increase with vitamin Ok deficiency. Vitamin K2 has been proven to decrease this ratio and enhance lumbar vertebrae bone mineral density.[34] Matrix Gla protein should bear vitamin Ok dependent phosphorylation and carboxylation. Elevated plasma focus of dephosphorylated, uncarboxylated MGP is indicative of vitamin Ok deficiency.[35] Unwanted effects[edit] No recognized toxicity is related to excessive oral doses of the vitamin K1 or (vitamin K2) types of vitamin Ok, so regulatory businesses from US, Japan and European Union concur that no tolerable higher consumption ranges must be set.[4][8][9] Nevertheless, vitamin K1 has been related to extreme hostile reactions comparable to bronchospasm and cardiac arrest when given intravenously. The response is described as a nonimmune-mediated anaphylactoid response, with incidence of three per 10,000 remedies. Nearly all of reactions occurred when polyoxyethylated castor oil was used because the solubilizing agent.[36]
Non-human makes use of[edit]
Types not present in nature, and thus not “vitamins” are menadione and 4-Amino-2-methyl-1-naphthol (“K5”). Menadione, an artificial compound generally known as vitamin K3, is used within the pet meals trade as a result of as soon as consumed it’s transformed to vitamin K2.[37] The US Meals and Drug Administration has banned this manner from sale as a human dietary complement as a result of massive doses have been proven to trigger allergic reactions, hemolytic anemia, and cytotoxicity in liver cells.[2] Analysis with K5 suggests it could inhibit fungal progress in fruit juices.[38]