Physical Health

Nutrition in plants

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It may be thought of as the plant form of vitamin K. 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. Animals may also convert it to vitamin K 2. Bacteria in the gut flora can also convert K 1 into vitamin K 2 menaquinone.

In addition, bacteria typically lengthen the isoprenoid side chain of vitamin K 2 to produce a range of vitamin K 2 forms, most notably the MK-7 to MK homologues of vitamin K 2. All forms of K 2 other than MK-4 can only be produced by bacteria, which use these forms in anaerobic respiration. The MK-7 and other bacterially derived forms of vitamin K 2 exhibit vitamin K activity in animals, but MK-7's extra utility over MK-4, if any, is unclear and is a matter of investigation. Because a synthetic form of vitamin K, vitamin K 3 menadione , may be toxic by interfering with the function of glutathione , it is no longer used to treat vitamin K deficiency.

A review of concluded that there is positive evidence that monotherapy using MK-4, one of the forms of Vitamin K 2 , reduces fracture incidence in post- menopausal women with osteoporosis , and suggested further research on the combined use of MK-4 with bisphosphonates. In contrast, an earlier review article of concluded that there is no good evidence that vitamin K supplementation helps prevent osteoporosis or fractures in postmenopausal women.

A review article of suggested to consider, as one of several measures for bone health, increasing the intake of foods rich in vitamins K 1 and K 2. Adequate intake of vitamin K is associated with the inhibition of arterial calcification and stiffening, [5] but there have been few interventional studies and no good evidence that vitamin K supplementation is of any benefit in the primary prevention of cardiovascular disease.

One year population study, the Rotterdam Study, did show a clear and significant inverse relationship between the highest intake levels of menaquinone mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese and cardiovascular disease and all-cause mortality in older men and women.

Vitamin K has been promoted in supplement form with claims it can slow tumor growth; however, no good medical evidence supports such claims.

Although allergic reaction from supplementation is possible, no known toxicity is associated with high doses of the phylloquinone vitamin K 1 or menaquinone vitamin K 2 forms of vitamin K, so no tolerable upper intake level UL has been set. Unlike the safe natural forms of vitamin K 1 and vitamin K 2 and their various isomers , a synthetic form of vitamin K, vitamin K 3 menadione , is demonstrably toxic at high levels. FDA has banned this form from over-the-counter sale in the United States because large doses have been shown to cause allergic reactions , hemolytic anemia , and cytotoxicity in liver cells.

Phylloquinone K 1 [15] [16] or menaquinone K 2 are capable of reversing the anticoagulant activity of the anticoagulant warfarin tradename Coumadin. Warfarin works by blocking recycling of vitamin K, so that the body and tissues have lower levels of active vitamin K, and thus a deficiency of vitamin K. Supplemental vitamin K for which oral dosing is often more active than injectable dosing in human adults reverses the vitamin K deficiency caused by warfarin, and therefore reduces the intended anticoagulant action of warfarin and related drugs.

The newer anticoagulants apixaban , dabigatran and rivaroxaban have different mechanisms of action that do not interact with vitamin K, and may be taken with supplemental vitamin K.

The three synthetic forms of vitamin K are vitamins K 3 menadione , K 4 , and K 5 , which are used in many areas, including the pet food industry vitamin K 3 and to inhibit fungal growth vitamin K 5. The MK-4 form of vitamin K 2 is produced by conversion of vitamin K 1 in the testes , pancreas , and arterial walls.

Vitamin K 2 menaquinone includes several subtypes. The two most studied ones are menaquinone-4 menatetrenone , MK-4 and menaquinone-7 MK Vitamin K 1 , the precursor of most vitamin K in nature, is a stereoisomer of phylloquinone , an important chemical in green plants, where it functions as an electron acceptor in photosystem I during photosynthesis. For this reason, vitamin K 1 is found in large quantities in the photosynthetic tissues of plants green leaves , and dark green leafy vegetables such as romaine lettuce , kale , and spinach , but it occurs in far smaller quantities in other plant tissues roots , fruits , etc.

Iceberg lettuce contains relatively little. The function of phylloquinone in plants appears to have no resemblance to its later metabolic and biochemical function as "vitamin K" in animals, where it performs a completely different biochemical reaction. Vitamin K in animals is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate Gla residues.

The modified residues are often but not always situated within specific protein domains called Gla domains.

Gla residues are usually involved in binding calcium , and are essential for the biological activity of all known Gla proteins. At this time [update] , 17 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:. Like other lipid-soluble vitamins A , D , and E , vitamin K is stored in the fatty tissue of the human body. Previous theory held that dietary deficiency is extremely rare unless the small intestine was heavily damaged, resulting in malabsorption of the molecule.

Another at-risk group for deficiency were those subject to decreased production of K 2 by normal intestinal microbiota, as seen in broad-spectrum antibiotic use. In instances such as these, the board sets Adequate Intakes AIs , with the understanding that at some later date, AIs will be replaced by more exact information. For infants up to 12 months, the AI is 2. As for safety, the IOM sets tolerable upper intake levels known as ULs for vitamins and minerals when evidence is sufficient.

Vitamin K has no UL, as human data for adverse effects from high doses are inadequate. These AIs are lower than the U. The original deadline to be in compliance was July 28, , but on September 29, , the FDA released a proposed rule that extended the deadline to January 1, for large companies and January 1, for small companies.

Vitamin K 1 is found chiefly in leafy green vegetables such as spinach , swiss chard , lettuce and Brassica vegetables such as cabbage , kale , cauliflower , broccoli , and brussels sprouts and often the absorption is greater when accompanied by fats such as butter or oils.

Some fruits , such as avocados , kiwifruit and grapes , also contain vitamin K. Some vegetable oils, notably soybean oil , contain vitamin K, but at levels that would require relatively large calorie consumption to meet the recommended amounts.

The tight binding of vitamin K 1 to thylakoid membranes in chloroplasts makes it less bioavailable. Average diets are usually not lacking in vitamin K, and primary deficiency is rare in healthy adults. Newborn infants are at an increased risk of deficiency. Other populations with an increased prevalence of vitamin K deficiency include those who suffer from liver damage or disease e.

Secondary vitamin K deficiency can occur in people with bulimia , those on stringent diets, and those taking anticoagulants. Other drugs associated with vitamin K deficiency include salicylates , barbiturates , and cefamandole , although the mechanisms are still unknown. Vitamin K 1 deficiency can result in coagulopathy , a bleeding disorder. Osteoporosis [52] [53] and coronary heart disease [54] [55] are strongly associated with lower levels of K 2 menaquinone.

Vitamin K 2 as menaquinones MK-4 through MK intake level is inversely related to severe aortic calcification and all-cause mortality. The function of vitamin K 2 in the animal cell is to add a carboxylic acid functional group to a glutamate Glu amino acid residue in a protein , to form a gamma-carboxyglutamate Gla residue.

This is a somewhat uncommon posttranslational modification of the protein, which is then known as a "Gla protein". The binding of calcium ions in this way very often triggers the function or binding of Gla-protein enzymes, such as the so-called vitamin K-dependent clotting factors discussed below. Within the cell, vitamin K undergoes electron reduction to a reduced form called vitamin K hydroquinone, catalyzed by the enzyme vitamin K epoxide reductase VKOR.

The carboxylation reaction only proceeds if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time.

The carboxylation and epoxidation reactions are said to be coupled. The reduction and subsequent reoxidation of vitamin K coupled with carboxylation of Glu is called the vitamin K cycle. Warfarin and other 4-hydroxycoumarins block the action of VKOR. This results in the production of clotting factors with inadequate Gla. Without Gla on the amino termini of these factors, they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury.

As it is impossible to predict what dose of warfarin will give the desired degree of clotting suppression, warfarin treatment must be carefully monitored to avoid overdose. The following human Gla-containing proteins "Gla proteins" have been characterized to the level of primary structure: The bone Gla protein osteocalcin , the calcification-inhibiting matrix Gla protein MGP , the cell growth regulating growth arrest specific gene 6 protein Gas6 , and the four transmembrane Gla proteins TMGPs , the function of which is at present unknown.

Gas6 can function as a growth factor to activate the Axl receptor tyrosine kinase and stimulate cell proliferation or prevent apoptosis in some cells. In all cases in which their function was known, the presence of the Gla residues in these proteins turned out to be essential for functional activity. Gla proteins are known to occur in a wide variety of vertebrates: The venom of a number of Australian snakes acts by activating the human blood-clotting system.

In some cases, activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones, leading to unwanted and potentially deadly clotting. Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus.

Several of the conotoxins contain two to five Gla residues. Many bacteria, such as Escherichia coli found in the large intestine , can synthesize vitamin K 2 menaquinone-7 or MK-7, up to MK , [71] but not vitamin K 1 phylloquinone. In these bacteria, menaquinone transfers two electrons between two different small molecules, during oxygen-independent metabolic energy production processes anaerobic respiration.

The menaquinone, with the help of another enzyme, then transfers these two electrons to a suitable oxidant, such fumarate or nitrate also called an electron acceptor. Adding two electrons to fumarate or nitrate converts the molecule to succinate or nitrite plus water , respectively. Some of these reactions generate a cellular energy source, ATP , in a manner similar to eukaryotic cell aerobic respiration , except the final electron acceptor is not molecular oxygen , but fumarate or nitrate.

In aerobic respiration , the final oxidant is molecular oxygen O 2 , which accepts four electrons from an electron donor such as NADH to be converted to water. Vitamin K 2 concentrations in human milk appear to be much lower than those of vitamin K 1.

Occurrence of vitamin K deficiency bleeding in the first week of the infant's life is estimated at 0. Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, blood transfusions , brain damage , and death. Supplementation can prevent most cases of vitamin K deficiency bleeding in the newborn.

Natural History