Phytonadione

Related Terms

2-Methyl-1,4-naphthoquinone, alpha-phylloquinone, AquaMEPHYTON?, dihydrophylloquinone, Konakion?, menadiol (not available in the United States), menadiol diphosphate (vitamin K3), menadione, menaquinone, menaquinone-7, menatetrenone, Mephyton?, MK-4, MK-7, phylloquinone, Phylloquinone?, phytomenadione, Phytomenadione?, phytonadione, vitamin K1, vitamin K2, vitamin K(2), VK(2).

Background

The name "vitamin K" refers to a group of chemically similar fat-soluble compounds called naphthoquinones. Vitamin K1 (phytonadione) is the natural form of vitamin K, which is found in plants and provides the primary source of vitamin K to humans through dietary consumption. Vitamin K2 compounds (menaquinones) are made by bacteria in the human gut and provide a smaller amount of the human vitamin K requirement. Vitamin K1 is commercially manufactured for medicinal use under several brand names (Phylloquinone?, Phytonadione?, AquaMEPHYTON?, Mephyton?, and Konakion?).
Vitamin K is necessary for normal clotting of blood in humans. Specifically, vitamin K is required for the liver to make factors that are necessary for blood to coagulate (properly clot), including factor II (prothrombin), factor VII (proconvertin), factor IX (thromboplastin component), and factor X (Stuart factor). Other clotting factors that depend on vitamin K are protein C, protein S, and protein Z. Deficiency of vitamin K or disturbances of liver function (for example, severe liver failure) may lead to deficiencies of clotting factors and excess bleeding.
Vitamin K deficiency is rare. People at risk for developing vitamin K deficiency include those with chronic malnutrition (including those with alcohol dependency) or conditions that limit absorption of dietary vitamins, such as biliary obstruction, celiac disease or sprue, ulcerative colitis, regional enteritis, cystic fibrosis, short bowel syndrome, and intestinal resection (particularly of the terminal ileum, where fat-soluble vitamins are absorbed). In addition, some drugs may reduce vitamin K levels by altering liver function or by killing intestinal flora (normal intestinal bacteria) that make vitamin K (for example, antibiotics, salicylates, antiseizure medications, and some sulfa drugs). Vitamin K is routinely given to newborn infants to prevent bleeding problems related to birth trauma or when surgery is planned.
Warfarin is a blood-thinning drug that functions by inhibiting vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions, such as atrial fibrillation, artificial heart valves, a history of serious blood clots, clotting disorders (hypercoagulability), and placement of indwelling catheters or ports. Usually, blood tests must be done regularly to evaluate the extent of blood thinning, using a test for prothrombin time (PT) or the international normalized ratio (INR). Vitamin K can decrease the blood-thinning effects of warfarin and will therefore lower the PT or INR value. This may increase the risk of clotting. Therefore, people taking warfarin are usually warned to avoid vitamin K supplements. Conversely, vitamin K is used to treat overdoses or any excess anticoagulant effects of warfarin and to reverse the effects of warfarin prior to surgery or other procedures.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


Vitamin K-dependent clotting factor disorder (VKCFD) is a very rare genetic disorder. This disorder results in decreased production of factors in the blood needed for clotting and therefore a bleeding tendency. Vitamin K administration is the main therapy in VKCFD, although the response may be variable. Other treatment is also provided as required.

 A


Vitamin K-dependent clotting factor disorder (VKCFD) is a very rare genetic disorder. This disorder results in decreased production of factors in the blood needed for clotting and therefore a bleeding tendency. Vitamin K administration is the main therapy in VKCFD, although the response may be variable. Other treatment is also provided as required.

 A


Vitamin K deficiency in infants can lead to hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). Although up to half of newborns may have some degree of vitamin K deficiency, serious hemorrhagic disease with bleeding is rare. In cases of true VKDB, bleeding may occur at injection sites, at the umbilicus, or in the gastrointestinal tract. Life-threatening intracranial bleeding (into the head) or retroperitoneal bleeding (in the area behind the lower abdomen) can also occur. Evaluation by a physician is imperative. Because vitamin K given by injection has been shown to prevent VKBD in newborns and young infants, the American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns. Dosing by mouth is not considered adequate as prevention, particularly in breastfeeding infants. Initial concerns of cancer risk were never proven and are generally not considered clinically relevant.

 A


Vitamin K deficiency in infants can lead to hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). Although up to half of newborns may have some degree of vitamin K deficiency, serious hemorrhagic disease with bleeding is rare. In cases of true VKDB, bleeding may occur at injection sites, at the umbilicus, or in the gastrointestinal tract. Life-threatening intracranial bleeding (into the head) or retroperitoneal bleeding (in the area behind the lower abdomen) can also occur. Evaluation by a physician is imperative. Because vitamin K given by injection has been shown to prevent VKBD in newborns and young infants, the American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns. Dosing by mouth is not considered adequate as prevention, particularly in breastfeeding infants. Initial concerns of cancer risk were never proven and are generally not considered clinically relevant.

 A


Vitamin K deficiency is rare in adults but can lead to defective blood clotting and increased bleeding, as well as osteoporosis. People at risk for developing vitamin K deficiency include those with chronic malnutrition (including those with alcohol dependency) or conditions that limit absorption of dietary vitamins, such as biliary obstruction, celiac disease or sprue, ulcerative colitis, regional enteritis, cystic fibrosis, short bowel syndrome, and intestinal resection (particularly of the terminal ileum, where fat-soluble vitamins are absorbed). In addition, some drugs may reduce vitamin K levels by altering liver function or by killing intestinal flora (normal intestinal bacteria) that make vitamin K (for example, antibiotics, salicylates, antiseizure medications, and some sulfa drugs). Evaluation by a physician should be sought.

 A


Vitamin K deficiency is rare in adults but can lead to defective blood clotting and increased bleeding, as well as osteoporosis. People at risk for developing vitamin K deficiency include those with chronic malnutrition (including those with alcohol dependency) or conditions that limit absorption of dietary vitamins, such as biliary obstruction, celiac disease or sprue, ulcerative colitis, regional enteritis, cystic fibrosis, short bowel syndrome, and intestinal resection (particularly of the terminal ileum, where fat-soluble vitamins are absorbed). In addition, some drugs may reduce vitamin K levels by altering liver function or by killing intestinal flora (normal intestinal bacteria) that make vitamin K (for example, antibiotics, salicylates, antiseizure medications, and some sulfa drugs). Evaluation by a physician should be sought.

 A


Warfarin is a blood-thinning drug that inhibits vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions, such as atrial fibrillation, artificial heart valves, a history of serious blood clots, clotting disorders (hypercoagulability), and placement of indwelling catheters or ports. Usually, blood tests are done regularly to evaluate the extent of blood thinning, using a test for prothrombin time (PT) or the international normalized ratio (INR). The range for the PT/INR depends on the condition being treated. The PT/INR can become elevated for many reasons and sometimes can get dangerously high and increase the risk of serious bleeding. Patients taking warfarin should be aware of these potential causes, which include many drugs that interact with warfarin, liver disorders, and accidental warfarin overdose. Because the effects of warfarin on anticoagulation are usually delayed by several days, the PT/INR may not increase immediately at the time of overdose. If a person's blood becomes too "thin," management should be under strict medical supervision and may include oral or injected vitamin K to help reverse the effects of warfarin.

 A


Warfarin is a blood-thinning drug that inhibits vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions, such as atrial fibrillation, artificial heart valves, a history of serious blood clots, clotting disorders (hypercoagulability), and placement of indwelling catheters or ports. Usually, blood tests are done regularly to evaluate the extent of blood thinning, using a test for prothrombin time (PT) or the international normalized ratio (INR). The range for the PT/INR depends on the condition being treated. The PT/INR can become elevated for many reasons and sometimes can get dangerously high and increase the risk of serious bleeding. Patients taking warfarin should be aware of these potential causes, which include many drugs that interact with warfarin, liver disorders, and accidental warfarin overdose. Because the effects of warfarin on anticoagulation are usually delayed by several days, the PT/INR may not increase immediately at the time of overdose. If a person's blood becomes too "thin," management should be under strict medical supervision and may include oral or injected vitamin K to help reverse the effects of warfarin.

 A


Agents that block vitamin K, such as warfarin and phenprocoumon, are often used in anticoagulant therapy. Because dietary intake of vitamin K can affect anticoagulant function, inconsistent levels of vitamin K in the diet may make it difficult to control anticoagulant stability. Some studies suggest that daily, low-dose vitamin K supplementation may help stabilize anticoagulant therapy.

 C


Agents that block vitamin K, such as warfarin and phenprocoumon, are often used in anticoagulant therapy. Because dietary intake of vitamin K can affect anticoagulant function, inconsistent levels of vitamin K in the diet may make it difficult to control anticoagulant stability. Some studies suggest that daily, low-dose vitamin K supplementation may help stabilize anticoagulant therapy.

 C


Dietary consumption of vitamin K may be associated with a decreased risk of certain types of cancers. More studies are needed to confirm these results.

 C


Dietary consumption of vitamin K may be associated with a decreased risk of certain types of cancers. More studies are needed to confirm these results.

 C


A relationship between vitamin K intake and reduced cardiovascular disease risk cannot be confirmed at this time. Further research is needed.

 C


A relationship between vitamin K intake and reduced cardiovascular disease risk cannot be confirmed at this time. Further research is needed.

 C


Cystic fibrosis is associated with decreased fat digestion, and suboptimal vitamin K status is common even in patients using vitamin K supplements. More research is needed to determine the clinical benefit of supplementation.

 C


Cystic fibrosis is associated with decreased fat digestion, and suboptimal vitamin K status is common even in patients using vitamin K supplements. More research is needed to determine the clinical benefit of supplementation.

 C


Evidence in support of vitamin K for bleeding associated with gastrointestinal disorders is lacking at this time. Further research is required.

 C


Evidence in support of vitamin K for bleeding associated with gastrointestinal disorders is lacking at this time. Further research is required.

 C


Vitamin K appears to prevent bone resorption, and adequate dietary intake is likely necessary to prevent excess bone loss. Elderly or institutionalized patients may be at particular risk, and adequate intake of vitamin K-rich foods should be maintained. Unless patients have a demonstrated vitamin K deficiency, there is no evidence that additional vitamin K supplementation is helpful. Some studies show that vitamin K supplements may increase bone mineral density and bone strength, while others show that vitamin K has no effect on bone turnover. However, vitamin K may play a role in the prevention and treatment of glucocorticoid-induced bone loss. Furthermore, vitamin D and calcium supplementation may enhance the beneficial effects of vitamin K. Further research is needed to confirm these results.

 C


Vitamin K appears to prevent bone resorption, and adequate dietary intake is likely necessary to prevent excess bone loss. Elderly or institutionalized patients may be at particular risk, and adequate intake of vitamin K-rich foods should be maintained. Unless patients have a demonstrated vitamin K deficiency, there is no evidence that additional vitamin K supplementation is helpful. Some studies show that vitamin K supplements may increase bone mineral density and bone strength, while others show that vitamin K has no effect on bone turnover. However, vitamin K may play a role in the prevention and treatment of glucocorticoid-induced bone loss. Furthermore, vitamin D and calcium supplementation may enhance the beneficial effects of vitamin K. Further research is needed to confirm these results.

 C


Infection with the hepatitis C virus (HCV) may lead to hepatocellular carcinoma (HCC), a form of liver cancer. So far, the results from clinical studies are unclear and do not indicate any beneficial effects of vitamin K in preventing HCC recurrence.

 D


Infection with the hepatitis C virus (HCV) may lead to hepatocellular carcinoma (HCC), a form of liver cancer. So far, the results from clinical studies are unclear and do not indicate any beneficial effects of vitamin K in preventing HCC recurrence.

 D
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Dosing

Adults (18 years and older)
The U.S. Dietary Reference Intake for an adequate intake (AI) of vitamin K for adults is 120 micrograms daily (for adult males) and 90 micrograms daily (for adult females). Foods rich in vitamin K include green leafy vegetables such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products.
Vitamin K deficiency management should be under medical supervision. If the prothrombin time (PT) is only slightly elevated and poor dietary intake is thought to be the cause, increasing the ingestion of vitamin K-rich foods can be tried. In nonemergency situations, vitamin K1 may be given by mouth. If necessary, vitamin K1 can be injected.
Injection into the muscle or vein should only be done by a healthcare professional. Many serious side effects have occurred after injection.
Elevated PT/INR (warfarin reversal) or acute liver dysfunction management should be under medical supervision.
For osteoporosis prevention, the following doses of vitamin K have been taken by mouth daily: 45 milligrams of prescribed menatetrenone; and up to 10 milligrams of vitamin K1.
Avoid use of vitamin K3 supplements or menadiol (not available in the United States).

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Interactions

Interactions with Drugs
Menadiol sodium diphosphase is a form of vitamin K that is not used in the United States. Multiple drugs may cause complications when taken with menadiol.
Warfarin is a blood-thinning drug that functions by inhibiting vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions, such as atrial fibrillation, artificial heart valves, a history of serious blood clots, clotting disorders (hypercoagulability), and placement of indwelling catheters or ports. Usually, blood tests must be done regularly to evaluate the extent of blood thinning, using a test for prothrombin time (PT) or the international normalized ratio (INR). Vitamin K can decrease the blood-thinning effects of warfarin and will therefore lower the PT or INR value. This may increase the risk of clotting. Therefore, people taking warfarin are usually warned to avoid foods with high vitamin K content (such as green leafy vegetables) and to avoid vitamin K supplements. Conversely, vitamin K is used to treat overdoses or any excess anticoagulant effects of warfarin and to reverse the effects of warfarin prior to surgery or other procedures. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. Vitamin K-depleted patients are sensitive to even small changes in vitamin K1 intake.
Vitamin K may affect blood sugar levels. Caution is advised when using medications that may also affect blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Vitamin K may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be altered in the blood, and change the intended effects. People taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Some antibiotics may decrease the bacteria in the human gut (which synthesize a small amount of the human vitamin K requirement). Broad-spectrum antibiotics, particularly sulfonamides such as Bactrim?, may lower vitamin K levels and increase the risk of deficiency in people not ingesting adequate amounts.
Drugs that may affect the absorption or metabolism of vitamin K include antacids, dactinomycin, salicylates (aspirin), tiratricol, orlistat, quinine, cholestyramine (Questran?), rifampin, and isoniazid.
Vitamin K may also interact with anticancer agents, antiseizure agents, anti-inflammatory agents, hormonal agents, lipid-lowering agents, osteoporosis medications, weight loss agents, vitamin A-, vitamin D-, or vitamin E-containing agents, and vitamin K antagonists.

Attribution

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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