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.

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 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

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

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

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

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

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: 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.

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.

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).

Children (under 18 years old)

The U.S. Dietary Reference Intake for an adequate intake (AI) of vitamin K for children is 2-2.5 micrograms daily (for infants) and 30-75 micrograms daily (for children and adolescents).

Vitamin K1 given by injection has been shown in newborns and young infants to prevent hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). The American Academy of Pediatrics therefore recommends administering a single intramuscular injection of 0.5-1 milligram of vitamin K1 to all newborns. Dosing by mouth is generally not regarded as adequate for prevention, particularly in breastfeeding infants.

Injection into the muscle or vein should only be done by a healthcare professional. Many serious side effects have occurred after injection.

Warfarin toxicity and reversal should be under strict medical supervision.

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.

Allergies

Intravenous or intramuscular vitamin K has been associated rarely with anaphylactoid reactions, including shock, heart attack, respiratory arrest, and death. Therefore, these routes of administration should be avoided if possible. If given intravenously, preparations should be under strict medical supervision.

Skin hypersensitivity reactions are rare and may occur in particular with injections of vitamin K1 (Phytonadione®, AquaMEPHYTON®). A raised, itchy plaque may arise at the injection site that may take 1-2 months to resolve and can cause a scar.

Red, painful swelling at vitamin K injection sites has been reported. A raised, itchy plaque that may take 1-2 months to resolve can arise at the injection site, and it can cause a scar. Transient flushing has been reported.

Nonsevere gastrointestinal side effects have been reported with vitamin K supplementation. Liver damage has been reported rarely in infants and children with use of the vitamin K preparation Menadiol (not available in the United States). An unusual taste in the mouth has been reported rarely with vitamin K injections.

Dizziness has been reported rarely with vitamin K injections.

Damage to red blood cells, causing anemia (hemolysis), has been reported rarely in infants and children with the use of the vitamin K preparation menadiol (not available in the United States). This type of vitamin K should be avoided in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, because vitamin K may cause hemolytic episodes.

Although initial concerns were voiced about the possible cancer risk of universally administering vitamin K by injection to newborns, scientific evidence to support this risk is currently lacking. This is generally considered not to be a concern in the medical community.

Vitamin K may affect blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

Use cautiously in patients with dermatological or gastrointestinal conditions, in pregnant women, and in those taking lipid-lowering agents.

Use parenteral forms of vitamin K cautiously. Injection into the muscle or vein should only be done by a healthcare professional. Many serious side effects have occurred after injection.

Avoid in patients with known allergy or hypersensitivity to vitamin K.

Avoid supplemental vitamin K in patients using warfarin or other anticoagulants unless otherwise directed by medical personnel, as oral or intravenous vitamin K has been shown to decrease elevated PT or INRs associated with warfarin use.

Avoid use of vitamin K3 supplements. The FDA has banned vitamin K3 (a synthetic menadione) from over-the-counter supplements, due to the potential for allergic reactions, hemolytic anemia, jaundice, and liver toxicity.

Avoid use of menadiol (not available in the United States), due to the potential for damage to red blood cells, causing anemia (hemolysis), as has been reported rarely in infants and children.

Pregnancy and Breastfeeding

The U.S. Food and Drug Administration (FDA) has categorized vitamin K as Pregnancy Category C drug. There is not sufficient scientific evidence in animals or humans to clearly conclude the effects on the fetus. Vitamin K given to mothers soon before giving birth is generally not recommended. Regular supplementation with vitamin K during pregnancy (beyond normal dietary intake) may increase the risk of jaundice in the newborn.

The American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns to prevent vitamin K deficiency bleeding (VKDB), a potentially life-threatening condition. Excessive amounts of vitamin K supplementation in newborns may lead to serious complications, including hemolytic anemia, hemoglobinuria, kernicterus, brain damage, or death. Reactions may be particularly severe in premature infants.

Vitamin K ingested by mothers is generally considered to be safe during breastfeeding. There is very little vitamin K transmitted to infants through breast milk (as opposed to many infant formulas, which do include vitamin K). The amount of vitamin K in breast milk is increased if mothers take vitamin K supplements. If an infant formula is used that is not fortified with vitamin K, a physician should be consulted to find another way for the infant to receive vitamin K.

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.

Vitamin K may decrease the blood-thinning effects of herbs that act like warfarin (Coumadin®) in the body by decreasing clotting factors made in the liver. In particular, this may apply to herbs with coumarin constituents, such as alfalfa (Medicago sativa), American ginseng (Panax quinquefolius), and angelica (Angelica archangelica).

Vitamin K may affect blood sugar levels. Caution is advised when using herbs or supplements that may also affect blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Vitamin K may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may be altered in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

Agents that may affect the absorption or metabolism of vitamin K include antibacterials, antacids, salicylates, and dietary fats such as butter and milk.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.