INDEX

Vitamin K

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.

Scientific Evidence

Uses Grade*
Coagulation disorders (VKCFD)

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
Hemorrhagic disease of newborn (vitamin K deficiency bleeding/VKDB)

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

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 reversal (elevated INR / pre-procedure)

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
Bleeding disorders (prevention of bleeding or thrombotic events in anticoagulant therapy)

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
Cancer

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
Cardiovascular conditions

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

C
Cystic fibrosis

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
Gastrointestinal disorders (bleeding)

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

C
Osteoporosis prevention

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
Hepatocellular carcinoma (recurrent hepatocellular carcinoma prevention)

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 against this use (it may not work);

F: Strong scientific evidence against this use (it likely does not work).

Tradition

  • Alzheimer’s disease, antioxidant, bruises, burns, celiac disease, cholestatic liver injury (vitamin K deficiency), coronary artery disease (calcification), diabetes, diarrhea (with bleeding), hemorrhage (bleeding in the brain), high cholesterol (dialysis patients), hyperpigmentation, inflammatory bowel conditions (osteoporosis or bone fractures), itching (primary biliary cirrhosis), liver function testing, metabolic syndrome (coronary heart disease), neuroprotective, obesity (following bariatric surgery), osteoarthritis, osteoporosis treatment, rosacea, scar healing, stretch marks, swelling, varicose veins (spider veins), weight loss.

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).

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).

References

  1. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics 2003;112(1 Pt 1):191-192. View Abstract
  2. Bügel S, Sørensen AD, Hels O, et al. Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Br J Nutr 2007 Feb;97(2):373-80. View Abstract
  3. Clarke, P., Mitchell, S. J., Wynn, R., Sandarac, S., Speed, V., Gardener, E., Roeves, D., and Shearer, M. J. Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics 2006;118(6):e1657-e1666. View Abstract
  4. Cockayne S, Adamson J, Lanham-New S, et al. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2006 Jun 26;166(12):1256-61. View Abstract
  5. Crowther CA, Crosby DD, Henderson-Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000229. View Abstract
  6. Dentali F, Ageno W, Crowther M. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost. 2006 Sep;4(9):1853-63. View Abstract
  7. Dezee KJ, Shimeall WT, Douglas KM, et al. Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med 2006 Feb 27;166(4):391-7. View Abstract
  8. Ford SK, Misita CP, Shilliday BB, et al. Prospective study of supplemental vitamin K therapy in patients on oral anticoagulants with unstable international normalized ratios. J Thromb Thrombolysis 2007 Aug;24(1):23-7. View Abstract
  9. Iwamoto, J., Matsumoto, H., and Takeda, T. Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials. Clin.Drug Investig. 2009;29(7):471-479. View Abstract
  10. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD008482. View Abstract
  11. Kakizaki S, Sohara N, Sato K, et al. Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection. J Gastroenterol Hepatol 2007 Apr;22(4):518-22. View Abstract
  12. Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 2007 Jul;18(7):963-72. View Abstract
  13. Kurnik D, Loebstein R, Rabinovitz H, et al. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial. Thromb Haemost 2004;92(5):1018-1024. View Abstract
  14. Rombouts EK, Rosendaal FR, Van Der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost 2007 Oct;5(10):2043-8. View Abstract
  15. Stevenson M, Lloyd-Jones M, Papaioannou D. Vitamin K to prevent fractures in older women: systematic review and economic evaluation. Health Technol Assess. 2009 Sep;13(45):iii-xi, 1-134. View Abstract