Vitamin K

Overview

In 1935, a scientist in Copenhagen observed that newly hatched chickens receiving a diet containing all of the known essential nutrients were developing a hemorrhagic disease. The problem was believed to be related to a decrease in prothrombin, a substance necessary for normal clotting of blood. The Danish scientist named this newly discovered antihemorrhagic factor vitamin K or “Koagulationsvitamin.”

Vitamin K refers to a group of three vitamins called the quinones. The K vitamins have a central ring structure with their varying pharmacokinetics being determined by varying side chains. Phytonadione (K1) is the only K vitamin commercially available in the United States. It is available by prescription in either tablet form or injection.

Dosage Info

Dosage Range

The dosage range is very broad; 10mcg to more than 10mg daily for certain bleeding conditions associated with anticoagulant medications have been used.

Most Common Dosage

Not able to be determined due to the varied doses associated with multiple medical conditions. It is estimated that most adults acquire the necessary RDA from a healthy diet. (1)

Dosage Forms

Tablets, capsules, and injectable (Rx only).

Adult RDI

None established

Adult ODA

Same as RDA

RDA

  • Infants < 6 months: 2mcg (Adequate Intake, AI)
  • Infants 7-12 months: 2.5mcg (AI)
  • Children 1-3 years: 30mcg (AI)
  • Children 4-8 years: 55mcg (AI)
  • Children 9-13 years: 60mcg (AI)
  • Children 14-18 years: 75mcg (AI)
  • Males >19 years: 120mcg (AI)
  • Females >19 years: 90mcg (AI)
  • Pregnancy 14-18 years: 75mcg (AI)
  • Pregnancy >19 years: 90mcg (AI)
  • Lactation 14-18 years: 75mcg (AI)
  • Lactation >19 years: 90mcg (AI)

Interactions and Depletions

Interactions

Depletions

Active Forms

Vitamin K1: produced in plants and is scientifically known as phytonadione, phylloquinone and phytomenadione.
Vitamin K2: produced in animals and is scientifically known as menaquinone.
Vitamin K3: synthetically produced, water-soluble and is scientifically known as menadione.

Absorption

Bile salts and pancreatic juice are necessary for the absorption of the various forms of vitamin K from the upper small intestine. Following absorption vitamin K concentrates in the liver for a short time. Minimal amounts of vitamin K accumulates in various other tissues. (2)

Toxicities & Precautions

General

There is no known toxicity associated with vitamin K.

Side Effects

If the injectable form of vitamin K is to be given, it should be administered subcutaneously (SC) or intramuscularly (IM). Intravenous (IV) administration has resulted in severe reactions that resemble an anaphylactic response. IV administration of vitamin K has resulted in death. (3)

Functions in the Body

Blood Clotting

The presence of vitamin K in the body is critical for the production of numerous clotting factors. These factors that are made in the liver include active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). Vitamin K converts specific precursors into active coagulation factors. These coagulation factors are then secreted by liver cells into the blood. (4)

Osteocalcin Activation

Vitamin K is necessary for the synthesis of osteocalcin, a unique protein in bone, which attracts calcium to bone tissue. Osteocalcin modulates the deposition of calcium into bone matrix. Therefore, vitamin K may play a role in the prevention and treatment of osteoporosis.

Clinical Applications

Blood Clotting

Vitamin K is a cofactor for several coagulant and anticoagulant proteins that regulate the blood clotting mechanism. These proteins are known as clotting factors and include factors II, VII, IX, and X. (5) Vitamin K is used clinically to treat hypoprothrombinemia resulting from medical conditions such as obstructive jaundice or the the use of certain medications such as antibiotics or salicylates. Vitamin K is also used to counteract the effects of excessive doses of oral anticoagulants, such as warfarin. (6) ,

Atherosclerosis.

Evidence has been found linking vitamin K status to atherosclerosis. (7) , (8) Postmenopausal women with abdominal aortic calcifications have demonstrated reduced vitamin K status. (9) Athersclerotic women have also demonstrated decreased bone mass. Via the activity of vitamin K, gammacarboxyglutamate (GLA) is formed. Evidence is now supporting the hypothesis that GLA proteins are involved in the regulation of the calcification processes of both bone tissue and athersclerotic vessels. (10)

Alzheimer's Disease

A recent hypothesis has been proposed concerning a relationship between vitamin K and the pathogenesis of Alzheimer's disease. The incidence of Alzheimer's disease increases with age as well as in carriers of the apolipoprotein E4 genotype. Research has also indicated that vitamin K has important functions in the brain. Vitamin K deficiency is more common as men and women get older and carriers of the apolipoprotein E4 genotype have lower levels of vitamin K in their blood. Considering this, it has been hypothesized that "vitamin K deficiency contributes to the pathogenesis of Alzheimer's disease and that vitamin K supplementation may have a beneficial effect in preventing or treating the disease." (11)

Osteoporosis

Vitamin K influences the synthesis of osteocalcin which regulates bone density. (12) This activity has led to studies demonstrating maintenance and possibly even an increase in bone mineral density as well as decreased fracture rates when people with osteoporosis use vitamin K, specifically vitamin K2. (13) , (14) Other studies evaluating postmenopausal women have noted that the rate of decrease in spinal bone mineral deposition could be slowed but not stopped, indicating that therapy should begin as early as possible. (15) One study evaluated the diets of over 72,000 women ranging in age from 38 to 63 years. This research found that the women who consumed greater amounts of vitamin K in their diets had a lower age-adjusted risk of hip fracture than the women who consumed lower amounts of vitamin K in their diets. (16) Vitamin K2 may also help prevent steroid induced osteoporosis. (17)

Symptoms and Causes of Deficiency

Vitamin K deficiency is rare except in newborn infants. However, it can cause hemorrhaging and death when it does occur. Deficiency symptoms include easy bleeding and skeletal disorders such as rickets, osteoporosis, and osteomalacia.

Dietary Sources

Best sources of phylloquinone (vitamin K1) are spinach and salad greens which contain more than 300mcg per 100g. Broccoli, brussel sprouts and cabbage contain 100 to 200mcg of vitamin K1 per 100g. Menaquinone (vitamin K2) is synthesized in the digestive tract by intestinal bacteria and can also be found in some types of cheese. Most individuals can acquire the necessary amount of vitamin K from their diet. (18) But, since vitamin K2 is also synthesized in the intestines, humans are not dependent upon food for this nutrient.

References

  1. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001:144.
  2. aquaMEPHYTON (Phytonadione), Product Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. May2001.
  3. aquaMEPHYTON (Phytonadione), Product Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. May2001.
  4. aquaMEPHYTON (Phytonadione), Product Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. May2001.
  5. View Abstract: Igarashi O. Vitamin K. Nippon Rinsho. Apr1993;51(4):910-18.
  6. aquaMEPHYTON (Phytonadione), Product Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. May2001.
  7. View Abstract: Burnier JP, Borowski M, Furie BC, Furie B. Gamma-carboxyglutamic acid. Mol Cell Biochem. Sep1981;39:191-207.
  8. View Abstract: Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S, et al. Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J Pharmacol. Oct1997;75(2):135-43.
  9. View Abstract: Jie KS, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis. Jul1995;116(1):117-23.
  10. View Abstract: Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int. Nov1996;59(5):352-6.
  11. View Abstract: Allison AC. The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Med Hypotheses. Aug2001;57(2):151-5.
  12. View Abstract: Kanai T, et al. Serum Vitamin K Level and Bone Mineral Density in Post-menopausal Women. Int J Gynaecol Obstet. Jan1997;56(1):25-30.
  13. View Abstract: Weber P. Vitamin K and bone health. Nutrition. Oct2001;17(10):880-7.
  14. View Abstract: Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. Mar2000;15(3):515-21.
  15. View Abstract: Iwamoto I, Kosha S, Noguchi S, Murakami M, Fujino T, Douchi T, Nagata Y. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas. Jan1999;31(2):161-4.
  16. View Abstract: Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. Jan1999;69(1):74-9.
  17. View Abstract: Yonemura K, Kimura M, Miyaji T, Hishida A. Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis. Calcif Tissue Int. Feb2000;66(2):123-8.
  18. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001:143-4.