VITAMIN K

Vitamin K is a coenzyme for a microsomal enzyme that catalyzes the posttranslational conversion of specific glutamyl residues to gamma-carboxyglutamyl (Gla) residues in a small number of proteins. Several of the Gla-proteins are essential for blood clotting and its regulation (coagulation factors II, VII, IX, and X; proteins C, S and Z). Others have a role in the regulation of tissue mineralization (osteocalcin, matrix Gla protein) and cell proliferation (gas6). Recently, additional Gla proteins have been identified whose function is not well defined to date. Phylloquinone (2-Me-3-polyisoprenyl-1,4-naphthoquinone) from plants and a series of bacterial menaquinones (2-Me-3-polyisoprenyl-1,4-naphthoquinone) are natural forms of the vitamin.

Deficiencies: Historically, vitamin K deficiency has been defined as a disruption of blood clotting due to diminished Gla content of the vitamin K-dependent coagulation factors. Infants are at risk for severe cerebral hemorrhage during the first three to four months after birth, if they do not get enough vitamin K. The reason for vitamin K deficiency in these children is usually impaired fat absorption in conjunction with a low vitamin intake from breastfeeding. (Human milk contains much less vitamin K than infant formulas). In the US and many other countries newborn infants routinely receive vitamin K. Bleeding due to the lack of vitamin K is very rare in older children and adults, presumably, because vitamin K is produced by intestinal bacteria and a small fraction is absorbed from ileum and colon. Oral antibiotic treatment, in conjunction with low vitamin K intake, can induce bleeding. Less than a few days' intake of vitamin K is stored, most of it in liver and bone; in the absence of dietary or intestinal vitamin K sources, symptoms appear rapidly.

Suboptimal vitamin K status which is far more common than outright deficiency may contribute to the progression of osteoporosis and atherosclerosis; research in these areas is promising but preliminary. 4-hydroxy coumarins are vitamin K antagonists that interfere with reactivation of the vitamin and suppress production of mature Gla-proteins needed for coagulation. Some 4-hydroxy coumarins are medically important anticoagulants, others are used as rodenticides.

Diet recommendations: The current Recommended Dietary Allowances (RDAs) for vitamin K (µg/day) are: 5 at age 0-6 months, 10 for 6-12 months, 15 for 1-3 years, 20 for 4-6 years, 30 for 7-10 years, 45 for 11-14 years, 55 for females 15-18 years, 60 for females 19-24 years, 65 for females 25 years and older, pregnant and lactating women and males 15-18; 70 for males 19-24 years, and 80 for males 25 years and older.

Past estimates of vitamin K intake were in the range of a few hundred µg/day; current data suggest that a range of intake of 75-125 µg of phylloquinone is more accurate. Most Americans obtain almost no menaquinones with their diet, but intakes may be very significant for Asians consuming traditional foods. While it is likely that some vitamin K (menaquinones) from bacterial production in the lower intestines is absorbed, the amounts appear to be much less than what is usually available from dietary sources.

Food Sources: Cooked dark green vegetables, such as spinach, kale and broccoli, can provide more than one RDA in a single serving. The bioavailability of vitamin K from different food sources and the effect of food processing is insufficiently known. A small amount of fat is needed for absorption. Natto and similar fermented Asian soy foods also are excellent vitamin K sources. Kiwi, cabbage, liver, soybean, canola and olive oils, including margarine and mayonnaise made from these oils, contain 20-50 % of current RDAs per serving.

Toxicity: Large amounts of phylloquinone or menaquinones can be consumed over extended periods with no toxic effects. Menadione (2-Me-1,4-naphthoquinone) is currently used in animal feeds, but not in foods for human consumption, because it causes hemolytic anemia, hyperbilirubinemia, and kernicterus in infants.

Recent Research: A number of reports point to a relationship between vitamin K status and skeletal health of the elderly. Another promising line of investigations concerns the role of matrix Gla protein and other vitamin K-dependent proteins in the control of arterial calcification. Definitive evidence is still lacking, however, that increased vitamin K consumption decreases the incidence or severity of osteoporosis or other diseases. Several prospective population studies have been initiated, therefore, to investigate whether increased vitamin K intakes may slow bone loss.

For Further Information:

Suttie, J. W. (1992) Vitamin K and human nutrition. J. Am. Diet. Assoc. 92: 585-590.

Kohlmeier, M., Salomon, A., Saupe, J. & Shearer, M. J. (1996) Transport of vitamin K to bone in humans. J. Nutr. 126: 1192S-1196S.

Booth, S. L., Pennington, J. A. T. & Sadowski, J. A. (1996) Food sources and dietary intakes of vitamin K-1 (phylloquinone) in the American diet. J. Am. Diet. Assoc. 96: 149-154.

Booth, S. L. & Suttie, J. W. (1998) Dietary intake and adequacy of vitamin K. J. Nutr. 128: 785-788.

Prepared By:

Martin Kohlmeier, M.D.
Research Professor of Nutrition
School of Medicine and School of Public Health
University of North Carolina
2205 A McGavran-Greenberg
Chapel Hill, NC 27599-7400
Phone: 919-966-7210
FAX: 919-966-7216
Email: mkohlmeier@unc.edu

John W. Suttie, Ph.D.
Professor
Department of Biochemistry
University of Wisconsin-Madison
420 Henry Mall
Madison, WI 53706-1569
Phone: 608-262-2247
FAX: 608-262-9338
Email: suttie@biochem.wisc.edu