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Vitamin K

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Principal Proposed UsesOther Proposed Uses


Vitamin K

Supplement Forms/Alternate Names

  • Vitamin K 1 (Phylloquinone)
  • Vitamin K 2 (Menaquinone)
  • Vitamin K 3 (Menadione)

Uses

Principal Proposed Uses

  • Osteoporosis
  • Treating Medication-induced Vitamin K Deficiency

Other Proposed Uses

  • Menorrhagia (Heavy Menstruation)
  • Nausea
Vitamin K plays a major role in the body's blood clotting system. There are three forms of vitamin K: K 1 (phylloquinone), found in plants; K 2 (menaquinone), produced by bacteria in your intestines; and K 3 (menadione), a synthetic form.
Vitamin K is used medically to reverse the effects of "blood-thinning" drugs, such as warfarin (Coumadin). Growing evidence suggests that it may also be helpful for osteoporosis.

Requirements/Sources

Vitamin K is an essential nutrient, but you need only a tiny amount of it. The official U.S. recommendations for daily intake have been set as follows:
  • Infants
    • 0-6 months: 2 mcg
    • 7-12 months: 2.5 mcg
  • Children
    • 1-3 years: 30 mcg
    • 4-8 years: 55 mcg
  • Males
    • 9-13 years: 60 mcg
    • 14-18 years: 75 mcg
    • 19 years and older: 120 mcg
  • Females
    • 9-13 years: 60 mcg
    • 14-18 years: 75 mcg
    • 19 years and older: 90 mcg
  • Pregnant Women
    • 18 years or younger: 75 mcg
    • 19 years and older: 90 mcg, preferably the K 1 variety (phylloquinone)
  • Nursing Women
    • 18 years or younger: 75 mcg
    • 19 years and older: 90 mcg, preferably the K 1 variety (phylloquinone)
Vitamin K (in the form of K 1 ) is found in green leafy vegetables. Kale and turnip greens are the best food sources, providing about 10 times the daily adult requirement in a single serving. Spinach, broccoli, lettuce, and cabbage are very rich sources as well, and you can get perfectly respectable amounts of vitamin K in such common foods as oats, green peas, whole wheat, and green beans, as well as watercress and asparagus.
Vitamin K (in the form of K 2 ) is also manufactured by bacteria in the intestines and is a major source of vitamin K. Long-term use of antibiotics can cause a vitamin K deficiency by killing these bacteria. However, this effect seems to be significant only in people who are deficient in vitamin K to begin with. 2-5 Pregnant and postmenopausal women are also sometimes deficient in this vitamin. 6-8 In addition, children born to women taking anticonvulsants while pregnant may be significantly deficient in vitamin K, causing them to have bleeding problems and facial bone abnormalities. 9-11 Vitamin K supplementation during pregnancy may be helpful for preventing this.
The blood-thinning drug warfarin (Coumadin) works by antagonizing the effects of vitamin K. Conversely, vitamin K supplements, or intake of foods containing high levels of vitamin K, block the action of this medication and can be used as an antidote. 12
Cephalosporins and possibly other antibiotics may also interfere with vitamin K-dependent blood clotting. 13-16 However, this interaction seems to be significant only in people who have vitamin K-poor diets.
People with disorders of the digestive tract, such as chronic diarrhea , celiac sprue, ulcerative colitis , or Crohn's disease , may become deficient in vitamin K. 17-20Alcoholism can also lead to vitamin K deficiency. 21

Therapeutic Dosages

In one study of osteoporosis described below, vitamin K was taken at the high dose of 1 mg daily, more than 10 times the necessary nutritional intake.

Therapeutic Uses

Growing, but not yet definitive, evidence suggests that vitamin K should be added to the list of nutrients helpful for preventing osteoporosis . 22-32,50,52,57-58
Based on its ability to help blood clot normally, vitamin K has been proposed as a treatment for excessive menstrual bleeding. 33 However, the last actual study testing this idea was carried out more than 55 years ago. 34 Vitamin K has also been recommended for nausea , although there is as yet no meaningful evidence that it really works.
Preliminary evidence suggests that vitamin K supplementation may help prevent liver cancer . 51 Very high doses of intravenous vitamin K have also been used to treat advanced liver cancer, with, perhaps, marginal benefits. 55

What Is the Scientific Evidence for Vitamin K?

Vitamin K plays a known biochemical role in the formation of bone. This has led researchers to look for relationships between vitamin K intake and osteoporosis.
Observational studies have found that people with osteoporosis often have low levels of vitamin K, 35-38 and that people with higher intake of vitamin K have a lower incidence of osteoporosis. 39,40
Research also suggests that supplemental vitamin K can reduce the amount of calcium lost in the urine. 41-43 This is indirect evidence of a beneficial effect on bone.
However, while these studies are interesting, only double-blind, placebo-controlled trials can actually prove a treatment effective. (For the reasons why, see Why Does This Database Rely on Double-blind Studies? ). Several such studies have been performed on vitamin K for osteoporosis, with generally positive results. 50,53, 56,57-58
One of these was a 3-year, double-blind, placebo-controlled trial of 181 women; it found that vitamin K significantly enhanced the effectiveness of supplementation with calcium , vitamin D , and magnesium . 50 Participants, postmenopausal women between the ages of 50 and 60, were divided into three groups: receiving either placebo, calcium plus vitamin D plus magnesium, or calcium plus vitamin D plus magnesium plus vitamin K 1 (at the high dose of 1 mg daily). Researchers monitored bone loss by using a standard DEXA bone density scan. The results showed that the study participants using vitamin K along with the other nutrients lost less bone than those in the other two groups.
Benefits were seen in other studies as well. 53,56,57-58 However, another placebo-controlled trial involving 452 older men and woman with normal levels of calcium and vitamin D failed to demonstrate any beneficial effects of 500 mcg per day of vitamin K supplementation on bone density and other measures of bone health over a3-year period. 60
If there is a favorable effect, it is appears to be quite modest. Vitamin K may show its influence most strongly when, instead of DEXA scan alone, more complex tests of bone strength are used. 57
Some evidence hints that vitamin K works by reducing bone breakdown, rather than by enhancing bone formation. 54
For more information, see the Osteoporosis article.

Safety Issues

Vitamin K is quite safe at the recommended therapeutic dosages.
Note : Vitamin K directly counters the effects of the anticoagulant warfarin (Coumadin) . If you are taking warfarin, you should not take vitamin K supplements or alter your dietary intake of vitamin K without doctor supervision. 44,45 (One study suggests a novel way of using this effect deliberately. 59 Researchers gave people on warfarin a fixed daily dose of vitamin K in order to override the changes in warfarin action caused by the natural variation in day-to-day dietary vitamin K consumption. The results were positive: INR values—the standard measurement of warfarin’s blood thinning effect—became more stable. Needless to say, however, this method should not be used except under close physician supervision.)
Newborns are commonly given vitamin K 1 injections to prevent bleeding problems. Although some have suggested that this practice may increase the risk of cancer, 46 enormous observational studies have found no such connection (one such trial involved more than one million participants). 47,48

Interactions You Should Know About

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References

1 Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74-79.

2 Cohen H, Scott SD, Mackie IJ, et al. The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K 1 levels. Br J Haematol. 1988;68:63-66.

3 Conly J, Stein K. Reduction of vitamin K 2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994;17:531-539.

4 Shearer MJ, Bechtold H, Andrassy K, et al. Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. J Clin Pharmacol. 1988;28:88-95.

5 Goss TF, Walawander CA, Grasela TH, et al. Prospective evaluation of risk factors for antibiotic-associated bleeding in critically ill patients. Pharmacotherapy. 1992;12:283-291.

6 Family Practice News. 1984;14:27.

7 Bloch CA, Rothberg AD, Bradlow BA. Mother-infant prothrombin precursor status at birth. J Pediatr Gastroenterol Nutr. 1984;3:101-103.

8 Ferland G. Subclinical vitamin K deficiency: a recent development. Nutr Rep. January 1994;12.

9 Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol. 1993;168:923-928.

10 Howe AM, Lipson AH, Sheffield LJ, et al. Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K. Am J Med Genet. 1995;58:238-244.

11 Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol. 1993;168:884-888.

12 Crowther MA, Donovan D, Harrison L,et al. Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin. Thromb Haemost. 1998;79:1116-1118.

13 Cohen H, Scott SD, Mackie IJ, et al. The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K 1 levels. Br J Haematol. 1988;68:63-66.

14 Shearer MJ, Bechtold H, Andrassy K, et al. Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. J Clin Pharmacol. 1988;28:88-95.

15 Goss TF, Walawander CA, Grasela TH, et al. Prospective evaluation of risk factors for antibiotic-associated bleeding in critically ill patients. Pharmacotherapy. 1992;12:283-291.

16 Lipsky JJ. Nutritional sources of vitamin K. Mayo Clin Proc. 1994;69:462-466.

17 Avery RA, Duncan WE, Alving BM. Severe vitamin K deficiency induced by occult celiac disease BR96-026. Am J Hematol. 1996;53:55.

18 Benitez L, Hernandez Hernandez L, Sanchez Arcos E, et al. Changes in the prothrombin complex as clinical manifestation of celiac sprue in adults. Rev Clin Esp. 1996;196:492-493.

19 Krasinski SD, Russell RM, Furie BC, et al. The prevalence of vitamin K deficiency in chronic gastrointestinal disorders. Am J Clin Nutr. 1985;41:639-643.

20 Krejs GJ. Diarrhea. As cited in Wyngaarden JB, Smith LH Jr, eds. Cecil Textbook of Medicine. 18th ed. Philadelphia, PA: WB Saunders; 1988.

21 Iber FL, Shamszad M, Miller PA, et al. Vitamin K deficiency in chronic alcoholic males. Alcohol Clin Exp Res. 1986;10:679-681.

22 Binkley N, Suttie J. Vitamin K nutrition and osteoporosis. J Nutr. 1995;125:1812-1821.

23 Vermeer C, Gijsbers BL, Craciun AM, et al. Effects of vitamin K on bone mass and bone metabolism. J Nutr. 1996;126:1187S-1191S.

24 Kanai T, Takagi T, Masuhiro K, et al. Serum vitamin K level and bone mineral density in post-menopausal women. Int J Gynaecol Obstet. 1997;56:25-30.

25 Hart JP, Shearer MJ, Klenerman L, et al. Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab. 1985;60:1268-1269.

26 Bitensky L, Hart JP, Catterall A, et al. Circulating vitamin K levels in patients with fractures. J Bone Joint Surg Br. 1988;70:663-664.

27 Hodges SJ, Pilkington MJ, Stamp TC, et al. Depressed levels of circulating menaquinones in patients with osteoporotic fractures of the spine and femoral neck. Bone. 1991;12:387-389.

28 Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74-79.

29 Jie KS, Gijsbers BL, Knapen MH, et al. Effects of vitamin K and oral anticoagulants on urinary calcium excretion. Br J Haematol. 1993;83:100-104.

30 Knapen MH, Hamulyak K, Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann Intern Med. 1989;111:1001-1005.

31 Tomita A, Fujita T, Takatsuki K, et al. 47 Ca kinetic study and vitamin K 2 in postmenopausal osteoporosis [in Japanese]. Horumon To Rinsho. 1971;19:731-736.

32 Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000;71:1201-1208

33 Suttie JW. Vitamin K and human nutrition. J Am Diet Assoc. 1992;92:585-590.

34 Gubner R, Ungerleider HE. Vitamin K therapy in menorrhagia. South Med. 1944;37:556-558.

35 Kanai T, Takagi T, Masuhiro K, et al. Serum vitamin K level and bone mineral density in post-menopausal women. Int J Gynaecol Obstet. 1997;56:25-30.

36 Hart JP, Shearer MJ, Klenerman L, et al. Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab. 1985;60:1268-1269.

37 Bitensky L, Hart JP, Catterall A, et al. Circulating vitamin K levels in patients with fractures. J Bone Joint Surg Br. 1988;70:663-664.

38 Hodges SJ, Pilkington MJ, Stamp TC, et al. Depressed levels of circulating menaquinones in patients with osteoporotic fractures of the spine and femoral neck. Bone. 1991;12:387-389.

39 Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74-79.

40 Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000;71:1201-1208.

41 Jie KS, Gijsbers BL, Knapen MH, et al. Effects of vitamin K and oral anticoagulants on urinary calcium excretion. Br J Haematol. 1993;83:100-104.

42 Knapen MH, Hamulyak K, Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann Intern Med. 1989;111:1001-1005.

43 Tomita A, Fujita T, Takatsuki K, et al. 47 Ca kinetic study and vitamin K 2 in postmenopausal osteoporosis [in Japanese]. Horumon To Rinsho. 1971;19:731-736.

44 Pederson FM, Hamberg O, Hess K, et al. The effect of dietary vitamin K on warfarin-induced anticoagulation. J Intern Med. 1991;229:517-520.

45 Chow WH, Chow TC, Tse TM, et al. Anticoagulation instability with life-threatening complication after dietary modification. Postgrad Med J. 1990;66: 855-857.

46 Golding J, Paterson M, Kinlon LJ. Factors associated with childhood cancer in a national cohort study. Br J Cancer. 1990;62:304-308.

47 Ekelund H, Finnstrom O, Gunnerskog J, et al. Administration of vitamin K to newborn infants and childhood cancer. BMJ. 1993;305:109.

48 Klebanoff MA, Read JS, Mills JL, Shiono PH. The risk of childhood cancer after neonatal exposure to vitamin K. N Engl J Med. 1993;329:905-908.

49 Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000;71:1201-1208.

50 Braam LA, Knapen MH, Geusens P, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003;73:21-26.

51 Habu D, Shiomi S, Tamori A, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358-361.

52 Purwosunu Y, Rachman IA, Reksoprodjo S, et al. Vitamin K treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res. 2006;32:230-234.

53 Purwosunu Y, Rachman IA, Reksoprodjo S, et al. Vitamin K treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res. 2006;32:230-234.

54 Martini LA, Booth SL, Saltzman E, et al. Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism. Osteoporos Int. 2006 Mar 18. [Epub ahead of print]

55 Sarin SK, Kumar M, Garg S, et al. High dose vitamin K3 infusion in advanced hepatocellular carcinoma. J Gastroenterol Hepatol. 2006;21:1478-1482.

56 Bolton-Smith C, McMurdo ME, Paterson CR, et al. A two-year randomized controlled trial of vitamin K(1) (phylloquinone) and vitamin D(3) plus calcium on the bone health of older women. J Bone Miner Res. 2007 Jan 23. [Epub ahead of print]

57 Knapen MH, Schurgers LJ, Vermeer C. Vitamin K(2) supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007 Feb 8. [Epub ahead of print]

58 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;166:1256-1261.

59 Rombouts EK, Rosendaal FR, van der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost. 2007 Jul 31. [Epub ahead of print]

60 Booth SL, Dallal G, Shea MK, et al. Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab. 2008 Feb 5.

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