Vitamin K

Vitamin K is a group of structurally similar, fat-soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue.

Both physiological and observational evidence indicate vitamin K plays a role in bone growth and the maintenance of bone density.

Other studies have shown vitamin K antagonists (usually a class of anticoagulants) lead to early calcification of the epiphysis and epiphysial line in mice and other animals, causing seriously decreased bone growth, due to defects in osteocalcin and matrix Gla protein. Their primary function is to prevent overcalcification of the bone and cartilage.

Vitamin K is important in the process of carboxylating glutamic acid (Glu) in these proteins to gamma-carboxyglutamic acid (Gla), which is necessary for their function. Vitamin D is reported to regulate the OC transcription by osteoblast thereby showing that vitamin K and vitamin D work in tandem for the bone metabolism and development. Lian and his group discovered two nucleotide substitution regions they named "osteocalcin box" in the rat and human osteocalcin genes. They found a region 600 nucleotides immediately upstream from the transcription start site that support a 10-fold stimulated transcription of the gene by 1,25-dihydroxy vitamin D.

Vitamin K1 and bone health

Data from the 1998 Nurses Health Study, an observational study, indicated an inverse relationship between dietary vitamin K1 and the risk of hip fracture. After being given 110 micrograms/day of vitamin K, women who consumed lettuce one or more times per day had a significantly lower risk of hip fracture than women who consumed lettuce one or fewer times per week. In addition to this, high intakes of vitamin D but low intakes of vitamin K were suggested to pose an increased risk of hip fracture. The Framingham Heart Study is another study that showed a similar result. Subjects in the highest quartile of vitamin K1 intake (median K1 intake of 254 .g/ day) had a 35% lower risk of hip fracture than those in the lowest quartile. 254 .g/day is above the US Daily Reference Intake (DRI) of 90 ug/day for women and 120 .g/day for men.

Vitamin K2 (MK4) and bone health

MK4 has been shown in numerous studies to reduce fracture risk, stop and reverse bone loss. In Japan, MK4 in the dose of 45 mg daily is recognized as a treatment for osteoporosis under the trade name Glakay. MK4 has been shown to decrease fractures up to 87%.In the amount of 45 mg daily MK4 has been approved by the Ministry of Health in Japan since 1995 for the prevention and treatment of osteoporosis.

MK4 prevented bone loss and/or fractures in the following circumstances:
  • caused by corticosteroids (e.g., prednisone, dexamethasone, prednisolone)
  • anorexia nervosa
  • cirrhosis of the liver
  • postmenopausal osteoporosis
  • disuse from stroke
  • Alzheimer's disease
  • Parkinson disease
  • primary biliary cirrhosis
  • leuprolide treatment (for prostate cancer).

Vitamin K2 (MK7) and bone health

Menaquinone-7 (MK7), which is abundant in fermented soybeans (natto), has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. In another study, use of MK-7 caused significant elevations of serum Y-carboxylated osteocalcin concentration, a biomarker of bone formation. MK-7 also completely inhibited a decrease in the calcium content of bone tissue by inhibiting the bone-resorbing factors parathyroid hormone and prostaglandin E2. On 19 February 2011, HSA (Singapore) approved a health supplement that contains vitamin K2 (MK7) and vitamin D3 for increasing bone mineral density.


While researchers in Japan were studying the role of vitamin K2 as the menaquinone-4 (MK-4) form in the prevention of bone loss in females with liver disease, they discovered another possible effect. This two-year study that involved 21 women with viral liver cirrhosis found that women in the supplement group were 90% less likely to develop liver cancer. A German study performed on men with prostate cancer found a significant inverse relationship between vitamin K2 consumption and advanced prostate cancer.

In 2006, a clinical trial showed that menatetenone (a subtype of Vitamin K2) might be able to reduce recurrence of liver cancer after surgery. It should be noted that this was a small pilot study and other similar studies did not show much effect. MK4 is now being tested along with other drugs to reduce liver cancer and has show promising early results.[2] [edit]

Vitamin K as antidote for poisoning by 4-hydroxycoumarin drugs Vitamin K, is a true antidote for poisoning by 4-hydroxycoumarin anticoagulant drugs (sometimes loosely referred to as coumarins). These include the pharmaceutical warfarin, and also anticoagulant-mechanism poisons such as bromadiolone, which are commonly found in rodenticides. 4-Hydroxycoumarin drugs possess anticoagulatory and rodenticidal properties because they inhibit vitamin K-dependent synthesis of some clotting factors by the liver. Death is usually a result of internal hemorrhage. Treatment usually consists of repeated intravenous doses of vitamin K, followed by doses in pill form for a period of at least two weeks, though possibly up to 2 months, afterwards (in the case of the more potent 4-hydoxycoumarins used as rodenticides). If caught early, prognosis is good, even when great amounts of the drug or poison are ingested.



. ^ Gerald JA, Katie JW, Asiri R W et al. (2009). "Vitamin K promotes mineralization, transition, and an anticatabolic phenotype by ..carboxylation.dependent and independent mechanisms". Am J Physiol Cell Physiol 297 (6): C1358.C1367. doi:10.1152/ajpcell.00216.2009. PMID 19675304.

. ^ Drenckhahn, D. & Kugler, P (2003), "Knochengewebe". In Benninhoff & D. Drenhahn, Anatomie Band 1:147. Munich, Germany: Urban & Fisher

. ^ a b Dr. Susan E. Brown, PhD. "Key vitamins for bone health . vitamins K1 and K2". Retrieved 11 August 2010.

. ^ Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, Zambetti G & Stein G (1989). "Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression". Proc. Natl. Acad. Sci. USA 86 (4): 1143.1147. doi:10.1073/pnas.86.4.1143. PMC 286642. PMID 2784002.

. ^ a b Kanai, T (1997). "Serum vitamin K level and bone mineral density in post-menopausal women". International Journal of Gynecology & Obstetrics 56: 25. doi:10.1016/S0020-7292(96)02790-7.

^ Booth SL, Tucker K, Chen H et al. (2000). "Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women". Am J Clin Nutr 71 (5): 1201.1208. PMID 10799384.

. ^ Cheung, AM; Weber, P; Willett, WC; Rockett, H; Booth, SL; Colditz, GA; Hu, H; Vieth, R et al. (2008). Torgerson, David. ed. "Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial". PLoS Med. 5 (10): e196. doi:10.1371/journal.pmed.0050196. PMC 2566998. PMID 18922041.

. ^ Feskanich, Diane; Weber, P; Willett, W; Rockett, H; Booth, S; Colditz, G (1999). "Vitamin K intake and hip fractures in women: a prospective study". American Journal of Clinical Nutrition 69 (1): 74.9. PMID 9925126.

. ^ Glakay prescribing information

. ^ Yamaguchi M (November 2006). "Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis". Yakugaku Zasshi 126 (11): 1117.37. doi:10.1248/yakushi.126.1117. PMID 17077614.

. ^ Tsukamoto Y (2004). "Studies on action of menaquinone-7 in regulation of bone metabolism and its preventive role of osteoporosis". BioFactors 22 (1.4): 5.19. doi:10.1002/biof.5520220102. PMID 15630245.

. ^ Ref. no. HPRG (HSU) 2011-02-0016

. ^ Allison (2001). "The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease". Medical hypotheses 57 (2): 151.5. doi:10.1054/mehy.2001.1307. PMID 11461163.

^ "Vitamin K Found to Protect Against Liver Cancer"

. ^ Saxena SP, Israels ED, Israels LG (2001). "Novel vitamin K-dependent pathways regulating cell survival". Apoptosis 6 (1.2): 57.68. doi:10.1023/A:1009624111275. PMID 11321042.

^ Nimptsch K, Rohrmann S, Linseisen J (April 2008). "Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. (EPIC-Heidelberg)". Am. J. Clin. Nutr. 87 (4): 985.92. PMID 18400723.

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