Vitamin K is involved in blood coagulation. Vitamin K deficiency can cause easy bruising. The primary form of vitamin K in the diet is "phylloquinone," which is found mostly in green leafy vegetables, but also in cheese, liver, coffee, and green tea. Insufficient intakes of vitamin K are not uncommon in the US and have already been shown to cause problems of blood coagulation in human.
     Vitamin K is getting more attention as a potential treatment for osteoporosis. Early research suggested that low vitamin K status is associated with low bone mass and an increased risk of fracture in elderly patients. Clinical research then began to develop showing that taking certain vitamin K supplements might also improve bone mineral density in some patients. Now a new analysis of studies suggests that taking vitamin K supplements can improve bone mineral density and possibly decrease fracture risk in at-risk patients...postmenopausal women, patients with osteoporosis, people taking steroids, etc. There are several forms of vitamin K. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-l,4-naphthoquinones, including phylloquinone (K1), menaquinones (K2), and menadione (K3).    Researchers have mainly focused on vitamin K2 (menaquinone).

Vitamin K in Food
Substances with vitamin K activity were originally identified in green leafy vegetables, hemp seeds, liver and fish meal. These substances were found to have anti bleeding activity and their collective name was derived from koagulation, the German word for clotting.

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Chemical Structure
Vitamin K is a group name for a number of related compounds, which have in common a methylated naphthoquinone ring structure, and which vary in the aliphatic side chain attached at the 3-position. Phylloquinone (also known as vitamin K1) contains in its side chain four isoprenid residues one of which is unsaturated. Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues. It is generally accepted that the naphthoquinone is the functional group, so that the mechanism of action is similar for all K-vitamins. Substantial differences may be expected, however, with respect to intestinal absorption, transport, tissue distribution, and bio-availability. These differences are caused by the different lipophilicity of the various side chains, and by the different food matrices in which they occur.

Menadione is vitamin K3
Menaquinone is vitamin K2
Phylloquinone is vitamin K1

Vitamin K daily requirement
Minimum daily requirements of vitamin K have not been fully evaluated. Adults may need about 50 to 100 mcg a day which can be obtained through diet. Studies have been done using much, much higher dosage of vitamin K, up to 45 mg a day. For long term supplementation, a daily dose in the range of 50 to 500 micrograms should be sufficient in those who are interested in using vitamin K supplements for bone strength. However, there should be a good reason to use this supplement. If there is no medical reason to take vitamin K, then there is no point in supplementation.

Vitamin K in food
There are two common forms of vitamin K: phylloquinone (vitamin K1) is found in green leafy vegetables such as lettuce, broccoli and spinach, and comprises about 90 per cent of the vitamin K in a normal Western diet; and menaquinones (vitamins K2), make up the rest. Vitamin K2 are found in some fermented foods such as cheese or natto, and can be also be made in the gut by bacteria.

Physiology
Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues). Gla-residues are usually involved in binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins. At this time fewer than 12 human Gla-proteins have been discovered, and they play key roles in the regulation of three physiological processes:

* blood coagulation (prothrombin (factor II), factors VII, IX, X, protein C, protein S and protein Z)
* bone metabolism
* vascular biology.

Phylloquinone (K1) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma.

Vitamin K role in disease
Vitamin K-deficiency may occur by disturbed intestinal uptake (such as would occur in a bile duct obstruction), by therapeutic or accidental intake of vitamin K-antagonists or, very rarely, by nutritional vitamin K-deficiency. As a result of the acquired vitamin K-deficiency, Gla-residues are not or incompletely formed and hence the Gla-proteins are inactive. Lack of control of the three processes mentioned above may lead to the following: risk of uncontrolled and massive bleeding, cartilage calcification and severe malformation of developing bone, or deposition of insoluble calcium salts in the arterial vessel walls.

Vitamin K and Cancer
Some rodent and laboratory studies have indicated that Vitamin K may have anti cancer activity. However I am not familiar with any human studies where oral vitamin K supplements have led this vitamin to effectively prevent, treat, or cure cancer.

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. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
In this study, the chemopreventive effects of vitamin K2 on the recurrence and survival of patients with hepatocellular carcinoma after curative therapy were evaluated. Sixty patients who were diagnosed to be free of hepatocellular carcinoma after radiofrequency ablation therapy or surgery were randomly assigned to either the vitamin K2 group or the control group. All patients were positive for the hepatitis C virus (HCV) antibody and hepatitis B surface antigen positive patients were excluded from this study. Patients in the vitamin K2 group received an oral dose of menatetrenone at 45 mg per day. Vitamin K2 may have a suppressive effect on the recurrence of hepatocellular carcinoma and a beneficial effect on tumor recurrence. However, there was no significant difference in the survival rates. The chemopreventive effects of vitamin K2 are not sufficient. The development of a further regimen such as combination therapy is required.

Vitamin K Deficiency and Osteoporosis
Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Whether vitamin K supplements help those with osteoporosis is yet to be determined. There is no consensus in the medical establishment whether vitamin K supplements offer benefits for osteoporosis beyond what calcium, vitamin D, and exercise would provide. No firm answers can be given as the benefits versus risks of taking vitamin K supplements for osteoporosis, and the ideal dosages are still being evaluated.

Effect of Vitamin K Supplementation on Bone Loss in Elderly Men and Women.
J Clin Endocrinol Metab. 2008 Feb. Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B.
USDA Human Nutrition Research Center on Aging at Tufts University; Yale University School of Medicine, Department of Orthopaedics.
The objective of this study was to determine the effect of three-year vitamin K phylloquinone supplementation on change in bone mineral density of the femoral neck bone in older men and women who were calcium and vitamin D-replete. In this three year, double-blind, controlled trial, 452 men and women (60-80 y) were randomized equally to receive a multivitamin that contained either 500 microg/d or no vitamin K phylloquinone, plus a daily calcium (600 mg elemental calcium) and vitamin D 400 IU supplement. There were no differences in changes in bone mineral density measurements at any of the anatomical sites measured between the two groups. The group that received the vitamin K phylloquinone supplement had significantly higher phylloquinone and significantly lower % undercarboxylated osteocalcin concentrations compared to the group that did not receive phylloquinone. No other biochemical measures differed between the two groups. Vitamin K Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin D.

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. Department of Human Nutrition/Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark.
While current intakes of phylloquinone (vitamin K1) in many populations are believed to be sufficient to maintain normal blood coagulation, these may be insufficient to cover the requirements for optimal bone metabolism. Therefore, the objective of the present study was to investigate the effect of increasing phylloquinone intakes above the usual dietary intake for 6 weeks on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Thirty-one postmenopausal women completed this 3 x 6-week randomised cross-over study, in which volunteers were supplemented with 0 (placebo), 200, and 500 micrograms phylloquinone per day. In addition, the volunteers were given 10 microg vitamin D3/d throughout the study period. With increasing phylloquinone intake, the concentration of serum gamma-carboxylated and under-gamma-carboxylated osteocalcin was significantly increased and decreased, respectively, in a dose-dependent manner. Mean serum phylloquinone concentration was significantly higher with daily supplementation with 500 microgram vitamin K1 compared with that during either of the placebo or 200 microg phylloquinone/d supplementation periods, which did not differ. Serum total osteocalcin was significantly increased in response to daily supplementation with 500 (but not 200) microgragrams vitamin K1 compared with placebo. Serum bone-specific alkaline phosphatase as well as the urinary markers of bone resorption (N-telopeptide cross-links of collagen, pyridinoline and deoxypyridinoline) and urinary gamma-carboxyglutamate were unaffected by phylloquinone supplementation. In conclusion, while daily supplementation with 200 and 500 microg vitamin K1 per day for 6 weeks increased vitamin K status in postmenopausal women, it had no effect on bone turnover.

Vitamin K and Osteoarthritis
There appears to be an association between low blood levels of vitamin K and an increased prevalence of hand and knee osteoarthritis. In one study, the lower the levels of vitamin K in the blood, the higher the prevalence of osteoarthritis. Patients with the lowest phylloquinone plasma levels are also the ones whose x-rays most often revealed the presence of large osteophytes, or "bone spurs" -- small outgrowths of the bone common in arthritis. Arthritis and Rheumatism April 2006.

Vitamin K, Warfarin and oral anticoagulants
Vitamin K is an essential co-factor for the synthesis of several coagulation factors. Oral anticoagulants competitively inhibit enzymes that participate in vitamin K metabolism. Vitamin K intake of more than 250 mcg/day decreases warfarin sensitivity in anticoagulated patients consuming regular diets. For each increase in 100 mcg of vitamin K intake, the INR may be reduced by 0.2. Some over-the-counter multivitamin supplements contain enough vitamin K1 to significantly alter coagulation parameters.
   The long-term use of warfarin, known as the product name Coumadin, a drug commonly prescribed to reduce the risk of blood clots, appears to increase the risk of fractures associated with osteoporosis, a bone-thinning condition that usually increased with age. Warfarin prevents coagulation by blocking vitamin K, which is needed to activate certain clotting factors. Because vitamin K is also used to activate proteins involved in bone formation, drugs like warfarin may increase the risk of fractures.
   A dose of 1-2.5mg of oral phytomenadione ( vitamin K1 ), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours in those who have had excess anticoagulation.

Vitamin K Research
Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.
nt J Oncol. 2005 Aug;27(2):505-11.
A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined. In the present study, we examined the antitumor effects of vitamins K2, K3 and K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vivo. Furthermore, to examine the mechanism of antitumor actions of these vitamins K, mRNA expression levels of various G1 phase-related cell cycle molecules were evaluated by using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. HCC-bearing animals were produced by implanting PLC/PRF/5 cells subcutaneously into athymic nude mice, and drinking water containing vitamin K2, K3 or K5 was given to the animals. Treatments with vitamins K2, K3 and K5 were shown to markedly inhibit the growth of HCC tumors. To examine the mechanism of in vivo antitumor effects of vitamins K, total RNA was extracted from HCC tumors, and the expression of G1 phase-related cell cycle molecules was quantitatively examined. Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5. These results indicate that vitamins K2, K3 and K5 exert antitumor effects on HCC by regulating the expression of G1 phase-related cell cycle molecules. These results also indicate that vitamins K2, K3 and K5 may be useful agents for the treatment of patients with liver cancer.

Pleiotropic actions of vitamin K: protector of bone health and beyond?
Nutrition. 2006 Jul-Aug;22(7-8):845-52. Kaneki M, Hosoi T, Ouchi Y, Orimo H.
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; Shriners Hospital for Children, Boston, Massachusetts, USA.
Vitamin K is a nutrient that was originally identified as an essential factor for blood coagulation. Recently, vitamin K has emerged as a potential protector against osteoporosis, atherosclerosis, and hepatocarcinoma. Accumulated evidence indicates that subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues, particularly in bone and possibly in vasculature, exists widely in the otherwise healthy adult population. Vitamins K1 and K2 have been shown to exert protective effects against osteoporosis. Increasing evidence implicates a role for vitamin K in calcification of arteries and atherogenesis. Most of the new biological functions of vitamin K in bone, vasculature, and hepatoma cells are considered attributable to promotion of gamma-carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is shared by vitamins K1 and K2.

Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.
Invest New Drugs. 2005 Jun;23(3):235-9. Lim D, Morgan RJ Jr, Akman S, Margolin K, Carr BI, Leong L, Odujinrin O, Doroshow JH. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA
Based on the activity of menadione (M) in the human tumor stem cell assay, we conducted a phase I trial of M in patients with advanced cancer. Forty patients (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are evaluable for toxicity. No objective partial or complete responses were observed.

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease.
J Hepatol. 2005 Mar;42(3):365-70. Institute of Liver Studies, King's College Hospital, London, UK.
In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K1 in such patients. METHODS: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K(1), or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment. A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K1. The intestinal absorption of mixed-micellar K1 is unreliable in adults with severe acute liver dysfunction.

Solanesol is an intermediate in the metabolism of vitamin K2

Vitamin K questions
Q. Was just wondering about Vitamin K and how it would help cure cancer? So many question about vitamin K. Your research is very important and very helpful, have emailed your web page to all my friends so they to can learn. A very very nice web site.  My sister is a RN and she says U know what your talking about. So I'm convinced so far.
     A. Thank you. We work hard to maintain our site. Some rodent and laboratory studies have indicated that Vitamin K may have anti cancer activity. However we are not familiar with any human studies where oral vitamin K supplements have led this vitamin to effectively prevent, treat, or cure cancer.

Q. Are you recommending vitamin K2 for osteoporosis?
     A. Whether vitamin K supplements help those with osteoporosis is yet to be determined.

Q. Hi. I'm 68 - exercise a lot and recently I take 500 mcg vitamin k a day. I've had a small calcified heart valve for a number of year but it doesn't seem to be getting any worse. I had the ultrasound of my heart a couple of years ago and was told I had the ejection rate of my tech who was 45 at the time. I used to have very thin blood and a low platelet count - lots of nose bleeds in the morning and high blood pressure. Would regular vitamin k supplements reduce or remove the calcium / cholesterol deposit in my aorta. I've read vitamin K prevents the formation - would it remove them. Also my 56 year old wife has an increasing number of calcium deposits in her breasts each year. Would vitamin k prevent those or remove them.
     A. It is unlikely that a vitamin K supplement would remove calcium deposits.

Q. My husband is on coumadin for a short while as he recovers from knee replacement surgery. His doctor said avoid anything with vitamin K. Does saw palmetto have vitamin K in it? He needs the help with the prostate gland function.
   A. Saw palmetto does not have vitamin K.

Q. Being 62, I am wanting to make sure I take supplements needed for prevention of osteoporosis. The bottle I have is called Osteo Support by Douglas Labs and contains 150 mcg of Vitamin K per dose. My concern is that being of the age for possible strokes, does taking Vitamin K influence stroke incidence?
   A. This is a difficult question to answer since one has to weigh the benefits of vitamin K supplementation versus the risk for stroke. Much depends on an individual person's risk factors for stroke and their clotting or bleeding tendencies. Some people clot too easily, others have a tendency to have very thin blood. One has to also consider whether vitamin K is necessary for osteoporosis prevention when there are other supplements that are quite effective. We have not seen much research to determine if taking vitamin K supplements has a measurable effect on increasing stroke risk. It is difficult to predict the benefits versus risks of vitamin K supplementation and to determine which option is better. Also, a stroke can occur either from a blood clot, which is more common, or bleeding into the brain, which is less common.

Q. I have read about the use in Japan of mk-7 vitamin k-2 for osteoporosis. All the research I've read says that 43 milligrams was the dosage used yet the makers of menaquinone 7 say that 43 micrograms is the correct dosage. I'm confused about this. Have you any clarifying information? I've found a supplement that has 90 mcg of mk-7. Thank you for all your work, for your newsletter and for your supplements.
   A. The full benefits and risks of vitamin K supplementation have not been fully established. Adults need about 50 to 100 micrograms a day through diet. Some research studies have used up to 40 to 50 mg a day of vitamin K, but this does not mean that it would be appropriate to use these high dosages for prolonged periods. The role of vitamin K in terms of osteoporosis help is still being evaluated and there is no consensus in the medical establishment whether vitamin K supplements offer benefits for osteoporosis beyond what calcium, vitamin D, and exercise would provide. As of November 2007 no firm answers can be given as the benefits versus risks of taking vitamin K supplements and the ideal dosages are still being evaluated.

Q. I was reading the information on your website regarding the benefits of vitamin K. I recently had a blood test that showed I have low blood platelets. My number is 118 and the lowest number on the scale is 140. My doctor was concerned and wanted to refer me to a specialist. I told her that I wasn't interested in that right now, that instead wanted to research and find out what I could do about this and get my blood retested in several weeks. She agreed. My question is, would a vitamin K deficiency be a possible cause of low blood platelets? I do muscle testing and after testing myself found my body to be low in vitamin K. This is at the same timeframe as the blood test. I am trying to determine the cause of my body having low platelets as this is the first time that this has showed up. My doctor did a finger prick in her office yesterday to retest my platelets and on this test it showed them to be 109.
   A. Vitamin K deficiency is not associated with low platelet levels. There are many causes for low platelets that your doctor is likely to look into over time.