Vitamin K supplements, blood clotting effects, bone health, dosage by Ray Sahelian, M.D.
Phylloquinone (K1), menaquinones (K2), and menadione (K3)
March 5 2014

Vitamin K is an organic exogenous compound required by humans for a vital function in clotting. It is a fat-soluble vitamin that is easily depleted and poorly stored, requiring dietary replenishing given that it cannot be synthesized in sufficient quantities to meet the requirements of humans and higher mammals. Vitamin K actually refers to not one but a group of fat-soluble (lipophilic, hydrophobic) vitamins that share a common methylated naphthoquinone characteristic chemical structure. There are two naturally occurring forms - vitamin K1 and vitamin K2. Vitamin K3 is a synthetic water-soluble substance that is chemically similar to natural vitamin K but with limited effectiveness

Since it is involved in blood coagulation, deficiency can cause easy bruising. The primary form 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 h cause problems of blood coagulation in human. Phytonadione is another effective form of vitamin K. Phytonadione is used to treat vitamin K deficiency and to treat certain bleeding or blood clotting problems.
   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. Studies regarding the role of vitamin K supplementation on bone mineral density and decrease fracture risk in at-risk patients have shown mixed results. 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).

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Vitamin K in food

Substances with vitamin K activity were originally identified in green leafy vegetables, spinach, Swiss chard, 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.
   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.

Function
Vitamin K is a fat-soluble vitamin, present in plants as phylloquinone and produced by bacteria as menaquinone. It is is a co-factor for gamma-glutamyl carboxylase. This enzyme is responsible for post-translational modification of some glutamate side chains to gamma-carboxyglutamate. The majority of gamma-carboxylated proteins function in blood coagulation; others play a role in calcium homeostasis.

Mol Nutr Food Res. Dec 27 2013. Vitamin K metabolism: Current knowledge and future research. This essential fat-soluble micronutrient is required for the post-translational γ-carboxylation of specific glutamic acid residues in hepatic and extra-hepatic proteins involved in blood coagulation and preventing cartilage and vasculature calcification. In humans, sources of vitamin K are derived from plants as phylloquinone and bacteria as the menaquinones. Menadione is a synthetic product used as a pharmaceutical but also represents an intermediate in the tissue-specific conversion of vitamin K to menaquinone-4, which preferentially resides in tissues such as brain. Research into its metabolism is essential for the understanding of vitamin K biology in health and disease. Progress in this area, driven by knowledge of vitamin K and the availability of markers of vitamin K status, has already proved beneficial in many areas of medicine and further opportunities present themselves. Areas of interest discussed in this review include prophylactic administration of vitamin K1 in term and preterm neonates, interactions between vitamins K and E, the industrial conversion of vitamin K to dihydro-vitamin K in foods, tissue-specific conversion of vitamin K to menaquinone-4, the biological activity of the five and seven carbon metabolites of vitamin K and circadian variations.

Lower risk for cancer
Dr. Jakob Linseisin at the German Cancer Research Center in Heidelberg reports individuals with higher intakes of vitamin K from food are less likely to develop or die of cancer, particularly lung or prostate cancers, than those who eat relatively few vitamin-K- containing foods. Dr. Jakob Linseisin says more studies are needed to clarify this finding. American Journal of Clinical Nutrition, 2010.

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 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.

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.

I read online that in the U.S., the recommended daily intake for vitamin K, in all forms, is 120 micrograms for men and 90 micrograms for women. Is this right?
    This is also my understanding. It is difficult to know exactly how much is best, but a range of 60 to 150 mcg is reasonable.

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.

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.

Aging
Ensuring optimal dietary intakes of vitamin K may help prevent age-related conditions such as bone fragility and heart disease. Children's Hospital Oakland Research Institute scientists Joyce McCann and Bruce Ames analyzed data from hundreds of published articles dating back to the 1970s designed to test Ames' "triage" theory that provides a new basis for determining the optimum intake of individual vitamins and minerals. The analysis supports recommendations by some experts that non-clotting functions requiring vitamin K may need higher intakes than are currently recommended. Vitamin K is known as the "Koagulation" vitamin because about half of the 16 known proteins that depend on vitamin K are necessary for blood coagulation. The other vitamin K-dependent proteins are involved in a variety of different functions involving the skeletal, arterial, and immune systems, the researchers said.

Vitamin K and cancer
Some rodent and laboratory studies have indicated that it 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 Hepatology. 2007.
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.

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. 2008. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
We evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. DESIGN: At baseline, habitual dietary intake was assessed by means of a food-frequency questionnaire. Dietary intake of phylloquinone and menaquinones (MK-4-14) was estimated by using previously published HPLC-based food-content data. During a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake. The association was stronger for advanced prostate cancer. Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone intake was unrelated to prostate cancer incidence. Our results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer. Further studies of dietary vitamin K and prostate cancer are warranted.

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.

J Clin Densitom. 2013 Oct-Dec. Vitamin K and bone health. tVitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women.

Effect of Vitamin K Supplementation on Bone Loss in Elderly Men and Women.
J Clin Endocrinology Metabolism. 2008.
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 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. 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 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.

Vascular conditions
Vitamin K and vascular calcifications. Acta Physiol Hung. 2010 Sep; Fodor D, Albu A, Poantă L, Porojan M. University of Medicine and Pharmacy, 2nd Internal Medicine, Clinic Iuliu Hatieganu, Cluj-Napoca, Romania.
The role of vitamin K in the synthesis of some coagulation factors is well known. The implication of vitamin K in vascular health was demonstrated in many surveys and studies conducted over the past years on the vitamin K-dependent proteins non-involved in coagulation processes. The vitamin K-dependent matrix Gla protein is a potent inhibitor of the arterial calcification, and may become a non-invasive biochemical marker for vascular calcification. Vitamin K(2) is considered to be more important for vascular system,

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. However, I suggest you also review the study below:

Although it is safe, low-dose vitamin K used to treat warfarin recipients with high INRs (international normalized ratios) does not reduce episodes of bleeding. "Our results support the practice of treating patients with INRs between 4.5 and 10.0 with simple warfarin therapy withdrawal and reinstitution once the INR has decreased into the desired range," says Dr. Mark A Crowther, at McMaster University in Hamilton, Ontario. The investigators note that warfarin's dose-response characteristics are highly unpredictable, frequently leading to elevated INRs and increased risk for bleeding, particularly intracranial bleeding. They studied the effects of oral vitamin K on clinical outcomes in over-anticoagulated patients with INRs between 4.5 and 10. The subjects were instructed to withhold warfarin for 1 day and were randomly assigned to vitamin K 1.25 mg or to placebo. The day after treatment, mean INR had decreased significantly more in the vitamin K group than the placebo group. However, there were no significant differences in the percentages of patients who had at least one bleeding complication within 7 days (8% in the vitamin K group vs 9% in the placebo group) or within 90 days (15% vs 16%). There were also no significant differences in 90-day rates of thromboembolism or death. Similarly, the number of patients experiencing a major bleeding event -- defined as fatal bleeding, bleeding requiring therapeutic intervention or transfusion of 2 or more units of red blood cells, or objectively confirmed bleeding into an enclosed space -- was similar in the two groups at day 90 (2.5% treated with vitamin K vs 1.1% treated with placebo). Dr. Crowther's team cautions that their findings "should not be applied to patients who present with active bleeding, those who require acute normalization of their INR (because of imminent surgery, for example), or those with INRs greater than 10.0." Ann Intern Med 2009.

Drug interactions
Vitamin K may enhance the effects of the cancer drug Nexavar, which may allow patients to take lower, less-toxic doses. Combining vitamin K with the cancer pill Nexavar, or sorafenib, sold by Onyx Pharmaceuticals Inc and German drugmaker Bayer AG helped it kill liver and pancreatic cancer in human cell cultures. Nexavar is approved for use in liver kidney cancer and is being tested for an array of other cancers, including melanoma, lung and breast cancer. Combining the drug with vitamin K may help patients avoid hand-foot syndrome, a common side effect of Nexavar that affects about 20 percent of patients. Vitamin K1 also enhanced the effects of sorafenib in hepatocellular carcinoma or primary liver cancer.

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.
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. 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. 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.

Solanesol is an intermediate in the metabolism of vitamin K2

Questions
Q. Was just wondering about vitamin K supplement and how it would help cure cancer? 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. 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 herb 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 April 2009 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.

Q. Dutch studies have shown that vitamin K2 is needed to guide Calcium into the right places in our bodies, otherwise calcium is deposited on soft tissue ranging from arteries to to heart valves. My wife had calcium deposits on her heart valve as found by heart murmur. After she was on vitamin K2 for six months, her heart murmur went away. The deposit on the heart valve was established by ultrasound and tracer ( Tc) radiography by her cardiologist. This suggests before we take high calcium supplements, make sure you have enough vitamin K2.
   A. One case report is interesting but not conclusive. We will await studies regarding the role of vitamin K supplements and heart valve calcification.

Q. Vitamin K-2 is said to aid in strengthening bones, and small doses are said not cause blood clotting. So why is it typically removed from nattokinase
supplements, when the two together might be a healthier supplement?
   A. There are few long term human studies regarding the benefits of vitamin K as a supplement for bone health. Most people get enough vitamin K in their diet. Nattokinase is used as a blood thinning agent and it makes no sense to have vitamin K with the possibility that it may cause better clotting.

Q. I understand that vitamin K helps clotting while the enzyme nattokinase is a blood thinner, is that true?
   A. Yes, nattokinase enzyme has blood-thinning potential while vitamin K helps clotting.

I find it very confusing to say that vitamin K helps clotting blood even though this is what the encyclopedia or dictionary says. My understanding is that K1 (man-made or from leafy greens) is responsible for blood clotting. However, K2 is different. Both MK4 and MK7 are grouped under K2. MK7 and nattokinase are the end products of the fermentation of natto beans. Both have fibrinolysis effects. So, MK7 which is also vitamin K is an anticoagulant agent. I don't know if MK4 (from tobacco leaves) is anticoagulant or not. I don't know about K3 either. Please help me sort this out and correct me if I am wrong. So far I have not found a person who can help me sort out vitamin K properties.
     As far as I know, any form of vitamin K is removed from nattokinase. I have not studied this topic in enough detail to know all the intricacies, perhaps an expert on this topic can email me with their insight.

I found your site interesting and informative and wanted to share what I consider the next up-and-coming superstar: vitamin K2! Please look into this vital, fat-soluble nutrient that is largely insufficient in our population. It appears that insufficiency of K2, along with D insufficiency and various other co-factors for calcium usage, has set us up for everything from osteoporosis, kidney stones, dementia, arthritis, and CVD.

Does Barley Grass powder supplement contain Vitamin K? If so, how much per serving? What about Wheat Grass power supplement?
    These products do contain vitamin K but each batch has to be analyzed individually to determine how much is present. The amount may depend on various factors including how the plants were grown, the soil, and various steps in the processing of the product to make it a supplement.

I really enjoy your website. Please let me know if the use of Vitamin K2 will negate the beneficial effect of Plavix.
    Although K2 and Plavix may influence different parts of blood clotting, it is difficult to say what the interaction would be or what conflict would occur when both are taken. I have not seen such studies with this combination.

My specific question is about vitamin K. I keep going back and forth on this, don't believe I'm deficient, but have continually been brought back to taking it a few times a week due to what I read. I am aware that it is a coagulant, and have questions on it's safety. Though I do take a few other supplements that I understand are thinners. I'm inclined to stop it completely.
    Most people do not need to take this vitamin, but your doctor would have to make the final decision.

I was wondering if you have any information about Vitamin K2 MK 7 and MK 4 to be precise. A lot of claims are being made all over the internet. Are any of these claims valid? And which form of K2 would be best to supplement MK 7, MK 4, or both?
    As of December 2009, there is not enough research to know the effectiveness of this vitamin for long term use and which form is best.

I would very much like to hear your opinion on something. Can taking a large dose of Vitamin D with a Vitamin K component contribute to a blood clot, or DVT? Specifically, 5,000 IU of Vitamin D per day with 80 mcg of Vitamin K included, over a period of 8 months.
   It is very difficult to predict these kinds of scenarios since so much depends on each person's intrinsic blood clotting or thinning potential along with food, spice and drink consumption, activity level, sleep, hormone status, other medications or supplements used, alcohol consumption, etc.

Do you have an opinion on taking vitamin K to reduce the chance of untoward effects from relatively high levels (e.g., 5,000IU or more) vitamin D supplementation? My integrative physician advocates this approach, as does the Life Extension Foundation, but I'm unclear on the quality of the evidence for this approach.
   I have not seen such studies and do not see the rational for it. I am not ready yet to recommend the widespread intake of vitamin D greater than 2 or 3 thousand units a day until long term studies are published.

Press release received in 2007
The Active Form of K2 With the Highest Bioavailability. Vitamk7, exclusively produced by Gnosis, is natural vitamin K2 as pure menaquinone 7 (MK7). Vitamk7 as MK7 is the MOST ACTIVE of K2 with THE HIGHEST BIOAVAILABILITY. Gnosis, an advanced biotechnology company, has conducted clinical studies for Vitamk7 demonstrating its unique properties. Vitamk7 has been shown to be involved in calcium uptake and bone mineralization through the gamma carboxylation pathway which reduces the incidence of arterial calcification. In addition, clinical human studies with vitamin K2 carried out by Prof Gian Paolo Littarru, Ph.D, (Institute of Biochemistry Polytechnic University of the Marche), president of the International Coenzyme Q10 Association, have shown it to reduce the incidence of coronary heart disease and promote cardiovascular health. Advantages of Vitamk7 include:
- Only active isomer MK7 contained
- Solvent free (no extraction process performed)
- Clinical trials performed in humans
- Pharmaceutical environment under cGMP manufacturing facility
For further information, visit the Vitamk7 web site or the Gnosis web site, About Gnosis. Headquartered in Desio, Italy, near Milan, Gnosis is a pro-active biotechnology-based company specializing in the manufacture and sale of raw materials and finished products produced through natural fermentation. With a solid commitment in biotechnological Research & Development, Gnosis is able to develop innovative active ingredients that can be made specific to the customer and market needs. Gnosis operates in two world-class facilities focused on R&D and manufacturing with a dedication in producing high-quality and proprietary products for its customers.

Press release March 2010
MenaQ7, the natural vitamin K2 for better heart and bone health. MenaQ7 from NattoPharma helps keep calcium in your bones and out of your arteries by activating relevant proteins in your body. NattoPharma and MenaQ7 have a strong position in the market and is by far the leading vitamin K2 brand, based on a superior quality product and numerous clinical studies. NattoPharma will through a series of newsletters communicate to you the benefits of this innovative product so that you will understand how this can fit into your portfolio. In this first issue we will provide you with an introduction to MenaQ7, the natural vitamin K2 (MK-7).