Vitamin K and magnesium, which also helps promote calcium deposition in bone, might also be found in the same supplement. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis (ie, porous bones), particularly in older adults and postmenopausal women. The EFSA Journal 2009;7:1228. Vitamin K actually has a protective effect on . Participants in this study who had dietary menaquinone intakes in the mid tertile (21.632.7 mcg/day) and upper tertile (>32.7 mcg/day) also had a 27% and 57% lower risk of coronary heart disease mortality, respectively, than those in the lower tertile of intake (<21.6 mcg/day). Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly. Again, though, more research is needed on the relationship between vitamin K and heart health. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular . Menaquinone intake was also inversely associated with severe aortic calcification in a prospective, population-based cohort study involving 4,807 men and women aged 55 years and older from the Netherlands [41]. Menaquinones have unsaturated isoprenyl side chains and are designated as MK-4 through MK-13, based on the length of their side chain [1,2]. All rights reserved. Osteoblasts produce osteocalcin, which helps take calcium from the blood circulation and bind it to the bone matrix. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. The researchers found that men, but not women, taking more than 1000 mg/day of calcium supplements had a risk of total cardiovascular death that was 20% higher than that of participants taking no calcium supplements. Elenius V et al. Biomarkers of Ossification of the Spinal Ligament. K2 is more potent and has the widest range of activity. (More information) With limited vitamin K storage capacity, the body recycles vitamin K in the vitamin K oxidation - reduction cycle in order to reuse it multiple times. Consuming vegetables at the same time as some fat improves phylloquinone absorption from the vegetables, but the amount absorbed is still lower than that from oils. The newly made osteocalcin, however, is inactive, and it needs vitamin K2 to become fully activated and bind calcium.15, That requirement alone makes vitamin K2 a major player in bone health, but its importance does not stop there. Osteoporosis, a disorder characterized by porous and fragile bones, is a serious public health problem that affects more than 10 million U.S. adults, 80% of whom are women. Drug-Nutrient Interaction Task Force, Clinical Center, National Institutes of Health. and transmitted securely. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Effects of vitamin K on calcium and bone metabolism The K vitamins, a group of napthoquinones, are required for the carboxylation of a limited number of proteins including the bone matrix protein osteocalcin. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular . [, Heber D, Greenway FL, Kaplan LM, Livingston E, Salvador J, Still C, et al. We encourage you to talk to your health care providers (doctor, registered dietitian, pharmacist, etc.) Produced by plants and algae, K1 is found in green leafy vegetables such as broccoli, kale and Swiss chard, and in plant oils, such as canola and soybean oil. People taking warfarin and similar anticoagulants need to maintain a consistent intake of vitamin K from food and supplements because sudden changes in vitamin K intakes can increase or decrease the anticoagulant effect [45]. As long as the bone-forming activity (ie, absorption) is greater than the breakdown of bone (ie, resorption), the process of maintaining a healthy bone structure is maintained. This effect might be more pronounced with cephalosporin antibiotics, such as cefoperazone (Cefobid), because these antibiotics might also inhibit the action of vitamin K in the body [6,46]. Careers. Finally, food composition databases provide information primarily on phylloquinone; menaquinoneseither dietary or from bacterial production in the gutlikely also contribute to vitamin K status [1,6,7]. Food sources of phylloquinone include vegetables, especially green leafy vegetables, vegetable oils, and some fruits. National Library of Medicine (Iwamoto J, Takeda T, et al. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. (Berkner KL, Rune KW, J Thromb Haemost 2004; Cranenburg EC, Schurgers LJ et al. Most of the trials were conducted in Japan and involved postmenopausal women; trial duration ranged from 6 to 36 months. Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Vitamin K contents of meat, dairy, and fast food in the U.S. Vitamin K deficiency can occur during the first few weeks of infancy due to low placental transfer of phylloquinone, low clotting factor levels, and low vitamin K content of breast milk [7]. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis. [, Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Several food sources of vitamin K are listed in Table 2. Dietary calcium is linked to many benefits, particularly bone health. Blogs are not reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other reason except for compliance with our Terms and Conditions. Just as lethal is arteriosclerosis, hardening of the arteries due to calcium deposits in their muscular midsection. American Society of Echocardiography. VKDB, especially late VKDB, can also be manifested as sudden intracranial bleeding, which has a high mortality rate [7,25]. Evid Rep Technol Assess (Full Rep). This section focuses on two conditions in which vitamin K might play a role: osteoporosis and coronary heart disease. 5 Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, et al. Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly. This is a fact sheet intended for health professionals. J Clin Endocrinol Metab 2008;93:1217-23. The effect of vitamin K intakes and status on bone health and osteoporosis has been a focus of scientific research. Studies have shown that a vitamin D deficiency during puberty can lead to an increased risk of heavy menstrual bleeding. New research reveals that vitamin K controls calcium, keeping it in your bones and out of your blood vessels. (Plaza S, Lamson D. K2 works synergistically with bisphosphonate drugs, such as Fosamax, which lessen bone loss by poisoning osteoclasts (the cells that break down old bone). Furie B, Furie BC. Would you like email updates of new search results? Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. Almost all menaquinones, in particular the long-chain menaquinones, are also produced by bacteria in the human gut [5,6]. History of changes to this fact sheet, U.S. Department of Health & Human Services, Division of Program Coordination, Planning, and Strategic Initiatives, Strengthening Knowledge and Understanding of Dietary Supplements, My Dietary Supplement and Medicine Record, Analytical Methods and Reference Materials (AMRM), NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program, Computer Access to Research on Dietary Supplements (CARDS) Database, Dietary Supplement Ingredient Database (DSID), ODS Participation in NIH Funding Initiatives, Administrative Supplements for Research on Dietary Supplements, Administrative Supplements for Validation Studies of Analytical Methods, Frequently Asked Questions About ODS Grants & Co-funding, Resources for Investigators Submitting Natural Products Research Grant Applications, Staff Bios, Publications, and Presentations, Federal Working Group on Dietary Supplements, NIH Dietary Supplement Research Coordinating Committee. Fujita Y, Iki M, Tamaki J, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Tomioka K, Okamoto N, Kurumatani N. Osteoporos Int. Staying Healthy Calcium, Nutrition, and Bone Health The health and strength of our bones rely on a balanced diet and a steady stream of nutrients most importantly, calcium and Vitamin D. Calcium is a mineral that people need to build and maintain strong bones and teeth. J. Clin. The DV for vitamin K is 120 mcg for adults and children age 4 years and older [17]. Does calcium supplementation increase cardiovascular risk? The molecular basis of blood coagulation. Wang L, Manson JE, Sesso HD. Major GC, Alarie F, Dor J, Phouttama S, Tremblay A. Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. The relationship between serum vitamin K concentration and coronary artery calcification in middle-aged and elderly people. Vitamin K deficiency is only considered clinically relevant when prothrombin time increases significantly due to a decrease in the prothrombin activity of blood [3,7]. . Bookshelf Studies of healthy adults have found high levels of uncarboxylated osteocalcin and matrix Gla-protein (MGP) in all subjects tested. Disclaimer. (Witteman JC, Kannel WB et al. Encyclopedia of Dietary Supplements. Summary Naturally occurring forms of vitamin K include phylloquinone (vitamin K 1) and a family of molecules called menaquinones (MKs or vitamin K 2 ). Some of these opinions may contain information about treatments or uses of drug products that have not been approved by the U.S. Food and Drug Administration. Before (Uotila L, Scand J Clin Lab Invest Suppl 1990; Schurgers LJ, Aebert H, et al. Manoury E, Jourdon K, Boyaval P, Fourcassi P. Quantitative measurement of vitamin K2 (menaquinones) in various fermented dairy products using a reliable high-performance liquid chromatography method. Calcium serves as the key structural component of the bones, and . 2001 Oct;17(10):880-7. doi: 10.1016/s0899-9007(01)00709-2. So if you're curious about the relationship between vitamin K2 and calcium, keep reading. In addition, certain medications can have an adverse effect on vitamin K levels. Clipboard, Search History, and several other advanced features are temporarily unavailable. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. There are several vitamin K-dependent proteins involved in coagulation, bone development, and cardiovascular health. If you think you may have a medical emergency, call your doctor or dial 911 immediately. The purpose of this review is to summarize available evidence of t Both of these effects increase the risk of heart disease.4,8,29,30, Eighty-four years ago, while investigating the effects of a low-fat diet fed to chickens, Danish scientist Henrik Dam discovered vitamin K. He found that the bleeding tendencies found in the chickens on that diet could be prevented when a diet with normal levels of fat was restored and vitamin K was added to their diets. The initial discovery was reported in a. Osteoporos Int 2013;24:2499-507. Calcif Tissue Int 2012;90:396-403. Vitamin K transport across the placenta is poor, increasing the risk of vitamin K deficiency in newborn babies [3]. Ikeda Y, Iki M, Morita A, et al. Vitamin K status can also be low in patients who have undergone bariatric surgery, although clinical signs may not be present [26]. You may have thought vitamin K was all about blood clotting the necessary kind that prevents you from bleeding to death when you get cut or injured but this nutrient plays other roles just as essential to your health. Calcium serves many important roles in the human body, including (1) providing structure and hardness to bones and teeth, (2) allowing muscles to contract and nerves to send signals, (3) making blood vessels expand and contract, (4) helping blood to clot, and (5) supporting protein function and hormone regulation.17 Even though dairy products represent a rich source of calcium, approximately 43% of the US population and 70% of older women regularly take calcium supplements.18 Calcium supplementation is supported by several studies that back its benefits for bone health and osteoporosis prevention as well as for overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice. Inadequate calcium intake can lead to decreased bone mineral density, which can increase the risk of bone fractures. Schlieper G, Westenfeld R, Krger T, et al. The site is secure. Vitamin K is required for the activity of coagulation and anticoagulation factors36 and for the binding of osteocalcin to hydroxyapatite in bone37; it is generally considered to be required for the function of MGP.38, Vitamin K is not a single entity but, rather, a family of structurally related molecules derived from different sources. Seven of the 13 trials also had fracture data that were combined in a meta-analysis. Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. A study published in 1984 found that patients who suffered fractures caused by osteoporosis had vitamin K levels 70% lower than age-matched controls. Theuwissen E, Magdeleyns EJ, Braam LA, et al. 2008;158:385-95. Jamal SA, Vandermeer B, Raggi P, et al. Foods, fortificants, and supplements: Where do Americans get their nutrients? Several forms of vitamin K are used in dietary supplements, including vitamin K1 as phylloquinone or phytonadione (a synthetic form of vitamin K1) and vitamin K2 as MK-4 or MK-7 [18]. Natural Medicines Comprehensive Database. Bile acid sequestrants, such as cholestyramine (Questran) and colestipol (Colestid), are used to reduce cholesterol levels by preventing reabsorption of bile acids. Further, due to modern manufacturing processes, the vitamin K content, particularly the vitamin K2 content, of the food supply today has significantly dropped, making vitamin K2 supplements a more reliable way to secure adequate intake.12 By striking the right balance in intake of calcium and K2, it may be possible to fight osteoporosis and simultaneously prevent the calcification and stiffening of the arteries. However, in subgroup analyses, calcium had no effect on femoral neck BMD. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. Federal government websites often end in .gov or .mil. [. The vitamin Kdependent protein, matrix GLA protein (MGP), is a central calcification inhibitor produced by the cells of vascular smooth muscles and regulates the potentially fatal accumulation of calcium.16. [, American Academy of Pediatrics Committee on F, Newborn. Pharmacotherapy 2002;22:814-22. Unauthorized use of these marks is strictly prohibited. Other fermented foods, such as cheese, also contain menaquinones. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. Controversies concerning vitamin K and the newborn. Vitamin K, does help the body make blood clotting proteins. 2023 Mar 7;15(6):1302. doi: 10.3390/nu15061302. In healthy people, fasting concentrations of phylloquinone in plasma have been reported to range from 0.29 to 2.64 nmol/L [12]. Conly JM, Stein K, Worobetz L, Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am J Gastroenterol 1994;89:915-23. The https:// ensures that you are connecting to the Pediatrics 2003;112:191-2. Schurgers LJ, Geleijnse JM, Grobbee DE, et al. The FNB did not establish ULs for vitamin K because of its low potential for toxicity [3]. Westenfeld R, Krueger T, Schlieper G, et al. Pilkey RM, Morton AR, Boffa MB, et al. The https:// ensures that you are connecting to the Kidney Int2013;83:782-4. All of these trials used MK-4 at either 15 mg/day (1 trial) or 45 mg/day (6 trials). Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). The Ann Pharmacother 2003;37:510-2. Important: The opinions expressed in WebMD Blogs are solely those of the User, who may or may not have medical or scientific training. There was no significant difference in coronary artery calcification between the treatment and control groups. Am J Cardiol 1990; Pohle K, Ropers D, et al. Cranenburg EC, Schurgers LJ, Uiterwijk HH, et al. Other supplements like vitamin K2 (VitK2) and magnesium (Mg) could contribute to the maintenance of skeletal health. Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products. and transmitted securely. These compounds include phylloquinone (vitamin K1) and a series of menaquinones (vitamin K2) [ 2 ]. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Table 1 lists the current AIs for vitamin K in micrograms (mcg). London and New York: Informa Healthcare; 2010:851-60. This combination of findings lends plausibility to the idea that supplementation can increases vascular risk.28 In other words, increased levels of blood calcium have been correlated with elevated blood clotting and calcium deposition in blood vessels, which leads to arterial hardening. Bethesda, MD 20894, Web Policies Vitamin K can have a serious and potentially dangerous interaction with anticoagulants such as warfarin (Coumadin), as well as phenprocoumon, acenocoumarol, and tioclomarol, which are commonly used in some European countries [7,8]. Present Knowledge in Nutrition. the contents by NLM or the National Institutes of Health. From that point forward, vitamin K became known as the coagulation vitamin, the K coming from the German word koagulation.31, Later, it was found that the fat-soluble compound needed for blood clotting existed in 2 forms: phylloquinone (vitamin K1) and menaquinone (vitamin K2).32 Vitamin K1 is made in plants and algae; green leafy vegetables are a particularly rich source. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Bruno RM, Bianchini E, Faita F, Taddei S, Ghiadoni L. Intima media thickness, pulse wave velocity, and flow mediated dilation. Nutrition Bulletin. PMC European Food Safety Authority. Blood 2007;109:3279-83. Calcium and vitamin D are two important micronutrients that work together in the body to support overall health. Although vitamin K1 can activate MGP, it is much less efficient because it is transported to the liver first to activate coagulation proteins.35 To render the proteins regulating calcium active, a sufficient amount of vitamin K2 has to be present in the body.58. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Federal government websites often end in .gov or .mil. In patients with kidney failure, supplemental calcium has also been linked to increased hardening of the arteries through calcification as well as to higher mortality.25,26 A meta-analysis combining and analyzing the results from different randomized, controlled trials of kidney disease also linked calcium supplementation with a 22% increase in the risk of death from cardiovascular issues.27, A possible explanation for the negative effects of high-dose (1000 mcg daily), long-term intake of calcium on cardiovascular health is that it renders the normal homeostatic control of calcium concentrations in the blood ineffective.6 Substantial epidemiological evidence has shown that levels of serum calcium in the upper part of the normal range are a risk factor for vascular disease and that calcium supplements acutely elevate serum calcium. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. Prothrombin is a vitamin K dependent protein vital for blood coagulation. Karpiski M, Popko J, Maresz K, Badmaev V, Stohs SJ. See this image and copyright information in PMC. J Am Coll Nutr 2014;33:94-102. [. Epub 2017 Feb 4. Gijsbers BL, Jie KS, Vermeer C. Effect of food composition on vitamin K absorption in human volunteers. Maresz K. (2015). These vitamin K-dependent proteins are needed for extrahepatic organs such as the bone and the vascular system. [, Gundberg CM, Lian JB, Booth SL. [, McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. and transmitted securely. Thromb Haemost 2007). government site. have found that vitamin K supplementation has no effect on bone mineral density in elderly men or women [37,38]. Association between vitamin K intake from fermented soybeans, natto, and bone mineral density in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study. The FDA has not authorized a health claim for vitamin K in the United States. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. doi: 10.1038/ejcn.2009.83. Estimation of total usual calcium and vitamin D intakes in the United States. (Geleijnse JM, Vermeer C, et al. Calciums ability to lower blood pressure19 and lower levels of blood cholesterol2022 contributes to heart health. Although the amount of vitamin K that the body obtains in this manner is unclear, experts believe that these menaquinones satisfy at least some of the body's requirement for vitamin K [6,7]. Vitamin K functions as a coenzyme for vitamin K-dependent carboxylase, an enzyme required for the synthesis of proteins involved in hemostasis (blood clotting) and bone metabolism, and other diverse physiological functions [3,5]. Theuwissen E, Smit E, Vermeer C. The role of vitamin K in soft-tissue calcification. Cranenburg EC, Vermeer C, Koos R, et al. Edwards SL. Warfarin (Coumadin) and some anticoagulants used primarily in Europe antagonize the activity of vitamin K and, in turn, prothrombin [8]. A review study of randomized controlled human trials of at least 6 months duration that assessed the use of vitamin K1 or K2 to lower fracture risk identified 13 trials. Am J Clin Nutr 2000;71:1201-8. and K2 (dairy, fermented foods) have some antioxidant properties, but clinical trials have not shown any evidence that vitamin K supplements can slow calcium deposits in artery walls. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. In nature, vitamin K is found in primarily in two forms K1 (phylloquinone) and K2 (menaquinone). The authors noted the importance of considering the effect of vitamin D on bone health when comparing the results of vitamin K supplementation studies, especially if both vitamin K and vitamin D (and/or calcium) are administered to the treatment group but not the placebo group [38]. Natto (fermented soybeans) is the richest dietary source of vitamin K2. Based on phylloquinone measurements, the body retains only about 30% to 40% of an oral physiological dose, while about 20% is excreted in the urine and 40% to 50% in the feces via bile [2,11]. Coronary calcium as a predictor of coronary events in four racial or ethnic groups . Both K1 (green leafy veg.) Institute of Medicine. Matrix Gla-protein, a vitamin K-dependent protein present in vascular smooth muscle, bone, and cartilage, is the focus of considerable scientific research because it might help reduce abnormal calcification [9]. March 29, 2021 American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Menadione, which is sometimes called "vitamin K3," is another synthetic form of vitamin K. It was shown to damage hepatic cells in laboratory studies conducted during the 1980s and 1990s, so it is no longer used in dietary supplements or fortified foods [3]. In Framingham study research, aortic calcification was associated with double the risk of death from cardiovascular disease in men and women younger than 65, even after other risk factors (e.g., cholesterol) were taken into account. 2014. J Bone Miner Res 2009;24:983-91. Other problems from calcium and vitamin D deficiencies include: Modern Nutrition in Health and Disease. However, it is not clear whether this measure can be used to quantitatively assess vitamin K status. Epub 2013 Oct 3. Important information to know when you are taking: warfarin (Coumadin) and vitamin K. Chicken, breast, rotisserie, 3 ounces (as MK-4), Chicken liver, braised, 3 ounces (as MK-4), Ham, roasted or pan-broiled, 3 ounces (as MK-4), Salmon, sockeye, cooked, 3 ounces (as MK-4). [, Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K interacts with a few medications. European Journal of Clinical Nutrition. At the end of the study, participants receiving either phylloquinone or MK-4 had significantly lower levels of undercarboxylated osteocalcin compared to those receiving placebo. Natto (a traditional Japanese food made from fermented soybeans) has high amounts of menaquinones [1,13].
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