What makes vitamin k

Perhaps because of its limited ability to store vitamin K, the body recycles it through a process called the vitamin K-epoxide cycle Figure 2. The vitamin K cycle allows a small amount of vitamin K to be reused many times for protein carboxylation , thus decreasing the dietary requirement.

Briefly, vitamin K hydroquinone reduced form is oxidized to vitamin K epoxide oxidized form. The recycling of vitamin K epoxide oxidized form to hydroquinone reduced form is carried out by two reactions that reduce vitamin K epoxide KO to vitamin K quinone and then to vitamin K hydroquinone KH 2 ; Figure 2.

Additionally, the enzyme vitamin K oxidoreductase VKOR catalyzes the reduction of KO to vitamin K quinone and may be involved — as well as another yet-to-defined reductase — in the production of KH 2 from vitamin K quinone 6, 7. The anticoagulant drug warfarin acts as a vitamin K antagonist by inhibiting VKOR activity, hence preventing vitamin K recycling see Coagulation.

The term, coagulation cascade, refers to a series of events, each dependent on the other, that stop bleeding through clot formation. Protein Z appears to enhance the action of thrombin the activated form of prothrombin by promoting its association with phospholipids in cell membranes. Protein C and protein S are anticoagulant proteins that provide control and balance in the coagulation cascade; protein Z also has an anticoagulatory function.

Control mechanisms for the coagulation cascade exist since uncontrolled clotting may be as life threatening as uncontrolled bleeding. Vitamin K-dependent coagulation factors are synthesized in the liver. Consequently, severe liver disease results in lower blood levels of vitamin K-dependent clotting factors and an increased risk for uncontrolled bleeding hemorrhage 8. Some people are at increased risk of forming clots, which could block the flow of blood in arteries of the heart, brain, or lungs, resulting in myocardial infarction heart attack , stroke , or pulmonary embolism, respectively.

Abnormal clotting is not related to excessive vitamin K intake, and there is no known toxicity associated with vitamin K 1 or vitamin K 2 see Toxicity. Some oral anticoagulants , such as warfarin Coumadin, Jantoven , inhibit coagulation by antagonizing the action of vitamin K.

Warfarin prevents the recycling of vitamin K by blocking VKOR activity, thus creating a functional vitamin K deficiency see Figure 2 above. Large quantities of dietary or supplemental vitamin K can overcome the anticoagulant effect of vitamin K antagonists , thus patients taking these drugs are cautioned against consuming very large or highly variable quantities of vitamin K see Drug interactions.

Finally, because of the high variability in patients' response to vitamin K antagonists, it has been suggested that daily supplementation of low-dose phylloquinone may improve the stability of anticoagulation therapy. Yet, several meta-analyses recently highlighted the lack of sufficient evidence to support this option for those taking warfarin Osteocalcin also known as bone Gla protein is synthesized by osteoblasts bone-forming cells ; the synthesis of osteocalcin is regulated by the active form of vitamin D , 1,dihydroxyvitamin D calcitriol.

Although its function in bone mineralization is not fully understood, osteocalcin is required for the growth and maturation of calcium hydroxyapatite crystals see Osteoporosis Protein S appears to play a role in the breakdown of bone mediated by osteoclasts.

Individuals with inherited protein S deficiency suffer complications related to increased blood clotting, as well as osteonecrosis 14, Protein S can bind and activate receptors of the TAM family that are involved in phagocytosis.

Mutations in TAM receptors can result in visual impairment, defective spermatogenesis , autoimmune disorders , and platelet disorders MGP has been found in cartilage , bone, and soft tissue, including blood vessel walls, where it is synthesized and secreted by vascular smooth muscle cells. MGP has been involved in the prevention of calcification at various sites, including cartilage, vessel wall, skin elastic fibers, or trabecular meshwork in the human eye see Vascular calcification The vitamin K-dependent proteins, GRP and periostin, are also synthesized in bone tissue, but their roles in bone metabolism are still unclear 20, Expressed in normal human skin and vascular tissues, GRP has been colocalized with abnormal mineral deposits in the extracellular matrix in calcified arteries and calcified skin lesions Expressed in most connective tissues, including skin and bone, periostin was initially associated with cell adhesion and migration.

This VKDP also appears to promote angiogenesis formation of new blood vessels during cardiac valve degeneration and tumor growth 23, Growth arrest-specific gene 6 protein Gas6 is a vitamin K-dependent protein that was identified in It has been found throughout the nervous system, as well in the heart, lungs, stomach, kidneys, and cartilage.

Identified as a ligand of the TAM family of transmembrane tyrosine kinase receptors , Gas6 appears to be a cellular growth regulation factor with cell-signaling activities. Gas6 has been involved in diverse cellular functions, including phagocytosis , cell adhesion, cell proliferation , and protection against apoptosis 5.

It may also play important roles in the developing and aging nervous system reviewed in Further, Gas6 appears to regulate platelet signaling and vascular hemostasis Expressed in most tissues and involved in many cellular functions, Gas6 has also been linked to several pathological conditions, including clot formation thrombogenesis , atherosclerosis , chronic inflammation , and cancer growth Overt vitamin K deficiency results in impaired blood clotting, usually demonstrated by laboratory tests that measure clotting time.

Symptoms include easy bruising and bleeding that may be manifested as nosebleeds, bleeding gums, blood in the urine, blood in the stool, tarry black stools, or extremely heavy menstrual bleeding.

In infants, vitamin K deficiency may result in life-threatening bleeding within the skull intracranial hemorrhage 8. Vitamin K deficiency is uncommon in healthy adults for a number of reasons: 1 vitamin K is widespread in foods see Food sources ; 2 the vitamin K cycle conserves vitamin K see Vitamin K oxidation-reduction cycle ; and 3 bacteria that normally inhabit the large intestine synthesize menaquinones vitamin K 2 , although it is unclear whether significant amounts are absorbed and utilized see Food sources.

Adults at risk for vitamin K deficiency include those taking vitamin K antagonists and individuals with significant liver damage or disease 8. Additionally, individuals with fat malabsorption disorders , including inflammatory bowel disease and cystic fibrosis , may be at increased risk of vitamin K deficiency Newborn babies who are exclusively breast-fed are at increased risk for vitamin K deficiency, because human milk is relatively low in vitamin K compared to formula.

Newborn infants, in general, have low vitamin K status for the following reasons: 1 vitamin K transport across the placental barrier is limited; 2 liver storage of vitamin K is very low; 3 the vitamin K cycle may not be fully functional in newborns, especially premature infants; and 4 the vitamin K content of breast milk is low 5.

Infants whose mothers are on anticonvulsant medication to prevent seizures are also at risk for vitamin K deficiency. Vitamin K deficiency in newborns may result in a bleeding disorder called vitamin K deficiency bleeding VKDB of the newborn reviewed in Because VKDB is life threatening and easily prevented, the American Academy of Pediatrics and a number of similar international organizations recommend that an intramuscular dose of phylloquinone vitamin K 1 be administered to all newborns Vitamin K and childhood leukemia: In the early s, two retrospective studies were published suggesting a possible association between phylloquinone injections in newborns and the development of childhood leukemia and other forms of childhood cancer.

However, two large retrospective studies in the US and Sweden, which reviewed the medical records of 54, and 1. Moreover, a pooled analysis of six case-control studies , including 2, children diagnosed with childhood cancer and 6, cancer-free children, found no evidence that phylloquinone injections for newborns increased the risk of childhood leukemia In a policy statement, the American Academy of Pediatrics recommended that routine vitamin K prophylaxis for newborns be continued because VKDB is life threatening and the risks of cancer are unproven and unlikely In the last few years, physicians have reported a rise in late-onset cases of VKDB due to an increasing trend of parental omission or refusal of newborn vitamin K prophylaxis Lower doses of vitamin K 1 for premature infants: The results of two studies of vitamin K levels in premature infants suggest that the standard initial dose of phylloquinone vitamin K 1 for full-term infants 1.

These findings have led some experts to suggest the use of an initial phylloquinone dose of 0. The AI for infants was based on estimated intake of vitamin K from breast milk The discovery of vitamin K-dependent proteins in bone has led to research on the role of vitamin K in maintaining bone health.

Vitamin K 1 : Observational studies have found a relationship between phylloquinone vitamin K 1 and age-related bone loss osteoporosis. The Nurses' Health Study followed more than 72, women for 10 years. Osteoporotic fractures are often linked to a reduction in bone mineralization. Yet, the investigators found no association between dietary phylloquinone intake and bone mineral density BMD in the Framingham subjects Moreover, recent cross-sectional and case-control studies have reported associations between higher phylloquinone intakes and lower incidence of hip fracture 48, However, because green leafy vegetables are the primary dietary source of phylloquinone and because they are usually part of a balanced diet, high phylloquinone consumption may be just an indicator of healthy eating habits which may, rather than phylloquinone itself, account for all or part of the association reported in observational studies The few studies that measured plasma phylloquinone generally found that higher circulating levels were associated with lower fracture risk 17 , For example, the incidence of vertebral fractures was inversely correlated with lumbar BMD and plasma phylloquinone in a four-year prospective study that included Japanese women ages years Yet, observational studies are not designed to making causal inferences, and only randomized controlled trials can evaluate whether phylloquinone may have beneficial effects on bone health see Vitamin K supplementation studies and osteoporosis.

Vitamin K 2 : There are few studies on associations between menaquinones vitamin K 2 and bone health, perhaps because of the limited number of dietary sources of menaquinone-4 MK-4 , the main form of vitamin K 2 present in Western diets. The Japanese food natto, made of cooked soybeans fermented by bacillus subtilis natto, is rich in MK In a prospective study that followed Japanese women ages years , total hip BMD at baseline was positively associated with natto intake in postmenopausal women No association was found between natto intake and BMD in premenopausal women Yet, increasing natto consumption also maximizes the intake of other dietary compounds e.

To date, observational studies have failed to unequivocally support an association between circulating menaquinone MK-7 and MK-4 levels and fracture risk 17 , Total circulating levels of the bone protein , osteocalcin OC , have been shown to be sensitive markers of bone formation.

Several hormones and growth factors, including vitamin D but not vitamin K, regulate osteocalcin synthesis by osteoblasts. Undercarboxylation of osteocalcin in human bone and serum has been linked to poor vitamin K status. Circulating levels of undercarboxylated osteocalcin ucOC were found to be higher in postmenopausal women than premenopausal women and markedly higher in women over the age of Although supplementation with phylloquinone decreased ucOC levels in all five studies, only one study reported an effect of supplemental phylloquinone on BMD The rate of BMD loss at the femoral neck , but not at the lumbar spine , was significantly lower in subjects with supplemental phylloquinone compared to the other two groups.

Thus, evidence of a putative benefit of phylloquinone on bone health in older adults is considered weak. None of the studies were designed to assess the effect of phylloquinone on osteoporotic -related fractures.

Further investigation may seek to evaluate whether phylloquinone supplementation could improve skeletal health in subjects at high-risk for vitamin K inadequacy e. Vitamin K 2 supplementation: Pharmacological doses of menaquinone-4 MK-4; brand name, menatetrenone are currently used in Japan in the treatment of osteoporosis.

Accordingly, most intervention trials investigating the effect of high-dose MK-4 on bone loss have been conducted in Japanese postmenopausal women. A meta-analysis of seven randomized controlled trials associated MK-4 supplementation with increased BMD and reduced fracture incidence However, the results of this meta-analysis were later downplayed because of the small size of the included studies and the fact that some of them were not placebo -controlled but instead used a concurrent or open-label treatment e.

Additionally, the analysis did not include data from an unpublished study with a larger sample size that reported no MK-4 effect on fracture risk and would have altered the conclusion of the meta-analysis At the end of an additional follow-up year four years total , there were no differences between groups regarding the incidence of vertebral fractures, and only a small reduction in the incidence of new clinical fractures was seen in those taking the combined treatment compared to calcium alone 4.

Equivocal results have been reported in additional trials conducted in Europe and the US. Of note, this MK-4 dose used in most of the cited studies is about times higher than the AI for vitamin K. In this study, all the subjects also received daily, open-label calcium mg and vitamin D 3 IU. At present, the potential role for supplemental menaquinones on bone health still needs to be established in large, randomized, and well-controlled trials.

Certain oral anticoagulants , such as warfarin, are known to be antagonists of vitamin K see Coagulation. Few studies have examined chronic use of warfarin and risk of fracture in older women. One study reported no association between long-term warfarin treatment and fracture risk 69 , while another one found a significantly higher risk of rib and vertebral fractures in warfarin users compared to nonusers Additionally, a study in elderly patients with atrial fibrillation reported that long-term warfarin treatment was associated with a significantly higher risk of osteoporotic fracture in men but not in women A meta-analysis of the results of 11 published studies found that oral anticoagulation therapy was associated with a very modest reduction in BMD at the wrist and no change in BMD at the hip or spine The development of new anticoagulants that do not block vitamin K recycling may offer a safer alternative to the use of vitamin K antagonists Adequate vs.

However, higher vitamin K intakes were not associated with lower CVD mortality in a prospective study that followed 7, older adults at risk for developing CVD This study associated higher phylloquinone intakes, but not menaquinones, with lower risk of all-cause mortality. In another recent prospective study, which followed 35, healthy Dutch men and women for a mean period of Earlier observational studies offer limited support to an inverse relationship between phylloquinone intake and risk of CVD, despite high intakes being sometimes regarded as a marker of healthy dietary habits associated with low cardiovascular risk reviewed in A prospective cohort of 16, Dutch women ages years followed for a mean period of 8.

In addition, menaquinone intake was found to be inversely associated with aortic calcification , a major risk factor for CVD One of the hallmarks of cardiovascular disease is the presence of atherosclerotic plaques in arterial walls.

Plaque rupture that causes blood clot formation thrombogenesis is the usual cause of a myocardial infarction heart attack or stroke. While calcification of the plaques occurs as the atherosclerosis progresses, it is unclear whether calcification increases plaque instability and could predict risk of rupture and thrombogenesis However, calcification may be predictive of future cardiovascular events.

A meta-analysis of 30 prospective cohort studies , including a total of , participants, found that the presence of vascular calcification was associated with an overall three- to four-fold increased risk of cardiovascular events and mortality An early population-based study of postmenopausal women ages, years observed that the younger women years with aortic calcifications had lower vitamin K intakes than those without aortic calcifications, but this was not true for older women years A prospective cohort study in men and women, years of age, did not find any correlation between dietary phylloquinone intake and coronary artery calcification, as measured non invasively by computed tomography Additionally, neither phylloquinone nor menaquinone intakes were associated with calcification of breast arteries in a cross-sectional study of 1, women ages years However, in another cross-sectional study, the upper vs.

Recent research has uncovered possible mechanisms by which vitamin K may inhibit mineralization calcification of vessels while promoting bone mineralization. The potential mechanisms, although not yet fully understood, implicate vitamin K-dependent proteins , including matrix Gla protein MGP and the newly described Gla-rich protein GRP. Secreted by various cell types, such as vascular smooth muscle cells VSMCs in arterial vessel walls, MGP appears to be important for the prevention of calcification of soft tissues, including cartilage , vasculature, skin, and trabecular meshwork cells in the eye 17 , In MGP knockout mice, conversion of VSMCs into bone-like cells and extensive vessel calcification results in large vessel rupture and premature death.

In humans, defective MGP gene has been linked to Keutel syndrome, a rare inherited condition characterized in particular by abnormal cartilage calcification and pulmonary artery stenosis narrowing.

Calcification prevention by MGP involved several mechanisms, including the binding to calcium crystals and the inhibition of proteins bone morphogenic proteins; BMPs known to promote ectopic bone formation reviewed in Calcium-binding activity of MGP is regulated by two types of modifications known as post-translational modifications since they take place after protein synthesis : the vitamin K-dependent carboxylation of up to five Glu residues and the phosphorylation of serine residues.

The AI amount is estimated to ensure nutritional adequacy. For adults 19 years and older, the AI for vitamin K is micrograms mcg daily for men and 90 mcg for women and for those who are pregnant or lactating. Vitamin K helps to make four of the 13 proteins needed for blood clotting, which stops wounds from continuously bleeding so they can heal. People who are prescribed anticoagulants also called blood thinners to prevent blood clots from forming in the heart, lung, or legs are often informed about vitamin K.

Because of its blood clotting action, vitamin K has the potential to counteract the effects of blood thinning medications. A common method that estimates blood levels of vitamin K is measuring prothrombin time PT , or how long it takes for blood to clot. People on anticoagulant medication such as warfarin Coumadin may be advised to eat a consistent amount of vitamin K from food and supplements.

Vitamin K is not a required listed nutrient on the Nutrition Facts label, but people taking anticoagulant medication are usually provided information about foods containing vitamin K from their health care provider. Vitamin K is involved with the production of proteins in bone, including osteocalcin, which is needed to prevent the weakening of bones. Some studies have shown that higher vitamin K intakes are associated with a lower incidence of hip fractures and low bone density.

In addition, low blood levels of vitamin K have been linked with low bone density. Data from the Framingham Heart Study also showed an association between high vitamin K intake and reduced risk of hip fracture in men and women and increased bone mineral density in women. A few studies have researched the role of vitamin K for heart health.

Vitamin K is involved with the production of matrix Gla proteins MGP , which help to prevent calcification or hardening of heart arteries, a contributor to heart disease. Because research in this area is very limited, additional studies are needed before a specific amount of vitamin K beyond the standard recommendation is proposed for this condition. Vitamin K deficiency in adults is rare, but may occur in people taking medications that block vitamin K metabolism such as antibiotics, or in those with conditions that cause malabsorption of food and nutrients.

A doctor or dietitian can help people make sure they are getting the right amount. Fat-soluable vitamins: A, D, E, and K. Colorado State University website. Accessed August 26, Vitamin K. The Linus Pauling Institute website. Exceptional Nurses Winchester Hospital was the first community hospital in the state to achieve Magnet designation, recognition for nursing excellence. Supporting Our Community Our tremendous staff gives back to our community by coordinating free health screenings, educational programs, and food drives.

What Our Patients are Saying A leading indicator of our success is the feedback we get from our patients. Home Health Library. Vitamin K Vitamin K is a fat-soluble vitamin. Symptoms of vitamin K deficiency are: Easy bruising and bleeding— nosebleeds , bleeding gums, blood in the urine, blood in the stool, or heavy menstrual bleeding Bleeding in the skull in infants Vitamin K Safety Vitamin K is stored in the body in small amounts.

To be safe, a person should follow the intake guidelines based on age and gender The medicines a person takes and the health problems they have may also play a role in how much vitamin K the body needs.

Add a little balsamic vinegar and pepper, and scoop out for a snack. Or, mash the avocado and mix with chopped tomatoes and red onions for a refreshing salsa. Pack a kiwi and spoon for an afternoon snack. The insides of the kiwi can be scooped out and eaten from this natural and easy container. Steam one-half cup broccoli or Brussels sprouts, add lemon juice 1 tbsp , pre-chopped garlic 1 tsp , and Dijon mustard 1 tbsp.

Or add broccoli to lasagna or hot dish. Mix 2 ounce packages of frozen chopped spinach, thawed, well drained, one 8-ounce package of softened low-fat cream cheese, one-fourth cup milk, and 1 tsp lemon pepper until well blended. Spoon into a 1-quart casserole dish and sprinkle with one-third cup crushed crackers or seasoned croutons.

Cancer Care. Emergency Services. Cesarean Birth.