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Nutrition Reviews Mar 2022Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However,... (Review)
Review
Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4-MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.
Topics: Animals; Humans; Kinetics; Osteoporosis; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 34472618
DOI: 10.1093/nutrit/nuab061 -
BMC Pediatrics Sep 2021We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn... (Review)
Review
We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.
Topics: Administration, Oral; Humans; Infant; Infant, Newborn; Infant, Premature; Injections, Intramuscular; Systematic Reviews as Topic; Vitamin K; Vitamin K Deficiency Bleeding
PubMed: 34496783
DOI: 10.1186/s12887-021-02701-4 -
Nutrients Nov 2020Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it... (Review)
Review
Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.
Topics: Fractures, Bone; Humans; Osteoporosis; Pregnane X Receptor; Vitamin K; Vitamin K Deficiency
PubMed: 33255760
DOI: 10.3390/nu12123625 -
Circulation Oct 2022Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain... (Review)
Review
Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.
Topics: American Heart Association; Anticoagulants; Heart Ventricles; Humans; Platelet Aggregation Inhibitors; Thrombosis; Vitamin K; Warfarin
PubMed: 36106537
DOI: 10.1161/CIR.0000000000001092 -
International Journal of Molecular... Feb 2019Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures,... (Review)
Review
Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.
Topics: Animals; Biological Availability; Blood Coagulation; Dietary Supplements; Disease Susceptibility; Humans; Metabolic Networks and Pathways; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 30791399
DOI: 10.3390/ijms20040896 -
Nature Aug 2022Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation, has a key role in organ injury, degenerative disease and vulnerability of...
Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K-a group of naphthoquinones that includes menaquinone and phylloquinone-confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-4, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.
Topics: Antidotes; Antioxidants; Carbon-Carbon Ligases; Coenzymes; Ferroptosis; Hydroquinones; Lipid Peroxidation; Oxidation-Reduction; S100 Calcium-Binding Protein A4; Vitamin K; Warfarin
PubMed: 35922516
DOI: 10.1038/s41586-022-05022-3 -
Nutrients Mar 2020Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI)... (Review)
Review
Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7.
Topics: Biological Availability; Bone Density; Bone and Bones; Collagen; Dietary Supplements; Humans; Osteocalcin; Recommended Dietary Allowances; Vitamin K 1; Vitamin K 2
PubMed: 32244313
DOI: 10.3390/nu12040965 -
Journal of Perinatology : Official... May 2016We conducted a systematic review to evaluate the burden of late vitamin K deficiency bleeding (VKDB) and the effect of vitamin K prophylaxis on the incidence of VKDB. We... (Review)
Review
We conducted a systematic review to evaluate the burden of late vitamin K deficiency bleeding (VKDB) and the effect of vitamin K prophylaxis on the incidence of VKDB. We searched MEDLINE and other electronic databases, and included all observational studies including population surveys as well as randomized controlled trials (RCT). The median (interquartile range) burden of late VKDB was 35 (10.5 to 80) per 100 000 live births in infants who had not received prophylaxis at birth; the burden was much higher in low- and middle-income countries as compared with high-income countries-80 (72 to 80) vs 8.8 (5.8 to 17.8) per 100 000 live births. Two randomized trials evaluated the effect of intramuscular (IM) prophylaxis on the risk of classical VKDB. Although one trial reported a significant reduction in the incidence of any bleeding (relative risk (RR) 0.73, 95% confidence interval (CI) 0.56 to 0.96) and moderate to severe bleeding (RR 0.19, 0.08 to 0.46; number needed to treat (NNT) 74, 47 to 177), the other trial demonstrated a significant reduction in the risk of secondary bleeding after circumcision in male neonates (RR 0.18, CI 0.08 to 0.42; NNT 9, 6 to 15). No RCTs evaluated the effect of vitamin K prophylaxis on late VKDB. Data from four surveillance studies indicate that the use of IM/subcutaneous vitamin K prophylaxis could significantly reduce the risk of late VKDB when compared with no prophylaxis (pooled RR 0.02; 95% CI 0.00 to 0.10). When compared with IM prophylaxis, a single oral dose of vitamin K increased the risk of VKDB (RR 24.5; 95% CI 7.4 to 81.0) but multiple oral doses did not (RR 3.64; CI 0.82 to 16.3). There is low-quality evidence from observational studies that routine IM administration of 1 mg of vitamin K at birth reduces the incidence of late VKDB during infancy. Given the high risk of mortality and morbidity in infants with late VKDB, it seems appropriate to administer IM vitamin K prophylaxis to all neonates at birth. Future studies should compare the efficacy and safety of multiple oral doses with IM vitamin K and also evaluate the optimal dose of vitamin K in preterm neonates.
Topics: Antifibrinolytic Agents; Humans; Incidence; Infant; Infant, Newborn; Observational Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk; Vitamin K; Vitamin K Deficiency Bleeding
PubMed: 27109090
DOI: 10.1038/jp.2016.30 -
Nutrients Jun 2020Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily... (Review)
Review
Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily Intake (RDI) for vitamin K based on early research, and its necessary role in the activation of vitamin K-dependent coagulation proteins is known. In the past few decades, the role of vitamin K-dependent proteins in processes beyond coagulation has been discovered. Various isoforms of vitamin K have been identified, and vitamin K2 specifically has been highlighted for its long half-life and extrahepatic activity, whereas the dietary form vitamin K1 has a shorter half-life. In this review, we highlight the specific activity of vitamin K2 based upon proposed frameworks necessary for a bioactive substance to be recommended for an RDI. Vitamin K2 meets all these criteria and should be considered for a specific dietary recommendation intake.
Topics: Diet; Dietary Supplements; Humans; Recommended Dietary Allowances; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency
PubMed: 32575901
DOI: 10.3390/nu12061852 -
Cell Reports May 2023Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects...
Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Recent clinical studies implicate vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse β cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced β cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identify endoplasmic reticulum Gla protein (ERGP) as a γ-carboxylated ER-resident Ca-binding protein expressed in β cells. Mechanistically, γ-carboxylation of ERGP protects cells against Ca overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated Ca entry. These results reveal a critical role of vitamin K-dependent carboxylation in regulation of Ca flux in β cells and in their capacity to adapt to metabolic stress.
Topics: Mice; Animals; Humans; Vitamin K; Osteocalcin; Protein Processing, Post-Translational; Insulin; Stress, Physiological; Calcium
PubMed: 37171959
DOI: 10.1016/j.celrep.2023.112500