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Nutrients Oct 2022Vitamin K is the common name for a group of compounds recognized as essential for blood clotting. The group comprises phylloquinone (K1)-a... (Review)
Review
Vitamin K is the common name for a group of compounds recognized as essential for blood clotting. The group comprises phylloquinone (K1)-a 2-methyl-3-phytyl-1,4-naphthoquinone; menaquinone (K2, MK)-a group of compounds with an unsaturated side chain in position 3 of a different number of isoprene units and a 1,4-naphthoquinone group and menadione (K3, MD)-a group of synthetic, water-soluble compounds 2-methyl-1,4-naphthoquinone. However, recent epidemiological studies suggest that vitamin K has various benefits that go beyond blood coagulation processes. A dietary intake of K1 is inversely associated with the risk of pancreatic cancer, K2 has the potential to induce a differentiation in leukemia cells or apoptosis of various types of cancer cells, and K3 has a documented anti-cancer effect. A healthy diet rich in fruit and vegetables ensures an optimal supply of K1 and K2, though consumers often prefer supplements. Interestingly, the synthetic form of vitamin K-menadione-appears in the cell during the metabolism of phylloquinone and is a precursor of MK-4, a form of vitamin K2 inaccessible in food. With this in mind, the purpose of this review is to emphasize the importance of vitamin K as a micronutrient, which not only has a beneficial effect on blood clotting and the skeleton, but also reduces the risk of cancer and other pro-inflammatory diseases. A proper diet should be a basic and common preventive procedure, resulting in a healthier society and reduced burden on healthcare systems.
Topics: Humans; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; DNA Damage; Micronutrients; Water
PubMed: 36296903
DOI: 10.3390/nu14204219 -
Hematology. American Society of... Dec 2016Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific... (Review)
Review
Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific interaction with the vitamin K cycle, and hence interference with hepatic synthesis of vitamin K-dependent coagulation factors. Monitoring the anticoagulant effect of VKAs by assessing the patient's international normalized ratio (INR) is essential because complications are closely related to the intensity of anticoagulation. Treatment with VKAs contains a substantial risk of bleeding with a high case fatality rate. Reversal of VKAs is required in case of bleeding or a supratherapeutic INR, but also prior to high-risk surgery or interventions. Choice of methods to reverse VKAs depends on whether or not the patient is bleeding or is in need of an urgent procedure, and has to be based on the pharmacokinetic and pharmacodynamic properties of the VKA. Reversal strategies include withholding the VKA, administration of vitamin K, and substitution of vitamin K-dependent procoagulant factors, and need to be combined with measures according to general bleeding management.
Topics: Anticoagulants; Blood Coagulation Factors; Hemorrhage; Humans; International Normalized Ratio; Vitamin K
PubMed: 27913535
DOI: 10.1182/asheducation-2016.1.605 -
Nephrology, Dialysis, Transplantation :... Sep 2023Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis.
METHODS
In a multicentre, double-blind, placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultradistal and total), femoral neck, lumbar spine (L1-L4) and whole body was assessed by dual-energy X-ray absorptiometry. Serum levels of vitamin K1 and MK-7 and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein and protein induced by vitamin K absence II were measured to assess vitamin K status.
RESULTS
After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation {mean difference of changes relative to placebo -0.023 g/cm2 [95% confidence interval (CI) -0.039 to -0.008]}, whereas the decrease in lumbar spine BMD seen in the placebo group was prevented [mean difference of changes between groups 0.050 g/cm2 (95% CI 0.015-0.085)]. No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7-supplemented participants.
CONCLUSION
Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis.
Topics: Humans; Bone Density; Vitamin K; Renal Dialysis; Absorptiometry, Photon; Vitamin K 2; Dietary Supplements; Double-Blind Method
PubMed: 36460034
DOI: 10.1093/ndt/gfac315 -
International Journal of Molecular... May 2022Vitamin K-dependent (VKD) proteins undergo an unusual post-translational modification, which is the conversion of specific Glu residues to carboxylated Glu (Gla). Gla... (Review)
Review
Vitamin K-dependent (VKD) proteins undergo an unusual post-translational modification, which is the conversion of specific Glu residues to carboxylated Glu (Gla). Gla generation is required for the activation of VKD proteins, and occurs in the endoplasmic reticulum during their secretion to either the cell surface or from the cell. The gamma-glutamyl carboxylase produces Gla using reduced vitamin K, which becomes oxygenated to vitamin K epoxide. Reduced vitamin K is then regenerated by a vitamin K oxidoreductase (VKORC1), and this interconversion of oxygenated and reduced vitamin K is referred to as the vitamin K cycle. Many of the VKD proteins support hemostasis, which is suppressed during therapy with warfarin that inhibits VKORC1 activity. VKD proteins also impact a broad range of physiologies beyond hemostasis, which includes regulation of calcification, apoptosis, complement, growth control, signal transduction and angiogenesis. The review covers the roles of VKD proteins, how they become activated, and how disruption of carboxylation can lead to disease. VKD proteins contain clusters of Gla residues that form a calcium-binding module important for activity, and carboxylase processivity allows the generation of multiple Glas. The review discusses how impaired carboxylase processivity results in the pseudoxanthoma elasticum-like disease.
Topics: Protein Processing, Post-Translational; Proteins; Vitamin K; Warfarin
PubMed: 35628569
DOI: 10.3390/ijms23105759 -
Clinical Cardiology Apr 1990Warfarin and other 4-hydroxycoumarins are effective antithrombotic agents. They affect four blood coagulation proteins that act sequentially to produce thrombin.... (Review)
Review
Warfarin and other 4-hydroxycoumarins are effective antithrombotic agents. They affect four blood coagulation proteins that act sequentially to produce thrombin. Coumarin therapy decreases the biological activity of these proteins, and therefore decreases the rate at which blood clots. As the mechanism by which these drugs act has become clear, it has also been found that vitamin K will overcome the effects of coumarin anticoagulation and can be used to control bleeding side effects of coumarin therapy. Vitamin K is necessary for activity of a liver enzyme, the vitamin K-dependent carboxylase. A second enzyme that recycles an inactive to an active form of the vitamin is inhibited by coumarins. The ability of other liver enzymes to bypass the coumarin-sensitive step greatly enhances the safety of 4-hydroxycoumarins.
Topics: Humans; Vitamin K; Warfarin
PubMed: 2191810
DOI: No ID Found -
Molecules (Basel, Switzerland) Aug 2018Current study reveals the likelihood to use pathogen and toxin mutually as an effective and eco-friendly strategy for (McGregor) management, which could reduce toxicant...
Current study reveals the likelihood to use pathogen and toxin mutually as an effective and eco-friendly strategy for (McGregor) management, which could reduce toxicant dose and host killing time. Therefore, phytol and in different proportions were evaluated to determine their effectiveness. Prior to ascertaining host mortality and defense mechanisms, we have recorded in vitro action of phytol using different concentrations (0.70, 1.40, 2.10, 2.80, and 3.50 mg/mL) against suspension. In vitro compatibility assays revealed that growth parameters (vegetative growth, sporulation, and viability) of were least affected by the action of phytol at all tested concentrations. Biological Index of exhibited compatibility with phytol allowed us to conduct Joint toxicity bioassays in which phytol and spores mixed in different proportions in order to attain maximum treatment effect in terms of high mortality at low concentration under short time. Results revealed that joint-application exhibited both synergistic (treatments with higher proportions of phytol), and antagonistic interaction (treatments with higher proportions of spores) interactions. Biochemical mechanisms involved in host antioxidant and detoxification response were explored by quantifying their respective enzymatic activities. Lethality of different treatments induced different patterns of detoxification enzymes including glutathione S-transferase (GST) and acetylcholinesterase (AchE). Overall, the least potent treatments (20% phytol:80% spores, and 40% phytol:60% spores) established in the current study induced relatively higher GST and AchE activities. On the other hand, the most potent treatment (80% phytol:20% spores) at its maximum concentration exhibited negligible relative GST and AchE activities. Antioxidant enzyme activities of CAT and SOD measured in the current study showed moderate to complex interaction might because of toxin-pathogen remarkable synergy. This study suggested that joint application of phytol with spores have shown tremendous acaricidal potential and found to be promising new strategy for controlling old world date mites.
Topics: Acetylcholinesterase; Animals; Antioxidants; Beauveria; Catalase; Glutathione Transferase; Inactivation, Metabolic; Phytol; Superoxide Dismutase; Tetranychidae; Toxicity Tests
PubMed: 30096781
DOI: 10.3390/molecules23081978 -
British Medical Journal Nov 1947
Topics: Humans; Vitamin A; Vitamin K; Vitamins
PubMed: 20340806
DOI: 10.1136/bmj.2.4532.788-b -
Nutrients Jan 2016A better understanding of vitamin K's role in health and disease requires the assessment of vitamin K nutritional status in population and clinical studies. This is... (Review)
Review
A better understanding of vitamin K's role in health and disease requires the assessment of vitamin K nutritional status in population and clinical studies. This is primarily accomplished using dietary questionnaires and/or biomarkers. Because food composition databases in the US are most complete for phylloquinone (vitamin K1, the primary form in Western diets), emphasis has been on phylloquinone intakes and associations with chronic diseases. There is growing interest in menaquinone (vitamin K2) intakes for which the food composition databases need to be expanded. Phylloquinone is commonly measured in circulation, has robust quality control schemes and changes in response to phylloquinone intake. Conversely, menaquinones are generally not detected in circulation unless large quantities are consumed. The undercarboxylated fractions of three vitamin K-dependent proteins are measurable in circulation, change in response to vitamin K supplementation and are modestly correlated. Since different vitamin K dependent proteins are implicated in different diseases the appropriate vitamin K-dependent protein biomarker depends on the outcome under study. In contrast to other nutrients, there is no single biomarker that is considered a gold-standard measure of vitamin K status. Most studies have limited volume of specimens. Strategic decisions, guided by the research question, need to be made when deciding on choice of biomarkers.
Topics: Biomarkers; Humans; Nutrition Assessment; Nutritional Status; Proteins; Vitamin K
PubMed: 26729160
DOI: 10.3390/nu8010008 -
Advances in Nutrition (Bethesda, Md.) Mar 2012In 2001, the US Food and Nutrition Board concluded that there were insufficient data with which to establish a RDA for vitamin K, in large part because of a lack of... (Review)
Review
In 2001, the US Food and Nutrition Board concluded that there were insufficient data with which to establish a RDA for vitamin K, in large part because of a lack of robust endpoints that reflected adequacy of intake. Knowledge of the relative bioavailability of multiple vitamin K forms was also poor. Since then, stable isotope methodologies have been applied to the assessment of the bioavailability of the major dietary form of vitamin K in its free state and when incorporated into a plant matrix. There is a need for stable isotope studies with enhanced sensitivity to expand knowledge of the bioavailability, absorption, disposition, and metabolism of different molecular forms of vitamin K. Another area for future research stems from evidence that common polymorphisms or haplotypes in certain key genes implicated in vitamin K metabolism might affect nutritional requirements. Thus far, much of this evidence is indirect via effects on warfarin dose requirements. In terms of clinical endpoints, vitamin K deficiency in early infancy continues to be a leading cause of intracranial bleeding even in developed countries and the reasons for its higher prevalence in certain Asian countries has not been solved. There is universal consensus for the need for vitamin K prophylaxis in newborns, but the effectiveness of any vitamin K prophylactic regimen needs to be based on sound nutritional principles. In contrast, there is still a lack of suitable biomarkers or clinical endpoints that can be used to determine vitamin K requirements among adults.
Topics: Adult; Biological Availability; Bone and Bones; Female; Humans; Infant; Infant, Newborn; Intestinal Absorption; Liver; Male; Nutritional Requirements; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 22516726
DOI: 10.3945/an.111.001800 -
Biochimica Et Biophysica Acta.... Apr 2023The effects of naringenin and the biflavonoids amentoflavone and tetrahydroamentoflavone on select bacterial lipids (carotenoids, fatty acids, and menaquinones) and...
The effects of naringenin and the biflavonoids amentoflavone and tetrahydroamentoflavone on select bacterial lipids (carotenoids, fatty acids, and menaquinones) and membrane fluidity based on Laurdan generalized polarization were investigated. For this purpose, the pigment-forming food-associated microorganisms Staphylococcus xylosus (DSM 20266 and J70), Staphylococcus carnosus DSM 20501, and Micrococcus luteus (ATCC 9341 and J3) were studied. The results suggest an envelope stress response by microorganisms due to flavonoids and an employment of adaptive mechanisms using carotenoids, fatty acids, and menaquinones. The flavonoid monomer naringenin impacted carotenoids, fatty acids, menaquinones, and membrane fluidity. Naringenin significantly influenced the carotenoid profile, particularly by an increase in the relative proportion of 4,4'-diaponeurosporenoic acid in Staphylococcus xylosus. Amentoflavone caused changes mainly in the membrane of Micrococcus luteus and decreased the menaquinone content. Tetrahydroamentoflavone mainly affected the carotenoids in the investigated strains. The noticeably different CCS value of tetrahydroamentoflavone compared to naringenin and amentoflavone revealed further insights into the structure-dependent effects of flavonoids. This study provides valuable insights into the response of pigment-forming food-associated microorganisms to naringenin, amentoflavone, and tetrahydroamentoflavone, which is important for the targeted and safe application of the latter as natural preservatives and useful for further research on the mechanisms of action.
Topics: Flavonoids; Vitamin K 2; Carotenoids; Fatty Acids
PubMed: 36746312
DOI: 10.1016/j.bbamem.2023.184137