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International Journal of Molecular... Jun 2019Vitamin K is classified into three homologs depending on the side-chain structure, with 2-methyl-1,4-naphthoqumone as the basic skeleton. These homologs are vitamin K... (Review)
Review
Vitamin K is classified into three homologs depending on the side-chain structure, with 2-methyl-1,4-naphthoqumone as the basic skeleton. These homologs are vitamin K (phylloquinone: PK), derived from plants with a phythyl side chain; vitamin K (menaquinone-: MK-), derived from intestinal bacteria with an isoprene side chain; and vitamin K (menadione: MD), a synthetic product without a side chain. Vitamin K homologs have physiological effects, including in blood coagulation and in osteogenic activity via γ-glutamyl carboxylase and are used clinically. Recent studies have revealed that vitamin K homologs are converted to MK-4 by the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) in vivo and accumulate in all tissues. Although vitamin K is considered to have important physiological effects, its precise activities and mechanisms largely remain unclear. Recent research on vitamin K has suggested various new roles, such as transcriptional activity as an agonist of steroid and xenobiotic nuclear receptor and differentiation-inducing activity in neural stem cells. In this review, we describe synthetic ligands based on vitamin K and exhibit that the strength of biological activity can be controlled by modification of the side chain part.
Topics: Animals; Humans; Neural Stem Cells; Neurogenesis; Pregnane X Receptor; Transcriptional Activation; Vitamin K; Vitamins
PubMed: 31226734
DOI: 10.3390/ijms20123006 -
Nutrients May 2023There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients.
METHODS
This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks ( = 50) or standard care (control group; = 46). The change in cfPWV was the primary outcome.
RESULTS
Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, = 0.37), especially in diabetes patients (21.4% vs. 72.7%, = 0.01). No serious adverse events were observed during the 24 weeks.
CONCLUSION
Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.
Topics: Humans; Vitamin K 2; Vascular Stiffness; Pulse Wave Analysis; Renal Dialysis; Vitamin K; Dietary Supplements
PubMed: 37299386
DOI: 10.3390/nu15112422 -
Clinical Chemistry and Laboratory... May 2017Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but... (Review)
Review
Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but recently has also aroused an increasing interest for its action in extra-hepatic tissues, in particular in the regulation of bone and vascular metabolism. The accurate measurement of vitamin K status in humans is still a critical issue. Along with indirect assays, such as the undercarboxylated fractions of vitamin K-dependent proteins [prothrombin, osteocalcin (OC), and matrix gla protein], the direct analysis of blood levels of phylloquinone and menaquinones forms might be considered a more informative and direct method for assessing vitamin K status. Different methods for direct quantification of vitamin K serum levels are available. High-performance liquid chromatography (HPLC) methods coupled with post-column reduction procedures and fluorimetric or electrochemical detection are commonly used for food and blood analysis of phylloquinone, but they show some limitations when applied to the analysis of serum menaquinones because of interferences from triglycerides. Recent advancements include liquid chromatography tandem mass spectrometry (LCMS/MS) detection, which assures higher specificity. The optimization and standardization of these methods requires specialized laboratories. The variability of results observed in the available studies suggests the need for further investigations to obtain more accurate analytical results.
Topics: Blood Chemical Analysis; Health; Humans; Vitamin K
PubMed: 27732556
DOI: 10.1515/cclm-2016-0783 -
Nutrients Aug 2022The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may... (Review)
Review
The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.
Topics: Aged; Blood Coagulation; Female; Humans; Neoplasms; Osteoporosis; Ovarian Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 36014904
DOI: 10.3390/nu14163401 -
The Journal of Nutrition, Health & Aging 2023In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support...
BACKGROUND
In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown.
OBJECTIVE
To examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women.
DESIGN
Cohort study.
PARTICIPANTS
1347 community-dwelling older Australian women ≥70 years.
MEASUREMENTS
A new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data.
RESULTS
Over 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52-0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59-0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ~70-100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls.
CONCLUSION
A higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted.
Topics: Humans; Female; Aged; Male; Cohort Studies; Vitamin K 1; Independent Living; Australia; Vitamin K
PubMed: 36651485
DOI: 10.1007/s12603-022-1866-9 -
Journal of Thrombosis and Haemostasis :... Aug 2005Post-translational modification of glutamate to gamma carboxyl glutamate is required for the activity of vitamin K-dependent proteins. Carboxylation is accomplished by... (Review)
Review
Post-translational modification of glutamate to gamma carboxyl glutamate is required for the activity of vitamin K-dependent proteins. Carboxylation is accomplished by the enzyme gamma glutamyl carboxylase (GGCX) which requires the propeptide-containing substrate and three co-substrates: reduced vitamin K, CO2, and O2. Most propeptides bind tightly to GGCX and all of the Glu residues that will be modified are modified during one binding event. Complete carboxylation is thus dependent upon the rate of carboxylation and the dissociation rate constant of the substrate from the GGCX enzyme. If the propeptide is released before carboxylation is complete, partially carboxylated vitamin K-dependent proteins are produced. The rate of carboxylation is mainly controlled by the level of reduced vitamin K available for the reactions while the dissociation rate constant is dependent upon both the propeptide and the Gla domain of the substrate. In addition, there are allosteric effects that increase the rate of dissociation of the fully carboxylated substrates. Carboxylation requires the abstraction of a proton from the 4-carbon of glutamate by reduced vitamin K and results in the conversion of vitamin K to vitamin K epoxide. The vitamin K epoxide must be recycled to vitamin K before it can be reused, a reaction catalyzed by the enzyme vitamin K epoxide reductase (VKOR). The gene for VKOR has recently been identified but the enzyme itself has not been purified to homogeneity. It appears, however, that most of the variability observed in patients response to warfarin may be attributed to variability in the VKOR gene.
Topics: Amino Acid Sequence; Animals; Binding Sites; Carbon; Cytoplasm; Genetic Variation; Glutamic Acid; Humans; Kinetics; Mixed Function Oxygenases; Models, Biological; Models, Chemical; Molecular Sequence Data; Oxygen; Protein Processing, Post-Translational; Protons; Time Factors; Vitamin K; Vitamin K Epoxide Reductases; Warfarin
PubMed: 16102054
DOI: 10.1111/j.1538-7836.2005.01419.x -
Animal Science Journal = Nihon Chikusan... 2022The effect of dietary vitamin K (VK3) on ruminant animals is not fully investigated. The aim of this study was to examine the effects of dietary VK3 on lactation...
The effect of dietary vitamin K (VK3) on ruminant animals is not fully investigated. The aim of this study was to examine the effects of dietary VK3 on lactation performance, rumen characteristics, and VK1 and menaquinone (MK, or VK2) dynamics in the rumen, plasma, and milk of dairy cows. Eight Holstein dairy cows in late lactation periods were used in two crossover trials including a control (nontreatment) and a 50 or 200 mg/day (d) VK3 supplementation group. After 14 days, plasma, ruminal fluid, and milk were sampled and their VK1 and MKs contents were measured using fluorescence-high-performance liquid chromatography (HPLC). Milk production was unchanged after feeding 50 mg/day VK3 but marginally decreased after feeding 200 mg/day VK3. The molar ratio of propionate in ruminal fluid was significantly increased on feeding 200 mg/day VK3. Additionally, MK-4 concentrations significantly increased in both plasma and milk after VK3 feeding (50 and 200 mg/day). In ruminal fluid, MK-4 concentrations increased after 200 mg/day VK3 feeding. These results suggest that VK3 may be a good source of MK-4, the biologically active form of VK, in Holstein dairy cows during their late lactation periods. This study provides a basis for understanding the physiological role of VK in dairy cows.
Topics: Animal Feed; Animals; Cattle; Diet; Dietary Supplements; Digestion; Female; Fermentation; Lactation; Milk; Rumen; Vitamin K 1; Vitamin K 2; Vitamin K 3
PubMed: 35029011
DOI: 10.1111/asj.13680 -
Nutrients Apr 2023Vitamin K is an essential fat-soluble vitamin for the human body and its functions, such as promoting blood coagulation, bone health and preventing atherosclerosis, have...
BACKGROUND
Vitamin K is an essential fat-soluble vitamin for the human body and its functions, such as promoting blood coagulation, bone health and preventing atherosclerosis, have attracted increasing attention. However, there is no recognized indicator and corresponding reference range for evaluating vitamin K status of different populations at present. The aim of this study is to establish a reference range for vitamin K evaluating indicators in healthy women of childbearing age in China.
METHODS
The population sample in this study was from the Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS) 2015-2017. A total of 631 healthy women of childbearing age (18-49 years) were included using a series of strict inclusion and exclusion criteria. The concentrations of VK1, MK-4 and MK-7 in serum were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The other commonly-reported indicators evaluating vitamin K nutritional status, including undercarboxylated osteocalcin (ucOC), osteocalcin (OC), matrix Gla protein (MGP), desphosphorylated undercaboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), were measured by enzyme-linked immunosorbent assay (ELISA). The reference range was obtained by calculating the 2.5% to 97.5% interval of the vitamin K evaluating indicators in the reference population.
RESULTS
The reference ranges of VK1, MK-4 and MK-7 in serum were 0.21-3.07 ng/mL, 0.02-0.24 ng/mL and 0.12-3.54 ng/mL, respectively. The reference ranges of ucOC, %ucOC, dp-ucMGP and PIVKA-II were 1.09-2.51 ng/mL, 5.80-22.78%, 2.69-5.88 ng/mL and 3.98-8.40 ng/mL, respectively. The cut-off values that can be used to evaluate subclinical vitamin K deficiency were as follows: VK1 < 0.21 ng/mL, MK-7 < 0.12 ng/mL, ucOC > 2.51 ng/mL, %ucOC > 22.78%, dp-ucMGP > 5.88 ng/mL and PIVKA-II > 8.40 ng/mL.
CONCLUSION
The reference range of VK1, MK-4, MK-7 and vitamin K-related indicators for healthy women of childbearing age established in this study could be used to assess the nutritional and health status of this population.
Topics: Adult; Humans; Female; Adolescent; Young Adult; Middle Aged; Vitamin K; Osteocalcin; Reference Values; Chromatography, Liquid; East Asian People; Tandem Mass Spectrometry; Vitamins; Vitamin K Deficiency; Vitamin K 2; Biomarkers; Vitamin K 1
PubMed: 37111196
DOI: 10.3390/nu15081977 -
Maternal and Child Health Journal May 2017Objectives Vitamin K deficiency bleeding (VKDB) in infants is a coagulopathy preventable with a single dose of injectable vitamin K at birth. The Tennessee Department of...
Objectives Vitamin K deficiency bleeding (VKDB) in infants is a coagulopathy preventable with a single dose of injectable vitamin K at birth. The Tennessee Department of Health (TDH) and Centers for Disease Control and Prevention (CDC) investigated vitamin K refusal among parents in 2013 after learning of four cases of VKDB associated with prophylaxis refusal. Methods Chart reviews were conducted at Nashville-area hospitals for 2011-2013 and Tennessee birthing centers for 2013 to identify parents who had refused injectable vitamin K for their infants. Contact information was obtained for parents, and they were surveyed regarding their reasons for refusing. Results At hospitals, 3.0% of infants did not receive injectable vitamin K due to parental refusal in 2013, a frequency higher than in 2011 and 2012. This percentage was much higher at birthing centers, where 31% of infants did not receive injectable vitamin K. The most common responses for refusal were a belief that the injection was unnecessary (53%) and a desire for a natural birthing process (36%). Refusal of other preventive services was common, with 66% of families refusing vitamin K, newborn eye care with erythromycin, and the neonatal dose of hepatitis B vaccine. Conclusions for Practice Refusal of injectable vitamin K was more common among families choosing to give birth at birthing centers than at hospitals, and was related to refusal of other preventive services in our study. Surveillance of vitamin K refusal rates could assist in further understanding this occurrence and tailoring effective strategies for mitigation.
Topics: Adult; Birthing Centers; Female; Humans; Infant, Newborn; Male; Parents; Retrospective Studies; Surveys and Questionnaires; Tennessee; Treatment Refusal; Vitamin K; Vitamin K Deficiency Bleeding
PubMed: 28054156
DOI: 10.1007/s10995-016-2205-8 -
Medicine Sep 2022Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR.
METHODS
CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test.
RESULTS
From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively).
CONCLUSION
The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.
Topics: Blood Coagulation Disorders; Heart Valves; Humans; International Normalized Ratio; Thromboembolism; Vitamin K; Vitamin K 1; Vitamins
PubMed: 36086772
DOI: 10.1097/MD.0000000000030388