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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 -
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 -
American Journal of Transplantation :... Apr 2023Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial.
Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 μg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; P = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; P = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; P < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs. TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Vitamin K; Vascular Stiffness; Kidney Transplantation; Pulse Wave Analysis; Vitamin K 2; Dietary Supplements; Double-Blind Method
PubMed: 36695702
DOI: 10.1016/j.ajt.2022.12.015 -
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 -
The association of the Affordable Care Act with nutrient consumption in adults in the United States.Frontiers in Public Health 2023The Patient Protection and Affordable Care Act, more commonly known as the ACA, was legislation passed in the United States in 2010 to expand access to health insurance...
The Patient Protection and Affordable Care Act, more commonly known as the ACA, was legislation passed in the United States in 2010 to expand access to health insurance coverage for millions of Americans with a key emphasis on preventive care. Nutrition plays a critical role in overall wellness, disease prevention and resilience to chronic illness but prior to the ACA many Americans did not have adequate health insurance coverage to ensure proper nutrition. With passage of the ACA, more individuals received access to nutritional counseling through their primary care physicians as well as prescription vitamins and supplements free of charge. The objective of this study was to evaluate the impact of a national health insurance reform on nutrient intake among general population, including more vulnerable low-income individuals and patients with chronic conditions. Using data from the National Health and Nutrition Examination Survey (NHANES), we identified 8,443 adults aged 21 years and older who participated in the survey before (2011-2012) and after the ACA (2015-2016) implementation and conducted a subgroup analysis of 952 respondents who identified as Medicaid beneficiaries and 719 patients with a history of cancer. Using pre-post study design and bivariate and multivariable logistic analyses, we compared nutrient intake from food and supplementation before and after the ACA and identified risk factors for inadequate intake. Our results suggest that intake of micronutrients found in nutrient-dense foods, mainly fruit and vegetables, has not changed significantly after the ACA. However, overall use of nutritional supplements increased after the ACA ( = 0.05), particularly magnesium (OR = 1.02), potassium (OR = 0.76), vitamin D (both D2, and D3, OR = 1.34), vitamin K (OR = 1.15) and zinc (OR = 0.83), for the general population as well as those in our subgroup analysis Cancer Survivors and Medicaid Recipients. Given the association of increased use of nutritional supplements and expansion of insurance access, particularly in our subgroup analysis, more research is necessary to understand the effect of increasing access to nutritional supplements on the overall intake of micro- and macronutrients to meet daily nutritional recommended allowances.
Topics: United States; Adult; Humans; Patient Protection and Affordable Care Act; Nutrition Surveys; Nutrients; Vitamins; Nutritional Status; Vitamin K
PubMed: 38186698
DOI: 10.3389/fpubh.2023.1244042 -
Scientific Reports Feb 2021The synthesis of phytol-derived γ-butyrolactones as well as their evaluation for deterrent activity towards peach-potato aphid Myzus persicae and antiproliferative...
The synthesis of phytol-derived γ-butyrolactones as well as their evaluation for deterrent activity towards peach-potato aphid Myzus persicae and antiproliferative activity against four selected cancer cell lines are reported. Products were obtained in good yields (19-96%) and their structures were fully characterized by spectroscopic data (NMR, HRMS). Four synthesized δ-halo-γ-lactones (4-7) are new and have not been previously described in the literature. In the choice test phytol (1) appeared deterrent to M. persicae, whereas modifications of its structure did not cause the avoidance of the treated leaves by the aphids. In contrast, aphids were attracted to the leaves treated with the new trans-δ-chloro-γ-lactone (6). Electrical Penetration Graph (EPG) technique applied to explore the aphid probing and feeding activity revealed that neither phytol nor lactone 6 affected aphid probing and the consumption of phloem sap, which means that both phytol and the lactone 6 might have acted as postingestive modifiers of aphid behavior. The results of in vitro antitumor assays showed that obtained phytol derivatives exhibit cytotoxic activity against studied cancer cell lines (leukemia, lung and colon carcinoma and its doxorubicin resistant subline). Halolactones 4-6 were identified as the compounds, which arrest cell cycle of leukemia cells mainly in G2/M and S phases.
Topics: 4-Butyrolactone; Animals; Antineoplastic Agents; Caspase 3; Caspase 7; Cell Cycle; Cell Line; Cell Proliferation; Chemistry Techniques, Synthetic; Chromatography, Thin Layer; Gas Chromatography-Mass Spectrometry; Gene Expression Regulation; Humans; Mice; Phytol; Structure-Activity Relationship
PubMed: 33608591
DOI: 10.1038/s41598-021-83736-6 -
Molecules (Basel, Switzerland) Oct 2022In this study, a novel galloyl phytol antioxidant was developed by incorporating the branched phytol chain with gallic acid through mild Steglich esterification. The...
In this study, a novel galloyl phytol antioxidant was developed by incorporating the branched phytol chain with gallic acid through mild Steglich esterification. The evaluation of the radical scavenging activity, lipid oxidation in a liposomal model, and glycerol trioleate revealed its superior antioxidant activities in both dispersed and bulk oils. Then, the antioxidant capacity enhancement of galloyl phytol was further explored using thermal gravimetry/differential thermal analysis (TG/DTA), transmission electron microscopy (TEM), and molecular modeling. The EC50 values of GP, GPa, and GE were 0.256, 0.262, and 0.263 mM, respectively, which exhibited comparable DPPH scavenging activities. These investigations unveiled that the branched aliphatic chain enforced the coiled molecular conformation and the unsaturated double bond in the phytol portion further fixed the coiled conformation, which contributed to a diminished aggregation tendency and enhanced antioxidant activities in dispersed and bulk oils. The remarkable antioxidant performance of galloyl phytol suggested intriguing and non-toxic natural antioxidant applications in the food industry, such as effectively inhibiting the oxidation of oil and improvement of the quality and shelf life of the oil, which would contribute to the use of tea resources and extending the tea industry chain.
Topics: Phytol; Antioxidants; Esterification; Plant Oils; Tea
PubMed: 36364126
DOI: 10.3390/molecules27217301 -
Frontiers in Endocrinology 2022Osteoporosis (OP) is an important risk factor for rotator cuff tears (RCTs). However, the relationship and mechanism between rotator cuff injury and osteoporosis are...
BACKGROUNDS
Osteoporosis (OP) is an important risk factor for rotator cuff tears (RCTs). However, the relationship and mechanism between rotator cuff injury and osteoporosis are unclear. Therefore, to investigate association between rotator cuff injury and osteoporosis, and find clinical characteristics, bone mineral density, bone metabolism markers, and nutrient levels in rotator cuff injury patients with or without osteoporosis.
METHODS
One hundred and four cases of patients (RCTs, n=32; RCTs-OP, n=72) who underwent rotator cuff injury and need arthroscopic rotator cuff repair between June 2021 and February 2022, along with the diagnosis of osteoporosis were identified from the dual-energy X-ray bone density screening(DXA). The outcome measure includes clinical characteristics, bone mineral density, bone metabolism markers, vitamins, and amino acids. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation.
RESULTS
OP with RCTs has a lower level of in 25-vitD, osteocalcin (OCN), serum Ca2+, ornithine, diaminocaproic_acid but the high level of Vitamin_B12, PTH, Vitamin_D3,γ_aminobutyric_acid, Vitamin_C and Vitamin_E than RCTs patients without OP. Predictors contained in the prediction nomogram included lumber T score, femur T score, Niacin_B3, and vitamin D, reflecting the combined effect of vitamins on RCTs-related OP progression. The model has good discriminative ability with a C-index of 0.938(95% CI:-1.83-1.39) and good scaling ability. The high C-index value of 0.95 is still achievable with range validation. Analysis of decision curves showed that non-adherence is clinically useful when intervention decisions are at the 14% probability limit of non-adherence.
CONCLUSION
This study supports the hypothesis that lumber T score, femur T score, Niacin_B3, and Vitamin D are valuable prognostic biomarkers on RCTs related OP progression.
WHAT IS KNOWN ABOUT THE SUBJECT
It is found that vitamin D are valuable prognostic biomarkers, reflecting the combined effect of vitamins on RCTs related OP progression.
WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE
These findings also highlight that nutrients condition such as vitamins and amino acids of patients provide a new understanding of the development of RCTs.
Topics: Humans; Vitamin D; Rotator Cuff Injuries; Niacin; Vitamins; Osteoporosis; Vitamin A; Vitamin K; Amino Acids; Biomarkers
PubMed: 36465653
DOI: 10.3389/fendo.2022.1017835 -
The American Journal of Clinical... Mar 2022
Topics: Adult; Calcification, Physiologic; Cardiovascular Diseases; Cohort Studies; Female; Humans; Male; Renal Insufficiency, Chronic; Vitamin K
PubMed: 35134829
DOI: 10.1093/ajcn/nqab423 -
Molecular Imaging and Biology Jun 2022To determine the sensitivity of the F-radiolabelled dihydroethidine analogue ([F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
PURPOSE
To determine the sensitivity of the F-radiolabelled dihydroethidine analogue ([F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
PROCEDURES
The sensitivity of [F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [F]DHE (50-150 kBq.min) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
RESULTS
[F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation.
CONCLUSION
[F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.
Topics: Animals; Dicarbethoxydihydrocollidine; Positron-Emission Tomography; Rats; Reactive Oxygen Species; Vitamin K 3
PubMed: 34820762
DOI: 10.1007/s11307-021-01683-0