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Vitamin K (phylloquinone and menaquinones) in foods - Cost-effective quantification by LC-ESI-MS/MS.Food Chemistry Aug 2022Further research on vitamin K is necessary as growing evidence of vitamin K's importance in human health beyond blood coagulation and bone health is emerging. We present...
Further research on vitamin K is necessary as growing evidence of vitamin K's importance in human health beyond blood coagulation and bone health is emerging. We present a cost-effective LC-ESI-MS/MS method for quantification of phylloquinone (PK), and menaquinones (MK) 4-10 in food using deuterium labelled (d7) compounds (d7-PK, d7-MK-4, d7-MK-7 and d7-MK-9) as internal standards. The validation of the method included assessment of matrix effect, limit of quantification (LOQ), precision, and trueness. The LC-ESI-MS/MS method runtime is 9 min. The method was compared to a validated LC-FLD method (CEN 14148), for quantification of vitamin K in broccoli, cheese, natto, liver, and microalgae. LOQs of the LC-ESI-MS/MS method were ≤4 µg/100 g food. The intra- and inter-assay precision was <15% for PK, MK-4, MK-7 and MK-9; <20% for MK-5, MK-8, and MK-10, and ≤25% for MK-6. No significant differences between the quantified content by the LC-ESI-MS/MS and LC-FLD methods were observed.
Topics: Cost-Benefit Analysis; Humans; Tandem Mass Spectrometry; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 35287105
DOI: 10.1016/j.foodchem.2022.132672 -
Archives of Osteoporosis Jun 2023This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K supplementation led to a modest effect on parameters of hip geometry.
PURPOSE
Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment.
METHODS
We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K (1 mg/day) arm, vitamin K arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed.
RESULTS
Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K arm: -1.02[5.07], p = 0.03).
CONCLUSION
The addition of vitamin K to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed.
TRIAL REGISTRATION
The study was registered at Clinicaltrial.gov:NCT01232647.
Topics: Female; Humans; Osteoporosis, Postmenopausal; Vitamin K; Diphosphonates; Calcium; Fractures, Bone; Bone Density; Vitamins; Vitamin D; Vitamin K 1; Femur Neck; Calcium, Dietary; Dietary Supplements
PubMed: 37338608
DOI: 10.1007/s11657-023-01288-w -
Respiratory Research Nov 2017Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require... (Review)
Review
Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.
Topics: Animals; Cardiovascular Diseases; Dietary Supplements; Humans; Pulmonary Disease, Chronic Obstructive; Vascular Calcification; Vitamin K; Vitamin K Deficiency
PubMed: 29132356
DOI: 10.1186/s12931-017-0673-z -
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 -
Nutrients Jan 2022Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular... (Review)
Review
Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process-matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.
Topics: Anticoagulants; Blood Coagulation; Bone and Bones; Calcium; Calcium-Binding Proteins; Cardiovascular Diseases; Extracellular Matrix Proteins; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Matrix Gla Protein
PubMed: 35057443
DOI: 10.3390/nu14020262 -
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 -
BMJ (Clinical Research Ed.) Aug 1992
Topics: Breast Feeding; Child; Humans; Infant, Newborn; Injections, Intramuscular; Neoplasms; Vitamin K; Vitamin K Deficiency Bleeding
PubMed: 1392882
DOI: 10.1136/bmj.305.6849.326 -
Respiratory Medicine Aug 2019Cystic fibrosis (CF) is an inherited genetic disorder with multiorgan involvement. Gastrointestinal tract dysfunction leads to fat and fat-soluble vitamins (A,D,E,K)... (Review)
Review
Cystic fibrosis (CF) is an inherited genetic disorder with multiorgan involvement. Gastrointestinal tract dysfunction leads to fat and fat-soluble vitamins (A,D,E,K) malabsorption and deficiency of these vitamins. Subclinical vitamin K (VK) deficiency seems to be a common problem in CF patients. However, despite the rest of fat-soluble vitamins being routinely supplemented, this is not a universal clinical practice for VK. Inefficient levels of VK may have significant effects on blood coagulation and bone formation. There are also some data indicating that VK may play a key role on regulation of inflammation. Supplementing CF patients with VK seems rational, but the appropriate dosing regimens are still a matter of debate. This review will try to delineate the problem and communicate the latest opinions on this controversial issue.
Topics: Blood Coagulation; Cystic Fibrosis; Humans; Osteogenesis; Vitamin K; Vitamin K Deficiency
PubMed: 31295676
DOI: 10.1016/j.rmed.2019.07.005 -
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 -
Molecules (Basel, Switzerland) Mar 2020Many natural coumarins and their chemically synthesized analogs and derivatives exert diverse properties, such as anticancer, antioxidant, anti-inflammatory, or... (Review)
Review
Many natural coumarins and their chemically synthesized analogs and derivatives exert diverse properties, such as anticancer, antioxidant, anti-inflammatory, or anticoagulant, with the latter being of the utmost importance. The widely used warfarin, acenocoumarol, and phenprocoumon exert anticoagulant properties by inhibiting the vitamin K epoxide reductase complex. In this interdisciplinary review, we present biochemical principles of the coagulation processes and possible methods for their tuning based on the use of coumarins. We also summarize chemical methods of synthesis of coumarins and discuss structures and properties of those that have been used for a long time, as well as newly synthesized compounds. Brief information on the clinical use of coumarins and other anticoagulant drugs is given, including the severe effects of overdosing and methods for reversing their action.
Topics: Animals; Cardiovascular Diseases; Coumarins; Factor Xa Inhibitors; Humans; Vitamin K
PubMed: 32213944
DOI: 10.3390/molecules25061465