Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study

2004 ◽  
Vol 91 (02) ◽  
pp. 373-380 ◽  
Author(s):  
Lavienja Braam ◽  
Arnold Hoeks ◽  
Fred Brouns ◽  
Karly Hamulyák ◽  
Monique Gerichhausen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Placebo Group ◽  
Postmenopausal Women ◽  
Elastic Properties ◽  
Vitamin K ◽  
Vessel Wall ◽  
Intima Media Thickness ◽  
Matrix Gla Protein ◽  
Vitamin K1 ◽  
Strong Inhibitor

SummaryMatrix-Gla Protein (MGP) is a strong inhibitor of vascular calcification, the expression of which is vitamin D dependent. MGP contains five γ-carboxyglutamic acid (Gla)-residues which are formed in a vitamin K-dependent carboxylation step and which are essential for its function. Hence vascular vitamin K-deficiency will result in undercarboxylated, inactive MGP which is a potential risk factor for calcification. In the present study we describe the effects of vitamin K1 and D supplementation on vascular properties in postmenopausal women. In a randomized placebo-controlled intervention study, 181 postmenopausal women were given either a placebo or a supplement containing minerals and vitamin D (MD-group), or the same supplement with vitamin K1 (MDK-group). 150 participants completed the study and analysis was performed on 108 participants. At baseline and after three years, vessel wall characteristics, including compliance coefficient (CC), distensibility coefficient (DC), intima-media thickness (IMT) and the Young’s Modulus (E) were measured to assess the effect of the supplements on the change of these parameters. The results showed that the elastic properties of the common carotid artery in the MDK-group remained unchanged over the three-year period, but decreased in the MDand placebo-group. Comparing the MDKand placebo-group, there were significant differences in decrease of DC (8.8%; p<0.05), CC (8.6%; p<0.05), and in increase of PP (6.3%; p<0.05) and E (13.2%, p<0.01).There were no significant differences between the MD-group and placebo. No significant differences were observed in the change of IMT between the three groups. It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall.

Matrix Gla Protein Synthesis and Gamma-carboxylation in the Aortic Vessel Wall and Proliferating Vascular Smooth Muscle Cells

1999 ◽  
Vol 82 (12) ◽  
pp. 1764-1767 ◽  
Author(s):  
Dean Cain ◽  
David Sane ◽  
Reidar Wallin
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vitamin K ◽  
Vessel Wall ◽  
Arterial Wall ◽  
Muscle Cells ◽  
Matrix Gla Protein ◽  
Dt Diaphorase

SummaryMatrix GLA protein (MGP) is an inhibitor of calcification in the arterial wall and its activity is dependent upon vitamin K-dependent γ-carboxylation. This modification is carried out by a warfarin sensitive enzyme system that converts specific Glu residues to γ-carboxyglutamic acid (GLA) residues. Recent studies have demonstrated that the γ-carboxylation system in the arterial wall, in contrast to that in the liver, is unable to use vitamin K as an antidote to warfarin.By use of immunohistochemistry we demonstrate that MGP is expressed in the arterial wall and immunocytochemistry localized the MGP precursors to the endoplasmic reticulum in vascular smooth muscle cells. Resting smooth vascular muscle cells in the aortic wall and proliferating cells from explants of the aorta have all the enzymes needed for γ-carboxylation of MGP. However, when compared to the liver system, expression of the enzymes of the γ-carboxylation system in vascular smooth muscle cells is different. Of particular interest is the finding that the specific activity of the warfarin sensitive enzyme vitamin K epoxide reductase is 3-fold higher in vascular smooth muscle cells than in liver. DT-diaphorase, which catalyses the antidotal pathway for vitamin K reduction in liver, is 100-fold less active in resting vascular smooth muscle cells than in liver. Data obtained from an in vitro γ-carboxylation system suggest that the antidotal pathway catalyzed by DT-diaphorase in the vessel wall is unable to provide the carboxylase with enough reduced vitamin K to trigger γ-carboxylation of MGP. This finding provides an explanation to the inability of vitamin K to work as an antidote to warfarin intoxication of the arterial wall. Therefore the vitamin K dependent γ-carboxylation system in the arterial wall share a common feature with the system in bone cells by being unable to utilize vitamin K as an antidote.

scholarly journals Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 152 ◽  
Author(s):  
Yi-Chou Hou ◽  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Ruei-Ming Chen ◽  
Yuh-Feng Lin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Matrix Vesicles ◽  
Vital Role ◽  
Matrix Gla Protein ◽  
Protein Receptor ◽  
Calciprotein Particles

Vascular calcification is a critical complication in patients with chronic kidney disease (CKD) because it is predictive of cardiovascular events and mortality. In addition to the traditional mechanisms associated with endothelial dysfunction and the osteoblastic transformation of vascular smooth muscle cells (VSMCs), the regulation of calcification inhibitors, such as calciprotein particles (CPPs) and matrix vesicles plays a vital role in uremic vascular calcification in CKD patients because of the high prevalence of vitamin K deficiency. Vitamin K governs the gamma-carboxylation of matrix Gla protein (MGP) for inhibiting vascular calcification, and the vitamin D binding protein receptor is related to vitamin K gene expression. For patients with chronic kidney disease, adequate use of vitamin D supplements may play a role in vascular calcification through modulation of the calciprotein particles and matrix vesicles (MVs).

scholarly journals Vitamin K & D Deficiency Are Independently Associated With Covid-19 Disease Severity

2021 ◽  
Author(s):  
Ankita P Desai ◽  
Sahera Dirajlal-Fargo ◽  
Jared C Durieux ◽  
Heather Tribout ◽  
Danielle Labbato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Disease Severity ◽  
Vitamin K ◽  
Matrix Gla Protein ◽  
Vitamin D Status ◽  
Hydroxyvitamin D ◽  
Moderate Disease ◽  
Unit Increase ◽  
The Status ◽  
25 Hydroxyvitamin D

Abstract Background We investigated the status of vitamin K and vitamin D and association to COVID-19 outcomes. Methods Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D levels (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age and sex matched to healthy controls. Unadjusted (UOR) and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were computed using cumulative logistic regression. Results 150 subjects were included, 100 COVID-19+ and 50 controls. Median agewas 55 (IQR: 48, 63), 50% were females. 34% had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (i.e. worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL, p &lt;0.0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL, p=0.09). Participants who were vitamin D deficient (&lt;20ng/mL) had the worse vitamin K status (dp-ucMGP &gt;780ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every one-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death [AOR 95%CI: 1.84 (1.01, 3.45)] and every one-unit decrease in the natural log 25(OH)D was associated with more than three times the likelihood of COVID-19 disease severity [AOR 95%CI: 0.29 (0.11, 0.67)]. Conclusion Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these two vitamins in COVID-19.

scholarly journals Causes of Vitamin K Deficiency in Patients on Haemodialysis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2513
Author(s):  
Signe Wikstrøm ◽  
Katrine Aagaard Lentz ◽  
Ditte Hansen ◽  
Lars Melholt Rasmussen ◽  
Jette Jakobsen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Absorption Capacity ◽  
Protein Supplementation ◽  
Matrix Gla Protein ◽  
Vitamin K1 ◽  
High Concentration ◽  
Vitamin K Deficiency ◽  
Before And After ◽  
K Deficiency ◽  
The Difference

Background: A low vitamin K status is common in patients on haemodialysis, and this is considered one of the reasons for the accelerated atherosclerosis in these patients. The vitamin is essential in activation of the protein Matrix Gla Protein (MGP), and the inactive form, dp-ucMGP, is used to measure vitamin K status. The purpose of this study was to investigate possible underlying causes of low vitamin K status, which could potentially be low intake, washout during dialysis or inhibited absorption capacity. Moreover, the aim was to investigate whether the biomarker dp-ucMGP is affected in these patients. Method: Vitamin K intake was assessed by a Food Frequency Questionnaire (FFQ) and absorption capacity by means of D-xylose testing. dp-ucMGP was measured in plasma before and after dialysis, and phylloquinine (vitamin K1) and dp-ucMGP were measured in the dialysate. Changes in dp-ucMGP were measured after 14 days of protein supplementation. Results: All patients had plasma dp-ucMGP above 750 pmol/L, and a low intake of vitamin K. The absorption capacity was normal. The difference in dp-ucMGP before and after dialysis was −1022 pmol/L (p < 0.001). Vitamin K1 was not present in the dialysate but dp-ucMGP was at a high concentration. The change in dp-ucMGP before and after protein supplementation was −165 pmol/L (p = 0.06). Conclusion: All patients had vitamin K deficiency. The reason for the low vitamin K status is not due to removal of vitamin K during dialysis or decreased absorption but is plausibly due to a low intake of vitamin K in food. dp-ucMGP is washed out during dialysis, but not affected by protein intake to a clinically relevant degree.

scholarly journals Impact of calcium, vitamin D, vitamin K, oestrogen, isoflavone and exercise on bone mineral density for osteoporosis prevention in postmenopausal women: a network meta-analysis

2019 ◽  
Vol 123 (1) ◽  
pp. 84-103
Author(s):  
Zijun Xu ◽  
Huwen Wang ◽  
Yue Shi ◽  
Qiuming Shen ◽  
Lhakpa Tsamlag ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Vitamin K ◽  
Meta Analysis ◽  
Mean Difference ◽  
Cochrane Library ◽  
Osteoporosis Prevention ◽  
Mineral Density

AbstractThe aim of this network meta-analysis is to compare bone mineral density (BMD) changes among different osteoporosis prevention interventions in postmenopausal women. We searched MEDLINE, Embase and Cochrane Library from inception to 24 February 2019. Included studies were randomised controlled trials (RCT) comparing the effects of different treatments on BMD in postmenopausal women. Studies were independently screened by six authors in three pairs. Data were extracted independently by two authors and synthesised using Bayesian random-effects network meta-analysis. The results were summarised as mean difference in BMD and surface under the cumulative ranking (SUCRA) of different interventions. A total of ninety RCT (10 777 participants) were included. Ca, vitamin D, vitamin K, oestrogen, exercise, Ca + vitamin D, vitamin D + vitamin K and vitamin D + oestrogen were associated with significantly beneficial effects relative to no treatment or placebo for lumbar spine (LS). For femoral neck (FN), Ca, exercise and vitamin D + oestrogen were associated with significantly beneficial intervention effects relative to no treatment. Ranking probabilities indicated that oestrogen + vitamin D is the best strategy in LS, with a SUCRA of 97·29 % (mean difference: +0·072 g/cm2 compared with no treatment, 95 % credible interval (CrI) 0·045, 0·100 g/cm2), and Ca + exercise is the best strategy in FN, with a SUCRA of 79·71 % (mean difference: +0·029 g/cm2 compared with placebo, 95 % CrI –0·00093, 0·060 g/cm2). In conclusion, in postmenopausal women, many interventions are valuable for improving BMD in LS and FN. Different intervention combinations can affect BMD at different sites diversely.

scholarly journals Effect of 6-Month Vitamin D Supplementation on Plasma Matrix Gla Protein in Older Adults

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 231 ◽  
Author(s):  
Adriana van Ballegooijen ◽  
Joline Beulens ◽  
Leon Schurgers ◽  
Elisa de Koning ◽  
Paul Lips ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin K ◽  
Controlled Trial ◽  
Vitamin K Antagonists ◽  
Functional Limitation ◽  
Vitamin D Supplementation ◽  
Vitamin K Antagonist ◽  
Matrix Gla Protein ◽  
Double Blind

Vitamin D supplementation has been widely promoted to restore 25-hydroxyvitamin D concentrations; however, experimental evidence suggests a nutrient interaction with vitamin K. We assessed the effects of 1200 IU vitamin D3 per day versus placebo for six months on vitamin K status in a randomized, double-blind, placebo-controlled trial with participants aged 60–80 years with depressive symptoms and ≥1 functional limitation for a secondary analysis. Stored baseline and six-month follow-up blood samples were available for 131 participants (n = 65 placebo vs. n = 66 vitamin D supplementation). We measured dephosphorylated uncarboxylated matrix gla protein (MGP) (dp-ucMGP) concentrations—a marker of vitamin K deficiency. Mean age was 68 years, and 89 participants (68%) were women. Vitamin K antagonists were used by 16 participants and multivitamin supplements by 50 participants. No differences in change between intervention and placebo were found (−38.5 ± 389 vs. 4.5 ± 127 (pmol/L), p = 0.562). When excluding vitamin K antagonist users and multivitamin users, dp-ucMGP at follow-up was significantly higher in the vitamin D group (n = 40) compared to placebo (n = 30), with a difference of 92.8 (5.7, 180) pmol/L, adjusting for baseline dp-ucMGP and sex. In conclusion, vitamin D supplementation for six months did not affect vitamin K status; however, among participants without vitamin K antagonist or multivitamin use, vitamin D supplementation influenced dp-ucMGP concentrations.

scholarly journals Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss

2009 ◽  
Vol 94 (9) ◽  
pp. 3356-3364 ◽  
Author(s):  
Sunil J. Wimalawansa ◽  
Julia P. Grimes ◽  
Alan C. Wilson ◽  
Donald R. Hoover
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Placebo Group ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Single Center ◽  
Mineral Density ◽  
Once Daily ◽  
Secondary Outcomes ◽  
Adjusted Dose

Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). Participants: Participants included 186 postmenopausal women aged 40–65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to −2.5. Intervention: Women, stratified by lumbar T-score (&lt;−1.50 and ≥−1.50) and years since menopause (≤5 and &gt;5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. Measurements: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. Results: After 36 months of therapy, changes of −2.1% in the active group (n = 88) and −2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval −1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P &lt; 0.001). Other adverse and serious adverse events were not different. Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only ∼16 mg/d); a sub-therapeutic dose. No substantial bone mineral density changes were observed between postmenopausal women receiving once-daily 22.5 mg of transdermal nitroglycerin, compared to calcium plus vitamin D (compliance adjusted dose = 16 mg/day).

scholarly journals Effects of Vitamin D and K on Interleukin-6 in COVID-19

2022 ◽  
Vol 8 ◽  
Author(s):  
Margot P. J. Visser ◽  
Anton S. M. Dofferhoff ◽  
Jody M. W. van den Ouweland ◽  
Henny van Daal ◽  
Cornelis Kramers ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Response ◽  
Vitamin K ◽  
Elastic Fiber ◽  
Matrix Gla Protein ◽  
Central Component ◽  
Hydroxyvitamin D ◽  
Fiber Degradation ◽  
Inflammatory Processes ◽  
25 Hydroxyvitamin D

BackgroundPathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.MethodsWe assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.ResultsComparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p &lt; 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p &lt; 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p &lt;0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.ConclusionsDp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.

scholarly journals Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients: An Observational Screening Study

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4101
Author(s):  
Ulf Schött ◽  
Cecilia Augustsson ◽  
Luukas Lilover ◽  
Caroline Ulfsdotter Nilsson ◽  
Louise Walther-Sturesson ◽  
...  
Keyword(s):  
Intensive Care ◽  
Vitamin K ◽  
Clinical Importance ◽  
Therapy Resistance ◽  
International Normalized Ratio ◽  
Matrix Gla Protein ◽  
Specific Gene ◽  
Vitamin K1 ◽  
Intensive Care Patients ◽  
Screening Study

Growth arrest-specific gene 6 protein (Gas6) is avitamin K-dependent tissue bound protein. Gas6 has been shown to promote growth and therapy resistance among different types of cancer as well as thromboembolism. The aim of this prospective screening study: ClinicalTrials.gov; Identifier: NTC3782025, was to evaluate the effects of intravenously administered vitamin K1 on Gas6 and its soluble (s)Axl receptor plasma levels in intensive care patients. Vitamin K1 was intravenously injected in non-warfarin treated patients with prolonged Owren prothrombin time international normalized ratio (PT-INR) > 1.2 and blood samples were retrieved before and 20–28 h after injection. Citrate plasma samples from 52 intensive care patients were analysed for different vitamin K dependent proteins. There was a significant, but small increase in median Gas6. Only one patient had a large increase in sAxl, but overall, no significant changes in sAxl Gas6 did not correlate to PT-INR, thrombin generation assay, coagulation factors II, VII, IX and X, but to protein S and decarboxylated matrix Gla protein (dp-ucMGP). In conclusion, there was a small increase in Gas6 over 20–28 h. The pathophysiology and clinical importance of this remains to be investigated. To verify a true vitamin K effect, improvement of Gas6 carboxylation defects needs to be studied.

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