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 < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <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 & 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 <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 (<20ng/mL) had the worse vitamin K status (dp-ucMGP >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 Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019

2020 ◽  
Author(s):  
Anton S M Dofferhoff ◽  
Ianthe Piscaer ◽  
Leon J Schurgers ◽  
Margot P J Visser ◽  
Jody M W van den Ouweland ◽  
...  
Keyword(s):  
Vitamin K ◽  
Elastic Fiber ◽  
Protein S ◽  
Coagulation Factors ◽  
Matrix Gla Protein ◽  
Arterial Calcification ◽  
Fiber Damage ◽  
Fiber Degradation ◽  
Factor Ii ◽  
Poor Outcomes

Abstract Background Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2–infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. Methods A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K–dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography. Results dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores. Conclusions dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.

scholarly journals Vitamin D deficiency is associated with anaemia among African Americans in a US cohort

2015 ◽  
Vol 113 (11) ◽  
pp. 1732-1740 ◽  
Author(s):  
Ellen M. Smith ◽  
Jessica A. Alvarez ◽  
Greg S. Martin ◽  
Susu M. Zughaier ◽  
Thomas R. Ziegler ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Bivariate Analysis ◽  
Vitamin D Status ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
The Us ◽  
Inflammatory Processes ◽  
25 Hydroxyvitamin D ◽  
Sectional Analysis

Vitamin D deficiency is highly prevalent in the US population and is associated with numerous diseases, including those characterised by inflammatory processes. We aimed to investigate the link between vitamin D status and anaemia, hypothesising that lower vitamin D status would be associated with increased odds of anaemia, particularly anaemia with inflammation. A secondary aim was to examine the effects of race in the association between vitamin D status and anaemia. We conducted a cross-sectional analysis in a cohort of generally healthy adults in Atlanta, GA (n 638). Logistic regression was used to evaluate the association between vitamin D status and anaemia. Serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l (compared to 25(OH)D ≥ 50 nmol/l) was associated with anaemia in bivariate analysis (OR 2·64, 95 % CI 1·43, 4·86). There was significant effect modification by race (P= 0·003), such that blacks with 25(OH)D < 50 nmol/l had increased odds of anaemia (OR 6·42, 95 % CI 1·88, 21·99), v. blacks with 25(OH)D ≥ 50 nmol/l, controlling for potential confounders; this association was not apparent in whites. When categorised by subtype of anaemia, blacks with 25(OH)D < 50 nmol/l had significantly increased odds of anaemia with inflammation than blacks with serum 25(OH)D ≥ 50 nmol/l (OR 8·42, 95 % CI 1·96, 36·23); there was no association with anaemia without inflammation. In conclusion, serum 25(OH)D < 50 nmol/l was significantly associated with anaemia, particularly anaemia with inflammation, among blacks in a generally healthy adult US cohort.

scholarly journals Association of 25-hydroxyvitamin D and Anemia parameters in elderly with anemia of inflammation and non-inflammation

2018 ◽  
Vol 17 (2) ◽  
pp. 302-306
Author(s):  
Vitasari Indriani ◽  
Nyoman Suci W ◽  
Herniah Asti W
Keyword(s):  
Vitamin D ◽  
Medical Science ◽  
The Elderly ◽  
World Health ◽  
Hydroxyvitamin D ◽  
Cell Counts ◽  
Inflammatory Mechanism ◽  
Inflammatory Processes ◽  
25 Hydroxyvitamin D ◽  
Anemia Of Inflammation

Background: Vitamin D deficiency and anemia are conditions commonly in eldery. Both result in significant morbidity in eldery. Relationship between 25-hydroxyvitamin D and anemia need to be concern, particularly in the elderly. including those characterized by inflammatory processes. The aim of this study is to analyze association and differentiations between of 25-hydroxyvitamin D levels and anemia parameters in elderly with anemia inflammation and non-inflammation.Methods: An observational study, at Posyandu Lansia Puskesmas Sokaraja, was conducted among 40 subjects aged ≥60 years consecutively, between September - November 2015. 25-Hydroxyvitamin D, hemoglobin levels, hematocrit and red blood cell counts were measured. 25-Hydroxyvitamin D deficiency defined in level <30 ng/mL and anemia defined by the World Health Organization.Results: After adjustment for CRP levels and leucocyte count, 25-Hydroxyvitamin D was inversely associated with anemia inflammation (p=0,018; p=0,010; p=0,000)and non-inflammation (p= 0,002; p=0,002; p=0,000). There was significantly differences 25-hydroxyvitamin D levels (p = 0.003) in elderly with anemia of inflammation and non-inflammation.Conclusion: 25-Hydroxyvitamin D levels was associated with anemia inflammation and non-inflammation in eldery. Vitamin D may suppress inflammatory mechanism, and studies to determine whether chronic disease involves anemia inflamation are warranted.Bangladesh Journal of Medical Science Vol.17(2) 2018 p.302-306

scholarly journals Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

2020 ◽  
Author(s):  
Anton S.M. Dofferhoff ◽  
Ianthe Piscaer ◽  
Leon J. Schurgers ◽  
Jona Walk ◽  
Jody M.W. van den Ouweland ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Elastic Fiber ◽  
Significant Proportion ◽  
Protein S ◽  
Matrix Gla Protein ◽  
Prothrombin Activity ◽  
Pneumonia Severity ◽  
Fiber Degradation ◽  
Thoracic Aortic Calcification

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P&lt;0.001), thoracic aortic calcification (P&lt;0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

scholarly journals Vitamin D – contrary to vitamin K – does not associate with clinical outcome in hospitalized COVID-19 patients

2020 ◽  
Author(s):  
Jona Walk ◽  
Anton S.M. Dofferhoff ◽  
Jody M.W. van den Ouweland ◽  
Henny van Daal ◽  
Rob Janssen
Keyword(s):  
Vitamin D ◽  
Clinical Outcome ◽  
Vitamin K ◽  
Elastic Fiber ◽  
Vitamin D Status ◽  
Vitamin K Deficiency ◽  
Fiber Degradation ◽  
K Deficiency ◽  
Mild Deficiency ◽  
Asymptomatic Individuals

AbstractSARS-CoV-2 causes remarkably variable disease from asymptomatic individuals to respiratory insufficiency and coagulopathy. Vitamin K deficiency was recently found to associate with clinical outcome in a cohort of COVID-19 patients. Vitamin D has been hypothesized to reduce disease susceptibility by modulating inflammation, yet little is known about its role in disease severity. Considering the critical interaction between vitamin K and vitamin D in calcium and elastic fiber metabolism, we determined vitamin D status in the same cohort of 135 hospitalized COVID-19 patients by measuring blood 25(OH)D levels. We found no difference in vitamin D status between those with good and poor outcome (defined as intubation and/or death). Instead, we found vitamin D sufficient persons (25(OH)D >50 nmol/L) had accelerated elastic fiber degradation compared to those with mild deficiency (25(OH)D 25-50 nmol/L). Based on these findings, we hypothesize that vitamin D might have both favorable anti-inflammatory and unfavorable pro-calcification effects during COVID-19 and that vitamin K might compensate for the latter.

Depressed Serum 25-Hydroxyvitamin D Levels Increase Hospital Stay and Alter Glucose Homeostasis in First-ever Ischemic Stroke

2019 ◽  
Vol 16 (4) ◽  
pp. 340-347
Author(s):  
Yuge Wang ◽  
Yanqiang Wang ◽  
Bingjun Zhang ◽  
Yinyao Lin ◽  
Sha Tan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ischemic Stroke ◽  
Hospital Stay ◽  
Functional Outcome ◽  
Vitamin D Deficiency ◽  
Glucose Homeostasis ◽  
Clinical Severity ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Deficiency Group

Background and Objective: Vitamin D deficiency is internationally recognized among the potentially modifiable risk factors for ischemic cardio-cerebrovascular diseases. However, the association between vitamin D deficiency and stroke morbidity or mortality remains insufficiently known. Our aim is to investigate their relevance to 25-hydroxyvitamin D [25(OH) D] levels and clinical severity and outcome after 3 months in first-ever ischemic stroke. Methods: Retrospective analysis of 356 consecutive patients in first-ever ischemic stroke between 2013 and 2015. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome after 3 months of onset was evaluated using the modified Rankin scale (mRS). Results: Among the 356 enrolled patients, HbA1c was higher in insufficiency/deficiency group than that in the sufficiency group (6.3 ± 1.7 vs. 5.9 ± 1.1, p =0.015). The hospital stay was longer in insufficiency/deficiency group than that in the sufficiency group (11 (8-17) vs. 9.5 (7-13), p = 0.035). There was a significant inversed trend between serum 25(OH) D levels and hospital stay (OR 0.960, P = 0.031), using logistic regression. Conclusions: 25(OH)D levels are associated with glucose homeostasis, 25(OH) D contributes to increase the length of hospital stay. Low serum 25-OHD level is an independent predictor for hospital stay in first-ever ischemic stroke. Vitamin D deficiency did not predict functional outcome in the span of 3 months.

scholarly journals Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice

2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.

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