scholarly journals Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study

2020 ◽  
Vol 111 (5) ◽  
pp. 1036-1047 ◽  
Author(s):  
Saranya Palaniswamy ◽  
Dipender Gill ◽  
N Maneka De Silva ◽  
Estelle Lowry ◽  
Jari Jokelainen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Acute Phase Proteins ◽  
Causal Effect ◽  
Vitamin D Supplementation ◽  
Inflammatory Biomarkers ◽  
Intercellular Adhesion Molecule ◽  
Hs Crp

ABSTRACT Background Obesity is associated with inflammation but the role of vitamin D in this process is not clear. Objectives We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. Methods Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. Results In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. Conclusions The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

scholarly journals Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiyong Cui ◽  
Yun Tian
Keyword(s):  
Vitamin D ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Sensitivity Analyses ◽  
Global Test ◽  
Serum Vitamin D

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial. Methods We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. Results We found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility [IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197–0.9988, p = 0.0473], severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699–1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819–1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy. Conclusions Our MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

scholarly journals The causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study

2021 ◽  
Author(s):  
Zhiyong Cui ◽  
Yun Tian
Keyword(s):  
Vitamin D ◽  
Fixed Effects ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Sensitivity Analyses ◽  
Global Test ◽  
Serum Vitamin D

AbstractBackgroundEvidence supporting the role of vitamin D in the coronavirus disease 2019 (COVID-19) pandemic remains controversial.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic.ResultsWe found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility (IVW-fixed: odds ratio [OR] = 0.9049, 95% confidence interval [CI] 0.8197∼0.9988, p = 0.0473), severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699∼1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819∼1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.ConclusionsOur MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study therefore did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

scholarly journals Effect of Vitamin D Supplementation on Some Inflammatory Biomarkers in Type 2 Diabetes Mellitus Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 73 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Yanting Yu ◽  
Liqiang Tian ◽  
Yanyu Xiao ◽  
Guowei Huang ◽  
Meilin Zhang
Keyword(s):  
Vitamin D ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
Inflammatory Biomarkers ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Tnf Α ◽  
Hs Crp

Background/Aims: The mechanism, by which vitamin D influences inflammatory biomarkers in type 2 diabetes mellitus (T2DM), is not very well known. Thus, a meta-analysis of randomized controlled trials was conducted to assess the effect of vitamin D supplementation on some inflammatory biomarkers in T2DM subjects. Methods: We searched randomized controlled trials from PubMed and the Cochrane Library in October 2017 and conducted a meta-analysis to evaluate the effectiveness of vitamin D supplementation on high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Either a fixed-effects or a random-effects model was used to calculate pooled effects. Results: We identified 13 studies that met our inclusion criteria. The results indicated that the vitamin D supplementation significant decreased the hs-CRP level by 0.45 μg/mL, whereas the vitamin D supplementation did not  influence the TNF-α and IL-6. Subgroup analysis showed that vitamin D significantly lowered hs-CRP by 0.34 μg/mL among trials with a daily vitamin D dose ≤4,000 IU and by 0.31 μg/mL among trials with time of vitamin D supplementation > 12 weeks. Conclusions: Vitamin D supplementation is beneficial for the reduction of hs-CRP inT2DM subjects but does not have a significant influence on TNF-α and IL-6 in T2DM subjects.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review

2020 ◽  
pp. 1-8
Author(s):  
Daniela Menichini ◽  
Gianpiero Forte ◽  
Beatrice Orrù ◽  
Giuseppe Gullo ◽  
Vittorio Unfer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Polycystic Ovary Syndrome ◽  
Embryo Quality ◽  
Polycystic Ovary ◽  
Vitamin D Supplementation ◽  
Endometrial Receptivity ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
Beneficial Role

Abstract. Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400–800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

A Preliminary Report on Alcohol-Associated DNA Methylation Changes and Suicidal Behavior: Evidence Using Mendelian Randomization

2021 ◽  
pp. 105413732095224
Author(s):  
Charleen D. Adams
Keyword(s):  
Public Health ◽  
Dna Methylation ◽  
Suicidal Behavior ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Economic Stress ◽  
Self Report ◽  
Health Concern ◽  
The Us

Suicide is a major public health concern. In 2015, it was the 10th leading cause of death in the US. The number of suicides increased by 30% in the US from 1999 to 2016, and a greater uptick in suicides is predicted to occur as a result of the COVID-19 crisis, for which the primary public-health strategy is physical distancing and during which alcohol sales have soared. Thus, current strategies for identifying at-risk individuals and preventing suicides, such as relying on self-reported suicidal ideation, are insufficient, especially under conditions of physical distancing, which exacerbate isolation, loneliness, economic stress, and possibly alcohol consumption. New strategies are urgent now and into the future. To that aim, here, a two-sample Mendelian randomization (an instrumental variables technique using public genome-wide association study data as data sources) was performed to determine whether alcohol-associated changes in DNA methylation mediate risk for suicidal behavior. The results suggest that higher alcohol-associated DNA methylation levels at cg18120259 confer a weak causal effect. Replication and triangulation of the results, both experimentally and with designs other than Mendelian randomization, are needed. If the findings replicate, the information might be utilized to raise awareness about the biological links between alcohol and suicide and possibly explored as a biomarker of risk, perhaps especially for early detection of those who may not self-report suicidal intent.

scholarly journals Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence

2021 ◽  
pp. bmjmilitary-2020-001686
Author(s):  
Iain T Parsons ◽  
R M Gifford ◽  
M J Stacey ◽  
L E Lamb ◽  
M K O'Shea ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Military Studies ◽  
Vitamin D Receptors ◽  
Area Of Interest ◽  
Military Populations ◽  
Tract Infections ◽  
Recruit Training

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed.

scholarly journals Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis

QJM ◽  
2021 ◽  
Author(s):  
K Shah ◽  
D Saxena ◽  
D Mavalankar
Keyword(s):  
Vitamin D ◽  
Randomized Controlled Trials ◽  
Usual Care ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
Hospitalized Patients ◽  
Controlled Trials ◽  
Randomized Controlled

Abstract Objective: Current meta-analysis aims to understand the effect of oral supplementation of vitamin D on intensive care unit (ICU) requirement and mortality in hospitalized COVID-19 patients. Methods: Databases PubMed, preprint servers, and google scholar were searched from December 2019 to December 2020. Authors searched for the articles assessing role of vitamin D supplementation on COVID-19. Cochrane RevMan tool was used for quantitative assessment of the data, where heterogeneity was assessed using I2 and Q statistics and data was expressed using odds ratio with 95% confidence interval. Results: Final meta-analysis involved pooled data of 532 hospitalized patients (189 on vitamin D supplementation and 343 on usual care/placebo) of COVID-19 from three studies (Two randomized controlled trials, one retrospective case-control study). Statistically (p<0.0001) lower ICU requirement was observed in patients with vitamin D supplementation as compared to patients without supplementations (odds ratio: 0.36; 95% CI: 0.210-0.626). However, it suffered from significant heterogeneity, which reduced after sensitivity analysis. In case of mortality, vitamin D supplements has comparable findings with placebo treatment/usual care (odds ratio: 0.93; 95% CI: 0.413-2.113; p=0.87). The studies did not show any publication bias and had fair quality score. Subgroup analysis could not be performed due to limited number of studies and hence dose and duration dependent effect of vitamin D could not be evaluated. Conclusions: Although the current meta-analysis findings indicate potential role of vitamin D in improving COVID-19 severity in hospitalized patients, more robust data from randomized controlled trials are needed to substantiate its effects on mortality.

scholarly journals The Causal Effect of Vitamin D Binding Protein (DBP) Levels on Calcemic and Cardiometabolic Diseases: A Mendelian Randomization Study

PLoS Medicine ◽  
2014 ◽  
Vol 11 (10) ◽  
pp. e1001751 ◽  
Author(s):  
Aaron Leong ◽  
Waheed Rehman ◽  
Zari Dastani ◽  
Celia Greenwood ◽  
Nicholas Timpson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Binding Protein ◽  
Vitamin D Binding Protein ◽  
Cardiometabolic Diseases
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