scholarly journals Vitamin D and Mortality: A Mendelian Randomization Study

2013 ◽  
Vol 59 (5) ◽  
pp. 793-797 ◽  
Author(s):  
Olivia Trummer ◽  
Stefan Pilz ◽  
Michael M Hoffmann ◽  
Bernhard R Winkelmann ◽  
Bernhard O Boehm ◽  
...  

BACKGROUND Decreased circulating 25-hydroxy-vitamin D (25-OH-vitamin D) concentrations have been associated with mortality rates, but it is unclear whether this association is causal. We performed a Mendelian randomization study and analyzed whether 3 common single-nucleotide polymorphisms (SNPs) associated with 25-OH-vitamin D concentrations are causal for mortality rates. METHODS Genotypes of SNPs in the group-specific component gene (GC, rs2282679), 7-dehydrocholesterol reductase gene (DHCR7, rs12785878), and cytochrome P450 IIR-1 gene (CYP2R1, rs10741657) were determined in a prospective cohort study of 3316 male and female participants [mean age 62.6 (10.6) years] scheduled for coronary angiography between 1997 and 2000. 25-OH-vitamin D concentrations were determined by RIA. The main outcome measures were all-cause deaths, cardiovascular deaths, and noncardiovascular deaths. RESULTS In a linear regression model adjusting for month of blood sampling, age, and sex, vitamin D concentrations were predicted by GC genotype (P < 0.001), CYP2R1 genotype (P = 0.068), and DHCR7 genotype (P < 0.001), with a coefficient of determination (r2) of 0.175. During a median follow-up time of 9.9 years, 955 persons (30.0%) died, including 619 deaths from cardiovascular causes. In a multivariate Cox regression adjusted for classical risk factors, GC, CYP2R1, and DHCR7 genotypes were not associated with all-cause mortality, cardiovascular mortality, or noncardiovascular mortality. CONCLUSIONS Genetic variants associated with 25-OH-vitamin D concentrations do not predict mortality. This suggests that low 25-OH-vitamin D concentrations are associated with, but unlikely to be causal for, higher mortality rates.

Neurology ◽  
2019 ◽  
Vol 92 (12) ◽  
pp. e1387-e1394 ◽  
Author(s):  
Kirsty Bowman ◽  
Lindsay Jones ◽  
Luke C. Pilling ◽  
João Delgado ◽  
George A. Kuchel ◽  
...  

ObjectiveTo estimate effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models, which minimize confounding and exclude reverse causation.MethodsLongitudinal analysis using the UK Biobank, community-based, volunteer cohort (2006–2010) with incident hospital-diagnosed delirium (ICD-10 F05) ascertained during ≤9.9 years of follow-up of hospitalization records (to early 2016). We included volunteers of European descent aged 60-plus years by end of follow-up. We used single-nucleotide polymorphisms previously shown to increase circulating vitamin D levels, and APOE variants. Cox competing models accounting for mortality were used.ResultsOf 313,121 participants included, 544 were hospitalized with delirium during follow-up. Vitamin D variants were protective for incident delirium: hazard ratio = 0.74 per 10 nmol/L (95% confidence interval 0.62–0.87, p = 0.0004) increase in genetically instrumented vitamin D, with no evidence for pleiotropy (mendelian randomization–Egger p > 0.05). Participants with ≥1 APOE ε4 allele were more likely to develop delirium (e.g., ε4ε4 hazard ratio = 3.73, 95% confidence interval 2.68–5.21, p = 8.0 × 10−15 compared to ε3ε3), but there was no interaction with vitamin D variants.Conclusions and relevanceIn a large community-based cohort, there is genetic evidence supporting a causal role for vitamin D levels in incident delirium. Trials of correction of low vitamin D levels in the prevention of delirium are needed.


Author(s):  
Meenakshi Bothra ◽  
Nandita Gupta ◽  
Vandana Jain

AbstractThe treatment practices for vitamin D deficiency rickets are highly variable. Though a single intramuscular (IM) megadose of vitamin D is economical, and ensures good compliance, it poses the risk of hypervitaminosis D. This observational study was conducted to assess the duration of effect and safety of single IM megadose of cholecalciferol in the treatment of vitamin D deficiency rickets.Children younger than 14 years with rickets were enrolled. Baseline investigations included radiograph of wrists and estimation of serum calcium, phosphate, alkaline phosphatase (ALP), 25(OH) vitamin D and parathormone (PTH) levels. All children received a single IM megadose of vitamin D3. Biochemical parameters were re-evaluated at 1.5, 3 and 6 months after the megadose and the values were compared to the baseline.We enrolled 21 children, out of which nine remained under active follow-up till 6 months. Radiological evidence of rickets was present in all 21 children, 14 had hypocalcemia at the time of presentation. After IM cholecalciferol megadose, median 25 hydroxy vitamin D [25(OH)D] level remained significantly more than the baseline till 6 months after the megadose. At 1.5 months after the vitamin D megadose, three (30%) of the children were found to develop toxic levels of vitamin D (>150 ng/mL), although none had hypercalcemia or any clinical manifestation of vitamin D toxicity. At 3 months and 6 months after the megadose, 25(OH)D levels remained in the sufficient range (20–100 ng/mL) in seven out of the eight children who came for follow-up.A single IM megadose of vitamin D may be effective in significantly increasing the 25(OH)D levels for at least 6 months in children with rickets, but elevation of 25(OH)D to toxic range raises concern regarding its safety.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Jaeun Yang ◽  
Christopher Naugler ◽  
Lawrence de Koning

Background: It is unclear whether vitamin D deficiency is associated with a higher risk of cardiovascular disease, and through what biochemical pathways this could occur. We investigated the relationship between serum 25-OH vitamin D and typical cardiovascular risk markers as well as incident myocardial infarction (MI) in a large group of high-risk individuals from the community of Calgary, Alberta, Canada. Methods: Calgary Laboratory Services databases were queried for age, sex, body mass index (BMI), personal healthcare number (PHN) and first available serum 25-OH vitamin D measure from patients who received an electrocardiogram or urine creatinine clearance test from 2010-2013. Data was linked by PHN to first available laboratory results for total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol, fasting glucose and HbA1c as well as Alberta Health Services hospital discharge data for first myocardial infarction (ICD-10: I21.1-9) occurring after 25-OH vitamin D measurement. Multiple linear and logistic regression were used to examine all associations. Results: There were 36 000-50 000 complete patient records for analysis of each of the risk markers, with a median follow-up of 8-11 months. A 30 mmol/L increase in serum 25-OH vitamin D was associated with significantly (p<0.001) lower total cholesterol (-0.07 mmol/L), LDL cholesterol (-0.06 mmol/L), triglycerides (-0.14 mmol/L), fasting glucose (-0.12 mmol/L), and HbA1c (-0.13% mmol/L), but higher HDL cholesterol (+0.06 mmol/L) after adjusting for age, sex, BMI, monthly hours of sun-exposure and time between measures. Among these individuals, there were 458 cases of MI occurring after 25-OH vitamin D measurement, with a median follow-up of 1 year. In a case-cohort analysis that included 2500 controls, a 30 mmol/L increase in 25-OH vitamin D was associated with a 21% (p<0.001) lower odds of MI after multivariate adjustment. This association was strongly attenuated after adjusting LDL, HDL, fasting glucose and HbA1c. Conclusion: In a high-risk group of community patients from Calgary, Alberta, Canada, higher serum 25-OH vitamin D was associated with a lower risk of MI, which was explained by changes in commonly measured cardiovascular risk markers. Further study is needed to determine whether changes in cardiovascular risk markers are causally related to changes in 25-OH vitamin D.


2013 ◽  
Vol 109 (05) ◽  
pp. 885-890 ◽  
Author(s):  
Gunhild Lerstad ◽  
Guri Grimnes ◽  
Sigrid K. Brækkan ◽  
Anders Vik ◽  
Jan Brox ◽  
...  

SummaryPrevious studies have provided indirect evidence for a possible association between vitamin D status and risk of venous thromboembolism (VTE). However, no study has so far investigated the association between serum levels of 25-hydroxyvitamin D (25(OH)D), the biomarker of vitamin D status, and risk of VTE. The aim of our study was to investigate whether high levels of 25(OH)D were associated with decreased risk of VTE in a prospective population-based study. Serum levels of 25(OH)D were measured in 6,021 men and women, aged 25–84 years, who participated in the Tromsø Study in 1994–1995. Incident VTE-events were registered from date of inclusion through the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. There were 201 incident VTE-events during a median of 10.7 years of follow-up. The risk of VTE did not decrease per one standard deviation (SD) (19.8 nmol/l) increase in serum 25(OH)D (multivariable HR 1.02; 95% CI 0.91–1.22). Moreover, subjects with serum 25(OH)D ≥ 70 nmol/l (upper quartile) did not have decreased risk of VTE compared to those ≤ 44 nmol/l (lower quartile) in age- and sex-adjusted analysis (HR 0.91, 95% CI: 0.60–1.37, p for trend across quartiles 0.9) or multivariable analysis adjusted for age, sex, body mass index, smoking, and physical activity (HR 0.76, 95% CI: 0.45–1.28, p for trend across quartiles 0.9). Subgroup analyses showed no associations between serum levels of 25(OH)D and unprovoked or provoked VTE. In conclusion, in our study, normal serum levels of 25(OH)D were not associated with future risk of VTE, suggesting that vitamin D status does not play an important role in the pathogenesis of VTE. However, our findings did not apply to subjects with vitamin D deficiency (< 30 nmol/l) due to lack of statistical power among these subjects.


Author(s):  
ABDULNASSER M AL-GEBORI ◽  
MOHAMMED HADI MUNSHED ALOSAMI ◽  
NAWAL HAIDER AL-HASHIMI

Objectives: The objectives of the study were to evaluate changes in 25(OH) Vitamin D levels and some biochemical parameters in rheumatoid arthritis (RA) patients compared with healthy controls and assess the correlation of 25-hydroxy Vitamin D, calcium, magnesium, and disease activity. Study the effects of anti-RA drugs on these biochemical parameters and also the role of supplements calcium and 25-OH Vitamin D in RA patients. Methods: This study conducted between 60 patients for RA and 20 healthy controls according to the American College of Rheumatology standards in 2010. In this study, 25-hydroxy Vitamin D was measured using an enzyme-linked immunosorbent assay, and also some biochemical parameters were measured with a spectrophotometer (Humalyzer 2000). Results: Serum 25(OH) Vitamin D, calcium, magnesium, and albumin levels were significantly lower in RA patients compared with healthy controls. Serum alanine aminotransferase aspartate aminotransferase levels were significantly increased in RA patients compared with healthy controls. The correlation was non-significantly among 25-hydroxy Vitamin D and clinical disease activity index (CDAI), while the results showed significantly inverse correlation calcium and magnesium concentrations with CDAI. Conclusion: 25-OH Vitamin D, calcium, albumin, and magnesium deficiency appear to be widespread in patients with RA. Thus, biochemical changes in RA are reflected in the pathogenesis of RA. Furthermore, in these results, there is no relationship between Vitamin D and the disease activity, while there is a relationship between calcium and magnesium with disease activity.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S484-S484
Author(s):  
Hrafnhildur Eymundsdottir ◽  
Milan Chang ◽  
Olof Geirsdottir ◽  
Maria Jonsdottir ◽  
Palmi V Jonsson ◽  
...  

Abstract Studies have indicated that low levels of serum 25 hydroxy vitamin D (25OHD) are associated with lower cognitive function among older adults while longitudinal studies have revealed controversial results. The aim was to investigate the longitudinal associations between 25OHD and cognitive function among older adults with 5-years follow up. The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (N=3411) assessed cognitive function measuring memory function, speed of processing and executive function. 25OHD was measured using the Liaison chemiluminescence immunoassay and used as a continuous variable. Multivariate linear analysis, adjusting for numerous confounding factors, was used to calculate the longitudinal associations. All analyses were performed separated by gender. There was a high tendency for low levels of 25OHD i.e. 29.6% men and 37.7% women had hypovitaminosis D (&lt;50 nmol/l). Both men and women had significantly lower scores in all aspects of cognitive function at the follow-up time period. Unadjusted correlations between 25OHD and cognitive functions showed a stronger correlation for women, whereas women had lower scores in all aspects of cognitive function associated with low 25OHD. After adjusting for potential confounders, e.g. age, education, lifestyle and health-related factors, 25OHD and cognitive function were not significantly associated. Observational studies indicate that lower levels of vitamin D are associated with lower cognitive function. Intervention studies are yet to show a clear benefit from vitamin D supplementation. More longitudinal- and interventional studies, with longer follow-up duration, are needed.


2018 ◽  
Vol 97 (08) ◽  
pp. 524-525
Author(s):  
Klaus Weckbecker

Martineau AR. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583 Vitamin D spielt Studien zufolge auch eine Rolle bei der Abwehr pathogener Keime: 25-Hydroxy-Vitamin D (25[OH] Vitamin D) unterstützt z. B. die Synthese antimikrobieller Peptide. Es gibt also eine mögliche Erklärung für die Beobachtung, dass Personen mit niedrigen Vitamin-D-Spiegeln besonders empfindlich gegenüber respiratorischen Infekten sind. Untersuchungen zu einer präventiven Wirkung des Vitamin D verliefen jedoch zum Teil widersprüchlich.


2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 6111-6111
Author(s):  
S. K. Taylor ◽  
M. Ennis ◽  
N. S. Hood ◽  
M. Graham ◽  
K. I. Pritchard ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
A. Martinez-Hernandez ◽  
E. E. Perez-Guerrero ◽  
M. A. Macias-Islas ◽  
C. A. Nava-Valdivia ◽  
A. Villagomez-Vega ◽  
...  

Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls ( p = 0.009 ). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression ( p = 0.88 ). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls ( p = 0.05 ). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 ( p = 0.65 ). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls ( p = 0.03 ). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 ( p = 0.63 ). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.


Sign in / Sign up

Export Citation Format

Share Document