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COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis.
Borsche, L, Glauner, B, von Mendel, J
Nutrients. 2021;(10)
Abstract
BACKGROUND Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. METHODS Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex, and diabetes. Data were analyzed using correlation and linear regression. RESULTS One population study and seven clinical studies were identified, which reported D3 blood levels preinfection or on the day of hospital admission. The two independent datasets showed a negative Pearson correlation of D3 levels and mortality risk (r(17) = -0.4154, p = 0.0770/r(13) = -0.4886, p = 0.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/mL (17.4-26.8), and a significant Pearson correlation was observed (r(32) = -0.3989, p = 0.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/mL D3. CONCLUSIONS The datasets provide strong evidence that low D3 is a predictor rather than just a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/mL to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.
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Vitamin D exposure and Risk of Breast Cancer: a meta-analysis.
Estébanez, N, Gómez-Acebo, I, Palazuelos, C, Llorca, J, Dierssen-Sotos, T
Scientific reports. 2018;(1):9039
Abstract
UNLABELLED The relationship between vitamin D and breast cancer is still controversial. The present meta-analysis examines the effects of the 25(OH)D, 1,25(OH)2D and vitamin D intake on breast cancer risk. For this purpose, a PubMed, Scopus and Web of Science-databases search was conducted including all papers published with the keywords "breast cancer" and "vitamin D" with at least one reported relative risk (RR) or odds ratio (OR). In total sixty eight studies published between 1998 and 2018 were analyzed. Information about type of study, hormonal receptors and menopausal status was retrieved. Pooled OR or RR were estimated by weighting individual OR/RR by the inverse of their variance Our study showed a protective effect between 25 (OH) D and breast cancer in both cohort studies (RR = 0.85, 95%CI:0.74-0.98) and case-control studies (OR = 0.65, 95%CI: 0.56-0.76). However, analyzing by menopausal status, the protective vitamin D - breast cancer association persisted only in the premenopausal group (OR = 0.67, 95%CI: 0.49-0.92) when restricting the analysis to nested case-control studies. No significant association was found for vitamin D intake or 1,25(OH)2D. CONCLUSION This systematic review suggests a protective relationship between circulating vitamin D (measured as 25(OH) D) and breast cancer development in premenopausal women.
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The seasonality of slipped upper femoral epiphysis--meta-analysis: a possible association with vitamin D.
Farrier, AJ, Ihediwa, U, Khan, S, Kumar, A, Gulati, V, Uzoigwe, CE, Choudhury, MZ
Hip international : the journal of clinical and experimental research on hip pathology and therapy. 2015;(6):495-501
Abstract
We performed a meta-analysis of studies evaluating the seasonality of slipped upper femoral epiphysis (SUFE). In addition we compared the monthly incidences of SUFE at latitudes greater than 40° with the established serum 25-hydroxyvitamin levels for children resident at a comparative latitude. In total 11 relevant studies were identified, involving 7451 cases of SUFE. There was significant variation in the month of onset of SUFE. The degree of variability increased with increasing latitude. The modal month of symptomatic onset was dependent upon latitude. At latitudes greater than 40°, the most common month of onset was August. At latitudes between 20° and 40°, this was earlier in the calendar year, around April. The seasonal variability was statistically significant (p<0.0001 and p<0.005 for latitudes >40° and 20°-40° respectively). The pattern of monthly fluctuation in onset of SUFE very closely mirrored the monthly pattern of variation for serum 25-hydroxyvitamin D3. There was a very strong positive correlation (Spearman rank rho = + 0.8, p = 0.001). There is a monthly variation in incidence of SUFE. The degree of variability increases with increasing latitude. There may be an association with vitamin D. We hypothesise that elevated serum 25-hydroxyvitamin D3 accelerates growth thus rendering the growth plate vulnerable to slippage in analogous manner to the pubertal growth spurt.
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Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis.
Lu, C, Yang, J, Yu, W, Li, D, Xiang, Z, Lin, Y, Yu, C
PloS one. 2015;(7):e0132036
Abstract
BACKGROUND There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD). AIM: To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD. METHODS We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs). RESULTS Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09-0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15-0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48-2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13-3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index ≥ 150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence. CONCLUSION Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study.
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Vitamin D in ankylosing spondylitis: review and meta-analysis.
Cai, G, Wang, L, Fan, D, Xin, L, Liu, L, Hu, Y, Ding, N, Xu, S, Xia, G, Jin, X, et al
Clinica chimica acta; international journal of clinical chemistry. 2015;:316-22
Abstract
BACKGROUND The role of vitamin D in ankylosing spondylitis (AS) is largely unknown. This paper aims to examine the association between serum vitamin D levels and susceptibility and disease activity of AS. METHODS We searched the relevant literatures in PubMed, Elsevier Science Direct, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) Database published before June 2014. Eight independent case-control studies with a total of 533 AS patients and 478 matching controls were selected into this meta-analysis. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the levels of serum vitamin D, parathyroid hormone (PTH), serum calcium and alkaline phosphatase (ALP) in cases and controls, respectively. Correlation coefficients (CORs) have been performed to value the correlationship between vitamin D and disease activity (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) of AS patients. RESULTS Meta-analysis results suggested that vitamin D may play a protective role in AS (for total vitamin D: SMD=-0.71, P<0.001; for 25OHD: SMD=-0.66, P=0.002; for 1,25OHD: SMD=-0.72, P=0.19). Differences in PTH and serum calcium levels were not significant in AS (SMD=-0.10, P=0.67; SMD=0.12, P=0.17 respectively), while ALP was associated with AS susceptibility (SMD=0.20, P=0.04). The relationship between serum vitamin D levels and disease activity was statistically significant except for 25OHD versus (vs.) CRP or BASDAI (for CRP vs. 25OHD: COR=-0.22, P=0.08; for BASDAI vs. 25OHD: COR=-0.20, P=0.06, respectively). CONCLUSION The higher levels of serum vitamin D were associated with a decreased risk of AS, and showed an inverse relationship with AS activity.
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Blood 25-hydroxyvitamin D3 concentrations and incident sporadic colorectal adenoma risk: a pooled case-control study.
Fedirko, V, Bostick, RM, Goodman, M, Flanders, WD, Gross, MD
American journal of epidemiology. 2010;(5):489-500
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Abstract
The authors examined the association between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)), the best indicator of total vitamin D exposure, and incident, sporadic colorectal adenoma risk in a pooled analysis of primary data from 3 colonoscopy-based case-control studies conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. The pooled study included 616 colorectal adenoma cases and 770 polyp-free controls. Multivariable logistic regression was used to estimate the association between circulating 25(OH)D(3) and colorectal adenoma risk. Stratified analyses and the likelihood ratio test were used to examine effect modification by various risk factors. In the pooled analysis, higher circulating 25(OH)D(3) concentrations were statistically significantly associated with decreased colorectal adenoma risk (highest vs. lowest quartile odds ratio = 0.59, 95% confidence interval: 0.41, 0.84). The observed inverse association was stronger among participants who used nonsteroidal antiinflammatory drugs regularly (highest vs. lowest quartile odds ratio = 0.33, 95% confidence interval: 0.19, 0.56). Inverse associations between 25(OH)D(3) and colorectal adenoma did not differ substantially by other risk factors or by adenoma characteristics. These findings support the hypothesis that greater vitamin D exposure may reduce the risk of colorectal adenoma and suggest that it may do so more strongly in combination with antiinflammatory agents.