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1.
Sunlight Exposure and Vitamin D Levels in Older People- An Intervention Study in Swedish Nursing Homes.
Samefors, M, Tengblad, A, Östgren, CJ
The journal of nutrition, health & aging. 2020;(10):1047-1052
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Abstract
OBJECTIVES Older people are recommended to take oral vitamin D supplements, but the main source of vitamin D is sunlight. Our aim was to explore whether active encouragement to spend time outdoors could increase the levels of serum 25-hydroxyvitamin D (25(OH)D) and increase the mental well-being of nursing home residents. DESIGN A cluster randomized intervention trial. SETTING Nursing homes in southern Sweden. PARTICIPANTS In total 40 people >65 years. INTERVENTION The intervention group was encouraged to go outside for 20-30 minutes between 11 a.m. and 3 p.m. every day for two months during the summer of 2018. MEASUREMENTS We analyzed serum 25(OH)D before and after the summer. Data from SF-36 questionnaires measuring vitality and mental health were used for the analyses. RESULTS In the intervention group, the baseline median (interquartile range (IQR)) of serum 25(OH)D was 42.5 (23.0) nmol/l and in the control group it was 52.0 (36.0) nmol/l. In the intervention group, the 25(OH)D levels increased significantly during the summer (p=0.011). In the control group, there was no significant change. The intervention group reported better self-perceived mental health after the summer compared to before the summer (p=0.015). In the control group, there was no difference in mental health. CONCLUSION Active encouragement to spend time outdoors during summertime improved the levels of serum 25(OH)D and self-perceived mental health significantly in older people in nursing homes and could complement or replace oral vitamin D supplementation in the summer.
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Vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children.
Chibuzor, MT, Graham-Kalio, D, Osaji, JO, Meremikwu, MM
The Cochrane database of systematic reviews. 2020;(4):CD012581
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Abstract
BACKGROUND Nutritional rickets is a disease which affects children, especially in low- and middle-income countries. It causes problems such as skeletal deformities and impaired growth. The most common cause of nutritional rickets is vitamin D deficiency. Vitamin D administered with or without calcium is commonly regarded as the mainstay of treatment. In some sunny countries, however, where children are believed to have adequate vitamin D production from exposure to ultraviolet light, but who are deficient in calcium due to low dietary intake, calcium alone has also been used in the treatment of nutritional rickets. Therefore, it is important to compare the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children living in different settings. OBJECTIVES To assess the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children. SEARCH METHODS We searched CENTRAL, MEDLINE, LILACS, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 25 July 2019. We applied no language restrictions. SELECTION CRITERIA We included randomised controlled trials (RCT) involving children aged 0 to 18 years with nutritional rickets which compared treatment with vitamin D, calcium or a combination of vitamin D and calcium. DATA COLLECTION AND ANALYSIS Two review authors independently screened the title and abstracts of all studies, extracted data and assessed the risk of bias of included studies. We resolved any disagreements by consensus or recourse to a third review author. We conducted meta-analyses for the outcomes reported by study authors. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI) and, for continuous outcomes, we calculated mean differences (MD) with 95% CIs. We assessed the certainty of the evidence of the included studies using GRADE. MAIN RESULTS We identified 4562 studies; of these, we included four RCTs with 286 participants. The studies compared two or more of the following: vitamin D, calcium or vitamin D plus calcium. The number of participants randomised to receive vitamin D was 64, calcium was 102 and vitamin D plus calcium was 120. Two studies were conducted in India and two were conducted in Nigeria. None of the included studies had a low risk of bias in all domains. Three studies had a high risk of bias in at least one domain. The age of the participants ranged between six months and 14 years. The duration of follow-up ranged between 12 weeks and 24 weeks. Two studies compared vitamin D to calcium. There is low-certainty evidence that, at 24 weeks' follow-up, calcium alone improved the healing of rickets compared to vitamin D alone (RR 3.26, 95% CI 1.59 to 6.69; P = 0.001; 1 study, 71 participants). Comparing vitamin D to calcium showed no firm evidence of an advantage or disadvantage in reducing morbidity (fractures) (RR 0.27, 95% CI 0.03 to 2.32; P = 0.23; 1 study, 71 participants; very low-certainty evidence). Adverse events were not reported. Two studies compared vitamin D plus calcium to vitamin D at 12 or 24 weeks. Vitamin D plus calcium improved healing of rickets compared to vitamin D alone at 24 weeks' follow-up (RR 3.06, 95% CI 1.49 to 6.29; P = 0.002; 1 study, 75 participants; low-certainty evidence). There is no conclusive evidence in favour of either intervention for reducing morbidity (fractures) (RR 0.24, 95% CI 0.03 to 2.08; P = 0.20; 1 study, 71 participants; very low-certainty evidence) or adverse events (RR 4.76, 95% CI 0.24 to 93.19; P = 0.30; 1 study, 39 participants; very low-certainty evidence). All four included studies compared vitamin D plus calcium to calcium at different follow-up times. There is no conclusive evidence on whether vitamin D plus calcium in comparison to calcium alone improved healing of rickets at 24 weeks' follow-up (RR 1.17, 95% CI 0.72 to 1.90; P = 0.53; 2 studies, 140 participants; very low-certainty evidence). Evidence is also inconclusive for morbidity (fractures) (RR 0.89, 95% CI 0.06 to 13.76; P = 0.94; 1 study, 72 participants; very low-certainty evidence) and adverse events (RR 4.29, 0.22 to 83.57; P = 0.34; 1 study, 37 participants; very low-certainty evidence). Most of the evidence in the review is low or very low certainty due to risk of bias, imprecision or both. None of the included studies assessed all-cause mortality, health-related quality of life or socioeconomic effects. One study assessed growth pattern but this was not measured at the time-point stipulated in the protocol of our review (one or more years after commencement of therapy). AUTHORS' CONCLUSIONS This review provides low-certainty evidence that vitamin D plus calcium or calcium alone improve healing in children with nutritional rickets compared to vitamin D alone. We are unable to make conclusions on the effects of the interventions on adverse events or morbidity (fractures).
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The Role of Vitamin D in the Development of Diabetes Post Gestational Diabetes Mellitus: A Systematic Literature Review.
Keller, A, Varela Vazquez, C, Dangol, R, Damm, P, Heitmann, BL, Händel, MN
Nutrients. 2020;(6)
Abstract
Women diagnosed with gestational diabetes mellitus (GDM) are more likely to later develop diabetes. Evidence from some previous reviews suggests that low vitamin D status during pregnancy increases the risk of developing GDM, but whether vitamin D during pregnancy also influences the risk of diabetes post GDM is less well studied. Thus, the aim of this systematic literature review was to summarize the current available literature on that topic. This review considered observational studies and randomized controlled trials (RCTs). Five databases were searched. The risk of bias of the included studies was assessed. A total of six studies were included: three observational studies and three RCTs. Findings were inconsistent across the six included studies. However, when considering RCTs only, the findings more strongly suggested that vitamin D supplementation during and after pregnancy did not have an influence on markers of diabetes development or diabetes development post GDM. This systematic review highlights inconsistent findings on the associations between vitamin D supplementation or concentration during and after pregnancy and markers of diabetes development or diabetes development post GDM; and although results from randomized interventional studies more strongly suggested no associations, the conclusion holds a high degree of uncertainty.
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Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC.
Currò, M, Visalli, G, Pellicanò, GF, Ferlazzo, N, Costanzo, MG, D'Andrea, F, Caccamo, D, Nunnari, G, Ientile, R
International journal of molecular sciences. 2020;(20)
Abstract
Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.
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A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection.
Ahmed, F
Frontiers in immunology. 2020;:590459
Abstract
BACKGROUND SARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response. RESULTS This study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub-network "Cluster 1" with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that "Cluster 1" is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as "host response signature network". Functional enrichment analysis with NDEx revealed that the "host response signature network" is predominantly associated with critical pathways, including "cytokines and inflammatory response", "non-genomic action of Vitamin D", "the human immune response to tuberculosis", and "lung fibrosis". Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-α induced Jak-STAT signaling pathway. CONCLUSION This comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-α to control severe COVID-19.
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Effects of vitamin D and/or magnesium supplementation on mood, serum levels of BDNF, inflammatory biomarkers, and SIRT1 in obese women: a study protocol for a double-blind, randomized, placebo-controlled trial.
Abiri, B, Vafa, M
Trials. 2020;(1):225
Abstract
BACKGROUND Emerging evidence has shown that vitamin D and magnesium have anti-inflammatory and anti-depressant effects. Dietary intake of magnesium is associated with reduced body mass index, waist circumference, body fat percentage, as well as inflammatory biomarkers and depressive symptoms. Vitamin D deficiency has been linked to inflammation, obesity, and depressive symptoms. This study will test the effects of vitamin D and magnesium co-supplementation on mood, serum level of brain-derived neurotrophic factor (BDNF), inflammation, and sirtuin 1 (SIRT1) in obese women. METHODS We will conduct an 8-week, double-blind, randomized, placebo-controlled clinical trial, in a factorial design, to evaluate the individual effects of vitamin D and magnesium, and co-supplementation of them, on mood, serum level of BDNF, inflammation, and SIRT1 in 108 obese women. DISCUSSION We hypothesize that vitamin D and magnesium co-supplementation may provide a new adjuvant therapy through modulation of BDNF, inflammation, and SIRT1 in obese women. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT20090822002365N23. Registered on 16 August 2019.
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How vitamin D level influences in vitro fertilization outcomes: results of a systematic review and meta-analysis.
Cozzolino, M, Busnelli, A, Pellegrini, L, Riviello, E, Vitagliano, A
Fertility and sterility. 2020;(5):1014-1025
Abstract
OBJECTIVE To investigate the impact of serum vitamin D level on in vitro fertilization (IVF) outcomes. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENTS Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI). INTERVENTIONS Systematic search of PubMed, MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science from inception until July 2019 with cross-checking of references from relevant articles in English. Vitamin D levels were categorized into three groups: deficient (<20 ng/mL), insufficient (20-30 ng/mL), and replete (>30 ng/mL). Before starting the data extraction, we registered the review protocol in PROSPERO (CRD42019134258). MAIN OUTCOME MEASURES We consider clinical pregnancy rate (CPR), live birth rate (LBR), and/or ongoing pregnancy rate (OPR) as primary outcomes. Likewise, the miscarriage rate was considered as a secondary outcome. RESULTS Primary analysis showed that women with a replete level of vitamin D had higher CPR and LBR/OPR compared to those with a deficient of insufficient level of vitamin D. However, sensitivity analysis led to non-significant differences between the comparators for CPR (odds ratio 0.71, 95% confidence interval 0.47-1.08, I2 = 61%) and OPR/LBR (odds ratio 0.78, 95% confidence interval 0.56-1.08], I2 = 61%). Also, for miscarriage a statistically different rate was not reached. CONCLUSION Serum vitamin D levels do not influence IVF outcomes in terms of CPR, LBR/OPR, and miscarriage rate. Future large cohort studies are warranted to determine whether the threshold of vitamin D affects reproductive outcomes. Currently, there is a lack of consensus between the appropriate vitamin D threshold to predict reproductive outcomes compared to the one established for bone health. PROSPERO NUMBER CRD42019134258.
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IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis.
De Martinis, M, Ginaldi, L, Sirufo, MM, Bassino, EM, De Pietro, F, Pioggia, G, Gangemi, S
Frontiers in immunology. 2020;:604055
Abstract
Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.
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Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review.
Menichini, D, Facchinetti, F
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2020;(1):1-5
Abstract
Increasing evidence supports the contribution of vitamin D deficiency (VDD) in metabolic disturbances among women with polycystic ovary syndrome (PCOS). This review aims to assess the associations between vitamin D levels and metabolic/endocrine dysregulations and to determine the effects of vitamin D supplementation on glucose metabolism, insulin sensitivity, lipid profile, and hormones functionality in PCOS patients. We searched in PubMed human randomized controlled trials (RCTs) published in English between 2016 and 2019 on the effects of vitamin D supplementation on PCOS. Nine studies were included and analyzed. Vitamin D supplementation restored physiological serum 25(OH)D levels in PCOS women in all the studies included. In six studies, it significantly decreased fasting plasma glucose and brought to improvements in insulin resistance (IR) and serum fasting insulin. In addition, four studies reported decreases of serum triglycerides, while discordant data are reported as far as LDL, HDL, and total cholesterol levels. High-doses of vitamin D (4000 IU), compared with low-dose (1000 IU), and placebo, showed beneficial effects on total testosterone, sex hormone-binding globulin (SHBG) and free androgen index (FAI). Vitamin D supplementation at high doses for a period of at least 12 weeks, may lead to improvement in terms of glucose level, insulin sensitivity, hyperlipidemia, and hormonal functionality in PCOS women.
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Vitamin D and liver cancer risk: A meta-analysis of prospective studies.
Guo, XF, Zhao, T, Han, JM, Li, S, Li, D
Asia Pacific journal of clinical nutrition. 2020;(1):175-182
Abstract
BACKGROUND AND OBJECTIVES The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies. METHODS AND STUDY DESIGN A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis. RESULTS Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration. CONCLUSIONS The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.