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      Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis

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      Critical Care
      BioMed Central

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          Abstract

          Introduction

          In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit.

          Methods

          Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D 3 (25 (OH)-D) concentrations, were meta-analysed.

          Results

          Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001).

          Conclusions

          This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-014-0660-4) contains supplementary material, which is available to authorized users.

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          Most cited references31

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          Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited.

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            Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.

            Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D(2)] or cholecalciferol [vitamin D(3)]) on any health condition. The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size-adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.
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              Vitamin D3: a helpful immuno-modulator.

              The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)(2) D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.
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                Author and article information

                Contributors
                k.dehaan@erasmusmc.nl
                a.b.j.groeneveld@erasmusmc.nl
                h.degeus@erasmusmc.nl
                m.egal@erasmusmc.nl
                a.struijs@erasmusmc.nl
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                5 December 2014
                5 December 2014
                2014
                : 18
                : 6
                : 660
                Affiliations
                [ ]Department of Intensive Care, Erasmus Medical Centre, Mailbox 2040, H603a, 3000CA Rotterdam, The Netherlands
                [ ]Department of Intensive Care, Erasmus Medical Centre, Mailbox 2040, H603, 3000CA Rotterdam, The Netherlands
                [ ]Department of Intensive Care, Erasmus Medical Centre, Mailbox 2040, H619, 3000CA Rotterdam, The Netherlands
                Article
                660
                10.1186/s13054-014-0660-4
                4277653
                25475621
                58b329cc-1a3b-4541-ae29-89ce274076c8
                © de Haan et al.; licensee BioMed Central Ltd. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 June 2014
                : 12 November 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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