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      Vitamin D deficiency and the risk of tuberculosis: a meta-analysis

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          Abstract

          Background and aim

          To conduct meta-analyses of all published studies on various aspects of association between vitamin D and tuberculosis (TB).

          Methods

          PubMed and Web of Knowledge were searched for all properly controlled studies on vitamin D and TB. Pooled odds ratio, mean difference or standardized mean difference, and its corresponding 95% confidence interval were calculated with the Cochrane Review Manager 5.3.

          Results

          A significantly lower vitamin D level was found in TB patients vs controls; vitamin D deficiency (VDD) was associated with an increased risk of TB, although such an association was lacking in the African population and in the human immunodeficiency virus-infected African population. A significantly lower vitamin D level was found in human immunodeficiency virus-TB-coinfected African patients receiving antiretroviral treatment who developed TB-associated immune reconstitution inflammatory syndrome vs those who did not develop TB-associated immune reconstitution inflammatory syndrome. VDD was associated with an increased risk of developing active TB in those subjects with latent TB infection and with an increased risk of tuberculin skin test conversion/TB infection conversion, and the trend toward a lower vitamin D level in active TB patients vs latent TB infection subjects did not reach statistical significance, indicating that VDD was more likely a risk factor than a consequence of TB. This concept was further strengthened by our result that anti-TB treatment did not affect vitamin D level in TB patients receiving the treatment.

          Conclusion

          Our analyses revealed an association between vitamin D and TB. VDD is more likely a risk factor for TB than its consequence. More studies are needed to determine whether vitamin D supplementation is beneficial to TB prevention and treatment.

          Most cited references51

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          Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis.

          To explore the association between low serum vitamin D and risk of active tuberculosis in humans. Systematic review and meta-analysis. Observational studies published between 1980 and July 2006 (identified through Medline) that examined the association between low serum vitamin D and risk of active tuberculosis. For the review, seven papers were eligible from 151 identified in the search. The pooled effect size in random effects meta-analysis was 0.68 with 95% CI 0.43-0.93. This 'medium to large' effect represents a probability of 70% that a healthy individual would have higher serum vitamin D level than an individual with tuberculosis if both were chosen at random from a population. There was little heterogeneity between the studies. Low serum vitamin D levels are associated with higher risk of active tuberculosis. Although more prospectively designed studies are needed to firmly establish the direction of this association, it is more likely that low body vitamin D levels increase the risk of active tuberculosis. In view of this, the potential role of vitamin D supplementation in people with tuberculosis and hypovitaminosis D-associated conditions like chronic kidney disease should be evaluated.
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            Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study.

            Susceptibility to disease after infection by Mycobacterium tuberculosis is influenced by environmental and host genetic factors. Vitamin D metabolism leads to activation of macrophages and restricts the intracellular growth of M. tuberculosis. This effect may be influenced by polymorphisms at three sites in the vitamin D receptor (VDR) gene. We investigated the interaction between serum vitamin D (25-hydroxycholecalciferol) concentrations and VDR genotype on susceptibility to tuberculosis. This study was a hospital-based case-control analysis of Asians of Gujarati origin, a mainly vegetarian immigrant population with a high rate of tuberculosis. We typed three VDR polymorphisms (defined by the presence of restriction endonuclease sites for Taq1, Bsm1, and Fok1) in 91 of 126 untreated patients with tuberculosis and 116 healthy contacts who had been sensitised to tuberculosis. Serum 25-hydroxycholecalciferol was recorded in 42 contacts and 103 patients. 25-hydroxycholecalciferol deficiency was associated with active tuberculosis (odds ratio 2.9 [95% CI 1.3-6.5], p=0.008), and undetectable serum 25-hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculosis (9.9 [1.3-76.2], p=0.009). Although there was no significant independent association between VDR genotype and tuberculosis, the combination of genotype TT/Tt and 25-hydroxycholecalciferol deficiency was associated with disease (2.8 [1.2-6.5]) and the presence of genotype ff or undetectable serum 25-hydroxycholecalciferol was strongly associated with disease (5.1 [1.4-18.4]). 25-hydroxycholecalciferol deficiency may contribute to the high occurrence of tuberculosis in this population. Polymorphisms in the VDR gene also contribute to susceptibility when considered in combination with 25-hydroxycholecalciferol deficiency.
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              Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.

              Heterogeneity between study results can be a problem in any systematic review or meta-analysis of clinical trials. Identifying its presence, investigating its cause and correctly accounting for it in analyses all involve difficult decisions for the researcher. Our objectives were: to collate recommendations on the subject of dealing with heterogeneity in systematic reviews of clinical trials; to investigate current practice in addressing heterogeneity in Cochrane reviews; and to compare current practice with recommendations. We review guidelines for those undertaking systematic reviews and examine how heterogeneity is addressed in practice in a sample of systematic reviews, and their protocols, from the Cochrane Database of Systematic Reviews. Advice to reviewers is on the whole consistent and sensible. However, examination of a sample of Cochrane protocols and reviews demonstrates that the advice is difficult to follow given the small numbers of studies identified in many systematic reviews, the difficulty of pre-specifying important effect modifiers for subgroup analysis or meta-regression and the unresolved debate concerning fixed versus random effects meta-analyses. There was disagreement between protocols and reviews, often either regarding choice of important potential effect modifiers or due to the review identifying too few studies to perform planned analyses. Guidelines that address practical issues are required to reduce the risk of spurious findings from investigations of heterogeneity. This may involve discouraging statistical investigations such as subgroup analyses and meta-regression, rather than simply adopting a cautious approach to their interpretation, unless a large number of studies is available. The notion of a priori specification of potential effect modifiers for a retrospective review of studies is ill-defined, and the appropriateness of using a statistical test for heterogeneity to decide between analysis strategies is suspect.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                28 December 2016
                : 11
                : 91-102
                Affiliations
                [1 ]Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China
                [2 ]Department of Nutrition and Food Hygiene, Institute of Human Nutrition, Medical College of Qingdao University, Qingdao, People’s Republic of China
                [3 ]Department of Pulmonary Medicine, Beijing Geriatric Hospital, Beijing, People’s Republic of China
                Author notes
                Correspondence: Shao-Fa Xu, Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, No 97 Machang, Tongzhou District, Beijing, People’s Republic of China, Tel +86 10 8950 9326, Email shaofaxu@ 123456yahoo.com
                Article
                dddt-11-091
                10.2147/DDDT.S79870
                5207333
                28096657
                98bac764-2dee-4e6a-879d-8eb78b3c86f9
                © 2017 Huang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                vitamin d,vitamin d deficiency,tuberculosis,25-hydroxyvitamin d,meta-analysis

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