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

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.

Keywords: 25-hydroxyvitamin D; meta-analysis; tuberculosis; vitamin D; vitamin D deficiency.

Figure 1

Flow diagram of the publication selection process.

Figure 2

(A) Forest plot of comparison of vitamin D level (serum 25-hydroxyvitamin D [25(OH)D]) in TB patients vs control: overall effect for continuous outcome using a random-effect model. (B) Forest plot of association between VDD and risk of TB: overall effect for dichotomous outcome using a random-effect model. The diamonds stand for pooled effect. Abbreviations: TB, tuberculosis; vit, vitamin; VDD, vitamin D deficiency; SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, independent variable.

Figure 3

(A) Forest plot of comparison of serum 25(OH)D level in active TB patients vs LTBI subjects/household contacts of active TB patients: overall effect for continuous outcome using a random-effect model. (B) Forest plot of association between VDD and risk of developing active TB in LTBI subjects or household contacts of TB patients: overall effect for dichotomous outcome using a random-effect model. (C) Forest plot of association between VDD and risk of TST conversion/TBIC: overall effect for dichotomous outcome using a fixed-effect model. The diamonds stand for pooled effect. Abbreviations: TB, tuberculosis; LTBI, latent TB infection; vit, vitamin; VDD, vitamin D deficiency; TST, tuberculin skin test; TBIC, TB infection conversion; SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, independent variable.

Figure 4

(A) Forest plot of comparison of serum 25(OH)D level in HIV-TB-coinfected patients vs HIV patients without active TB: overall effect for continuous outcome using a random-effect model. (B) Forest plot of association between VDD and risk of TB in HIV-infected patients: overall effect for dichotomous outcome using a random-effect model. (C) Forest plot comparing 25(OH)D level in HIV-TB-coinfected patients receiving ART who developed TB-IRIS vs HIV-TB-coinfected patients receiving ART who did not develop TB-IRIS: overall effect for continuous outcome using a fixed-effect model. The diamonds stand for pooled effect. Abbreviations: HIV, human immunodeficiency virus; TB, tuberculosis; ART, antiretroviral therapy; TB-IRIS, TB-associated immune reconstitution inflammatory syndrome; vit, vitamin; VDD, vitamin D deficiency; SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, independent variable.

Figure 5

(A) Forest plot of the effect of 1–4 months of anti-TB treatment on vitamin D level (25(OH)D) in TB patients: overall effect for continuous outcome using a random-effect model. (B) Forest plot of the effect of a full course of anti-TB treatment on vitamin D level (25(OH)D) in TB patients: overall effect for continuous outcome using a random-effect model. (C) Forest plot of comparison of vitamin D level (25(OH)D) in TB patients after anti-TB treatment vs control without TB: overall effect for continuous outcome using a random-effect model. The diamonds stand for pooled effect. Abbreviations: TB, tuberculosis; SD, standard deviation; CI, confidence interval; vit, vitamin; df, degrees of freedom; IV, independent variable.

Figure 6

Forest plot of comparison of the level of the vitamin D metabolite – serum/plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in TB patients vs control without TB: overall effect for continuous outcome using a random-effect model. Note: The diamonds stand for pooled effect. Abbreviations: TB, tuberculosis; SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, independent variable.