Efficacy and Safety of Vitamin D Supplementation for Pulmonary Tuberculosis: A Systematic Review and Meta-analysis
Background: Vitamin D might be promising to serve as an adjunctive therapy for pulmonary tuberculosis (TB). However, the results remained controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of vitamin D in patients with pulmonary TB.
Methods: Medline, SCOPUS, Google Scholar, EMBASE, Springer, and Science Direct were searched electronically from inception to Oct 2016. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effect of vitamin D plus anti-tuberculosis treatment (ATT) versus placebo plus ATT on the treatment of pulmonary TB were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Data were analyzed using RevMan 5.3 software.
Results: Five studies were included in this meta-analysis. Overall, compared with placebo intervention, vitamin D supplementation was found to have no significant effect on sputum smear negative conversion rates (RR=0.99; 95% CI=0.91 to 1.07; P=0.77), BMI (MD=0.11; 95% CI=-0.85 to 1.07; P=0.82) and ESR (MD=-2.29; 95% CI=-8.87 to 4.30; P=0.50).
Conclusion: Vitamin D supplementation showed no influence on the improvement of sputum smear-negative conversion rates and BMI, as well as the decrease in ESR.
Lienhardt C, Vernon A, Raviglione MC (2010). New drugs and new regimens for the treatment of tuberculosis: review of the drug development pipeline and implications for national programmes. Curr Opin Pulm Med, 16(3):186-93.
Jenkins HE, Plesca V, Ciobanu A et al (2013). Assessing spatial heterogeneity of MDR-TB in a high burden country. Eur Respir J, 42(5):1291-301.
Cohen T, Jenkins HE, Lu C et al (2014). On the spread and control of MDR-TB epidemics: an examination of trends in anti-tuberculosis drug resistance surveillance data. Drug Resist Updat, 17(4-6):105-23.
Wingfield T, Boccia D, Tovar M et al (2014). Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru. PLoS Med, 11(7):e1001675.
Marks SM, Flood J, Seaworth B et al (2014). Treatment Practices, Outcomes, and Costs of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis, United States, 2005–2007. Emerg Infect Dis, 20(5):812-21.
Naidoo P, van Niekerk M, du Toit E et al (2015). Pathways to multidrug-resistant tuberculosis diagnosis and treatment initiation: a qualitative comparison of patients’ experiences in the era of rapid molecular diagnostic tests. BMC Health Serv Res, 15:488.
Wejse C, Olesen R, Rabna P et al (2007). Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr, 86(5):1376-83.
Yamshchikov AV, Kurbatova EV, Kumari M et al (2010). Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr, 92(3):603-11.
Martineau AR, Nhamoyebonde S, Oni T et al (2011). Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa. Proc Natl Acad Sci U S A, 108(47):19013-7.
Desai NS, Tukvadze N, Frediani JK et al (2012). Effects of sunlight and diet on vitamin D status of pulmonary tuberculosis patients in Tbilisi, Georgia. Nutrition, 28(4):362-6.
Kim JH, Park JS, Cho YJ et al (2014). Low serum 25-hydroxyvitamin D level: An independent risk factor for tuberculosis? Clin Nutr, 33(6):1081-6.
Mehta S, Mugusi FM, Bosch RJ et al (2013). Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study. BMJ Open, 3(11):e003703.
Gibney KB, MacGregor L, Leder K et al (2008). Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis, 46(3):443-6.
Chocano-Bedoya P, Ronnenberg AG (2009). Vitamin D and tuberculosis. Nutr Rev,67(5):289-93.
Holick MF (2007). Vitamin D deficiency. N Engl J Med, 357(3):266-81.
Nnoaham KE, Clarke A (2008). Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol, 37(1):113-9.
Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ (2007). Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol, 103(3-5):793-8.
Ralph AP, Waramori G, Pontororing GJ et al (2013). L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial. PLoS One, 8(8):e70032.
Salahuddin N, Ali F, Hasan Z et al (2013). Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'. BMC Infect Dis, 13:22.
Tukvadze N, Sanikidze E, Kipiani M et al (2015). High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Am J Clin Nutr, 102(5):1059-69.
Martineau AR, Timms PM, Bothamley GH et al (2011). High-dose vitamin D 3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet, 377(9761):242-50.
Moher D, Liberati A, Tetzlaff J et al (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol, 62(10):1006-12.
Higgins JPT, Green S (2011). Cochrane Handbook for Systematic Reviews of Interventions Version5.1 [updated March 2011]. http://handbook-5-1.cochrane.org
Kota SK, Jammula S, Kota SK et al (2011). Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. Diabetes Metab Syndr, 5(2):85-9.
Liu PT, Stenger S, Tang DH, Modlin RL (2007). Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol, 179(4):2060-3.
Martineau AR, Wilkinson RJ, Wilkinson KA et al (2007). A single dose of vitamin D enhances immunity to mycobacteria. Am J Respir Crit Care Med, 176(2):208-13.
Lappe JM, Heaney RP (2012). Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrinol, 4(2):95-100.
Narang NK, Gupta RC, Jain MK (1984). Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India, 32(2):185-8.
Vieth R (2011). Vitamin D nutrient to treat TB begs the prevention question. Lancet,377(9761):189-90.