Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jul 11

PMID 23840373

Citations 182

Authors

Peter Bergman

Asa U Lindh

Linda Bjorkhem-Bergman

Jonatan D Lindh

Affiliations

Soon will be listed here.

Abstract

Background: Low levels of 25-OH vitamin D are associated with respiratory tract infection (RTI). However, results from randomized controlled trials are inconclusive. Therefore, we performed a systematic review and meta-analysis to assess the preventive effect of vitamin D supplementation on RTI.

Methods: Randomized, controlled trials of vitamin D for prevention of RTI were used for the analysis. The risks of within-trial and publication bias were assessed. Odds ratios of RTI were pooled using a random-effects model. Heterogeneity was assessed using Cochran's Q and I(2). Meta-regressions and subgroup analyses were used to assess the influence of various factors on trial outcome. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013003530.

Findings: Of 1137 citations retrieved, 11 placebo-controlled studies of 5660 patients were included in the meta-analysis. Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cohran's Q p<0.0001, I(2) = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias.

Interpretation: Results indicate that vitamin D has a protective effect against RTI, and dosing once-daily seems most effective. Due to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution.

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References

Choudhary N, Gupta P . Vitamin D supplementation for severe pneumonia--a randomized controlled trial. Indian Pediatr. 2011; 49(6):449-54. DOI: 10.1007/s13312-012-0073-x. View

Manaseki-Holland S, Qader G, Masher M, Bruce J, Mughal M, Chandramohan D . Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health. 2010; 15(10):1148-55. DOI: 10.1111/j.1365-3156.2010.02578.x. View

Murdoch D, Slow S, Chambers S, Jennings L, Stewart A, Priest P . Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012; 308(13):1333-9. DOI: 10.1001/jama.2012.12505. View

Moreira-Pfrimer L, Pedrosa M, Teixeira L, Lazaretti-Castro M . Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial. Ann Nutr Metab. 2009; 54(4):291-300. DOI: 10.1159/000235874. View

Jorde R, Witham M, Janssens W, Rolighed L, Borchhardt K, de Boer I . Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials. Scand J Infect Dis. 2011; 44(2):126-32. PMC: 3917712. DOI: 10.3109/00365548.2011.621446. View

Laaksi I, Ruohola J, Mattila V, Auvinen A, Ylikomi T, Pihlajamaki H . Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish men. J Infect Dis. 2010; 202(5):809-14. DOI: 10.1086/654881. View

Rivas-Santiago B, Rivas Santiago C, Castaneda-Delgado J, Leon-Contreras J, Hancock R, Hernandez-Pando R . Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and CP26 against Mycobacterium tuberculosis. Int J Antimicrob Agents. 2012; 41(2):143-8. DOI: 10.1016/j.ijantimicag.2012.09.015. View

Brok J, Thorlund K, Wetterslev J, Gluud C . Apparently conclusive meta-analyses may be inconclusive--Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol. 2008; 38(1):287-98. DOI: 10.1093/ije/dyn188. View

Aloia J, Li-Ng M . Re: epidemic influenza and vitamin D. Epidemiol Infect. 2007; 135(7):1095-6. PMC: 2870688. DOI: 10.1017/S0950268807008308. View

10.

Chinn S . A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med. 2000; 19(22):3127-31. DOI: 10.1002/1097-0258(20001130)19:22<3127::aid-sim784>3.0.co;2-m. View

11.

Khoo A, Chai L, Koenen H, Kullberg B, Joosten I, van der Ven A . 1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses. J Infect Dis. 2010; 203(1):122-30. PMC: 3086448. DOI: 10.1093/infdis/jiq008. View

12.

Hollis B, Conrad H, HIBBS J . Changes in plasma 25-hydroxycholecalciferol and selected blood parameters after injection of massive doses of cholecalciferol or 25-hydroxycholecalciferol in non-lactating dairy cows. J Nutr. 1977; 107(4):606-13. DOI: 10.1093/jn/107.4.606. View

13.

Ginde A, Mansbach J, Camargo Jr C . Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009; 169(4):384-90. PMC: 3447082. DOI: 10.1001/archinternmed.2008.560. View

14.

Li-Ng M, Aloia J, Pollack S, Cunha B, Mikhail M, Yeh J . A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect. 2009; 137(10):1396-404. DOI: 10.1017/S0950268809002404. View

15.

Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J . High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2012; 156(2):105-14. DOI: 10.7326/0003-4819-156-2-201201170-00004. View

16.

Hewison M . Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011; 7(6):337-45. DOI: 10.1038/nrendo.2010.226. View

17.

Trivedi D, Doll R, Khaw K . Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003; 326(7387):469. PMC: 150177. DOI: 10.1136/bmj.326.7387.469. View

18.

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V . Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859):2095-128. PMC: 10790329. DOI: 10.1016/S0140-6736(12)61728-0. View

19.

Hollis B . Short-term and long-term consequences and concerns regarding valid assessment of vitamin D deficiency: comparison of recent food supplementation and clinical guidance reports. Curr Opin Clin Nutr Metab Care. 2011; 14(6):598-604. DOI: 10.1097/MCO.0b013e32834be798. View

20.

Bischoff-Ferrari H, Dawson-Hughes B, Platz A, Orav E, Stahelin H, Willett W . Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Arch Intern Med. 2010; 170(9):813-20. DOI: 10.1001/archinternmed.2010.67. View