Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583 (Published 15 February 2017)Cite this as: BMJ 2017;356:i6583

Adrian R Martineau, professor of respiratory infection and immunity1 2, 

David A Jolliffe, postdoctoral research fellow1, 

Richard L Hooper, reader in medical statistics1, 

Lauren Greenberg, medical statistician1, 

John F Aloia, professor of medicine3, 

Peter Bergman, associate professor4, 

Gal Dubnov-Raz, consultant paediatrician5, 

Susanna Esposito, professor of paediatrics6, 

Davaasambuu Ganmaa, assistant professor7, 

Adit A Ginde, professor of emergency medicine8, 

Emma C Goodall, assistant professor9, 

Cameron C Grant, associate professor10, 

Christopher J Griffiths, professor of primary care1 2 11, 

Wim Janssens, professor of pneumonology12, 

Ilkka Laaksi, chief administrative medical officer13, 

Semira Manaseki-Holland, senior clinical lecturer14, 

David Mauger, professor of public health sciences and statistics15, 

David R Murdoch, professor of pathology16, 

Rachel Neale, associate professor17, 

Judy R Rees, assistant professor18, 

Steve Simpson Jr, postdoctoral research fellow19, 

Iwona Stelmach, professor of paediatric allergy20, 

Geeta Trilok Kumar, associate professor21, 

Mitsuyoshi Urashima, professor of molecular epidemiology22, 

Carlos A Camargo Jr, professor of emergency medicine, medicine, and epidemiology23

Author affiliations

1. Correspondence to: A R Martineau a.martineau@qmul.ac.uk

Abstract

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.

Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.

Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.

Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.

Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity -0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels -25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.

Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.

Systematic review registration PROSPERO CRD42014013953.

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