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

Research output: Contribution to journalReview articlepeer-review

Authors

  • Adrian R Martineau
  • David A Jolliffe
  • Richard L Hooper
  • Lauren Greenberg
  • John F Aloia
  • Peter Bergman
  • Gal Dubnov-Raz
  • Susanna Esposito
  • Davaasambuu Ganmaa
  • Adit A Ginde
  • Emma C Goodall
  • Cameron C Grant
  • Christopher J Griffiths
  • Wim Janssens
  • Ilkka Laaksi
  • David Mauger
  • David R Murdoch
  • Rachel Neale
  • Judy R Rees
  • Steve Simpson
  • Iwona Stelmach
  • Geeta Trilok Kumar
  • Mitsuyoshi Urashima
  • Carlos A Camargo

Colleges, School and Institutes

External organisations

  • Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
  • Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK.
  • Bone Mineral Research Center, Winthrop University Hospital, Mineola, NY, USA.
  • Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Department of Exercise, Lifestyle and Nutrition Clinic, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
  • Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
  • Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
  • Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
  • Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
  • Department of Paediatrics: Child & Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Blizard Institute, Queen Mary University of London, London, UK.
  • Universitair ziekenhuis Leuven, Leuven, Belgium.
  • Tampere School of Public Health, University of Tampere, Tampere, Finland.
  • Department of Public Health, Epidemiology and Biostatistics, Institute of Applied Health Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Department of Statistics, The Pennsylvania State University, Hershey, PA, USA.
  • Mackenzie Cancer Research Group, Department of Pathology, University of Otago Christchurch, Christchurch 8011, New Zealand.
  • Cancer Control, QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03756, USA.
  • Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Department of Pediatrics and Allergy, Medical University of Lodz, Lodz, Poland.
  • Institute of Home Economics, University of Delhi, New Delhi, India.
  • Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
  • Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

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.

Details

Original languageEnglish
Article numberi6583
JournalBMJ
Volume356
Publication statusPublished - 15 Feb 2017

Keywords

  • Dietary Supplements, Humans, Randomized Controlled Trials as Topic, Respiratory Tract Infections, Vitamin D, Journal Article, Meta-Analysis, Review