title: Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
abstract: ObjectivesTo assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.DesignSystematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sourcesMedline, 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 selectionRandomised, double blind, placebo controlled trials of supplementation with vitamin D3or vitamin D2of 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.Results25 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.ConclusionsVitamin 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 registrationPROSPERO CRD42014013953.
authors.affiliation: 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 a.martineau@qmul.ac.uk.|Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Jolliffe
authors.affiliation: 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.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hooper
authors.affiliation: 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.
authors.forename: Lauren
authors.initials: L
authors.lastname: Greenberg
authors.affiliation: Bone Mineral Research Center, Winthrop University Hospital, Mineola, NY, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Aloia
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.affiliation: Department of Exercise, Lifestyle and Nutrition Clinic, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Dubnov-Raz
authors.affiliation: Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Davaasambuu
authors.initials: D
authors.lastname: Ganmaa
authors.affiliation: Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Adit A
authors.initials: AA
authors.lastname: Ginde
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Goodall
authors.affiliation: Department of Paediatrics: Child & Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Grant
authors.affiliation: 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.|Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
authors.affiliation: Universitair ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Janssens
authors.affiliation: Tampere School of Public Health, University of Tampere, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Laaksi
authors.affiliation: Department of Public Health, Epidemiology and Biostatistics, Institute of Applied Health Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Semira
authors.initials: S
authors.lastname: Manaseki-Holland
authors.affiliation: Department of Statistics, The Pennsylvania State University, Hershey, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mauger
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: David R
authors.initials: DR
authors.lastname: Murdoch
authors.affiliation: QIMR Berghofer Medical Research Institute, Queensland, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Neale
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Judy R
authors.initials: JR
authors.lastname: Rees
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Simpson
authors.affiliation: Department of Pediatrics and Allergy, Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Stelmach
authors.affiliation: Institute of Home Economics, University of Delhi, New Delhi, India.
authors.forename: Geeta Trilok
authors.initials: GT
authors.lastname: Kumar
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
mesh_terms: D019587:Dietary Supplements / Q000009:adverse effects; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000178:diet therapy* / Q000517:prevention & control*; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014807:Vitamin D