Meta-Analysis

. 2017 Feb 15:356:i6583.

doi: 10.1136/bmj.i6583.

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

Adrian R Martineau^{1

2}, David A Jolliffe³, Richard L Hooper³, Lauren Greenberg³, John F Aloia⁴, Peter Bergman⁵, Gal Dubnov-Raz⁶, Susanna Esposito⁷, Davaasambuu Ganmaa⁸, Adit A Ginde⁹, Emma C Goodall¹⁰, Cameron C Grant¹¹, Christopher J Griffiths^{3

2

12}, Wim Janssens¹³, Ilkka Laaksi¹⁴, Semira Manaseki-Holland¹⁵, David Mauger¹⁶, David R Murdoch¹⁷, Rachel Neale¹⁸, Judy R Rees¹⁹, Steve Simpson Jr²⁰, Iwona Stelmach²¹, Geeta Trilok Kumar²², Mitsuyoshi Urashima²³, Carlos A Camargo Jr²⁴

Affiliations

¹ 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.
² Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
³ 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.
⁴ Bone Mineral Research Center, Winthrop University Hospital, Mineola, NY, USA.
⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Exercise, Lifestyle and Nutrition Clinic, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
⁷ Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
⁸ Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
⁹ Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁰ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
¹¹ Department of Paediatrics: Child & Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
¹² MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Blizard Institute, Queen Mary University of London, London, UK.
¹³ Universitair ziekenhuis Leuven, Leuven, Belgium.
¹⁴ Tampere School of Public Health, University of Tampere, Tampere, Finland.
¹⁵ Department of Public Health, Epidemiology and Biostatistics, Institute of Applied Health Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁶ Department of Statistics, The Pennsylvania State University, Hershey, PA, USA.
¹⁷ Department of Pathology, University of Otago, Christchurch, New Zealand.
¹⁸ QIMR Berghofer Medical Research Institute, Queensland, Australia.
¹⁹ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
²⁰ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
²¹ Department of Pediatrics and Allergy, Medical University of Lodz, Lodz, Poland.
²² Institute of Home Economics, University of Delhi, New Delhi, India.
²³ Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
²⁴ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 28202713
PMCID: PMC5310969
DOI: 10.1136/bmj.i6583

Meta-Analysis

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

Adrian R Martineau et al. BMJ. 2017.

. 2017 Feb 15:356:i6583.

doi: 10.1136/bmj.i6583.

Authors

Affiliations

¹ 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.
² Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
³ 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.
⁴ Bone Mineral Research Center, Winthrop University Hospital, Mineola, NY, USA.
⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Exercise, Lifestyle and Nutrition Clinic, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
⁷ Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
⁸ Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
⁹ Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁰ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
¹¹ Department of Paediatrics: Child & Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
¹² MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Blizard Institute, Queen Mary University of London, London, UK.
¹³ Universitair ziekenhuis Leuven, Leuven, Belgium.
¹⁴ Tampere School of Public Health, University of Tampere, Tampere, Finland.
¹⁵ Department of Public Health, Epidemiology and Biostatistics, Institute of Applied Health Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁶ Department of Statistics, The Pennsylvania State University, Hershey, PA, USA.
¹⁷ Department of Pathology, University of Otago, Christchurch, New Zealand.
¹⁸ QIMR Berghofer Medical Research Institute, Queensland, Australia.
¹⁹ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
²⁰ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
²¹ Department of Pediatrics and Allergy, Medical University of Lodz, Lodz, Poland.
²² Institute of Home Economics, University of Delhi, New Delhi, India.
²³ Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
²⁴ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 28202713
PMCID: PMC5310969
DOI: 10.1136/bmj.i6583

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare financial support for this work from the National Institute for Health Research under its Health Technology Assessment programme. No author has had any financial relationship with any organisations that might have an interest in the submitted work in the previous three years. No author has had any other relationship, or undertaken any activity, that could appear to have influenced the submitted work.

Figures

None — **Fig 1** Flow of study selection. IPD=individual participant data

See this image and copyright information in PMC

Comment in

Making uncertainty work.
Cook S. Cook S. BMJ. 2017 Feb 16;356:j815. doi: 10.1136/bmj.j815. BMJ. 2017. PMID: 28209588 No abstract available.
Review: In children and adults, vitamin D3 supplementation reduces risk for acute respiratory tract infection.
Sacks HS. Sacks HS. Ann Intern Med. 2017 May 16;166(10):JC51. doi: 10.7326/ACPJC-2017-166-10-051. Ann Intern Med. 2017. PMID: 28505635 No abstract available.
Vitamin D reduces respiratory tract infections frequency.
Bhutta ZA. Bhutta ZA. J Pediatr. 2017 Jul;186:209-212. doi: 10.1016/j.jpeds.2017.04.021. J Pediatr. 2017. PMID: 28648275 No abstract available.
Weniger akute Atemwegsinfekte durch Vitamin-D-Supplementation?
Weckbecker K. Weckbecker K. Laryngorhinootologie. 2018 Aug;97(8):524-525. doi: 10.1055/a-0648-6964. Epub 2018 Aug 6. Laryngorhinootologie. 2018. PMID: 30081412 German.
PURL: Can vitamin D prevent acute respiratory infections?
Marshall B, Bennett N, Smith A, Oh R, Burket J. Marshall B, et al. J Fam Pract. 2019 May;68(4):230-231. J Fam Pract. 2019. PMID: 31226177 Free PMC article.
Vitamin D deficiency and the COVID-19 pandemic.
Zemb P, Bergman P, Camargo CA Jr, Cavalier E, Cormier C, Courbebaisse M, Hollis B, Joulia F, Minisola S, Pilz S, Pludowski P, Schmitt F, Zdrenghea M, Souberbielle JC. Zemb P, et al. J Glob Antimicrob Resist. 2020 Sep;22:133-134. doi: 10.1016/j.jgar.2020.05.006. Epub 2020 May 29. J Glob Antimicrob Resist. 2020. PMID: 32474141 Free PMC article.
Facing COVID-19 and Refugee Camps on the U.S. Border.
Leiner A, Sammon M, Perry H, Dunavant S. Leiner A, et al. J Emerg Med. 2020 Jul;59(1):143-145. doi: 10.1016/j.jemermed.2020.04.041. J Emerg Med. 2020. PMID: 32900460 Free PMC article. No abstract available.

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

Affiliations

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

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Abstract

Conflict of interest statement

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