Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis
Background: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives: To assess th...
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NIHR Journals Library
2019-01-01
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Series: | Health Technology Assessment |
Online Access: | https://doi.org/10.3310/hta23020 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adrian R Martineau David A Jolliffe Lauren Greenberg John F Aloia Peter Bergman Gal Dubnov-Raz Susanna Esposito Davaasambuu Ganmaa Adit A Ginde Emma C Goodall Cameron C Grant Wim Janssens Megan E Jensen Conor P Kerley Ilkka Laaksi Semira Manaseki-Holland David Mauger David R Murdoch Rachel Neale Judy R Rees Steve Simpson Iwona Stelmach Geeta Trilok Kumar Mitsuyoshi Urashima Carlos A Camargo Christopher J Griffiths Richard L Hooper |
spellingShingle |
Adrian R Martineau David A Jolliffe Lauren Greenberg John F Aloia Peter Bergman Gal Dubnov-Raz Susanna Esposito Davaasambuu Ganmaa Adit A Ginde Emma C Goodall Cameron C Grant Wim Janssens Megan E Jensen Conor P Kerley Ilkka Laaksi Semira Manaseki-Holland David Mauger David R Murdoch Rachel Neale Judy R Rees Steve Simpson Iwona Stelmach Geeta Trilok Kumar Mitsuyoshi Urashima Carlos A Camargo Christopher J Griffiths Richard L Hooper Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis Health Technology Assessment |
author_facet |
Adrian R Martineau David A Jolliffe Lauren Greenberg John F Aloia Peter Bergman Gal Dubnov-Raz Susanna Esposito Davaasambuu Ganmaa Adit A Ginde Emma C Goodall Cameron C Grant Wim Janssens Megan E Jensen Conor P Kerley Ilkka Laaksi Semira Manaseki-Holland David Mauger David R Murdoch Rachel Neale Judy R Rees Steve Simpson Iwona Stelmach Geeta Trilok Kumar Mitsuyoshi Urashima Carlos A Camargo Christopher J Griffiths Richard L Hooper |
author_sort |
Adrian R Martineau |
title |
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
title_short |
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
title_full |
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
title_fullStr |
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
title_full_unstemmed |
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
title_sort |
vitamin d supplementation to prevent acute respiratory infections: individual participant data meta-analysis |
publisher |
NIHR Journals Library |
series |
Health Technology Assessment |
issn |
1366-5278 2046-4924 |
publishDate |
2019-01-01 |
description |
Background: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Study selection: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study appraisal: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. Results: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Limitations: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Conclusions: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. Study registration: This study is registered as PROSPERO CRD42014013953. Funding: The National Institute for Health Research Health Technology Assessment programme. |
url |
https://doi.org/10.3310/hta23020 |
work_keys_str_mv |
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doaj-a6696430a77942bea008a0eb9da596c72020-11-25T00:10:48ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242019-01-0123210.3310/hta2302013/03/25Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysisAdrian R Martineau0David A Jolliffe1Lauren Greenberg2John F Aloia3Peter Bergman4Gal Dubnov-Raz5Susanna Esposito6Davaasambuu Ganmaa7Adit A Ginde8Emma C Goodall9Cameron C Grant10Wim Janssens11Megan E Jensen12Conor P Kerley13Ilkka Laaksi14Semira Manaseki-Holland15David Mauger16David R Murdoch17Rachel Neale18Judy R Rees19Steve Simpson20Iwona Stelmach21Geeta Trilok Kumar22Mitsuyoshi Urashima23Carlos A Camargo24Christopher J Griffiths25Richard L Hooper26Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKBone Mineral Research Center, Winthrop University Hospital, Mineola, NY, USADepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDeptartment of Exercise, Lifestyle and Nutrition Clinic, Edmond and Lily Safra Children’s Hospital, Tel Hashomer, IsraelPediatric Highly Intensive Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, ItalyDepartment of Nutrition, Harvard School of Public Health, Boston, MA, USADepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USADepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, CanadaDepartment of Paediatrics: Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandUniversitaire ziekenhuizen Leuven, Leuven, BelgiumCentre for Asthma and Respiratory Diseases, University of Newcastle, Newcastle, NSW, AustraliaDublin City University, Dublin, IrelandCentre for Military Medicine, Finnish Defense Forces, University of Tampere, Tampere, FinlandDepartment of Public Health, Epidemiology and Biostatistics, Institute of Applied Health Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKDepartment of Statistics, The Pennsylvania State University, Hershey, PA, USADepartment of Pathology, University of Otago, Christchurch, New ZealandQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, QLD, AustraliaDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USAMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, AustraliaDepartment of Pediatrics and Allergy, Medical University of Łódź, Łódź, PolandInstitute of Home Economics, University of Delhi, New Delhi, IndiaDivision of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, JapanDepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USACentre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKCentre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKBackground: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Study selection: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study appraisal: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. Results: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Limitations: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Conclusions: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. Study registration: This study is registered as PROSPERO CRD42014013953. Funding: The National Institute for Health Research Health Technology Assessment programme.https://doi.org/10.3310/hta23020 |