Funded in part by Vifor Pharma
Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis
Martineau AR, Jolliffe DA, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Janssens W, Jensen ME, Kerley CP, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Trilok Kumar G, Urashima M, Camargo CA, Griffiths CJ, Hooper RL
Health technology assessment (Winchester, England) · 200 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Meta-analysis (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Industry funded
- University or hospital
- Dartmouth College
- Government
- National Institute for Health and Care Research
- Government
- Department of Health and Social Care
- University or hospital
- University of Southampton
- Company
- Vifor Pharma
- Government
- Vlaamse regering
- Government
- National Institutes of Health
- Government
- Medical Research Council
- Government
- Health Technology Assessment Programme
- Government
- Health Services and Delivery Research Programme
- Government
- Programme Grants for Applied Research
- Government
- National Heart, Lung, and Blood Institute
- Government
- NHLBI NIH HHS
- Government
- National Institute for Health Research (NIHR)
- Grants
- National Heart, Lung, and Blood Institute (U10 HL064313); Health Technology Assessment Programme (13/03/25); National Heart, Lung, and Blood Institute (U10 HL098115); National Institute for Health and Care Research (13/03/25); National Institute for Health and Care Research (HTA/13/03/25)
Based on 14 listed funder(s).
Publication
- Published
- 2019-01-01 · Health Technol Assess · vol. 23 · issue 2 · pp. 1–44
- Publisher
- NIHR Journals Library
- Cited
- 367 citations · more than 100% of similar papers · 13.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 72 works
- Access
- Open access (free to publish) · CC-BY
- Research areas
- Vitamin D Research Studies · Vitamin C and Antioxidants Research · Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- Medicine, Meta-analysis, Placebo, Blinding, Odds ratio, Confidence interval, Internal medicine, Randomized controlled trial, Number needed to treat, Relative risk, Subgroup analysis, Alternative medicine
- MeSH
- humans, respiratory tract infections, vitamin d deficiency, cholecalciferol, ergocalciferols, vitamin d, influenza vaccines, body mass index, drug administration schedule, double-blind method, age factors, comorbidity, dose-response relationship, drug, dietary supplements, adolescent, adult, aged, aged, 80 and over, middle aged, child, child, preschool, infant, female, male, randomized controlled trials as topic, young adult
27 authors
From GB, US, SE, IL, IT, CA, NZ, BE, AU, IE, FI, PL, IN, JP
- Adrian R. MartineauQueen Mary University of London; Asthma UK; Blizard Institute
- David A. JolliffeQueen Mary University of London
- Lauren GreenbergQueen Mary University of London
- John F. AloiaWinthrop-University Hospital
- Peter BergmanKarolinska Institutet
- Gal Dubnov‐RazEdmond and Lily Safra Children's Hospital
Abstract
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 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 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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