Abstract

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: , or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (=12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs =65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: =0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Authors	Jolliffe, David A; Camargo, Carlos A; Sluyter, John D; Aglipay, Mary; Aloia, John F; Ganmaa, Davaasambuu; Bergman, Peter; Bischoff-Ferrari, Heike A; Borzutzky, Arturo; Damsgaard, Camilla T; Dubnov-Raz, Gal; Esposito, Susanna; Gilham, Clare; Ginde, Adit A; Golan-Tripto, Inbal; Goodall, Emma C; Grant, Cameron C; Griffiths, Christopher J; Hibbs, Anna Maria; Janssens, Wim; Khadilkar, Anuradha Vaman; Laaksi, Ilkka; Lee, Margaret T; Loeb, Mark; Maguire, Jonathon L; Majak, Pawel; Mauger, David T; Manaseki-Holland, Semira; Murdoch, David R; Nakashima, Akio; Neale, Rachel E; Pham, Hai; Rake, Christine; Rees, Judy R; Rosendahl, Jenni; Scragg, Robert; Shah, Dheeraj; Shimizu, Yoshiki; Simpson-Yap, Steve; Trilok-Kumar, Geeta; Urashima, Mitsuyoshi; Martineau, Adrian R
Journal	The lancet. Diabetes & endocrinology
Pages	276-292
Volume	9
Date	1/01/2021
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/S2213-8587(21)00051-6