Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data.
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Jolliffe David A, Camargo Carlos A, Sluyter John D, Aglipay Mary, Aloia John F, Bergman Peter, Bischoff-Ferrari Heike A, Borzutzky Arturo, Bubes Vadim Y, Damsgaard Camilla T, Ducharme Francine M, Dubnov-Raz Gal, Esposito Susanna, Ganmaa Davaasambuu, 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 Paweł, Manaseki-Holland Semira, Manson JoAnn E, Mauger David T, 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, Kumar Geeta Trilok, Urashima Mitsuyoshi, Martineau Adrian R
Аннотация
METHODS: Updated systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Subgroup analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, dosing regimen, or age. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov between May 1, 2020 (end-date of search of our previous meta-analysis) and April 30, 2024. No language restrictions were imposed. Double-blind RCTs supplementing vitamin D for any duration, with placebo or lower-dose vitamin D control, were eligible if approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. The study was registered with PROSPERO (no. CRD42024527191).
FINDINGS: We identified six new RCTs (19 337 participants). Data were obtained for 16 085 (83·2%) participants in three new RCTs and combined with data from 48 488 participants in 43 RCTs identified in our previous meta-analysis. For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88-1·00], p=0·057; 40 studies; 61 589 participants; I2=26·4%). Pre-specified subgroup analysis did not reveal evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0·96 [95% CI 0·90-1·04]; 38 studies; I2=0·0%). A funnel plot showed left-sided asymmetry (p=0·0020, Egger's test).
INTERPRETATION: This updated meta-analysis yielded a similar point estimate for the overall effect of vitamin D supplementation on ARI risk to that obtained previously, but the 95% CI for this effect estimate now includes 1·00, indicating no statistically significant protection.
FUNDING: None.