TY - JOUR
T1 - Vitamin D supplementation to prevent acute respiratory infections
T2 - systematic review and meta-analysis of stratified aggregate data
AU - Jolliffe, David A.
AU - Camargo, Carlos A.
AU - Sluyter, John D.
AU - Aglipay, Mary
AU - Aloia, John F.
AU - Bergman, Peter
AU - Bischoff-Ferrari, Heike A.
AU - Borzutzky, Arturo
AU - Bubes, Vadim Y.
AU - Damsgaard, Camilla T.
AU - Ducharme, Francine M.
AU - Dubnov-Raz, Gal
AU - Esposito, Susanna
AU - Ganmaa, Davaasambuu
AU - Gilham, Clare
AU - Ginde, Adit A.
AU - Golan-Tripto, Inbal
AU - Goodall, Emma C.
AU - Grant, Cameron C.
AU - Griffiths, Christopher J.
AU - Hibbs, Anna Maria
AU - Janssens, Wim
AU - Khadilkar, Anuradha Vaman
AU - Laaksi, Ilkka
AU - Lee, Margaret T.
AU - Loeb, Mark
AU - Maguire, Jonathon L.
AU - Majak, Paweł
AU - Manaseki-Holland, Semira
AU - Manson, Jo Ann E.
AU - Mauger, David T.
AU - Murdoch, David R.
AU - Nakashima, Akio
AU - Neale, Rachel E.
AU - Pham, Hai
AU - Rake, Christine
AU - Rees, Judy R.
AU - Rosendahl, Jenni
AU - Scragg, Robert
AU - Shah, Dheeraj
AU - Shimizu, Yoshiki
AU - Simpson-Yap, Steve
AU - Kumar, Geeta Trilok
AU - Urashima, Mitsuyoshi
AU - Martineau, Adrian R.
N1 - Publisher Copyright:
© 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2025/4
Y1 - 2025/4
N2 - Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs. 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.
AB - Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs. 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.
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U2 - 10.1016/S2213-8587(24)00348-6
DO - 10.1016/S2213-8587(24)00348-6
M3 - Article
C2 - 39993397
AN - SCOPUS:105000449895
SN - 2213-8587
VL - 13
SP - 307
EP - 320
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 4
ER -
