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.
Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data / Jolliffe, D.A., Camargo, C.A., Sluyter, J.D., Aglipay, M., Aloia, J.F., Bergman, P., Bischoff-Ferrari, H.A., Borzutzky, A., Bubes, V.Y., Damsgaard, C.T., Ducharme, F.M., Dubnov-Raz, G., Esposito, S., Ganmaa, D., Gilham, C., Ginde, A.A., Golan-Tripto, I., Goodall, E.C., Grant, C.C., Griffiths, C.J., et al.. - In: THE LANCET DIABETES & ENDOCRINOLOGY. - ISSN 2213-8587. - 13:4(2025), pp. 307-320. [10.1016/S2213-8587(24)00348-6]
Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data
Esposito S.;Pham H.;
2025-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
