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.
| Specialty | Score |
|---|---|
| Public Health | |
| Infectious Disease | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) |
As a primary care doctor, I have not been basing my recommendations about whether or not to use vitamin D supplementation on their possibly small effects on the prevention of respiratory infections. This newly updated meta-analysis showing that the effect estimate is slightly lower than in the previous meta-analysis and with a confidence interval that overlaps the null finding will not change that.
This meta-analysis updates a previous meta-analysis from 2021 with now 64,086 participants showoing that Vitamin D is probably helpful in pediatric patients aged 1-15 in the shortening of symptoms of a viral URI. The improvement was marginal but trials with Vitamin D at a dose of 400-1000 units preformed better.
Very large and detailed meta-analysis finds no significant benefit from vitamin D supplements in preventing acute respiratory infections.
This is an update of a previous meta-analysis of vitamin D supplementation in acute respiratory infections. A previous analysis showed a modest effect; this addition showed no effect. It is hard to imagine that a meta-analysis of such a heterogeneous condition like acute respiratory disease coupled with varied regimens of vitamin D could produce clinically relevant information.
Although vitamin D deficiency clearly impairs immunity, this latest rigorous and comprehensive meta-analysis casts ever more doubt that proactive replacement provides increased resistance to infection. This conclusion is greatly strengthened by the finding that every large RCT with >1000 participants found no benefit at whatsoever. Back to the drawing board. Perhaps the conventional approaches to correction of deficiency are flawed physiologically.
The cost of a Vitamin D drug test is another factor to consider. In some Public Health offices, it was being included as "routine." Not only was it costly, compliance was poor and the results were not impressive (PO intake, not injection).
, McMaster University