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Johari F. Effect of vitamin d supplementation on prevention of acute respiratory infections. Academic Emergency Medicine. Published online July 2025:acem.70097.

Study Population: 46 randomized controlled trials with 64,573 adults and children in aggregate

Efficacy Endpoints

Risk of ARI (primary), hospitalization, antibiotic use, and work/school absence

Harm Endpoints

Death from any cause, hypercalcemia, renal stones, or other serious adverse events

Narrative

Acute respiratory infections (ARIs) are a global health burden and a leading cause of morbidity and mortality worldwide, especially in low- and middle-income countries. ARIs are one of the top reasons for hospital admissions among both children and adults worldwide.1^, 2

Some observational studies have suggested that vitamin D might offer protection against such infections.3 A 2017 randomized controlled trial (RCT) concluded that vitamin D at daily doses of 400–1000 IU did not reduce the risk of ARI in children.4

The systematic review and meta-analysis published in 2021 analyzed the data from 43 RCTs comparing vitamin D supplementation to placebo. Subgroup analyses examined baseline vitamin D levels (individuals with levels < 25 nmol/L often considered deficient), age, dosing regimens, and airway disease status.5^, 6 The updated meta-analysis discussed here included three new RCTs (total 46 RCTs) with 64,573 participants in aggregate. The systematic review included RCTs that compared vitamin D supplementation (of any duration) to placebo or lower-dose vitamin D controls. Eligible studies were those that prospectively collected ARI incidence as a pre-specified efficacy outcome. The incidence of ARI was the primary outcome. The secondary outcomes included hospitalizations, antibiotic use, work/school absences, and adverse events. While the specific follow-up periods for each study are not detailed in the systematic review, previous analyses by the same research group have indicated that vitamin D supplementation was administered for durations of up to 12 months in similar studies.6

The meta-analysis found no statistically significant overall effect of vitamin D supplementation on reducing the incidence of ARIs (OR 0.94 [95% CI 0.88–1.00]). Secondary outcome analyses also did not find statistically significant effects on upper or lower respiratory infections, hospitalizations, mortality, antimicrobial use, or adverse events.5 The subgroup analyses did not reveal significant effect modifications based on age, baseline vitamin D status, dosing frequency, or dose size.5

Caveats

There was substantial clinical and methodological heterogeneity across trials—including differences in dosage and formulation of vitamin D, baseline vitamin D status of participants, age groups, comorbidities, geographic locations, definitions, and ascertainment of ARI outcomes. While this reinforces vitamin D's lack of impact across multiple populations and using various forms of the intervention, it also limits the power of these data to rule out the possibility of very small effects in small subgroups.

Many included trials also had limited follow-up periods (typically < 6 months), leaving open the possibility of undetected protective effects after long-term use.

Importantly, high-dose vitamin D has been linked to harms that were not tracked in most trials. These include dizziness and falls, particularly in the elderly (a group often targeted for ARI prevention).7 Therefore, it is likely that harms are underreported and underestimated by these data. This looms large based on the 2021 meta-analysis which optimistically reported a possible benefit of, at best, 1% based on a finding in which 63% of placebo vs. 62% of vitamin D participants experienced an ARI.5 This difference is probably not important to most people and, dubiously, was confined to a narrow age range, a narrow dosing range, and a narrow duration of therapy. With the newer studies added, even this small benefit has disappeared, suggesting there never was a meaningful impact of vitamin D on ARIs and raising the question of whether any risk of harm is worthwhile.

As of May 2025, expert society guidelines do not recommend the routine use of vitamin D supplementation for the prevention of ARI. The World Health Organization (WHO) has reviewed the role of vitamin D in preventing respiratory infections in children and concluded that further research is needed before specific recommendations can be made.8 However, based on over 60,000 participants in trials, it seems highly probable that vitamin D has either no impact or a clinically unimportant impact on the incidence of ARIs.

In summary, the existing evidence does not support the use of vitamin D supplementation to prevent ARI. We have assigned an NNT color recommendation of red (no benefit) to this intervention, though we recognize that with better reporting of harms, this could readily shift to black (harms outpace benefits).

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Fatima Johari, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

September 23, 2025