Vitamin D and respiratory infections: the post-VITAL 2024-2025 update

The proposition that vitamin D protects against acute respiratory infections has been studied for over a decade, and the evidence has not stayed still. A widely cited 2017 individual-patient-data meta-analysis suggested a modest protective effect, particularly with daily dosing in deficient adults. Subsequent large trials, including VITAL and ViDA, found no signal in iron-replete populations. The 2024-2025 update tries to reconcile those findings rather than litigate them.

Where the headline numbers actually came from

Martineau and colleagues pooled individual-participant data from 25 randomized trials covering more than 11,000 participants and reported a 12% relative reduction in the proportion of people experiencing at least one acute respiratory infection (adjusted OR 0.88, 95% CI 0.81-0.96), with the strongest effect in those whose baseline 25(OH)D was below 25 nmol/L (OR 0.30 in that subgroup) [1]. A 2021 update with 46 trials and 75,000 participants softened the headline effect to OR 0.92 and emphasized that bolus dosing produced no benefit [2].

The negative megatrials

The VITAL trial randomized 25,871 generally healthy U.S. adults to 2,000 IU vitamin D3 daily or placebo and reported no reduction in respiratory tract infections over a median of 5.3 years [3]. The New Zealand ViDA trial (5,110 adults, 100,000 IU monthly) similarly found no benefit on incidence or duration of acute respiratory infections [4]. Both trials enrolled populations with mean baseline 25(OH)D near 75 nmol/L, well above the deficiency threshold.

The 2024-2025 meta-analyses

A 2024 Cochrane-style systematic review of 43 placebo-controlled trials concluded that daily or weekly oral vitamin D supplementation reduced the proportion of participants with at least one acute respiratory infection (RR 0.94, 95% CI 0.89-0.99) but with substantial heterogeneity (I² = 51%), and that the effect was not significant once trials with baseline 25(OH)D above 50 nmol/L were excluded [5]. A 2025 dose-response analysis found a non-linear relationship: maximum benefit at supplementation levels that raised 25(OH)D from below 25 to roughly 75 nmol/L, with no further gain above that range [6].

What the COVID-era trials added

Several pandemic-era randomized trials tested vitamin D as an adjunct to standard care for SARS-CoV-2 infection. The CORONAVIT trial (6,200 UK adults) found no reduction in self-reported acute respiratory infection or COVID-19 incidence using 800 IU or 3,200 IU daily for six months, although correction of deficiency was confirmed by 25(OH)D measurement [7]. Hospital-based trials of high-dose calcifediol in patients with COVID-19 produced mixed signals that the 2024 living systematic review classified as inconclusive [8].

How clinicians read it now

The Endocrine Society's 2024 clinical practice guideline on vitamin D recommends against routine empirical supplementation in healthy adults under 75 specifically to prevent respiratory infections, while continuing to support treatment of biochemically confirmed deficiency [9]. The U.S. Preventive Services Task Force has not extended its recommendations to respiratory outcomes. In practice, the most defensible position is that vitamin D supplementation corrects deficiency and produces a small reduction in respiratory infection risk in that specific group, with no measurable benefit in already-replete adults.

Bottom line

Vitamin D is not a cold preventive in the general population. The post-VITAL evidence supports daily (not bolus) dosing in adults with 25(OH)D below 50 nmol/L, with a target around 75 nmol/L. Beyond that range, the marginal benefit for respiratory outcomes disappears and the dose-response curve flattens.