The Role Of Vitamin D Supplementation In The Prevention Of Acute Respiratory Infections: A Double-Blind Randomized Controlled Trial

Background: Acute respiratory infections (ARIs) remain among the most common causes of morbidity and mortality worldwide, particularly in children, the elderly, and immunocompromised individuals. Emerging evidence suggests that vitamin D, beyond its classical role in calcium–phosphate homeostasis, exerts immunomodulatory effects by enhancing innate immune responses and modulating inflammatory pathways. Previous observational and meta-analytic studies have indicated an inverse relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and susceptibility to respiratory infections. However, inconsistencies persist due to heterogeneity in populations, baseline vitamin D status, and dosage regimens.

Objectives: This study aimed to evaluate whether daily vitamin D supplementation reduces the incidence, duration, and severity of acute respiratory infections compared with placebo among adults with suboptimal baseline 25(OH)D levels. Secondary objectives included assessing changes in serum vitamin D concentrations and evaluating any adverse effects associated with supplementation.

Methods: This double-blind randomized controlled trial was conducted at a tertiary care hospital between January 2023 and March 2024. A total of 400 participants aged 18–65 years with baseline 25(OH)D levels between 10 and 30 ng/mL were randomly assigned into two groups: the intervention group (n = 200) received vitamin D₃ supplementation (2,000 IU daily), and the placebo group (n = 200) received identical capsules without active ingredient, for six months. Incidence of ARIs was documented through monthly follow-up visits and self-reported symptom diaries validated by physician assessment. Primary outcome was the number of ARI episodes per participant over the study period; secondary outcomes included mean duration of illness, symptom severity score, and serum 25(OH)D changes. Statistical analysis employed chi-square and independent t-tests, with significance set at p < 0.05.

Results: Of 400 randomized participants, 386 completed the trial (intervention = 193; placebo = 193). Mean baseline 25(OH)D levels were 21.6 ± 5.1 ng/mL in both groups. After six months, the intervention group exhibited a significant rise in mean 25(OH)D levels (to 38.9 ± 6.2 ng/mL; p < 0.001) compared with minimal change in the placebo group (22.4 ± 5.3 ng/mL). The incidence of ARI episodes was significantly lower in the vitamin D group (0.68 ± 0.9 per person) versus placebo (1.43 ± 1.2 per person; p < 0.001). Additionally, the mean duration of symptoms was shorter (4.1 ± 1.8 days vs. 6.3 ± 2.5 days; p < 0.001), and symptom severity scores were reduced. No serious adverse events or cases of hypercalcemia were observed.

Conclusion: Daily supplementation with 2,000 IU of vitamin D₃ significantly reduced both the incidence and duration of acute respiratory infections among adults with suboptimal baseline vitamin D levels, suggesting a protective immunomodulatory role. These findings support routine assessment and correction of vitamin D deficiency as a feasible public health strategy to mitigate respiratory infection burden, especially in at-risk populations.