INTRODUCTION
Acute respiratory infections (ARIs) continue to represent one of the most pervasive public health challenges globally, accounting for substantial morbidity, hospitalization, and mortality across all age groups. According to the World Health Organization, ARIs are responsible for nearly 20% of global deaths in children under five years of age, with a rising burden among adults, particularly those with underlying chronic diseases and compromised immunity. In low- and middle-income countries, frequent viral and bacterial respiratory infections further strain healthcare resources and lead to significant socioeconomic consequences.
Over the past two decades, increasing attention has been directed toward the non-skeletal actions of vitamin D, particularly its immunomodulatory potential in preventing infectious diseases. Vitamin D is a secosteroid hormone synthesized in the skin upon ultraviolet B radiation exposure and obtained from dietary sources or supplements [1]. The active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D], interacts with the vitamin D receptor (VDR) expressed on immune cells such as macrophages, dendritic cells, and T lymphocytes. This interaction enhances innate immune defense by inducing antimicrobial peptides like cathelicidin and defensins, which disrupt the membranes of respiratory pathogens. Moreover, vitamin D modulates adaptive immunity by suppressing excessive pro-inflammatory cytokine release, thus reducing tissue damage during infection [2].
Multiple epidemiological and mechanistic studies have demonstrated an association between low serum 25-hydroxyvitamin D [25(OH)D] levels and increased susceptibility to respiratory tract infections [3]. For instance, Martineau et al. (2017) conducted a meta-analysis of 25 randomized controlled trials encompassing over 11,000 participants, which revealed that vitamin D supplementation reduced the risk of ARIs, especially among individuals with severe deficiency (<10 ng/mL) and those receiving daily or weekly dosing. Similarly, other cohort and observational studies have linked seasonal variations in vitamin D levels with peaks in influenza and common cold incidence during winter months, suggesting a possible causal relationship [4].
Nevertheless, despite these promising observations, inconsistencies persist in the literature. Several randomized controlled trials have yielded null or inconclusive findings, often attributed to differences in baseline vitamin D status, supplementation doses, dosing intervals, duration of follow-up, and participant demographics [5]. Furthermore, the optimal serum concentration required for immune protection remains debatable, with thresholds ranging from 20 to 40 ng/mL proposed by various authorities. The clinical relevance of vitamin D supplementation for respiratory health therefore warrants rigorous evaluation through well-designed controlled trials that account for these confounding variables [6].
The biological plausibility of vitamin D’s protective role against respiratory infections is supported by its ability to regulate both innate and adaptive immune responses. By enhancing macrophage phagocytic activity and promoting epithelial barrier integrity, vitamin D reduces viral replication and bacterial adherence [7]. Simultaneously, it attenuates the cytokine storm commonly implicated in severe respiratory infections by downregulating IL-6, TNF-α, and IFN-γ while promoting anti-inflammatory IL-10 production. Such dual regulation is of particular importance in conditions like influenza, COVID-19, and community-acquired pneumonia, where exaggerated inflammation contributes to morbidity and mortality.
Given these immunological mechanisms and the persistent global prevalence of vitamin D deficiency, investigating whether daily vitamin D supplementation confers measurable protection against ARIs remains a question of high clinical and public health significance
Therefore, it is of interest to evaluate the efficacy of daily vitamin D supplementation in reducing the incidence, duration, and severity of acute respiratory infections among adults with suboptimal baseline vitamin D levels through a double-blind randomized controlled trial.
MATERIALS AND METHODS
Study Design and Setting
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