Modulatory role of vitamin D in atopic dermatitis and allergic rhinitis

Abstract

Vitamin D, beyond its classical role in calcium homeostasis, has emerged as a key regulator of immune function and epithelial barrier integrity. Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases. While extensively studied in asthma, its role in non-respiratory allergic conditions such as atopic dermatitis (AD) and allergic rhinitis (AR) remains comparatively underexplored. This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR. In AD, vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis, and enhances antimicrobial defense via induction of antimicrobial peptides. Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children, particularly those with allergic sensitization. Select randomized controlled trials suggest clinical improvement with supplementation, especially at doses > 2000 IU/day in deficient individuals. In AR, epidemiological data indicate stronger inverse associations with seasonal (pollen-induced) disease. Proposed mechanisms include modulation of dendritic cells, regulatory T cells, T helper 2 cytokines, and mucosal barrier integrity. The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance. Although promising, clinical evidence remains heterogeneous. Future research should prioritize phenotype-stratified trials to clarify optimal dosing, timing, and individual response determinants, including genetics and microbiome composition.

Key Words: Vitamin D; Atopic dermatitis; Allergic rhinitis; Pediatric allergy; Immune modulation; Epithelial barrier function; Vitamin D receptor; Allergic sensitization; Early-life immunity; Genetic polymorphism

Core Tip: Vitamin D has emerged as a key modulator of immune responses and epithelial barrier integrity relevant to pediatric atopic dermatitis and allergic rhinitis (AR). Recent evidence highlights phenotype-specific effects, particularly in children with allergic sensitization, and suggests stronger associations with seasonal AR. Advances in vitamin D receptor biology and genomics support a personalized approach to supplementation. Early-life vitamin D exposure may influence immune development and disease trajectory, underscoring the potential for preventive and therapeutic applications in pediatric allergy care.

INTRODUCTION

Vitamin D, beyond its classical role in calcium homeostasis, has increasingly been recognized as a key regulator of immune responses and epithelial barrier integrity. Deficiency in 25-hydroxyvitamin D [25(OH)D] is now implicated in the pathogenesis of various allergic diseases, particularly during early childhood, when immune and barrier systems are still developing. While the association between vitamin D and asthma has been widely studied, less attention has focused on allergic conditions such as atopic dermatitis (AD) and allergic rhinitis (AR), despite their high prevalence and early onset[1]. These conditions often coexist and may reflect distinct phenotypes of a shared immunological predisposition. Clarifying the role of vitamin D in modulating these early-life allergic presentations could open new avenues for targeted prevention and therapeutic intervention. Recent insights into immune-driven mechanisms underlying vitamin D deficiency in children suggest a broader complexity beyond nutrition and sunlight exposure alone[2].

This review explores the evolving role of vitamin D in pediatric allergic diseases, emphasizing its immunomodulatory and barrier-supporting functions, the phenotype-specific implications of deficiency, and emerging insights from molecular and genetic studies that that may guide individualized prevention and management strategies.

VITAMIN D AND AD

AD is a chronic, relapsing inflammatory skin condition characterized by impaired epidermal barrier function and immune dysregulation. Vitamin D supports skin integrity by upregulating filaggrin, a key barrier protein frequently mutated in AD[3], and by promoting the expression of antimicrobial peptides (AMPs), such as cathelicidin, which protect against colonization by Staphylococcus aureus[4]. Observational studies and meta-analyses consistently report lower serum 25(OH)D levels in children with AD compared with healthy controls[1]. Notably, emerging evidence suggests that vitamin D’s impact on AD severity may be modulated by allergic sensitization. Among sensitized children, lower 25(OH)D levels are associated with more severe disease—a pattern not clearly observed in non-sensitized individuals[5]. This points to a potential phenotype-specific effect, with vitamin D conferring greater benefit in sensitized subgroups.

Randomized controlled trials (RCTs) investigating vitamin D supplementation in pediatric AD have yielded mixed outcomes. A recent meta-analysis synthesizing data from both pediatric and adult populations underscores this variability yet reveals modest but statistically significant improvements in AD severity, particularly among vitamin D-deficient individuals[6]. Some studies report improvements in Scoring Atopic Dermatitis or Eczema Area and Severity Index scores, especially with dosages > 2000 IU/day or in children with baseline deficiency[7,8]. However, other trials have shown no significant benefit, likely due to heterogeneity in study populations, dosing protocols, and intervention durations[9]. Still, recent meta-analyses—including pediatric subgroups—support an overall beneficial effect of vitamin D supplementation on AD severity, particularly in deficient children[10]. Nevertheless, more methodologically rigorous, large-scale RCTs are warranted to resolve current inconsistencies and to standardize supplementation strategies.

VITAMIN D AND AR

AR, an IgE-mediated mucosal disorder triggered by aeroallergens such as pollen and animal dander, has received comparatively less attention in the context of vitamin D research. Nonetheless, emerging data support a contributory role for vitamin D in AR. Epidemiological studies link low serum 25(OH)D levels with increased prevalence of AR, particularly in pollen-induced seasonal forms[11]. Mechanistically, vitamin D modulates immune responses in AR by influencing dendritic cell activity, promoting T regulatory cell (Treg) differentiation, and altering cytokine profiles to reduce T helper 2 (Th2) mediated inflammation[12]. It also supports mucosal barrier integrity and promotes local immune tolerance. However, interventional studies remain limited. Few RCTs have evaluated vitamin D as an adjunct to antihistamines or allergen immunotherapy, and those available are often small and methodologically heterogeneous[13]. Interestingly, the association between vitamin D status and AR appears to vary by allergen type, with stronger inverse correlations reported for seasonal (pollen) AR than for perennial allergens such as dust mites or pet dander[14]. The underlying reasons remain speculative but may involve differences in mucosal exposure, immune memory, or individual responsiveness to vitamin D.

Recent advances in mucosal immunology and transcriptomics suggest that vitamin D may influence epithelial-immune interactions in a context-specific manner, potentially modulating gene expression patterns relevant to allergen tolerance. Future studies should integrate molecular biomarkers and adopt larger, standardized, multicenter designs to better identify AR subgroups most likely to benefit from targeted vitamin D interventions.

RCTs IN AD AND AR

A concise and structured overview of RCTs examining vitamin D supplementation in AD and AR is provided in Table 1[15-18]. This section summarizes key findings from existing studies, identifies gaps in dosing regimens, target populations, and treatment duration, and clarifies the intended role of vitamin D—whether as a preventive strategy, adjunctive therapy, or monotherapy.

Table 1 Summary of randomized controlled trials and meta-analyses assessing vitamin D supplementation in pediatric atopic dermatitis and allergic rhinitis.

Ref.	Population	Intervention	Comparator	Duration	Key outcomes
Siddiqui et al[15], 2022	5–12 years with moderate AD	1000 IU/day vitamin D	Placebo	3 months	Significant improvement in SCORAD scores; no adverse effects reported
Borzutzky et al[16], 2024	2-17 years with AD; 57% were vitamin D -deficient at baseline	8000 IU-16000 IU, weekly oral vitamin D3	Placebo	6 weeks	Vitamin D3 supplementation significantly raised blood vitamin D levels compared to placebo. However, there was no significant change in atopic dermatitis severity (SCORAD) between the groups
Javanbakht et al[17], 2020	4-12 years with AD and low vitamin D levels	2000 IU daily vitamin D3	Placebo	3 months	Vitamin D supplementation significantly reduced the severity of atopic dermatitis compared to placebo. The study concluded that vitamin D may be a helpful additional treatment for children with AD who have low vitamin D levels
Li et al[18], 2022	Pediatric population	Vitamin D supplementation (various doses, mostly oral)	Placebo	Variable, from weeks to months	Vitamin D significantly reduced disease severity in atopic dermatitis (SCORAD, EASI scores) and improved symptoms and medication use in allergic rhinitis. These findings support vitamin D as a helpful add-on treatment, but more consistent study methods are needed

AD: Atopic dermatitis; SCORAD: Scoring atopic dermatitis; EASI: Eczema area and severity index.

Recent RCTs have explored the therapeutic potential of vitamin D in pediatric allergic diseases. For example, Siddiqui et al[15] conducted a placebo-controlled RCT in children with AD and AR, reporting significant improvements in symptom severity following vitamin D supplementation. Borzutzky et al[16] in which children with AD received weekly vitamin D3 or placebo; although vitamin D status improved, no significant changes were observed in clinical severity scores or type 2 immunity biomarkers. However, the RCT by Javanbakht et al[17] demonstrated that vitamin D supplementation significantly reduced AD severity in children. Collectively, multiple RCTs and meta-analyses support the role of vitamin D supplementation in improving clinical outcomes in pediatric AD and AR, as highlighted in a systematic review and meta-analysis by Li et al[18].

SHARED MECHANISMS AND CLINICAL IMPLICATIONS

AD and AR share immunopathological features, including Th2 polarization, IgE production, and compromised epithelial barriers (Figure 1). Vitamin D’s regulatory role in these pathways underscores its relevance to both conditions[19]. However, their clinical trajectories differ: AD typically presents early in life and may initiate the atopic march, whereas AR more commonly develops later, following allergic sensitization. This temporal distinction has implications for intervention strategies. Early vitamin D supplementation may be more effective in preventing the onset of AD and subsequent sensitization, while its role in established AR may focus on symptom modulation or enhancing responsiveness to allergen-specific immunotherapy[20].

Figure 1 Overlapping roles of vitamin D in pediatric allergic disease: Mechanisms, clinical timing, and genetic influences. VDR: Vitamin D receptor; CYP: Cytochrome P450.

MOLECULAR AND GENETIC CONSIDERATIONS

At the molecular level, vitamin D exerts its effects via the vitamin D receptor (VDR), a nuclear receptor expressed in keratinocytes, dendritic cells, and T lymphocytes. VDR activation regulates gene expression involved in skin barrier repair, tight junction formation, and immune modulation[21] (Figure 1). In AD, VDR signaling enhances filaggrin synthesis and restores ceramide balance—both essential for epidermal integrity. In AR, VDR activation inhibits dendritic cell maturation and antigen presentation, thereby attenuating IgE-mediated sensitization[22].

Genetic polymorphisms in the VDR and vitamin D–metabolizing cytochrome P450 enzymes (CYP27B1 and CYP24A1) can significantly modulate individual responses to vitamin D (Figure 1). Variations in these genes influence vitamin D metabolism and immune function, shaping cytokine profiles and guiding T-cell differentiation, which in turn may increase susceptibility to allergic diseases and influence disease severity[23,24]. Certain allelic variants have been associated with altered immune responses and heightened atopic risk[24]. These findings underscore the potential for personalized vitamin D supplementation strategies based on genotyping and biomarker profiling to optimize clinical outcomes[23].

PRENATAL AND EARLY -LIFE VITAMIN D EXPOSURE

Prenatal vitamin D exposure is another emerging area of interest. Several large cohort studies suggest that higher maternal 25(OH)D levels during pregnancy are associated with lower risks of AD and AR in offspring[25]. Mechanistic data indicate that in utero vitamin D may modulate fetal immune development, promoting Treg differentiation and suppressing Th2 bias[26]. It may also improve neonatal epithelial barriers, reducing susceptibility to early sensitization. Trials such as the Vitamin D Antenatal Asthma Reduction Trial and the Copenhagen Prospective Studies on Asthma in Childhood have evaluated prenatal supplementation, with modest benefits observed—most notably in asthma outcomes[27,28]. These findings highlight the potential for early immune programming mediated by maternal vitamin D status. However, variability in study design and population characteristics underscores the need for further research to define optimal supplementation protocols. The effectiveness of prenatal vitamin D likely depends on the timing and dosage of supplementation, maternal baseline vitamin D status, and interacting genetic factors.

VITAMIN D AND THE MICROBIOTA

Vitamin D also influences the microbiota of the skin and nasal mucosa, both of which are increasingly recognized as key players in allergic disease. Dysbiosis—marked by reduced microbial diversity and overgrowth of pathogens like Staphylococcus aureus—contributes to AD pathogenesis[29]. Vitamin D enhances colonization resistance by inducing AMPs such as cathelicidin (LL-37) and β-defensins, which inhibit pathogenic bacteria and support microbial balance. It also modulates innate immune responses by binding to the VDR expressed on keratinocytes and immune cells, thereby enhancing barrier integrity and immune tolerance. Some studies suggest that sufficient vitamin D levels may promote colonization by beneficial commensals such as Staphylococcus epidermidis, which can secrete peptides that suppress inflammation and foster regulatory immune responses[30]. Similar immunomodulatory effects may extend to the nasal microbiota, potentially affecting allergic sensitization and exacerbations of AR[31].

PEDIATRIC IMMUNITY AND ENVIRONMENTAL MODIFIERS

Recent studies emphasize vitamin D’s multifaceted role in pediatric immune function. Notably, two investigations demonstrate vitamin D’s immunomodulatory effects in respiratory infections, highlighting its influence on host-microbe interactions during immune system development[32,33]. Furthermore, physical activity, which affects both vitamin D status and immune competence, has been associated with enhanced endocrine and immune balance in children[34]. Vitamin D has been implicated in pediatric asthma, with evidence supporting its involvement in allergic inflammation and respiratory health, although clinical benefits of supplementation remain under investigation[35,36]. These interrelated factors underscore the importance of maintaining optimal vitamin D levels during critical periods of immune maturation. Addressing vitamin D insufficiency may therefore have broad implications for reducing allergic disease burden and enhancing pediatric immune resilience. Collectively, these findings position vitamin D as a critical regulator of pediatric allergic diseases, particularly those involving the skin and mucosal tissues.

FUTURE DIRECTIONS AND CLINICAL CONSIDERATIONS

Despite growing evidence, several critical questions remain unanswered. What serum 25(OH)D concentration is required to confer immunological protection in atopic children? Do these effects vary by age, ethnicity, or geographic latitude? Is there an optimal developmental window for intervention? Furthermore, how should clinicians balance potential benefits against the risk of toxicity, particularly in younger children? While definitive guidance is still lacking, ensuring adequate vitamin D status—especially in at-risk pediatric populations—remains a sound clinical approach. Public health strategies may benefit from incorporating vitamin D screening and targeted supplementation into broader allergy prevention programs[37].

Key areas for future research include VDR polymorphisms, epigenetic mechanisms, and gut microbiome interactions. These emerging fields highlight the potential for personalized treatment strategies and represent promising avenues to advance our understanding and management of allergic diseases.

CONCLUSION

In summary, vitamin D plays a pivotal yet incompletely defined role at the intersection of epithelial barrier integrity and immune regulation in pediatric allergic diseases. Its significance in both AD and AR is supported by mechanistic and clinical evidence; however, important questions remain regarding phenotype-specific effects and optimal intervention strategies. Future research should focus on rigorously designed, stratified clinical trials alongside integrative mechanistic studies. Meanwhile, clinicians should consider maintaining vitamin D sufficiency as a modifiable factor within the broader framework of preventing and managing pediatric atopy.

ACKNOWLEDGEMENTS

The author gratefully acknowledges Prasantha Devulapalli for her valuable assistance with the production of the audio core tip and Figure 1 for this article.