Vitamin D status and supplementation as potential modifiers of allergen immunotherapy outcomes in respiratory allergy: A structured narrative review.

Allergen immunotherapy (AIT) represents a cornerstone in managing IgE-mediated allergic diseases, such as allergic rhinitis and asthma. By administering controlled doses of allergens over time, AIT aims to readjust immune tolerance, thereby modifying allergic responses. However, clinical responses to AIT remain heterogeneous, with a subset of patients achieving only partial benefit. This heterogeneity underlines the need for novel adjunctive approaches to potentiate the immunomodulatory effects of AIT. In this context, vitamin D has gained considerable interest, given its well-established role in immune homeostasis and regulation, as well as its emerging relevance in modulating allergic disease. This structured narrative review aims to assess the potential role of vitamin D supplementation during AIT on clinical outcomes as well as the significance of endogenous vitamin D levels on AIT clinical efficacy. A total of 18 studies were reviewed, 13 evaluating the impact of vitamin D supplementation during AIT and 5 assessing the influence of endogenous vitamin D levels on AIT outcomes. Most supplementation studies reported clinical outcomes favoring the addition of vitamin D to AIT, but three found no additional benefit, and two reported a benefit only at an earlier time point, respectively in vitamin D-deficient patients. Of the five studies examining endogenous status, three reported that higher 25-hydroxyvitamin D (25(OH)D) levels were associated with better AIT outcomes. Other findings that were reported as secondary outcomes included favorable immunologic changes, such as IL-10 production, decreased allergen-specific IgE levels, and enhanced regulatory Treg-cell activity, without formal assessment of their contribution to clinical benefit. Nevertheless, findings remain inconsistent across studies due to heterogeneity in study design, supplementation regimens, and outcome measures. While the available evidence suggests that adequate vitamin D status or supplementation may be associated with better clinical responses to AIT, the current findings remain limited by heterogeneity in study design, supplementation regimens, outcome measures, and generally small sample sizes. Therefore, the evidence should be considered suggestive rather than conclusive. Although correction of vitamin D deficiency is appropriate on general clinical grounds, its specific use as an adjunct to improve AIT outcomes cannot yet be routinely recommended. Further adequately powered, standardized, placebo-controlled studies are needed to clarify its role and inform clinical recommendations.