Immunonutritional effects elicited by a novel multicomponent food supplement in children with cow's milk allergy: results from a randomized, placebo-controlled trial

Introduction Cow's milk allergy (CMA) is one of the most common food allergies in childhood frequently associated with body growth impairment and micronutrient deficiencies. Immunonutrition approach with selected bioactive compounds may have beneficial effects on nutritional status and immune tolerance mechanisms. We evaluated the effects of an immunonutrition approach, based on the use of a novel multicomponent food supplement containing prebiotics, postbiotics, vitamin D3, docosahexaenoic acid (DHA), Perilla frutescens extracts, and Quercetin in children with CMA. Methods Randomized, double-blind, placebo-controlled pilot trial, involving 30 pediatric CMA patients (both sexes, age 36–60 months) randomly assigned to receive the study product or placebo (maltodextrins) for 6 months. The active study product and placebo were provided as powder sachets with identical features. Primary outcomes were changes in body growth. Co-primary exploratory outcomes were serum 25-hydroxyvitamin D (25(OH)D) and DHA levels. Secondary endpoints included the evaluation of Th2 interleukins (ILs) and IL-10, regulatory T cells (Tregs), and growth factors and cytokines modulating ILs production (Tgfb1, Ifna2, Ptgs2, Csf2) in peripheral blood mononuclear cells (PBMCs) collected from CMA pediatric patients. Results All participants completed the study without adverse events and with >90% adherence to the allocated treatment. At 6-month follow-up, children in the study product group showed greater improvement in body weight, and height, compared with the patients in the placebo group. Serum 25(OH)D and DHA concentrations significantly improved only in the active study group. In PBMCs collected from the patients, the active study product, but not the placebo exposure, resulted in an inhibition of Th2 cytokines (IL- 4, IL-5, IL-13) response to the stimulation with antigenic peptide β-lactoglobulin and in an increase in IL-10 production and Treg activation rate. The expression of Tgfb1, Ifna2, Ptgs2, Csf2 resulted also upregulated, suggesting an overall modulation toward immune tolerance in these patients. Conclusions This novel multicomponent food supplement improved growth parameters and nutritional status while modulating immune tolerance mechanisms in children with CMA. These findings support the potential of an immunonutrition-based approach using this innovative supplement in managing pediatric food allergy. Clinical Trial Registration clinicaltrial.gov , identifier NCT06751810.