D2.504 - Novel food supplement containing a combination of bioactive compounds in pediatric cow’s milk protein allergy: results from a randomized, placebo-controlled trial

Cow’s milk protein allergy (CMPA) is the most common food allergy in childhood and often requires prolonged elimination diets that can impair growth and cause micronutrient deficiencies. Nutritional immunomodulation through selected bioactive compounds may represent a novel adjunctive approach to support immune tolerance and nutritional status. The aim of the trial is to evaluate the clinical and immunological effects of a new multi-component nutritional supplement containing sodium butyrate, Fructooligosaccharides (FOS), vitamin D3, Docosahexaenoic acid (DHA), Perilla frutescens extract, quercetin, and heat-inactivated L. rhamnosus GG in children with IgE-mediated CMPA

In this 6-month, randomized, double-blind, placebo-controlled pilot trial, 30 children aged 36–60 months with confirmed CMPA were assigned to receive either the study product (2 g/day) or placebo. Primary outcomes included changes in body weight, height, and head circumference. Co-primary exploratory outcomes were serum 25-hydroxyvitamin D [25(OH)D] and DHA levels. Secondary endpoints included in vitro analyses of cytokine production, regulatory T cells (Tregs), and tolerogenic dendritic cell (DC) markers in peripheral blood mononuclear cells (PBMCs)

All participants completed the study without adverse events and with >90% compliance. Compared with placebo, the study product group showed significantly greater increases in body weight (16.7 ± 0.9 kg vs 15.8 ± 0.9 kg, p < 0.05), height, and head circumference. Serum 25(OH)D and DHA concentrations significantly improved only in the intervention group (p < 0.05 for both compounds). In PBMCs, co-exposure to β-lactoglobulin and study product markedly reduced Th2 cytokines (IL- 4, IL-5, IL-13) while enhancing IL-10 secretion and Treg number. Expression of tolerogenic DC markers (Tgfb1, Ifna2, Ptgs2, Csf2) was significantly upregulated, indicating the induction of a regulatory immune profile

This novel supplement safely improved growth and corrected key micronutrient deficiencies while promoting immunological tolerance pathways in children with CMPA. These findings support its potential as an adjunctive nutritional strategy to restore immune balance and enhance tolerance acquisition in pediatric food allergy