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

## TL;DR

A new food supplement improved growth and immune tolerance in children with cow's milk allergy over six months.

## Contribution

A novel multicomponent supplement was tested and shown to modulate immune responses and improve growth in children with CMA.

## Key findings

- Children receiving the supplement showed greater improvements in body weight and height compared to the placebo group.
- The supplement significantly increased serum 25(OH)D and DHA levels in the active group.
- The supplement inhibited Th2 cytokines and increased IL-10 and Treg activation, promoting immune tolerance.

## Abstract

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.

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.

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.

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.

clinicaltrial.gov, identifier NCT06751810.