Zinc-L-Carnosine (Polaprezinc) in managing infant regurgitation: a two-center randomized controlled trial

Background: Gastroesophageal reflux (GER) is a common physiological phenomenon in infants, typically self-limited, but often a source of parental concern. When non-pharmacological measures fail to improve symptoms, thickened formulas are commonly used. Zinc-L-carnosine (Polaprezinc) is a mucosal protectant with anti-inflammatory and antioxidant properties. It is widely used in gastrointestinal disorders in adults but has not yet been extensively studied in infants. We aim to evaluate the clinical effectiveness and cost impact of a Zinc-L-carnosine-based supplement (Hepilor liquido®) compared to thickened formula in infants with persistent regurgitation.Methods: This was a two-center, prospective, single-blind, randomized, non-inferiority study conducted in two Italian pediatric hospitals. Infants aged 4 weeks to 7 months with persistent regurgitation despite appropriate nutritional and behavioral management were randomized to receive either Hepilor liquido® or thickened formula for 8 weeks. The primary outcome was symptom improvement based on the I-GERQ-R (Infant Gastro-Esophageal Reflux Questionnaire-Revised) score. Secondary outcomes included a reduction in regurgitation frequency and treatment cost analysis.Results: Sixty infants aged 4 weeks to 7 months were randomized to receive either Hepilor liquido® (n = 30, 50%) or thickened formula (n = 30, 50%) for 8 weeks. Both groups showed significant improvement in I-GERQ-R scores at 8 weeks. Although no statistically significant difference was observed in overall symptomatic remission, the Hepilor liquido® group demonstrated a greater reduction in regurgitation frequency. Notably, the average treatment cost was significantly lower in the Hepilor® group compared to the thickened formula. No severe adverse events were recorded in both groups.Conclusions: Zinc-L-carnosine is a safe and effective alternative to thickened formula in treating persistent infant regurgitation, after the failure of non-pharmacological measures. Its lower cost and promising clinical effect support further investigation in larger pediatric cohorts.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06678997, identifier: NCT06678997.