SUN-181 Sweeteners and Puberty: Investigating Genetic and Dietary Influences on Central Precocious Puberty

Abstract Disclosure: Y. Chen: None. Introduction: Central Precocious Puberty (CPP), marked by early secondary sexual characteristics due to premature hypothalamic-pituitary-gonadal axis activation, is increasingly prevalent. Understanding genetic and dietary factors, particularly sweeteners, is crucial for mitigating CPP's health impacts. Our prior research, which was published in 2024, revealed that Acesulfame Potassium (AceK) promotes GnRH expression via sweet taste receptors and ROS production (J of Hazardous Material 2024), while Glycyrrhizin alters gut microbiota, reducing puberty-related genes (Kiss1 and GPR54), slowing the progression of CPP (Life Sciences 2024). Aspartame delays puberty by modulating the KISS1/GPR54 system, increasing RFRP-3, and reducing SCFAs (Molecular Nutrition Food Res 2024). This study investigates sweetener consumption, genetic predisposition, and CPP risk interactions to inform prevention strategies. Methods: A population-based cohort of 1,407 children from the Taiwan Pubertal Longitudinal Study was analyzed. Sweetener intake was assessed through validated questionnaires and urinary biomarkers. Genetic predisposition was quantified using polygenic risk scores (PRS) derived from 19 CPP-related single nucleotide polymorphisms (SNPs). CPP diagnosis was confirmed through clinical, hormonal, and imaging criteria. Associations between sweetener intake, PRS, and CPP were evaluated using regression models adjusted for demographic and lifestyle covariates. Results: CPP was diagnosed in 481 participants. Aspartame, sucralose, glycyrrhizin, and added sugars were significantly associated with an increased risk of CPP, particularly in genetically predisposed individuals. A dose-dependent relationship was observed, with higher intake of these sweeteners amplifying CPP risk. Notable gender-specific effects included sucralose showing a stronger association with CPP in boys and glycyrrhizin, sucralose, and added sugars being particularly impactful in girls. Interaction effects between genetic predisposition and sweetener intake were non-significant. Conclusion: The findings indicate that sweetener consumption and genetic predisposition are independently associated with CPP risk. Integrating genetic and dietary assessments could guide prevention strategies for children at heightened risk, mitigating the long-term health impacts of early puberty. Presentation: Sunday, July 13, 2025