New insights into pubertal onset: Exploring the impact of low-calorie sweeteners exposure in school-aged children.

The safety of low-calorie sweeteners (LCSs) as food additives remains a contentious issue, particularly concerning their influence on precocious puberty for children. The cross-sectional study aims to explore the potential dose-response relationship between internal exposure to multiple LCS species and onset of pubertal in the school-age population. In total 473 children were recruited from Sanya District, Hainan Province, China, comprising precocious puberty (PP) cases (n = 61) with controls (n = 48), and early puberty (EP) cases (n = 185) with controls (n = 179). Results showed that in all groups, five LCSs were detected in over 55 % urine samples, with the concentration of xylitol in the EP group (464 µg/g vs. 387 µg/g) was significantly higher than its controls (p < 0.05). In the multivariate logistic regression, after creatinine adjustment, cyclamate was associated with a decreased PP risk (odds ratio (OR): 0.67, 95 % CI: 0.49, 0.93), while xylitol (OR: 1.48, 95 % CI: 1.06, 2.07) was associated with higher EP risk. Bayesian kernel machine regression model proved that mixed LCS exposure markedly increased EP risk. Mechanistically, LCSs may significantly interfere with DNA oxidative damage and be associated with changes in body mass index (BMI). Mediation analysis further suggested that xylitol exposure may indirectly increase the EP risk by increasing BMI. The epidemiological findings underscore that LCSs may influence pubertal onset, providing a scientific basis for food safety assessments.