The prevalence of precocious puberty and the consumption of nonnutritive sweeteners (NNS) is rapidly growing worldwide. However, the effects of NNSs on precocious puberty remain unclear. We examined the impact of acesulfame potassium (AceK), one of the most widely used NNS, on central precocious puberty (CPP) development using ex vivo and in vitro studies. 884 girls aged 6-12 were enrolled with complete AceK consumption data and CPP outcome assessment in the Taiwan Pubertal Longitudinal Study from 2018 to 2022. After adjustment for confounders, compared with no AceK consumption, AceK consumption at more than the median dose was associated with higher CPP risk in girls (odds ratio = 1.88, 95% confidence interval = 1.16-3.06; p for trend = 0.003). In rats, AceK consumption from in-utero to post-weaning stages accelerated puberty onset, accompanied by increased brain gonadotropin-releasing hormone (GnRH) expression. Intracerebroventricular AceK injection also induced early puberty onset in rats. In N44 hypothalamic neuron cells, AceK treatment increased reactive oxygen species production, which led to protein kinase A (PKA) activation and increased GnRH expression. These findings suggest that prepubertal girls should consume soft drinks or food products containing AceK more cautiously.
Keywords: Acesulfame potassium; Central precocious puberty; Gonadotropin-releasing hormone; Hypothalamic neuron; Nonnutritive sweeteners.
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