Supplementary Material for: Caffeine and its metabolites are associated with overactive bladder: evidence from multiple statistical analysis models in NHANES.

Background: To offer valuable insights into potential dietary influences on bladder health, the study investigate the relationship between urinary caffeine metabolites and Overactive bladder syndrome (OAB).
Methods: The data for this investigation consisted of individuals who were 20 years old or older, obtained from the National Health and Nutrition Examination Survey (NHANES) database. To assess the correlation between urinary caffeine metabolites and OAB, logistic regression analyses were utilized. In addition, Quantile g-computation model (Qgcomp) and Bayesian kernel machine regression (BKMR) model were used to determine the combined effect of urine caffeine metabolites on OAB risk.
Results: In the analyses of a dataset comprising 4,354 participants, 815 were diagnosed with OAB. After adjusting for various covariates, logistic regression analyses revealed the highest tertiles of caffeine metabolites and ln-transformed caffeine metabolites were negatively associated with OAB risk. Subsequent analyses using the Qgcomp demonstrated that an increase in the quartiles of caffeine metabolites mixture was associated with a decreased risk of developing OAB. The OR were 0.89 (95% CI: 0.81, 0.99). Moreover, such negative correlation was primarily driven by 1,3-dimethylxanthine (1,3-DMX) and 1-methylxanthine(1-MX). The BKMR model confirmed a strong inverse link between urinary caffeine metabolites and OAB.
Conclusion: Our work demonstrates a strong inverse relationship between urine caffeine metabolites and the occurrence of overactive bladder (OAB). Among these metabolites, 1,3-DMX and 1-MX have the most pronounced impact on the combined effect. These findings suggest that the way caffeine is metabolized in the body could play a crucial role in the development of OAB.

背景：为深入探究饮食因素对膀胱健康的潜在影响，本研究聚焦于尿液咖啡因代谢物与膀胱过度活动症（Overactive bladder syndrome, OAB）之间的关联。
方法：本研究的研究对象为20岁及以上人群，数据来源于美国国家健康与营养检查调查（National Health and Nutrition Examination Survey, NHANES）数据库。为评估尿液咖啡因代谢物与OAB的相关性，本研究采用逻辑回归分析方法。此外，本研究还采用分位数g计算模型（Quantile g-computation model, Qgcomp）与贝叶斯核机器回归（Bayesian kernel machine regression, BKMR）模型，以探究尿液咖啡因代谢物混合物对OAB发病风险的联合效应。
结果：本研究纳入的4354名参与者中，共有815名被诊断为OAB。在校正各类协变量后，逻辑回归分析结果显示，咖啡因代谢物最高三分位组及其对数转换后的水平与OAB发病风险呈负相关。后续通过Qgcomp模型开展的分析表明，咖啡因代谢物混合物的四分位水平升高与OAB发病风险降低存在关联，其比值比（Odds Ratio, OR）为0.89（95%置信区间（Confidence Interval, CI）：0.81, 0.99）。进一步分析显示，这种负相关主要由1,3-二甲基黄嘌呤（1,3-dimethylxanthine, 1,3-DMX）与1-甲基黄嘌呤（1-methylxanthine, 1-MX）所驱动。BKMR模型亦证实，尿液咖啡因代谢物与OAB之间存在显著的负向关联。
结论：本研究证实，尿液咖啡因代谢物与膀胱过度活动症（OAB）的发生存在显著负相关。在上述代谢物中，1,3-DMX与1-MX对联合效应的影响最为显著。本研究结果提示，机体对咖啡因的代谢方式可能在OAB的发病过程中发挥关键作用。