Petrovic Dusan, Pruijm Menno, Ponte Belén, Dhayat Nasser A, Ackermann Daniel, Ehret Georg, Ansermot Nicolas, Vogt Bruno, Martin Pierre-Yves, Stringhini Silvia, Estoppey-Younès Sandrine, Thijs Lutgarde, Zhang Zhenyu, Melgarejo Jesus D, Eap Chin B, Staessen Jan A, Bochud Murielle, Guessous Idris
Department of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland; Department and Division of Primary Care Medicine, Geneva University Hospitals (HUG), Switzerland; Centre for Environment and Health, School of Public Health, Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Department of Nephrology and Hypertension, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
Mayo Clin Proc. 2021 Dec;96(12):3071-3085. doi: 10.1016/j.mayocp.2021.05.030. Epub 2021 Sep 25.
To investigate the relations between caffeine-derived metabolites (methylxanthines) and plasma lipids by use of population-based data from 2 European countries.
Families were randomly selected from the general population of northern Belgium (FLEMENGHO), from August 12, 1985, until November 22, 1990, and 3 Swiss cities (SKIPOGH), from November 25, 2009, through April 4, 2013. We measured plasma concentrations (FLEMENGHO, SKIPOGH) and 24-hour urinary excretions (SKIPOGH) of 4 methylxanthines-caffeine, paraxanthine, theobromine, and theophylline-using ultra-high-performance liquid chromatography-tandem mass spectrometry. We used enzymatic methods to estimate total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels and the Friedewald equation for low-density lipoprotein cholesterol levels in plasma. We applied sex-specific mixed models to investigate associations between methylxanthines and plasma lipids, adjusting for major confounders.
In both FLEMENGHO (N=1987; 1055 [53%] female participants) and SKIPOGH (N=990; 523 [53%] female participants), total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels increased across quartiles of plasma caffeine, paraxanthine, and theophylline (total cholesterol levels by caffeine quartiles in FLEMENGHO, male participants: 5.01±0.06 mmol/L, 5.05±0.06 mmol/L, 5.27±0.06 mmol/L, 5.62±0.06 mmol/L; female participants: 5.24±0.06 mmol/L, 5.15±0.05 mmol/L, 5.25±0.05 mmol/L, 5.42±0.05 mmol/L). Similar results were observed using urinary methylxanthines in SKIPOGH (total cholesterol levels by caffeine quartiles, male participants: 4.54±0.08 mmol/L, 4.94±0.08 mmol/L, 4.87±0.08 mmol/L, 5.27±0.09 mmol/L; female participants: 5.12±0.07 mmol/L, 5.21±0.07 mmol/L, 5.28±0.05 mmol/L, 5.28±0.07 mmol/L). Furthermore, urinary caffeine and theophylline were positively associated with high-density lipoprotein cholesterol in SKIPOGH male participants.
Plasma and urinary caffeine, paraxanthine, and theophylline were positively associated with plasma lipids, whereas the associations involving theobromine were less clear. We postulate that the positive association between caffeine intake and plasma lipids may be related to the sympathomimetic function of methylxanthines, mitigating the overall health-beneficial effect of caffeine intake.
利用来自2个欧洲国家的基于人群的数据，研究咖啡因衍生代谢物（甲基黄嘌呤）与血浆脂质之间的关系。
1985年8月12日至1990年11月22日，从比利时北部的普通人群（FLEMENGHO）中随机选取家庭；2009年11月25日至2013年4月4日，从瑞士的3个城市（SKIPOGH）中随机选取家庭。我们使用超高效液相色谱-串联质谱法测量了4种甲基黄嘌呤（咖啡因、副黄嘌呤、可可碱和茶碱）的血浆浓度（FLEMENGHO、SKIPOGH）和24小时尿排泄量（SKIPOGH）。我们采用酶法估算总胆固醇、高密度脂蛋白胆固醇和甘油三酯水平，并使用Friedewald方程计算血浆中低密度脂蛋白胆固醇水平。我们应用性别特异性混合模型来研究甲基黄嘌呤与血浆脂质之间的关联，并对主要混杂因素进行了调整。
在FLEMENGHO（N = 1987；1055名[53%]女性参与者）和SKIPOGH（N = 990；523名[53%]女性参与者）中，血浆咖啡因、副黄嘌呤和茶碱的四分位数范围内，总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平均升高（FLEMENGHO中男性参与者按咖啡因四分位数划分的总胆固醇水平：5.01±0.06 mmol/L、5.05±0.06 mmol/L、5.27±0.06 mmol/L、5.62±0.06 mmol/L；女性参与者：5.24±0.06 mmol/L、5.15±0.05 mmol/L、5.25±0.05 mmol/L、5.42±0.05 mmol/L）。在SKIPOGH中使用尿甲基黄嘌呤也观察到了类似结果（男性参与者按咖啡因四分位数划分的总胆固醇水平：4.54±0.08 mmol/L、4.94±0.08 mmol/L、4.87±0.08 mmol/L、5.27±0.09 mmol/L；女性参与者：5.12±0.07 mmol/L、5.21±0.07 mmol/L、5.28±0.05 mmol/L、5.28±0.07 mmol/L）。此外，在SKIPOGH男性参与者中，尿咖啡因和茶碱与高密度脂蛋白胆固醇呈正相关。
血浆和尿中的咖啡因、副黄嘌呤和茶碱与血浆脂质呈正相关，而涉及可可碱的关联则不太明确。我们推测，咖啡因摄入与血浆脂质之间的正相关可能与甲基黄嘌呤的拟交感神经功能有关，从而削弱了咖啡因摄入对整体健康的有益影响。
