Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption. The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested. Moreover there is a polymorphism at the level of another critical enzyme, N-acetyltransferase 2. At the pharmacodynamic level, there are several polymorphisms at the main brain target of caffeine, the adenosine A2A receptor or ADORA2. Genetic studies, including genome-wide association studies, identified several loci critically involved in caffeine consumption and its consequences on sleep, anxiety, and potentially in neurodegenerative and psychiatric diseases. We start reaching a better picture on how a multiplicity of biologic mechanisms seems to drive the levels of caffeine consumption, although much more knowledge is still required to understand caffeine consumption and effects on body functions.

中文翻译：

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咖啡因代谢的个体差异和驱动咖啡因消耗的因素

大多数人会根据甲基黄嘌呤引起的客观和主观影响来调整咖啡因的摄入量。但是，为了达到理想的效果，咖啡因的摄入量在个体之间差异很大。几十年来，众所周知，咖啡因的代谢，清除率和药代动力学受许多因素的影响，例如年龄，性别和激素，肝脏疾病，肥胖，吸烟和饮食。咖啡因还与许多药物相互作用。所有这些因素都将在本文档中进行回顾，并根据有关影响咖啡因水平的遗传变异性以及在药代动力学和药效动力学水平上均至关重要地驱动咖啡因消耗水平的影响的最新数据进行讨论。咖啡因的药代动力学在个体之间高度可变，这是由于细胞色素P450的CYP1A2亚型水平的多态性所致，该酶代谢了95％摄入的咖啡因。此外，在另一种关键酶的水平上存在一个多态性，N-乙酰转移酶2.在药效学水平上，咖啡因的主要大脑靶标，腺苷A2A受体或ADORA2有多种多态性。遗传研究，包括全基因组关联研究，确定了几个与咖啡因消耗有关的基因座，咖啡因的消耗及其对睡眠，焦虑的影响，以及潜在的神经退行性疾病和精神疾病。尽管仍然需要更多的知识来了解咖啡因的摄入及其对身体功能的影响，但我们仍开始就多种生物学机制如何驱动咖啡因摄入的水平取得更好的认识。