酒精是世界上滥用最广泛的物质，是 15-49 岁人群死亡的主要来源，也是心脏病、肝病、糖尿病和癌症的主要危险因素。尽管如此，酒精在更广泛的社会中经常被滥用。过量饮酒的消费者经常会出现一系列负面症状，称为酒精宿醉。然而，临床医生或消费者并不认为酒精宿醉具有长期临床意义。我们对文献进行了严格审查，以证明酒精宿醉的病理生理机制。此后，酒精宿醉被重新定义为继发于酒精引起的炎症的疾病行为的表现，使用布拉德福德-希尔标准来证明因果关系高于相关性。酒精通过氧化应激和内毒素血症引起炎症。酒精代谢是氧化性的，摄入量增加会导致相对组织缺氧和自由基产生增加。脂质过氧化和 DNA/蛋白质加合物的形成导致组织损伤。酒精代谢的副产物（如乙醛和同系物）、睡眠剥夺以及酒精暴露组织中非特异性诱导型 CYP2E1 的激活都会加剧自由基的产生。组织损伤和细胞死亡会导致炎症，但在肠道中，上皮细胞的损失会导致肠道通透性增加，从而使病原菌易位至体循环（内毒素血症）。这导致了一系列明显的全身炎症级联反应，另外还激活了 Toll 样受体 4 来诱发疾病行为。考虑到这些证据，有人认为宿醉的频率和严重程度可能是以后酒精相关疾病发展的预测因素，值得前瞻性研究的正式证实。鉴于酒精介导的炎症机制，对肠道通透性和肠道微生物组的研究可能是预防酒精宿醉和其他酒精相关疾病的令人兴奋的未来治疗途径。© 2024 作者。 《酒精、临床和实验研究》由 Wiley periodicals LLC 代表酒精研究协会出版。

Alcohol is the most widely abused substance in the world, the leading source of mortality in 15-49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.© 2024 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.