The alcohol hangover--a puzzling phenomenon.

The alcohol hangover develops when blood alcohol concentration (BAC) returns to zero and is characterized by a feeling of general misery that may last more than 24 h. It comprises a variety of symptoms including drowsiness, concentration problems, dry mouth, dizziness, gastro-intestinal complaints, sweating, nausea, hyper-excitability, and anxiety. The alcohol hangover is an intriguing issue since it is unknown why these symptoms are present after alcohol and its metabolites are eliminated from the body. Although numerous scientific papers cover the acute effects of alcohol consumption, researchers largely neglected the issue of alcohol hangover. This lack of scientific interest is remarkable, since almost everybody is familiar with the unpleasant hangover effects that may arise the day after an evening of excessive drinking, and with the ways these symptoms may affect performance of planned activities. Many people favour the (unproven) popular belief that dehydration is the main cause of alcohol hangover symptoms. However, taking a closer look at the present research on biological changes during alcohol hangovers suggests otherwise. A limited number of experiments have studied biological changes that are present the day after excessive drinking (for a review, see Ylikahri and Huttunen, 1977). Significant changes were reported on endocrine parameters (increased concentrations of vasopressin, aldosterone, and renin) and metabolic acidosis (reduced blood pH values due to increased concentrations of lactate, ketone bodies, and free fatty acids). These effects are related to dehydration and cause symptoms such as dry mouth and thirst. In addition, changes in immune system parameters (increased concentrations of pro-inflammatory cytokine [IL-12] and interferon-gamma [IFNγ]) have been reported (Kim et al ., 2003). It is likely that these changes in immune system parameters cause the more ‘cognitive’ alcohol hangover effects such as memory impairment and mood changes. Moreover, these findings suggest that alcohol hangover and dehydration are two independent yet co-occurring processes that have different underlying mechanisms. The idea that alcohol hangover symptoms (i.e. memory impairment) are related to immune system activation is strengthened by a relatively new discovery that the immune system and central nervous system (CNS) operate in close communication with each other (Maier and Watkins, 1998; Maier, 2003). The first line of evidence for the hypothesis that effects of immune activity on the CNS may be the cause of alcohol hangover comes from studies showing that cytokines