The key to a bad hangover

Various old-wives’ tales are used to explain why certain individuals are more prone to hangovers in particular circumstances, but studies have shown that two of the key factors are genetics and gut microbiota.

Acetaldehyde, a toxic metabolite of alcohol, is a principal cause of hangover symptoms and liver damage. The rate at which acetaldehyde is both formed and metabolised varies between individuals. Most East Asian people, for example, carry a gene mutation that increases the speed at which acetaldehyde is formed. They therefore experience more alcohol-related side effects, such as flushing and nausea, than caucasians.

A study of more than 4,000 twins in Australia has highlighted the importance of genetics in hangover susceptibility. This work found that genetic factors accounted for 24% and 16% of the variation in hangover susceptibility in men and women, respectively. Hangover frequency (which is directly linked to intoxication frequency) was found to have an even stronger genetic link, with genetic factors accounting for 45% of the variation in men and 40% in women. Other twins studies have shown that liking or disliking the taste of alcohol, drinking levels, and alcohol addiction are also heritable traits.

But while the genes controlling the enzymes responsible for breaking down acetaldehyde (acetaldehyde dehydrogenase and glutathione) play a part in hangover susceptibility, other factors are at play. Last year, a US study investigated for the first time the effect of binge drinking on gut microbes, and their subsequent role in hangovers.

Investigators gave 25 volunteers who were not regular drinkers a wine glass of vodka, eliciting a wide range of responses. Those with the worst symptoms had the highest levels of an endotoxin (lipopolysaccharide) coming from the cell walls of their gut microbes. This endotoxin leaked out of their intestine as a result of the inflammation produced by the alcohol. There was also a brief, but large increase in pro-inflammatory microbes in the gut, stimulating the immune system and contributing to the general ‘sick’ feeling of hangovers.

The gut microbiota in general does not change as a result of binge drinking, but a few species increase markedly. One such species, Erysipelotrichia, which can produce alcohol dehydrogenase (which converts alcohol to acetaldehyde), increases five-fold. To underline their role in liver damage further, experiments in mice have shown that, if all microbes are absent (so-called ‘germ-free’ animals have no micro-organisms living in or on them), simulated binge drinking does not harm the liver.