A product of alcohol metabolism that is more toxic than alcohol itself, acetaldehyde is created when the alcohol in the liver is broken down by an enzyme called alcohol dehydrogenase. The acetaldehyde is then attacked by another enzyme, acetaldehyde dehydrogenase, and another substance called glutathione, which contains high quantities of cysteine (a substance that is attracted to acetaldehyde). Together, the acetaldehyde dehydrogenase and the glutathione form the nontoxic acetate (a substance similar to vinegar). This process works well, leaving the acetaldehyde only a short amount of time to do its damage if only a few drinks are consumed.
Unfortunately, the liver’s stores of glutathione quickly run out when larger amounts of alcohol enter the system. This causes the acetaldehyde to build up in the body as the liver creates more glutathione, leaving the toxin in the body for long periods of time. In studies that blocked the enzyme that breaks down acetaldehyde (acetaldehyde dehydrogenase) with a drug called Antabuse, designed to fight alcoholism, acetaldehyde toxicity resulted in headaches and vomiting so bad that even alcoholics were wary of their next drink. Although body weight is a factor (see How Alcohol Works), part of the reason women should not keep up with men drink-for-drink is because women have less acetaldehyde dehydrogenase and glutathione, making their hangovers worse because it takes longer for the body to break down the alcohol.
Some of the most common hangover symptoms — fatigue, stomach irritation and a general sense of illness all over — can be further attributed to something called glutamine rebound.
After a night of alcohol consumption, a drinker won’t sleep as soundly as normal because the body is rebounding from alcohol’s depressive effect on the system. When someone is drinking, alcohol inhibits glutamine, one of the body’s natural stimulants. When the drinker stops drinking, the body tries to make up for lost time by producing more glutamine than it needs.
The increase in glutamine levels stimulates the brain while the drinker is trying to sleep, keeping them from reaching the deepest, most healing levels of slumber. This is a large contributor to the fatigue felt with a hangover. Severe glutamine rebound during a hangover also may be responsible for tremors, anxiety, restlessness and increased blood pressure.
Because alcohol is absorbed directly through the stomach, the cells that line the organ become irritated. Alcohol also promotes secretion of hydrochloric acid in the stomach, eventually causing the nerves to send a message to the brain that the stomach’s contents are hurting the body and must be expelled through vomiting. This mechanism can actually lessen hangover symptoms in the long run because vomiting gets rid of the alcohol in the stomach and reduces the number of toxins the body has to deal with. The stomach’s irritation may also be a factor in some of the other unpleasant symptoms of a hangover, such as diarrhea and lack of appetite.