A hangover is the experience of various unpleasant physiological effects following heavy consumption of alcoholic beverages. An alcohol hangover is associated with a variety of symptoms that may include dehydration, fatigue, headache, body aches, vomiting, diarrhea, flatulence, weakness, elevated body temperature and heart rate, hypersalivation, difficulty concentrating, sweating, anxiety, dysphoria, irritability, sensitivity to light and noise, erratic motor functions (including tremor), trouble sleeping, severe hunger, halitosis, and lack of depth perception. Many people will also be repulsed by the thought, taste or smell of alcohol during a hangover.
While a hangover can be experienced at any time, generally speaking it is experienced the morning after a night of heavy drinking. Hypoglycemia, dehydration, acetaldehyde intoxication, and glutamine rebound are all theorized causes of hangover symptoms. Hangover symptoms may persist for several days after alcohol was last consumed. Approximately 25-30% of drinkers may be resistant to hangover symptoms.
Some aspects of a hangover are viewed as symptoms of acute ethanol withdrawal, similar to the longer-duration effects of withdrawal from alcoholism, as determined by studying the increases in brain reward thresholds in rats (the amount of current required to receive from two electrodes implanted in the lateral hypothalamus) following ethanol injection. Dehydration is caused by alcohol’s ability to inhibit the effect of anti-diuretic hormone on kidney tubules, which leads to a hyperosmolar state, which in turn causes shrinking of (by loss of water) the brain cells which causes hangover.
Ethanol has a dehydrating effect by causing increased urine production (diuresis), which causes headaches, dry mouth, and lethargy. Dehydration also causes fluids in the brain to be less plentiful. This can be mitigated by drinking water before, during and after consumption of alcohol. Alcohol’s effect on the stomach lining can account for nausea. Another contributing factor is the presence of products from the breakdown of ethanol by liver enzymes. Ethanol is converted to acetaldehyde (ethanal), which is between 10 and 30 times more toxic than alcohol itself. That reaction also results in
These two reactions also require the conversion of NAD+ to NADH. With an excess of NADH, three enzymes of the Citric Acid Cycle are inhibited (citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase) essentially shutting it down. Pyruvate (the end product of glycolysis) starts to accumulate, and the excess NADH drives lactate dehydrogenase to produce lactate from pyruvate in order to regenerate NAD+ and sustain life. This diverts pyruvate from other pathways such as gluconeogenesis, thereby impairing the ability of the liver to compensate for a drop in blood glucose levels, especially for the brain. Because glucose is the primary energy source of the brain, this lack of glucose (hypoglycemia) contributes to symptoms such as fatigue, weakness, mood disturbances, and decreased attention and concentration. It is often said that hangovers grow worse as one ages; this is thought to be caused by declining supplies of alcohol dehydrogenase.
Alcohol consumption can result in depletion of the liver’s supply of glutathione and other reductive detoxification agents, reducing its ability to effectively remove acetaldehyde and other toxins from the bloodstream. Additionally, alcohol induces the CYP2E1 enzyme, which itself can produce additional toxins and free radicals.
In addition, it is thought that the presence of other alcohols (fusel oils) and other by-products of alcoholic fermentation (also called congeners), exaggerate many of the symptoms; this probably accounts for the mitigation of the effects when distilled alcohol, particularly vodka, is consumed instead. A 2009 study provided evidence that darker-colored liquors, such as bourbon, cause worse hangovers than lighter-colored liquors, such as vodka. The higher amount of congeners found in darker liquors compared to lighter ones was indicated as the cause.
Studies that attempt to compare hangover producing potential and hangover severity of different alcoholic drinks suggest the following ordering (starting with the least hangover-inducing): distilled ethanol diluted in fruit juice; beer; vodka; gin; white wine; whisky; rum; red wine; brandy. In a 2006 study, an average of 14 standard drinks (330 ml bottles) of beer was needed to produce a hangover, compared with only 7 to 8 drinks of wine or liquor. One potent congener is methanol. It is naturally formed in small quantities during fermentation and it can be accidentally concentrated by improper distillation techniques. Metabolism of methanol produces an extremely toxic compound, formaldehyde; however, its metabolism is suppressed when ethanol is present in the bloodstream. This is thought to provide a mechanism for hangover that starts when blood alcohol content approaches zero and can be ‘cured’ by alcohol.
Most people of East Asian descent have a mutation in their alcohol dehydrogenase gene that makes this enzyme unusually effective at converting ethanol to acetaldehyde, and about half of such people also have a form of acetaldehyde dehydrogenase that is less effective at converting acetaldehyde to acetic acid. This combination causes them to suffer from alcohol flush reaction, in which acetaldehyde accumulates after drinking, leading to immediate and severe hangover symptoms. These people are therefore less likely to become alcoholics.
However, in a model of migraine, it was demonstrated that acetate is the primary metabolite of alcohol responsible for alcohol induced periorbital hypersensitivity. Furthermore, in the same model they recapitulated the effectiveness of caffeine, ketorolac for ameliorating this hypersensitivity. This model raises questions about the status quo hypothesis of hangover headache.
Hangovers are poorly understood from a medical point of view. Health care professionals prefer to study alcohol abuse from a standpoint of treatment and prevention, and there is a view that the hangover provides a useful, natural and intrinsic disincentive to excessive drinking. Within the limited amount of serious study on the subject, there is debate about whether a hangover might be prevented or at least mitigated; additionally, there is a vast body of folk medicine and simple quackery. There is currently no empirically proven mechanism for prevention except reducing the amount of ethanol consumed, or for making oneself sober other than waiting for the body to metabolize ingested alcohol, which occurs via oxidation through the liver before alcohol leaves the body. A four-page literature review in the ‘British Medical Journal’ concludes: ‘No compelling evidence exists to suggest that any conventional or complementary intervention is effective for preventing or treating alcohol hangover. The most effective way to avoid the symptoms of alcohol induced hangover is to avoid drinking.’
Modern hangover remedies include: Rehydration, Tolfenamic acid, Vitamin B6, Chlormethiazole, Pedialyte, Vegemite, Oxygen, Rosiglitazone, Acetylcysteine, and Tanganil. The ancient Romans, on the authority of Pliny the Elder, favored raw owl’s eggs or fried canary, while the ‘Prairie Oyster’ restorative, introduced at the 1878 Paris World Exposition, calls for raw egg yolk mixed with Worcestershire sauce, Tabasco sauce, salt and pepper. By 1938, the Ritz-Carlton Hotel provided a hangover remedy in the form of a mixture of Coca-Cola and milk (Coca-Cola itself having been invented, by some accounts, as a hangover remedy). Alcoholic writer Ernest Hemingway relied on tomato juice and beer. Certain mixtures were developed specifically for the purpose. The ‘Black Velvet’ consists of equal parts champagne and flat Guinness Stout. A 1957 survey by a Wayne State University folklorist found widespread belief in the efficacy of heavy fried foods, tomato juice, and sexual activity.