Hangover

A hangover describes the sum of unpleasant physiological effects following heavy consumption of alcoholic beverages. The most commonly reported characteristics of a hangover include headache, nausea, sensitivity to light and noise, lethargy, dysphoria, diarrhea and thirst, typically after the intoxicating effects of the alcohol begin to wear off. While a hangover can be experienced at any time, generally speaking a hangover is experienced the morning after a night of heavy drinking. In addition to the physical symptoms, a hangover may also induce psychological symptoms including heightened feelings of depression and anxiety.

Hypoglycemia, dehydration, acetaldehyde intoxication, glutamine rebound, and vitamin B12 deficiency 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 to electrodes implanted in the lateral hypothalamus) following ethanol injection. Dehydration is caused by alcohol's ability to inhibit the release of anti-diuretic hormone.

Etymology
The term hangover was originally a 19th century expression describing unfinished business—something left over from a meeting—or "survival." In 1904, the meaning "morning after-effect of drinking too much" first surfaced.

In Norwegian, veisalgia derives from kveis (uneasiness following debauchery) and the Greek algia (pain).

Symptoms
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, 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. The symptoms vary from person to person, and occasion to occasion, usually beginning several hours after drinking. It is not clear whether hangovers directly affect cognitive abilities.

Causes
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 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 by the enzyme alcohol dehydrogenase, and then from acetaldehyde to acetic acid by the enzyme acetaldehyde dehydrogenase. Acetaldehyde (ethanal) is between 10 and 30 times more toxic than alcohol itself.

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 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.

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 (such as fusel oils), by-products of the alcoholic fermentation also called congeners, exaggerate many of the symptoms (congeners may also be zinc or other metals added primarily to sweet liqueurs to enhance their flavor); this probably accounts for the mitigation of the effects when distilled alcohol, particularly vodka, is consumed instead. A 2009 study provided evidence that darker-coloured liquors, such as bourbon, cause worse hangovers than lighter-coloured liquors, such as vodka. The higher amount of congeners found in darker liquors compared to lighter ones was indicated as the cause.

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.

It is often said that hangovers grow worse as one ages; this is thought to be caused by declining supplies of alcohol dehydrogenase, the enzyme involved in metabolizing alcohol.

Possible remedies
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 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."

Ineffective or unproven remedies
Recommendations for foods, drinks and activities to relieve hangover symptoms abound. 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.

Activities said to be restorative include a shower—alternating very hot and very cold water, exercise, and steambath or sauna (although medical opinion holds this to be very dangerous, as the combination of alcohol and hyperthermia increases the likelihood of dangerous cardiac arrhythmias).

Other untested or discredited treatments include:
 * Globe artichoke (Cynara scolymus) extract: "Our results suggest that artichoke extract is not effective in preventing the signs and symptoms of alcohol-induced hangover."
 * Propranolol: "We conclude that propranolol does not prevent the symptoms of hangover."
 * Fructose and glucose: A 1976 research came to the conclusion that "The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover." Nevertheless, consumption of honey (a significant fructose and glucose source) is often suggested as a way to reduce the effect of hangovers.
 * Kudzu (Pueraria montana var. lobata): The main ingredient in remedies such as kakkonto. A study concluded, "The chronic usage of Pueraria lobata at times of high ethanol consumption, such as in hangover remedies, may predispose subjects to an increased risk of acetaldehyde-related neoplasm and pathology. ... Pueraria lobata appears to be an inappropriate herb for use in herbal hangover remedies as it is an inhibitor of ALDH2."

Potentially beneficial remedies

 * Cannabis: Cannabis has had applications in the treatment of nausea and stimulates hunger, facilitating the replenishment of complex carbohydrates
 * Hair of the dog: The belief that consumption of further alcohol after the onset of a hangover will relieve symptoms, based upon the theory that hangover represents a form of withdrawal and that by satiating the body's need for alcohol the symptoms will be relieved. Certainly the additional alcohol has a sedating and anaesthetic effect. While the practice is affirmed by tradition and by many hospitality providers, medical opinion holds that the practice merely postpones the symptoms, and courts addiction. Favored choices include Fernet Branca and Bloody Mary.
 * Food and water: consumption of foods such as eggs, which contain cysteine, and water may be enough to replenish lost moisture and at least rehydrate the body, making a hangover shorter. A bacon sandwich has also been claimed to effectively relieve hangovers.
 * Rehydration: "Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6".
 * Oxygen: In a double-blind random study of 231 patients at two Vienna hospitals, published in Anesthesiology in 1999 and reported by The New York Times, it was found that the side-effects of general anesthesia could be diminished by giving patients a mix of 80 percent oxygen and 20 percent nitrogen during the surgery, and for two hours afterward. Only 17 percent of the patients receiving supplemental oxygen experienced nausea and vomiting, compared with 30 percent of the group who were given the standard 30 percent oxygen and 70 percent nitrogen. The study's leader characterized the results for the Times, "Extra oxygen is cheap, risk-free and reduces the incidence of nausea as well as any known drug."  A related study by members of Dr. Sessler's team, published in Anesthesiology in October 1999, indicated that patients given oxygen in amounts up to 80 percent did not suffer impaired lung function.  In addition, there have been anecdotal reports from those with easy access to a breathing oxygen supply — medical staff, SCUBA divers and military pilots — that oxygen can also reduce the symptoms of hangovers sometimes caused by alcohol consumption.  The theory is that the increased oxygen flow resulting from oxygen therapy improves the metabolic rate, and thus increases the speed at which toxins are broken down. However, one source states that (in an aviation context) oxygen has no effect on physical impairment caused by hangover.
 * Tolfenamic acid (TA): A study concludes, "TA was found significantly better than placebo in the subjective evaluation of drug efficacy (p < 0.001) and in reducing the reported hangover symptoms in general (p < 0.01). In the TA group, significantly lower symptom scores were obtained for headache (p < 0.01), and for nausea, vomiting, irritation, tremor, thirst, and dryness of mouth (all p < 0.05)."
 * Vitamin B6 (pyritinol): Some studies have found large doses of Vitamin B6 (several hundred times the recommended daily intake) can help to reduce hangovers.
 * Chlormethiazole: "Chlormethiazole was found to lower blood pressure and adrenaline output and, furthermore, to relieve unpleasant physical symptoms, but did not affect fatigue and drowsiness. The cognitive test results were only slightly influenced by this agent, while psychomotor performance was significantly impaired. Subjects with severe subjective hangover seemed to benefit more from the chlormethiazole treatment than subjects with a mild hangover." "However, all 8 subjects had unpleasant nasal symptoms following chlormethiazole, and it is therefore not an ideal hypnotic for this age group."
 * Rosiglitazone: [Study in rats] "Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression..."
 * Acetylcysteine: There are claims that N-acetylcysteine can relieve or prevent symptoms of hangover through scavenging of acetylaldehyde, particularly when taken concurrently with alcohol.  Additional reduction in acetaldehyde toxicity can be achieved if NAC is taken in conjunction with vitamin B1 (thiamine).