A hangover play /ˈhæŋvər/ is the experience of various 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 effect of the alcohol begins 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, and glutamine rebound are all theorized causes of hangover symptoms.[1] Hangover symptoms may persist for several days after alcohol was last consumed. Approximately 25-30% of drinkers may be resistant to hangover symptoms.[2] 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.[3] Dehydration is caused by alcohol's ability to inhibit the effect of anti-diuretic hormone on kidney tubules[4], which leads to an interruption of the body's Krebs cycle[citation needed] and the swelling of the brain against the lining of the skull.

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. The symptoms vary significantly from person to person, and it is not clear whether hangovers directly affect cognitive abilities.

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.[citation needed]

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.[5]

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.[citation needed]

Alcohol consumption can result in depletion of the liver's supply of glutathione[6] and other reductive detoxification agents,[7] 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.[8]

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.[9] 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.[10] 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.[11][12] 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.[12] 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.[13] 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.[14][15]

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.[16]

However, in a model of migraine, it was demonstrated that acetate is the primary metabolite of alcohol responsible for alcohol induced periorbital hypersensitivity.[17] 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.

Potentially beneficial remedies

  • Rehydration: "Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6".[21]
  • Tolfenamic acid (TA): A study concludes that "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)."[22]
  • Vitamin B6 (pyritinol): Some studies have found large doses of Vitamin B6 (several hundred times the recommended daily intake) can help to reduce hangovers.[21][23]
  • 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."[24] "However, all 8 subjects had unpleasant nasal symptoms following chlormethiazole, and it is therefore not an ideal hypnotic for this age group."[25]
  • Pedialyte: Pedialyte may be an effective remedy for hangovers due to its replacement of lost electrolytes.
  • 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 the hangover represents a form of withdrawal[19] 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.[26] While the practice is affirmed by tradition[27] and by many hospitality providers,[28] medical opinion holds that the practice merely postpones the symptoms, and courts addiction.[29] Favored choices include Fernet Branca[30] and Bloody Mary.[26]
  • Yeast-based extracts: There is some evidence that the consumption of a yeast-based extract rich in thiamine and riboflavin (such as Vegemite or Marmite) is effective in the relief of hangover symptoms.[20] These extracts are commonly manufactured from a by-product of beer production.
  • 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 traditional hangover remedy in India is coconut water, the natural electrolytes of which will assist in rehydration of the body. A bacon sandwich has also been claimed to effectively relieve hangovers.[31]
  • Oxygen: 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.[32] However, one source states that (in an aviation context) oxygen has no effect on physical impairment caused by hangover.[33]
  • Rosiglitazone: [Study in rats] "Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression..."[34]
  • Acetylcysteine: There are claims that N-acetylcysteine can relieve or prevent symptoms of hangover through scavenging of acetylaldehyde, particularly when taken concurrently with alcohol.[35] Additional reduction in acetaldehyde toxicity can be achieved if NAC is taken in conjunction with vitamin B1 (thiamine).[5]
  • Acétyl-leucine: Sold under the brand name of Tanganil. One of the pre-hangover inconvenients is to find yourself in the "whirling pit." This is caused by a dysfunction between the nerves which control the notion of balance in the ears and the brain. Tanganil is the standard remedy prescribed to people suffering from chronic vertigo.

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,[36] 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.[37] By 1938, the Ritz-Carlton Hotel provided a hangover remedy in the form of a mixture of Coca-Cola and milk[37] (Coca-Cola itself having been invented, by some accounts,[38][39] as a hangover remedy). Alcoholic writer Ernest Hemingway relied on tomato juice and beer.[40] Certain mixtures were developed specifically for the purpose. The "Black Velvet" consists of equal parts champagne and flat Guinness Stout,[40] A 1957 survey by a Wayne State University folklorist found widespread belief in the efficacy of heavy fried foods, tomato juice and sexual activity.[27]

Activities said to be restorative include a shower—alternating very hot and very cold water,[41] exercise,[42][unreliable source?] 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).[43]

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."[44]
  • Propranolol: "We conclude that propranolol does not prevent the symptoms of hangover."[45][46]
  • 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."[47] Nevertheless, consumption of honey (a significant fructose and glucose source) is often suggested as a way to reduce the effect of hangovers.[48]
  • 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."[49]

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