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A hangover (veisalgia) describes the sum of unpleasant physiological effects following heavy consumption of drugs, particularly alcoholic beverages. The most commonly reported characteristics of a hangover include headache, nausea, sensitivity to light and noise, lethargy, dysphoria, diarrhea and thirst.

Hypoglycemia, dehydration, acetaldehyde intoxication, and vitamin B12 deficiency are all theorized causes of hangover symptoms. Hangovers may last up to two or three days after alcohol was last consumed.[1] 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 to electrodes implanted in the lateral hypothalamus) following ethanol injection.[3]


[edit] Etymology

Look up hangover in Wiktionary, the free dictionary.
Look up veisalgia in Wiktionary, the free dictionary.

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.[4][5]

[edit] Symptoms

An alcohol hangover is associated with a variety of symptoms that may include dehydration, fatigue, headache, nausea, vomiting, diarrhoea, flatulence, weakness, elevated body temperature, hypersalivation, difficulty concentrating, anxiety, irritability, sensitivity to light and noise, erratic motor functions (including tremor), trouble sleeping, 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. In some rare cases, these symptoms can be additive to the point of hospitalization.

[edit] 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 or an oral electrolyte solution after consumption of alcohol. Alcohol's effect on the stomach lining can account for nausea. Because of the increased NADH production during metabolism of ethanol by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, excess NADH can build up and slow down gluconeogenesis in the liver, thus causing hypoglycemia.

Another factor contributing to a hangover are the products from the breakdown of ethanol via 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,[6] as well as being cocarcinogenic (not carcinogenic solely by itself) and mutagenic.[7]

These two reactions also require the conversion of NAD+ to NADH. With an excess of NADH, the lactate dehydrogenase reaction is driven to produce lactate from pyruvate (the end product of glycolysis) 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 supply glucose to tissues, especially the brain. Because glucose is the primary energy source of the brain, this lack of glucose contributes to hangover symptoms such as fatigue, weakness, mood disturbances, and decreased attention and concentration as well as the possibility of waking up next to a nasty piece of gash.

Alcohol consumption can result in depletion of the liver's supply of glutathione[8] and other reductive detoxification agents,[9] 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.[10]

There are various nervous system effects: the removal of the depressive effects of alcohol in the brain probably account for the light and noise sensitivity.

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[11].

Red wines have more congeners than white wines, and some people note less of a hangover with white wine. Some individuals have a strong negative reaction to red wine, distinct from hangover, called red wine headache that can affect them within 15 minutes after drinking a single glass of red wine. The headache is usually accompanied by nausea and flushing[citation needed].

In alcohol metabolism, one molecule of ethanol (the primary active ingredient in alcoholic beverages) produces 2 molecules of NADH, utilizing vitamin B12 as a coenzyme. Over-consumption of ethanol may cause vitamin B12 deficiency as well.

[edit] Possible remedies

There is debate about whether a hangover might be prevented or at least mitigated. There is currently no known proven mechanism for making oneself sober short of waiting for the body to metabolize ingested alcohol, which occurs via oxidation through the liver before alcohol leaves the body. However, drinking a large amount of water or a rehydration drink prior to sleep will effectively reduce a large proportion of the symptoms. It may also be helpful to replenish with electrolytes via food to avoid aggrevating electrolyte disturbances induced by alcohol through consuming only water. This increases the need to urinate in the relevant timeline, thus cleaning the body and ridding it of many chemicals more quickly, including those that cause or heighten hangover symptoms.

A four page literature review in British Medical Journal on hangover cures by Max Pittler of the Peninsula Medical School at Exeter University and colleagues 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."[12]

[edit] Potentially beneficial remedies

  • Food and water: Simple 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.[citation needed]
  • Milk, water and orange juice. The Calcium, re-hydration properties, and vitamin C contained in each product respectively is found to combat the symptoms of a hangover if taken shortly after consumption.[citation needed] Milk is also a dietary source of cysteine.
  • Rehydration: "Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6".[13]
  • Sodium bicarbonate; A slightly heaped teaspoon of baking soda suspended in a glass of water when consumed deals very effectively with the nausea, and indirectly with 'the shakes' associated with a hangover.[citation needed]
  • Exercise: Light exercise helps the heart pump blood around the body and increases the amount of oxygen in the body.
  • Opioids: Opioids such as hydrocodone, codeine, and oxycodone can potentially provide relief to the pain associated with a hangover. Caution should be exercised when using opioids that are combined with acetaminophen, as the combined effects of alcohol and acetaminophen can be toxic to the liver.
  • 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.[14] 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 doctors, nurses and SCUBA divers, 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.[15]
  • 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)."[16]
  • Vitamin B1 (thiamine): there are claims[citation needed] that apart from helping prevent Wernicke-Korsakoff syndrome, thiamine supplements may substantially enhance the activity of alpha-ketoglutarate dehydrogenase and so prevent a build up of glutamate and hence GABA in the cerebellum of the brain (thus reducing some symptoms of hangovers).
  • Vitamin B6 (pyritinol): Some studies have found large doses of Vitamin B6 (several hundred times the recommended daily intake) to reduce hangovers.[13][17]
  • 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."[18] "However, all 8 subjects had unpleasant nasal symptoms following chlormethiazole, and it is therefore not an ideal hypnotic for this age group."[19]
  • Rosiglitazone: [Study in rats] "Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression…"[20]
  • Acetylcysteine: There are claims that N-acetylcysteine can relieve or prevent symptoms of hangover through scavenging of acetylaldehyde, particularly when taken concurrently with alcohol. [21][22] Additional reduction in acetaldehyde toxicity can be achieved if NAC is taken in conjunction with vitamin B1 (thiamine). [23]

[edit] Ineffective remedies

  • Antipokhmelin: Also known under its tradename RU-21, it is an over-the-counter dietary supplement whose primary active ingredient is succinic acid, an extract of amber. It has been touted by internet marketers as a miracle cure for alcohol hangovers, alleged to have been produced by Soviet scientists for a KGB spy program. To-date, however, no double-blind, placebo-controlled scientific studies confirming the marketers' claims have been released.
  • Globe artichoke (Cynara scolymus) extract: "Our results suggest that artichoke extract is not effective in preventing the signs and symptoms of alcohol-induced hangover."[24]
  • Artichoke and Sarsaparilla extract: A November 2004 issued U.S. Patent No. 6,824,798 states that the method described in the patent "results in complete elimination of veisalgia (hangover) in more than 80% of individuals". These plant extracts, when administered separately, do not seem to have a similar effect. The patent further states that the right combination of the extracts of both of these plants are required and that they then contain a complex of polyphenols, flavonoids, and phytosterols that are effective. However, no evidence is required for such statements to appear in a patent application or in the patent itself. The existence of a patent is merely legal evidence of intellectual property, not evidence of efficacy.
  • Propranolol: "We conclude that propranolol does not prevent the symptoms of hangover."[25][26]
  • Fructose and glucose: A 1976 research has come 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."[27] Nevertheless, consumption of honey (a significant fructose and glucose source) is often suggested as a way to reduce the effect of hangovers.[28]
  • Kudzu (Pueraria lobata): 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."[29]

[edit] References

  1. ^ Federal Aviation Administration. Pilot Safety Brochure
  2. ^ PMID 18412754
  3. ^ PMID 16938626
  4. ^ Online Etymology Dictionary Hangover
  5. ^ Frank Kelly Rich On the Cuff & Under the Table: The Origins and History of Drinking Words and Phrases Modern Drunkard Magazine
  6. ^ Herbert Sprince, Clarence M. Parker, George G. Smith and Leon J. Gonzales Protection against Acetaldehyde Toxicity in the rat by L-cysteine, thiamin and L-2-Methylthiazolidine-4-carboxylic acid Inflammation Research April, 1974
  7. ^ F Stickel, D Schuppan, E G Hahn, H K Seitz Cocarcinogenic effects of alcohol in hepatocarcinogenesis Gut 21 August 2001
  9. ^ F Stickel, D Schuppan, E G Hahn, H K Seitz Cocarcinogenic effects of alcohol in hepatocarcinogenesis Gut 21 August 2001
  10. ^ Kessova I, Cederbaum AI. CYP2E1: biochemistry, toxicology, regulation and function in ethanol-induced liver injury. Current Molecular Medicine 2003 Sep
  11. ^ The Alcohol Hangover. Jeffrey Wiese, Michael Shlipak, Warren S. Browner. Annals of Internal Medecine, 6 June 2000, Volume 132 Issue 11, Pages 897-902. [1]
  12. ^ Max H Pittler, et al.Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials BMJ 2005;331:1515-1518 (24 December), doi:10.1136/bmj.331.7531.1515
  13. ^ a b Jeffrey G. Wiese, Michael G. Shlipak, Warren S. Browner The Alcohol Hangover Annals of Internal Medicine 6 June 2000 Volume 132 Issue 11 pp897–902
  14. ^ Dr. Daniel Sessler Extra Oxygen for Anesthesia's Hangover The New York Times 9 November 1999
  15. ^ Timothy Walker and Mary Fitzgerald A drinker's guide to hangover cures The Independent 17 April 2007
  16. ^ S. Kaivola1, J. Parantainen, T. Österman and H. Timonen Hangover headache and prostaglandins: Prophylactic treatment with tolfenamic acid Cephalalgia Volume 3 Page 31 - March 1983 doi:10.1046/j.1468–2982.1983.0301031.x
  17. ^ Khan MA, Jensen K, Krogh HJ. Alcohol-induced hangover: A double-blind comparison of pyritinol and placebo in preventing hangover symptoms Q J Stud Alcohol. 1973;34:1195–201
  18. ^ Myrsten AL, Rydberg U, Idestrom CM, Lamble R. Alcohol intoxication and hangover: modification of hangover by chlormethiazole Psychopharmacology (Berl). 1980;69(2):117–25.
  19. ^ Castleden CM, George CF, Sedgwick EM. Chlormethiazole--no hangover effect but not an ideal hypnotic for the young Postgrad Med J. 1979 Mar;55(641):159–60.
  20. ^ Jung TW, Lee JY, Shim WS, Kang ES, Kim SK, Ahn CW, Lee HC, Cha BS. Rosiglitazone relieves acute ethanol-induced hangover in sprague-dawley rats Alcohol Alcohol 2006 May-Jun;41(3):231-5. Epub 2006 Mar 22
  21. ^ Fawkes, SW CERI: Living with Alcohol Smart Drug News 1996 Dec 13
  22. ^ Resat Ozaras, Veysel Tahan, Seval Aydin, Hafize Uzun, Safiye Kaya, Hakan Senturk. N-acetylcysteine attenuates alcohol-induced oxidative stress in rats World Journal of Gastroenterology 2003 Apr 15
  23. ^ Herbert Sprince, Clarence M. Parker, George G. Smith and Leon J. Gonzales Protection against Acetaldehyde Toxicity in the rat byl -cysteine, thiamin andl -2-Methylthiazolidine-4-carboxylic acid Inflammation Research April, 1974
  24. ^ Max H. Pittler, Adrian R. White, Clare Stevinson and Edzard Ernst Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial CMAJ December 9, 2003; 169 (12)
  25. ^ Bogin RM, Nostrant TT, Young MJ. Propranolol for the treatment of the alcoholic hangover Am J Drug Alcohol Abuse. 1986;12(3):279–84.
  26. ^ Bogin RM, Nostrant TT, Young MJ Propranolol for the treatment of the alcoholic hangover Am J Drug Alcohol Abuse. 1987;13(1-2):175–80.
  27. ^ Ylikahri RH, Leino T, Huttunen MO, Poso AR, Eriksson CJ, Nikkila Effects of fructose and glucose on ethanol-induced metabolic changes and on the intensity of alcohol intoxication and hangover Eur J Clin Invest 1976 Jan 30;6(1):93–102.
  28. ^ UMDNJ Experts Suggest Remedies for Holiday Headaches
  29. ^ Neil R. McGregor Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk Alcohol Volume 41, Issue 7, November 2007, Pages 469-478 doi:10.1016/j.alcohol.2007.07.009

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