Hangover

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 and thirst.

Hypoglycemia, dehydration, Acetaldehyde intoxication, and vitamin B12 deficiency are all theorized causes of hangover symptoms. Hangovers usually last 1 to 4 hours, but may last up to two or three days after alcohol was last consumed.

Symptoms
An alcohol hangover is associated with a variety of symptoms that may include dehydration, fatigue, headache, nausea, vomiting, diarrhea, weakness, elevated body temperature, hypersalivation, difficulty concentrating, anxiety, irritability, sensitivity to light and noise, erratic motor functions, and trouble sleeping. Many people will also be repulsed by the thought or taste 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 affect cognitive abilities.

Causes
Hangovers are multi-causal. Ethanol has a dehydrating effect by causing increased urine production (such substances are known as diuretics), which causes headaches, dry mouth, and lethargy. Dehydration causes the brain to shrink away from the skull slightly. 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 mildly toxic, contributing to hangover. 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.

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 (cogeners 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.

The amount of congeners in the drink may also have an effect. 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 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.

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.

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.

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 practise moderation."

Potentially beneficial remedies

 * Rehydration: "Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6".


 * Narcotics: Codeine, dihydrocodeine, tilidine and other such medication directly work against many of the effects of alcohol hangover.  It is believed that analgesic preparations containing acetaminophen (paracetamol/Tylenol)may predispose people to the risk of potentially fatal hepatotoxicity. However, this is unproven and would potentially only occur if the maximal dose of acetaminophen was exceeded . Therefore, acetaminophen is a suitable agent at combating the symptomatic effects of a hangover. Consumption of narcotics along with alcohol or shortly after consumption thereof is potentially dangerous in itself because of added depressant effects on the central nervous system.


 * Magnesium: It is well studied that excessive alcohol consumption can lead to a magnesium deficiency, or reduce levels of magnesium, as well as depleting zinc and other minerals. Individuals with lower magnesium levels may experience more severe hangovers.  A healthy diet that contains an adequate intake of magnesium and other minerals may help in the long term to reduce the effects of hangovers.  The hangover symptoms of headache, and light and sound sensitivity, are very similar to those of migraine.  A common treatment for chronic migraine headaches is magnesium.  Some scientists hypothesize that a hangover may be exhibiting at least some symptoms of an acute magnesium deficiency.


 * Opuntia ficus indica: A 2004 clinical study suggests that taking an extract of a prickly pear cactus fruit (Opuntia ficus indica) five hours before drinking had a statistically significant effect on three hangover symptoms. "Three of the 9 symptoms – nausea, dry mouth, and anorexia – were significantly reduced by OFI." (Anorexia in this context simply means loss of appetite, not to be confused with anorexia nervosa.) The authors conclude, "The symptoms of the alcohol hangover are largely due to the activation of inflammation. An extract of the OFI plant has a moderate effect on reducing hangover symptoms, apparently by inhibiting the production of inflammatory mediators."


 * 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 that Vitamin B6 reduces 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.


 * "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.


 * Food and Water: Simple consumption of food and water may be enough to replenish lost moisture and at least rehydrate the body, making a hangover shorter.

Possibly ineffective remedies

 * 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: "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."


 * Kudzu (Pueraria lobata): With respect to preventing hangovers, "The evidence regarding kudzu's effectiveness is mixed" and "There are no studies to demonstrate that kudzu can serve as a morning-after potion for eliminating hangovers as used in traditional Chinese practice."

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 "after-effect of drinking too much" first surfaced.