Hangovers

Not the ethanol–perhaps the methanol

“Wine is only sweet to happy men,” wrote an unhappy John Keats to his sweetheart.1 His observation seems to have been vindicated. Harburg et al found that psychosocial factors such as guilt about drinking, a neurotic personality, becoming angry or depressed while drinking, and having suffered “negative life events” in the past 12 months are better predictors of symptoms of hangover than the amount of ethanol drunk.2

In fact, ethanol itself may play only a minor part in producing the thirst, headache, fatigue, nausea, sweating, tremor, remorse, and anxiety that hangover sufferers report. Hangover symptoms are worst at a time when almost all ethanol and its metabolite acetaldehyde have been cleared from the blood, and peak blood ethanol or acetaldehyde levels are not related to the severity of hangover.3 Between a quarter and a half of drinkers claim not to experience hangover symptoms despite having been intoxicated.2 3 4

Congeners–complex organic molecules such as polyphenols, higher alcohols including methanol, and histamine, which occur in varying amounts in ethanolic drinks–are probably more to blame than ethanol. Chapman found that hangover symptoms were almost twice as common in volunteers who drank 1.5 ml/kg of bourbon whiskey–which has methanol concentrations of 260 mg/l–as in those drinking the same dose of vodka (0.039 mg of methanol per litre).5 Pawan compared the hangover produced by different types of drink (but only one brand of each) in his study of 20 volunteers. The severity of hangover symptoms declined in the order of brandy, red wine, rum, whisky, white wine, gin, vodka, and pure ethanol.6 Vodka and pure ethanol caused only mild headaches in two volunteers.

Jones has suggested that it is the metabolism of methanol to formaldehyde and formic acid that causes symptoms of hangover, with quicker methanol metabolisers suffering more.7 The justification for this suggestion is threefold: the types of drink associated with more severe hangovers contain higher levels of methanol; the time course of methanol metabolism corresponds to the onset of symptoms; and a small dose of ethanol, which blocks the formation of formaldehyde and formic acid, provides an effective treatment for hangovers (“the hair of the dog”).

The economic and social consequences of hangovers are probably considerable but difficult to quantify. Performance accuracy is impaired synergistically by sleep deprivation and hangover.8 Drivers perform less well in simulators when tested the morning after drinking ethanol.9 Making driving with a hangover a criminal offence might be logical, but is probably impractical in the absence of a simple diagnostic test like breath alcohol.

Many pathophysiological disturbances occur during hangover, including dehydration; metabolic acidosis; hypoglycaemia; disturbed prostaglandin synthesis; abnormal secretion of vasopressin, cortisol, aldosterone, renin, and testosterone; increased cardiac output; tachycardia; and vasodilatation. Hypoglycaemia and acidosis can be treated with fructose or glucose,9 and the cardiovascular abnormalities with ß blockade,10 but symptoms are not alleviated. However, rehydration and anti-inflammatory analgesics are helpful, particularly if treatment is started before bedtime.11 A completely effective treatment is probably unattainable (since so many factors–such as lack of sleep, active or passive smoking, dietary indiscretions, unaccustomed physical activity, intermittent upper airway obstruction, and emotional disturbances–must play a part) and is arguably undesirable since the fear of hangover prompts most people to moderate their ethanol intake.4 Even moderate amounts of ethanol can be damaging,12 so a penalty for consumption is in our interests. Perhaps those who aspire to be one of Dr Johnson's “heroes” by drinking brandy13 are sensible as well as brave.