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Alcohol Intolerance, Allergy and Headache

Ethanol or other substances in alcoholic beverages may trigger allergic or other adverse reactions in sensitive individuals. Intolerance to histamine, tyramine, phenylethylamine does not seem to be related with alcohol intolerance [1].

Ethanol

Ethanol in amounts as low as one milliliter (1/1000 liter; ~20 drops) may, rarely–within few minutes of consumption–trigger an anaphylactic reaction with skin rash (hives, urticaria), swollen lips and eyes (angioedema), difficulty breathing, stomach cramps and collapse. This is apparently not a true allergic reaction, since no increase of IgE antibodies can be detected and the the prick skin test is negative. Susceptibility for anaphylactic reactions to ethanol may resolve spontaneously with time [2].

Ethanol may trigger vasomotor rhinitis [vasomotor = dilating vessels; rhinitis = inflammation of the nasal mucosa], a non-allergic condition with runny, itchy nose and sneezing [3] and increase the risk of developing perennial allergic rhinitis [continuous, non-seasonal allergic inflammation of the nose] [4].

Sulfites

Sulfites are naturally present in wines and beers. Sulfites may be added as preservatives or stabilizers to wines, beers, cider, cocktail mixes, wine coolers, fruit juices, dried fruits (prunes, raisins) and certain other foods [5,6]. Most wines, including “organic wines,” contain sulfites.

Sulfites may be irritant for some asthmatics and also for some individuals without history of asthma and may, within 30 minutes of ingestion, trigger wheezing and cough [6,7]. Rarely, within few minutes to 2 hours of ingestion, sulfites may trigger a more severe anaphylactic reaction with difficulty breathing, swelling in the lips and around the eyes (angioedema), hives (urticaria), nausea, diarrhea, stroke or even death [5,8,9].

At least 3 mechanisms of sulfite sensitivity have been suggested so far: 1) sulfur dioxide can be released from foods and, when inhaled, irritate breathing pathways, 2) some sensitive individuals may have a reduced activity of sulfite oxidase, an enzyme that breaks down sulfur oxide and 3) sulfites may trigger an allergic reaction [7].

Skin patch test with sulfites is positive only in some sulfite-sensitive individuals [7,11].

Diagnosis can be made on the basis of positive challenge test with sulfites and the improvement of symptoms within 4 weeks of a low-sulfite diet [7,11].

Treatment depends on the symptoms: prescribed bronchodilators (inhalers) for asthmatic attack, steroids or antihistamines (H1 blockers, such as loratadine) for hives or an epinephrine (adrenaline) injection in severe anaphylactic reaction with difficulty breathing [12].

It is not clear if sulfites can trigger headache. In non-asthmatics, adverse reactions to sulfites are rare [6]. There is no evidence that sulfite sensitivity would resolve with time [7].

Histamine

Histamine is naturally present in certain alcoholic beverages (in decreasing order): red wine, champagne, beer, white wine [13]. Histamine is also in cider and wine coolers.

Ethanol stimulates the release of histamine in the body.

Foods relatively high in histamine include fish, aged cheese, bacon, ham, sausages, cured meat, chicken, pickled cabbage, sauerkraut, brewer’s yeast, vinegar (see more histamine-rich foods). Foods that may trigger the release of histamine in the body include berries, citrus fruits, chocolate, egg white, liquorice, nuts, papaya, pork, spinach, tomatoes, certain spices and food additives [8,14,15,16].

Blood histamine levels may be also increased in allergies, atopic eczema, gastrointestinal bleeding, scombroid fish poisoning, Crohn’s disease, ulcerative colitis and, in women, during ovulation [8].

In one study, 1 from 10 healthy women without history of food intolerance reacted to 75 mg of histamine dissolved in tea with sneezing and fast heartbeat within 60 minutes after drinking, and 4 women reacted with headache, itchy skin, diarrhea and flatulence within 3-24 hours [13].

Individuals with histamine intolerance have deficiency of diamine oxidase (DAO), an enzyme in the small intestine that breaks down histamine from food [8]. After consuming foods high in histamine they have increased blood levels of histamine, which causes symptoms, such as facial flushing, headache, diarrhea, generalized itch, sneezing, runny nose, shortness of breath, sudden fall of blood pressure, dizziness, increased heart rate [14,17]. DAO deficiency may be hereditary or acquired. Acquired DAO deficiency may be caused by heavy alcohol drinking or certain drugs (certain antibiotics, amitriptyline, aspirin, cimetidine, isoniazid, metoclopramide, morphine, NSAIDs and verapamil) [8,18].

In one 2007 study, participants with a self-reported history of histamine intolerance did not always react to repeated challenges with 75 mg histamine, but sometimes reacted to placebo (inactive substance), which may mean that psychological factors may affect the reaction to histamine [19].

In one 1994 study, 22 from 28 participants with a history of wine intolerance reacted to 125 mL of red wine (50 mg histamine) with symptoms, such as sneezing, runny nose, nausea and headache [13].

In one 2004 study, 75 mg of liquid histamine (the amount in average meals) provoked symptoms (headache, sneezing, itch, diarrhea) 20 minutes to 24 hours after ingestion in 5 from 10 healthy female participants without history of food intolerance [13].

One 2001 review of scientific literature has revealed no relation between histamine content of wine and wine intolerance [20].

Histamine intolerance is not an allergy, so a skin prick test is negative [14]. 

Diagnosis of histamine intolerance can be made after the exclusion of allergies, the occurrence of symptoms after a challenge with histamine, or symptoms decrease after a low-histamine diet. Low DAO activity or high histamine levels in the blood or urine further support the diagnosis [8,15,21].

Low-histamine diet, H1 antihistamines, such as loratadine, and vitamin C and B6 may help to reduce symptoms [8].

Tyramine

Tyramine can be found in red wine, especially Chianti, tap beer, Korean beer, non-alcoholic beer or wine, vermouth, sherry, aged cheeses, cured meats, soy products, sauerkraut and other aged, fermented, stored or non-fresh foods. In some studies, tyramine did, but in other studies did not trigger migraine in the known migraine sufferers [22]. One explanation is that some migraine sufferers are deficient in monoamine oxidase (MAO), an enzyme in the gut that breaks down tyramine from foods, so they absorb more tyramine, which may cause high blood pressure and headache [22,23].

Alcoholic beverages or foods high in tyramine consumed along with MAO inhibitors (a type of antidepressants, including isocarboxazid, phenelzine, selegiline and tranylcypromine) may trigger a dangerous increase of blood pressure, headache, rapid heart beat, vomiting, excessive sweating and flushing [5,8,23].

Acetaldehyde

In heavy drinkers, acetaldehyde, a breakdown product of alcohol, may cause transient facial flushing [3,24]. Acetaldehyde may trigger hives (urticaria) in individuals suffering from chronic urticaria [2].

In individuals with ALDH2 deficiency (mostly east Asians), acetaldehyde may trigger facial flushing or, in ALDH2 deficient asthmatics, an asthmatic attack (alcohol-induced asthma) [25].

Salicylates

Salicylates (e.g. aspirin) may trigger hives and eczema, but it is not known if salicylates in amounts naturally present in wine, beer, sherry and rum cause any adverse reactions [26].

Allergic Reactions to Various Alcohol Beverages Ingredients

Malted barley, hops or, very rarely, yeasts, in beers may trigger anaphylactic reaction with facial tingling, swelling of the lips and tongue, hives (urticaria), flushing, difficult breathing, coughing, generalized itch and fainting. Anaphylactic reactions may, rarely, be fatal.

Vodka or whiskey derived from wheat may trigger allergic reaction in sensitive individuals. Pure, wheat-derived distilled beverages should not contain gluten.

Alcohol and Exercise-Induced Anaphylaxis

Alcohol consumed within 3 hours before exercise or, possibly, shortly after exercise, may trigger “food-dependent exercise-induced anaphylaxis” (a strong allergic reaction) within 45 minutes of starting exercise or even walking [27,28]. Reaction may start as fatigue, feeling of warmth and itching, continue with generalized patchy hives (urticaria) and, in severe cases, swollen lips and tongue, difficulty breathing, diarrhea, headache or fainting [27,29]. Rarely, the reaction may be fatal [29]. Symptoms may last for few hours (headache for up to 72 hours) and are less pronounced if a person stops exercising immediately after first warning signs, such as feeling of warmth or itching [29].

Other triggers (in combination with exercise) include heat, cold, menstrual cycle, food, either any food or, in some individuals, only certain food, such as wheat (gluten), shrimps, shellfish, nuts, apples, strawberries, cabbage, celery, milk or certain medications, such as aspirin or ibuprofen [27]. Affected individuals often already have asthma, eczema or certain allergy.

Diagnosis is made by a challenge with a suspected trigger and exercise. Skin prick tests for triggering foods may be positive. Treatment after the attack includes epinephrine (adrenaline) injection into the muscle (personal injectors are available), H1 antihistamines (diphenhydramine) and H2 antihistamines (ranitidine, cimetidine). Prevention includes avoiding known triggers for 6 hours before the planned exercise. Antihistamines or other drugs do not likely prevent the reaction [27].

Alcohol and Urticaria

In individuals suffering from chronic urticaria, alcohol consumption may aggravate symptoms, such as hives, fatigue, insomnia and mood changes [30]. Prevention is by avoiding alcohol and other triggers, such as aspirin, ACE inhibitors, opiates and certain foods. Sometimes, an underlying condition, such as autoimmune thyroiditis or systemic lupus erythematosus (SLE), is the cause of chronic urticaria [30].

In individuals suffering from cholinergic urticaria, alcohol, hot foods, exercise, emotional stress, increase of environmental temperature or any other cause of sweating may trigger itchy, bumpy hives within few minutes after starting sweating; symptoms may persist for few hours [31,32]. Rapid cooling or H1 antihistamines cetirizine or loratadine may stop symptoms [31]. Cholinergic urticaria may resolve spontaneously.

Alcohol and Headache

Hangover usually includes headache and nausea few to several hours after heavy drinking.

Alcohol may trigger tension headache in women before menstruation [33].

Asian flush reaction includes headache, flushing and nausea, usually in East Asians, within minutes after starting drinking may speak for ALDH2 deficiency [35].

Alcohol-drug interactions. Headache may be triggered by combining alcohol with antibiotics (furazolidone, griseofulvin, metronidazole, nitromidazole, quinacrine), a type of antidepressants called MAO inhibitors (phenelzine, tranylcypromine) and bronchodilators (albuterol, epinephrine, theophylline).

Paroxysmal hemicrania is a throbbing headache affecting one side of the face, lasting for 2-45 minutes and occurring several times a day. Triggers include alcohol, pressure to the neck and certain head moves [34].

Migraine

Moderate or severe throbbing pain that usually starts on one side of the head and gradually spreads all over the head may occur 30 minutes to 3 hours after consuming different amounts of alcohol and lasts 4-72 hours [36,37]. Headache is aggravated by moving around and relieved by lying down [36]. Other symptoms may include sensitivity to light and sound, nausea, vomiting, lightheadedness, chills or sweating. Sometimes, warning signs (aura) like vision disturbances (blurred vision, tunnel vision, flashing lights, zigzag lines), difficulty speaking, stiffness, tingling or heaviness on one side of the body, appear, usually within 1 hour before headache and last from few minutes to 1 hour [36].

Commonly reported triggers of migraine headaches: ethanol, histamine, tyramine [8] or other ingredients in alcoholic beverages, especially in beer and red wine, certain foods (chocolate, cheese, nuts, non-fresh food), food additives (aspartame, nitrates, MSG, tyramine), irregular meals, drugs (nitroglycerine, reserpine, hydralazine, estrogen), oral contraceptives, smoking, irregular sleep, menstruation, exercise, fatigue, stress [36]. Migraines sufferers often have first-degree relatives with migraine history [38]. The mechanism of migraine is not clear, but vasodilation of the arteries inside and outside of the skull may be involved [38]. In one study, histamine inhalation triggered migraine in some, but not all, chronic migraine sufferers and in some healthy individuals [39].

Migraine headache may be relieved by analgesics, such as sumatriptan, ibuprofen, aspirin, naproxen, acetaminophen, ergotamine and other drugs [40]. Migraines may be partly prevented by avoiding alcohol, especially red wine, and foods high in histamine or tyramine [41,42].

Red Wine Headache (RWH)

It is still not known what exactly causes red wine headache. Ethanol, histamine, tyramine, phenylethylamine, tannins and sulfites have been suggested so far, but results of studies are contradictory. Low-histamine diet may prevent headache in some individuals [17].

Cluster Headache

Sudden, sharp, excruciating one-sided headache that may extend from the shoulder or neck to the temple or eyebrow within 5 minutes to several hours after starting drinking alcohol [10]. The pain usually occurs at night and may last from 15 minutes to 3 hours. Cluster headaches comes in clusters: they may last for weeks to months, then disappear for months or years and may or not appear again [10]. Cluster headaches run in families [10].

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