Critique 044: The association of alcohol drinking with migraine headache. – 12 June 2011

Panconesi A, Bartolozzi ML, Guidi L.   Alcohol and migraine: What should we tell patients?  Curr Pain Headache Rep 2011;15:177–184.  DOI 10.1007/s11916-011-0184-4

Authors’ Abstract

Alcoholic drinks are a migraine trigger in about one third of patients with migraine in retrospective studies on trigger factors.  Many population studies show that patients with migraine consume alcohol in a smaller percentage than the general population.  Moreover, research has shown a decreased prevalence of headache with increasing number of alcohol units consumed.  The classification criteria of alcohol-related headaches remain problematic.  

We discuss the role and mechanism of action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache.  In accordance with data from a recent prospective study, we believe that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.  If a relationship between the intake of alcohol and the migraine attack is not clear, a small dose of alcohol is not contraindicated either for enjoyment or its protective effect on cardiovascular disease.

Forum Comments

Although the public, and most physicians, consider alcohol as an important factor for many types of headache, the medical evidence on this topic is limited.  This review article summarizes data on alcohol as a trigger for headache, the time relation between drinking and headache, “hang-over” headaches the morning after excessive drinking, and potential mechanisms for the associations found.  The authors conclude that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.

Background:  Migraine is a neurovascular disease that affects about 15% of the western population.  As stated by the authors of the current paper, compounds in foods and beverages (chocolate, wine, citrus, etc) that have been implicated as migraine triggers include tyramine, phenylethylamine and possibly histamine and phenolic compounds.  Avoiding those triggers may significantly reduce the frequency of migraines in some patients.  However, only a small percentage of patients in one study became headache-free simply by excluding those foods.1   Epidemiological studies are pointing out that genetic factors may be an underlying cause.2  For example, one genetic factor that could affect the migraine etiopathogenesis is by the control of the metabolism of monoaminergic neurotransmitters3 or the phenol sulfotransferases (PST).4  Discrepancies in the way people are reacting to wine intake, and whether or not it triggers migraine, may be potentially explained by genetic polymorphisms in specific enzymes related to metabolism.

Most studies on triggers of headache are from retrospective reports.  These generally find that alcohol consumption is listed as a common factor triggering an attack, as summarized by an earlier publication by Panconesi.5  However, a prospective analysis of factors related to migraine attacks by Wober et al6 produced interesting results.  They examined 327 migraineurs recruited via newspapers who kept a comprehensive diary for 3 months.  Menstruation had the most prominent effect, increasing the hazard of occurrence or persistence of headache and migraine by up to 96%.  All other factors changed the hazard by <35%.  The two days before menstruation and muscle tension in the neck, psychic tension, tiredness, noise and odors on days before headache onset increased the hazard of headache or migraine, whereas days off, a divorced marriage, relaxation after stress, and consumption of beer decreased the hazard.  They concluded that menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine.  Other factors increase the risk less markedly or decrease the risk.  These authors found no evidence that alcohol drinking was a trigger (and even found that beer consumption decreased the risk of a migraine attack during the following day).  On the other hand, excessive alcohol, dehydration, and perhaps psychogenic mechanisms may play a role in subjects experiencing headaches after drinking.

Comments on the present paper:  Forum reviewers were unanimous in considering this paper to be excellent, providing straightforward and sensible advice.  Several pointed out the difficulties in the diagnosis of migraine headache.  The problem in differentiating true migraines versus other types of headaches should be noted, as it is not uncommon for migraines to be wrongly diagnosed in cases of cluster headaches, tension headaches, etc. 

One reviewer stated that migraines are vascular headaches caused by intracerebral vasodilation, as a response to initial vasospasm.  Patients with migraines have a higher incidence of cardiovascular disease, and it would seem that migraineurs might reap an enhanced benefit from moderate wine/alcohol consumption.  On the other hand, if wine/alcohol does trigger migraine attacks, injury as a result of intense cerebral vasospasm would be a risk for drinking at all in this group.  As another reviewer noted, “In agreement with the authors, it would appear reasonable for migraine patients, with their informed consent and desire to consume alcohol in a healthy and responsible manner, be allowed to ‘try’ moderate drinking and report back to their physician as to whether it is tolerated or not.  At that time risk factoring in symptoms versus potential benefits (decreased cardiovascular risk) can be reasonably discussed with respect to continued alcohol use.”

Triggers of migraine headache attacks:  One Forum reviewer responded: “As a migrainuer myself, I have come to the conclusion that there are many different triggers for migraines, and that it is very individual, such that even members of the same family can have different triggers.  There has been no comment made to me or that I have read to date that suggests alcohol per se can cause a migraine, although I know that certain individuals avoid red wine, chocolate and cheese as the biogenic amines contained therein are a trigger for those individuals.  Also, for some individuals it is a collection of triggers – more than one – that initiates a migraine.  Further, in my experience alcohol consumption during a migraine will exacerbate it but generally not trigger an attack, unless perhaps the trigger is dehydration.” 

It has been postulated that dietary biogenic amines such as histamine might cause adverse reactions such as migraine headaches and other adverse effects.  The foods implicated in these adverse reactions have included cheese, chocolate, fish and fermented foods such as wine.7-8  Wine has also been implicated in the etiology of migraine headaches9-11 and the histamine H2 receptor antagonist, cimetidine, has been observed to block the headache provoked by the ingestion of red wine.12

Stockley13 points out, however, that an adverse reaction to a food can either be a food allergy or a food intolerance.  An immune or IgE-mediated allergy occurs on subsequent exposure of an individual to an allergen, such as a food protein, where the sensitized mast and blood basophil cells release histamine and other anaphylaxis-associated chemicals.  A food intolerance, on the other hand, is a form of hypersensitivity and is not mediated by the immune system.  A relatively large amount of a food is needed to trigger a histamine-induced food intolerance in contrast to a small amount needed to trigger an IgE-mediated food allergy.  After the oral ingestion of histamine, however, a food intolerance can be indistinguishable from a food allergy since histamine is also a mediator in a food allergy.13  However, in one study,14 no relationship between histamine ingestion and migraine headaches was observed when histamine-spiked beverages were administered.

One reviewer stated that white wines produce headaches in himself, and he has found that the higher the sulfite content of a wine the higher the risk of a headache.  Another Forum reviewer (a medical practitioner) wrote, however, “The sulfites business is very interesting, as people do have allergy to sulfites.  But in one case that I had investigated extremely well, the white wine that gave her the headache had a lower concentration of sulfite than one that did not.  I also know of people who get headaches from red wine A consistently, but not from red wine B.  Maybe it is the combination of molecules in the wine that causes the effect and not one particular molecule.” 

To make the topic of triggers of headache even more complicated, one reviewer stated that sometimes it not a food that is the trigger for migraine, but that the craving for chocolate (or other specific foods) may be part of the aura for migraine.  The confusion about triggers of migraine led one Forum reviewer to conclude: “Migraine, to me, as a subject, like headache in general, has always seemed murky, tending to give me one if I pondered on it.”

Forum Summary:  An excellent paper from a headache center in Italy summarizes the scientific data relating alcohol ingestion to migraine headaches.  The factors that trigger an attack of migraine, or of other headaches as well, are poorly understood.  While retrospective studies tend to include alcohol as a trigger for an attack, the authors describe that in a recent prospective study (in which information on the factors that could potentially trigger an attack were collected prior to the migraine attack), menstruation, stress, and fatigue were found most commonly to relate to a subsequent attack, but not alcohol consumption (in fact, beer consumption on the previous day reduced the risk of a migraine attack).  In the present paper, the authors reviewed the role and mechanism of action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache.  They conclude from their review that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine.

Forum members thought that this was a very balanced review of the subject, and that it provided straightforward and sensible advice.  Although some individuals surely have the onset of a migraine or other type of headache after the consumption of wine or alcohol, the findings are not consistent.  Forum members suggest that given that subjects reporting migraine headaches have been found to be at increased risk of cardiovascular disease, it would not be appropriate to advise all such sufferers to avoid alcohol.  As suggested by the authors of this paper, it may be reasonable for those subjects who had a desire to consume alcohol to drink small amounts of specific beverages to see if each beverage was tolerated or not.  After seeing the effects, and factoring in symptoms versus potential benefits from moderate drinking, a reasonable discussion can be carried out with respect to continued alcohol use by subjects with migraine.

References from Forum review

1.  Grant EC.  Food allergies and migraine.  Lancet 1979;1:966–969.

2.  Russell MB, Iselius L, Olesen J.  Migraine without aura and migraine with aura are inherited disorders.  Cephalalgia 1996;16:305-309. 

3.  Filic V, Vladic A, Stefulj J, Cicin-Sain L, Balija M, Sucic Z, Jernej B.  Monoamine oxidases A and B gene polymorphisms in migraine patients.  J Neurol Sci 2005:228:149-153.

4.  Littlewood JT, Glover V, Sandler M.  Red wine contains a potent inhibitor of phenolsulphotransferase.  Br J Clin Pharmacol 1985;19:275-278.

5.  Panconesi A.  Alcohol and migraine: trigger factor, consumption, mechanisms. A review.  J Headache Pain 2008;9:19-27.

6.  Wöber C, Brannath W, Schmidt K, Kapitan M, Rudel E, Wessely P, Wöber-Bingöl C; PAMINA Study Group.  Prospective analysis of factors related to migraine attacks: the PAMINA study.  Cephalalgia 2007; 27:304-314.

7.  Askar A., Treptow H.  Biogene Amine in Lebensmitteln.  Stuttgart, Germany: Vrelag Eugen Ulmer; 1986.

8.  Malone MH, Metcalf DD.  Histamine in foods: its possible role in non-allergenic adverse reactions to ingestants.  NER Allergy Proc 1986; 7:241-245.

9.  Ough CS, Crowell EA, Kunkee RE, Vilas MR, Lagier S.  A study of histamine production by various wine bacteria in model solutions and in wine.  J. Food Process Preserv 1987;12:63-70. 

10.  Trethewie ER, Khaled L.  Wine and migrainous neuralgia.  B Med J 1972;821:290-291.

11.  Mariné A, Codony R, Godia O, Montoro JB, Vidal MC.  Manual de interacciones alimentos-medicamentos, Colegio Oficial de Farmaceuticos 1986, pages 71-72.

12.  Glaser D, de Tarnowsky GO.  Cimetidine and red wine headaches.  Ann Intern Med 1983;98:413.

13.  Stockley, C. Can histamine in wine cause adverse reactions for consumers?  Australian & New Zealand Grapegrower & Winemaker 2004;485:77-82.

14.  Lüthy, J.; Schlatter, C. Biogene amine in lebensmitteln: zur wirkung von histamin, tyramin und phenylethylamin auf den menschen. Z. Lebensm. Unters. Forsch 1983;177:439-443. 

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Comments on the present paper were provided by the following members of the International Scientific Forum on Alcohol Research:

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA. 

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA.

Creina Stockley, clinical pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia. 

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.

Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.

Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy.

David Vauzour, PhD, Senior Research Associate, Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa.