ISSN 0017-8748

Headache doi: 10.1111/head.12365

© 2014 American Headache Society Published by Wiley Periodicals, Inc.

Review Articles
Wine and Headache
Abouch Valenty Krymchantowski, MD, MSci, PhD, FAHS; Carla da Cunha Jevoux, MD, MSci, PhD

Background.—The notion of migraine attacks triggered by food and beverages has been posited for centuries. Red wine
in particular has been acknowledged as a migraine trigger since antiquity when Celsus (25 B.C.-50 A.D.) described head pain
after drinking wine. Since then, references to the relationship between alcohol ingestion and headache attacks are numerous.
The most common initiator of these attacks among alcoholic beverages is clearly wine. The aim of this review is to present and
discuss the available literature on wine and headache.
Methods.—A Medline search with the terms headache, migraine, and wine was performed. Data available on books and
written material about wine and medicine as well as abstracts on alcohol, wine, and headache available in the proceedings of
major headache meetings in the last 30 years were reviewed. In addition, available technical literature and websites about wine,
grapes, and wine making were also evaluated.
Results.—Full papers specifically on headache and wine are scarce. General literature related to medicine and wine is
available, but scientific rigor is typically lacking. The few studies on wine and headache were mostly presented as abstracts
despite the common knowledge and patients’ complaints about wine ingestion and headache attacks. These studies suggest that
red wine, but not white and sparkling wines, do trigger headache and migraine attacks independently of dosage in less than 30%
of the subjects.
Discussion.—Wine, and specifically red wine, is a migraine trigger. Non-migraineurs may have headache attacks with wine
ingestion as well. The reasons for that triggering potential are uncertain, but the presence of phenolic flavonoid radicals and the
potential for interfering with the central serotonin metabolism are probably the underlying mechanisms of the relationship
between wine and headache. Further controlled studies are necessary to enlighten this traditional belief.

Key words: migraine, headache, wine, red

(Headache 2014;54:967-975)

The idea of dietary migraine or the triggering of Particularly with regards to wine, medicine has
migraine attacks with food and beverages has long been imaginative in correlating its consumption with
been disseminated. In 1778, Fothergill first described bad and good consequences throughout the centuries,
headache attacks after the ingestion of specific with the first references about a possible relationship
dietary factors, but the variability of clinical presen- between wine and medicine in Mesopotamia 7000
tations among and within migraine and non-migraine years B.C.3,4
sufferers has cast doubts about the real existence of When wine making arrived in ancient Greece, it
such entity.1,2 was enjoyed by the whole spectrum of society, and
became a popular theme in literature, religion,
From the Headache Center of Rio, Headache, Rio de Janeiro, leisure, medicine, and mythology. Hippocrates pro-
Brazil (A.V. Krymchantowski and C. da Cunha Jevoux).
moted wine as part of a healthy diet. He also claimed
Address all correspondence to A.V. Krymchantowski, The that wine was good for disinfecting wounds, as well as
Headache Center of Rio, Rio de Janeiro, Brazil, email:
[email protected] a liquid in which medications could be mixed and

Accepted for publication January 03, 2014. Conflict of Interest: None.

967
968 June 2014

taken more easily by patients. Hippocrates said wine most notorious headache trigger is red wine. This is
should be used to alleviate pain during childbirth, for certainly the case in the United Kingdom.10 White
symptoms of diarrhea, and even lethargy.3-5 Around wine and champagne may also trigger attacks.11
1863, a French Corsican chemist called Angelo However, red wine is a proven traditional headache
Mariani developed a beverage containing Bordeaux trigger even in non-migraineurs,7,12-16 despite the work
wine and cocaine (approximately 6 mg of cocaine per of a French neurologist from Bordeaux, Dr. Pierre
fluid ounce of wine). This beverage named Vin Henry, who lectured extensively on the fact that white
Tonique Mariani was suggested as a substitute for wine was a bigger trigger for migraine than the red
opiates and was awarded a Vatican Gold Medal by wine.17
Pope Leo XIII in addition to an endorsement of its The reasons why alcohol may induce headache
use.6 and even hangover syndrome were studied by
Wine’s intrinsic link with the practice of medi- Maxwell et al, who demonstrated in animal models
cine was also featured prominently in the first (rats) that not only ethanol induced delayed trigemi-
printed book on wine written by Arnaldus de Villa nal hypersensitivity, 4 to 6 hours after administration,
Nova (circa. 1235-1311 A.D.), a physician, who wrote but also acetate, rapid forming from acetaldehyde, are
at length on wine’s benefits for the treatment of in fact the responsible for a suggested induced
many illnesses and conditions, including sinus prob- headache-like pain using a dietary trigger.18,19
lems and dementia.5 Specifically with wine triggering headache, it was
For triggering migraine and/or headache attacks, discussed in depth by Panconesi, who competently
red wine is well known as a trigger and has been so dissected the possible substances responsible for ini-
since antiquity when Celsus (25 B.C.-50 A.D.) tiating an attack.7
described pain contracted by drinking wine. Six cen- Histamine.—Starting with histamine, which can cer-
turies later, Paul of Aegina (625-690 A.D.) also tainly provoke migraine, it was hypothesized that in
described drinking wine as a trigger of headache, pos- patients suffering from histamine intolerance, the high
sibly of migraine etiology.1,7 content observed in red wines (20- to 200-fold more
Although the term headache trigger has rarely than in white wine) could be held responsible for
been consistently defined,8 the current version of the headache occurrence regardless of the existence of
International Headache Society9 defines in its group migraine. However, a review of studies did not dem-
of headaches attributed to a substance use or expo- onstrated differences in headache-attack occurrence
sure, the so-called alcohol-induced headache. It can between different wine types, beer, and even foods
be caused immediately, or after a delay, by the inges- containing high content of histamine. In addition,
tion of alcoholic beverages. If the headache occurs other symptoms occurring in patients with histamine
within 3 hours of alcohol ingestion and resolves intolerance do not occur in headache sufferers after
within 72 hours after alcohol ingestion has ceased, the the ingestion of wine, as well as no difference was
headache is classified as immediate alcohol-induced found in the level of plasma diamine-oxidase between
headache (8.1.4.1 of the International Classification red wine sensitive and nonsensitive migraineurs.20-24
of Headache Disorders [ICHD]-III beta). If it has Tyramine and phenylethylamine were also sug-
developed within 5-12 hours after alcohol ingestion gested as responsible substances for headache and
and has resolved within 72 hours of onset, it is known migraine triggering after wine consumption.7 However,
as delayed alcohol-induced headache (8.1.4.2 of the in addition to the negligible content of these amines in
ICHD-III beta). wine (1-2 mg/L), studies performing oral challenges in
The alcohol-induced headache has a bilateral and sensible and non-sensible migraineurs were inconclu-
pulsating quality, aggravated by physical activity, and sive regarding this possible relationship.25
the commonest initiator of headache attacks among Sulfites.—Sulfites were once linked to headache
alcoholic beverages is definitely wine.7,9 Although not after wine ingestion.26 However, most of this belief is
without dispute, in some countries at least, by far the either speculative or in fact wrong, since the food and
Headache 969

wine preservative sulfur dioxide (SO2), called generi- ability to inhibit the process of sulphation by at least
cally sulfite, although present in wines, is much more 50%. These facts, observed in in vitro studies, and
existent in common foods that do not trigger head- confirmed by measurements of p cresol in urine after
ache attacks, such as dried fruit. While red wines oral challenges using red and white wine, as well as
contain around 160 parts per million (ppm) of sulfites, beer, suggest that the presence of flavonoid radicals
white wines reach 210 ppm and dried fruit up to are responsible for the red wine capacity of triggering
1000 ppm. Moreover, recently produced organic migraine and perhaps headache attacks in non-
wines contain lower levels of sulfites or, indeed, have migraineurs.2,7,12,15,20
none at all, but the persistence of the headache trig- 5-Hydroxytryptamine (5-HT).—Red wine is a
gering potential remains.26 In addition, published lit- powerful releaser of 5-HT from the platelet. Even in
erature has not yet established any links between the dilutions of 1:20 and in different types of wine or
presence of sulfite and headache.7 samples of the same wine type, this unique releasing
Flavonoid Phenolic Compounds.—The flavonoid ability seems to lie mainly in two flavonoid fractions
phenolic compounds are probably the most likely con- with molecular weight greater than 500 Da.2,31 Inter-
tender responsible for red wine induced headache estingly, neither white wine nor beer have any releas-
either for migraineurs or non-migraineurs.15 These ing effect on 5-HT.32 Despite the existence of
compounds – natural phenol and polyphenols – sensitivity to red wine among migraineurs and non-
include a large group of several hundred chemical radi- migraineurs, red wine, but not white wine, causes an
cals that affect the taste, color, and mouth feel of the increase of whole blood 5-HT levels even in con-
wine. It includes phenolic acids, stilbenoids, flavonols, trols.31,33 In addition, wine inhibits 5-HT and nor-
dihydroflavonols, anthocyanins, flavonol monomers adrenaline reuptake as well as mono amine oxidase
(cathecins) and polymers (proanthocianins), which can (MAO) activity, through its polyphenolic component
be separated into two categories – flavonoids and non- resveratrol and through an action on 5-HT receptors.
flavonoids. The flavonoids include the anthocianins Moreover, red wine strongly inhibits the binding of
and tannins which contribute to the color and mouth 5-HT to 5-HT1 receptors, and no conclusive results
feel of the wine, while the non-flavonoids include the were demonstrated regarding a mediation of induced
thestilbenoids such as resveratrol and the phenolic headache through 5-HT2 receptors.20 Therefore, the
acids such as benzoic, caffeic, and cinnamic acids.27-30 release of 5-HT, possibly from central stores and due
Phenols are the substrate for the enzyme to the flavonoid content of red wine, is a plausible
phenosulphotransferase (PST), which exists in the mechanism for wine-induced headache.7
forms of PST-M (inactivates phenolic monoamines Studies on Headache and Wine.—Several studies
such as tyramine and dopamine) and PST-P have been conducted to explore the relationship
(degradates phenol itself and p-cresol) in the gut. between headache and wine ingestion. One of the
Extracts of red wine contain high amounts of flavo- first studies on headache and wine, specifically red
noids able to potently inhibit PST, particularly its P wine, was performed by Kaufman, who tested the
form, and red wine may present up to 50 times more prophylactic ingestion of acetylsalicylic acid (ASA)
flavonoid when compared to white wine.20 Catechin, to prevent the so-called red wine headache syndrome
quercetin, narigin, anthocyanin, and others are the (RWH).34 Although poor in details, the small study
flavonoid molecules absorbed through the gastroin- observed that red wine indeed provoked a headache
testinal tract able to inhibit PST-P.10 The inhibition of attack and ASA had little or no effect in altering
conjugation of PST-P carried out by phenolic flavo- headache evolution once it already began (Table 1).
noids could result in buildup of free phenols in the Kaufman and Starr also studied 12 patients (9
circulation, which may be toxic in several ways.13 In women and 3 men) who examined previous attacks of
addition, the inhibition of PST-P by red wine is much headache after red wine ingestion. Following a 4-hour
more potent than previously thought, with 2000-fold fasting period, patients consumed 90 mL of red wine.
dilution even with dealcoholized red wine having the After being closely observed every 10 minutes and
970 June 2014

Table 1.—Summary of Studies on the Relationship of Headache and Wine

N Objectives Procedures Results

Kaufman34 n/d To assess the efficacy of n/d 1. Red wine provoked attacks.
ASA to prevent RWH. 2. ASA showed little or no effect to
treat established headache.
Kaufman and 12 To assess the efficacy of 1. Participants ingested 90 mL of 1. RWH happened in all
Starr35 three IPS in preventing red wine after 4-hour fasting. participants within 2 hours.
RWH. 2. Use of one capsule of an IPS or 2. Two subjects using placebo still
placebo followed (after 60 had RWH within 2 hours.
minutes) by 180 mL of red wine. 3. Two acetaminophen patients had
3. Blinded assessments. RWH between 6–12 hours.
Peatfield et al10 6† To compare RWH and 1. 5 mL/kg of Valpolicella and 1. RWH happened in 10 out of 12
blood levels of PST-P Chianti were given 2 weeks apart. participants.
and -M after ingestion of 2. Blood levels were collected 2 and 2. No difference was seen between
2 types of red wine. 3 hours after wine ingestion. wine types.
3. PST-P significantly decreased
after 2 hours compared to PST-M

n/d = not disclosed.

†Three migraineurs without aura and 3 migraineurs with aura.
ASA = acetylsalicylic acid; IPS = inhibitors of prostaglandin synthesis; PST-P or -M = phenosulphotransferase types P or M;
RWH = red wine headache syndrome.

after a total period of 120 minutes, patients were dis- Valpolicella wines are generally composed of 3
charged and oriented to return 1 week later, main- red-wine grape varieties grown in the Veneto region,
taining the same fasting time. All 12 patients of the Italy’s northeast. Corvina, Rondinella, and
presented a headache within 2 hours35 (Table 1). Molinara grapes are the trio primarily constituting
The second step of the study was performed with the blend, but Valpolicella DOC (Denominazione di
the same 12 patients, who were randomized to take Origine Controllata) also allows for up to 15% of
one capsule of 650 mg ASA or 500 mg acetamino- other red-wine varieties grown in the province of
phen or 400 mg ibuprofen or placebo and 180 mL of Verona, including Rossignola, Negrara Trentina,
red wine after 60 minutes. None of the patients receiv- Barbera, and Sangiovese.36 The Corvina plays the
ing an active drug developed a headache within 2 starring role in Valpolicella (up to 75%) and is
hours contrarily to the 2 patients who received regarded as the blend’s central element. It is known
placebo. Two of the 4 patients who received acet- more for its acidity and sour-cherry flavors than for its
aminophen developed a headache within 6-12 hours depth. The Rondinella grape, used primarily to add
after the red wine ingestion (Table 1). color and body to the blend (up to 35%), offers some
Peatfield et al tried to compare the headache trig- herbal notes and further accentuates the gentle
gering potential of two types of red wine.10 Testing spiciness of Corvina. Additional tannins and fresh
what the study authors nominated as wine-sensitive acid are provided by the grape Molinara, though it is
patients, the authors gave 5 mL/kg of Valpolicella and the least regarded of the three main grapes, and its
Chianti red wines to 6 migraineurs. Blood was col- use is on the decline.
lected immediately and after 2 and 3 hours. A head- The Chianti wine type refers to any wine pro-
ache attack developed on 10 of the 12 occasions, but duced in the Chianti region of central Tuscany. It is
no difference was found between wine types. Platelet composed of 70% Sangiovese, 15% Canaiolo, and up
PST type P was significantly decreased when com- to 20% Cabernet Sauvignon, Merlot, or Shiraz.37
pared to PST type M, after 2 hours on all occasions Theoretically, sangiovese wines have more tannins
(Table 1). than Valpolicella wines, but in truth its content is
Headache 971

similar especially if the Chianti is not purely made

with a variety called sangiovese grosso. High acidity
15
and light weight, thus the need to blend with other
10
grapes to give it a bit more structure, defines Chianti 5
wines. In general wines are lower in tannins, especially 0
if the grapes are picked before becoming fully ripe 4 3
(which can be mid-October in Tuscany). Sour cherry, aacksaacks 2 1 no
aacks aack aacks
plum, and even blackberry notes, if fully ripe, are
possible. Otherwise, notes of spice and mocha or
vanilla are prevalent if aged in oak.38 Perhaps, the Figure.—Number of patients presenting migraine attacks after
study by Peatfield and colleagues did not show any the ingestion of 4 wine types (n = 33).
difference between patients because the tannin
content of both wines was, in truth, similar.10 the “national grape.”39 It is also grown in Argentina,
Personal Experience.—The authors of this review Australia, Brazil, Peru, Bolivia, and in Italy’s Puglia
article have compared the potential for triggering region, where it is used as a blending grape. In the US
migraine attacks among different red wine types.39 states of Maryland and Virginia, there are small
The wines studied were from South America and experimental plantings of the vine, and plantings in
belonged to the varietal types: Cabernet Sauvignon, California have increased dramatically in the first
Merlot, Malbec, and Tannat, which have at least 75% years of the 21st century.41
of the nominal grapes. The 40 patients (28 women The Tannat wine is notable for its very high-
and 12 men, ages 32-53 years) had a diagnosis of tannin levels and is often blended with cabernet
migraine according to the ICHD-II criteria,40 were sauvignon and cabernet franc to soften the astrin-
regular patients of a tertiary center (the Headache gency and make it more approachable. In addition,
Center of Rio) under various preventive treatments, modern wine making has begun utilizing oak aging to
considered themselves wine drinkers, and had self- help soften the tannins.42,43 Now, the wines typically
identified a relationship between wine intake and spend about 20 months in oak prior to release.
migraine attacks. For the purposes of the study, the Tannats from Uruguay are particularly high in
patients had to consume half bottles of various tannins and depending on the wine-making tech-
wines, from any kind of producer, at their discretion, niques may present the highest contents among South
with a minimum interval of 4 days between the wine American red wines.44,45
types. In addition, they were asked to avoid any Malbec is a purple grape variety with an inky
other kinds of alcohol through the duration of the dark color and robust tannins known as one of the six
study and to not drink more than one-half bottle at a grapes allowed in the blend of red Bordeaux wine. It
time. needs more sun and heat than either Cabernet
Thirty-three patients (23 women, 10 men) com- Sauvignon or Merlot to mature. It ripens mid-season
pleted the study. Twenty-nine patients (87.8%) and can bring very deep color, ample tannin, and a
reported a migraine attack on at least one occasion particular plum-like flavor component to add com-
within 12 hours of consuming the wine, and 11 plexity to claret blends. The French plantations of
(33.4%) reported migraine attacks after all 4 times in Malbec are now found primarily in Cahors in South
which the wine was consumed. Four patients (12.2%) West France. It is increasingly celebrated as an Argen-
drank the four wine types and didn’t present any tine varietal wine and is becoming more widely grown
headache attack (Figure). The triggering power of around the world.46 Also called Auxerrois or Côt Noir
each specific wine is shown in Table 2. in Cahors, called Malbec in Bordeaux, and Pressac in
Tannat is a red wine grape, historically grown in other places, the grape became less popular in Bor-
South West France. It is now one of the most promi- deaux after 1956 when frost killed off 75% of the
nent grapes grown in Uruguay, where it is considered crop. Despite Cahors being hit by the same frost,
972 June 2014

Table 2.—Personal Experience on the Relationship Between Wine Consumption and Headaches

N Objectives Steps of the Study Results

Krymchantowski 40 To assess the prevalence of headaches 375 mL of red wines were given Rates of migraine were
and Jevoux39 within 12 hours of consuming different† at least 4 days apart 1. Tannat = 51.7%
South American red wines 2. Malbec = 48.2%
3. CS < 30%
4. Merlot < 30%
Krymchantowski 28 To assess the prevalence of headaches 375 mL of different CS were Rates of migraine were
and Jevoux49 within 12 hours of consuming CS from given at least 4 days apart 1. French CS = 60.9%
France and from South America 2. South American
CS = 39.1% (P < .001)

†Cabernet Sauvignon (CS), Merlot, Malbec, Tannat.

which devastated the vineyards, Malbec was out, and any headache attack within 12 hours had to
replanted and continued to be popular in that area be reported. No other alcohol source and no more
where it was mixed with Merlot and Tannat to make than 375 mL were allowed during the study.
dark, full-bodied wines, and more recently has been Twenty-three patients (13 women and 10 men)
made into 100% Malbec varietal wines.47 In Argen- completed the study. French wine ingestion triggered
tina, Malbec becomes softer with a plusher texture a migraine attack more often than reporting in the
and riper tannins. The wines tend to have juicy fruit South American wines (Table 2). Four patients had
notes with violet aromas. Malbec grown in the state of no attacks, and 4 patients presented attacks with both
Washington tends to be characterized by dark fruit wines. Five patients reported a migraine attack after
notes and herbal aromas.44,46 the South American Cabernet but not with the
We then studied the potential for triggering French Cabernet. None of the patients from the last 2
migraine attacks between Cabernet Sauvignons from studies had a headache attack not fulfilling migraine
France and South America.48 French Bordeaux from after the wine ingestions.
the left margin of the Gironde River are richer in Cabernet Sauvignon is one of the world’s most
tannins because they have a minimum of 75% widely recognized red wine grape varieties. It is
Cabernet Sauvignon grapes.They usually are complex grown in nearly every major wine producing country
and very good wines with a high potential from aging. among a diverse spectrum of climates. This grape
Cabernet Sauvignons from South America have also became internationally recognized through its promi-
improved in quality in recent years. nence in Bordeaux wines where it is often blended
In a study the authors of this review article con- with Merlot and Cabernet Franc in amounts varying
ducted, we evaluated 28 regular patients (14 women with the region in which it is produced. Although well
and 14 men, ages 25 to 67 years, mean 54.5) from the known among wine producers and consumers, the
Headache Center of Rio under various preventive Cabernet Sauvignon is relatively new, representing a
treatments, who were also self-considered wine drink- chance crossing between Cabernet Franc and
ers and reported a clear-cut relationship between Sauvignon Blanc during the 17th century in south-
wine intake and a headache attack. They were all western France.49,50
migraineurs according to the ICHD-II.40 The patients The Cabernet Sauvignon is a very small grape
took two half bottles of any French and any South with a thick skin, creating a high 1:12 ratio of seed to
American Cabernet Sauvignons (minimum 4 days fruit.50-52 This results in the high proportions of
between wines). French wines had to be from the phenols and tannins observed in this wine, especially
Medoc or Haut Medoc regions, specified in the bottle if the must is subjected to long periods of maceration
label. A detailed headache calendar had to be filled (skin contact) before fermentation. In Bordeaux, the
Headache 973

maceration period is traditionally 3 weeks, which CONCLUSIONS

results in very tannic and flavorful wines that require Wines, especially red wines, are very different in
years of aging. Reducing the maceration time to as a composition, producing processes and therefore, taste
little as a few days, may create light and more and the ability to please. Consumption habits of dif-
approachable wines as with some South American ferent grapes and varietal wines are very peculiar
wine makers. Following maceration, the Cabernet among countries and people. For the good or bad,
must can be fermented at high temperatures up to wine has been linked to headache and migraine
30°C (86°F), which will play a role in the result, pro- attacks as a traditional trigger. Tannins and the phe-
viding deeper colors and more flavor components nolic flavonoid components of the red wine, with its
being extracted at higher temperatures.53,54 ability to interact with the metabolism of certain
In the Medoc and Haut-Medoc regions in France monoamines as well as its capacity of mobilizing
(left margin of the Gironde River), the wines are 5-HT, are probably related. However, the methodol-
primarily made of Cabernet Sauvignon grapes (up to ogy of most of the studies discussed in this review and
75%), while in the right bank of the Gironde River, the analysis of the available literature do not allow
due to the arenous soil, the typical wines are primarily definitive conclusions regarding the real role of wine
made with Merlot grapes as those from the Pomerol in headache. We believe that red wine is indeed a
district, which originates the legendary Chateau migraine trigger, at least for a percentage of
Petrus.47,50-52 migraineurs, even under regular preventive treat-
Merlot is a dark blue wine grape used as a blend- ment. In addition, red wines with more tannins are
ing grape and for varietal wines. The name Merlot is probably worse in triggering migraine attacks. Con-
thought to be a diminutive of merle, the French name trolled studies with well-known wines are important
for the blackbird, probably a reference to the color of to clarify this common belief.
the grape. Merlot-based wines usually have medium
body with hints of berry, plum, and currant. Its soft- STATEMENT OF AUTHORSHIP
ness and “fleshiness,” combined with its earlier ripen-
ing, makes Merlot a popular grape for blending with Category 1
the sterner, later ripening Cabernet Sauvignon, which (a) Conception and Design
is much higher in tannins.50 Abouch Krymchantowski; Carla Jevoux
Along with Cabernet Sauvignon, Cabernet Franc, (b) Acquisition of Data
Malbec, and Petit Verdot, Merlot is one of the Abouch Krymchantowski; Carla Jevoux
primary grapes used in Bordeaux wine, and it is the (c) Analysis and Interpretation of Data
most widely planted grape in the Bordeaux wine Abouch Krymchantowski; Carla Jevoux
regions. Merlot is also one of the most popular red
Category 2
wine varietals in many markets throughout the
(a) Drafting the Manuscript
world.50-54 This flexibility has helped to make it one of
Abouch Krymchantowski; Carla Jevoux
the world’s most planted grape varieties.
(b) Revising It for Intellectual Content
As a varietal wine, Merlot can make soft, velvety
Abouch Krymchantowski
wines with plum flavors.44,46,47,53 Some of the fruit
notes commonly associated with Merlot include Category 3
cassis, black and red cherries, blackberry, blueberry, (a) Final Approval of the Completed Manuscript
and plum. Vegetable and earthy notes include black Abouch Krymchantowski; Carla Jevoux
and green olives, nuts, leather, mushrooms, and
tobacco. When Merlot has spent significant time in REFERENCES
oak (longer than 8 months), the wine may show notes
of caramel, chocolate, coconut, coffee bean, smoke, 1. Clifford Rose F. Food and headache. Headache Q.
vanilla, and walnut.46,47,53 1997;8:319-329.
974 June 2014

2. Sandler M, Li N-Y, Jarret VG. Dietary migraine: 16. Raskin N. Chemical headaches. Annu Rev Med.
Recent progress in the red (and white) wine story. 1981;32:63-71.
Cephalalgia. 1995;15:101-103. 17. Chabriat H, Danchot J, Michel P, Joire JE, Henry P.
3. Lagrange M. Le Vin & La Médicine: À l‘ usage des Precipitating factors of headache: A prospective
bons vivants et des médicins. Nièvre-Chiddes: Féret; study in a national control-matched survey in
2004:18-187. migraineurs and nonmigraineurs. Headache. 1999;
4. Harry WP. Bacchic Medicine: Wine and Alcohol 39:335-338.
Therapies from Napoleon to the French Paradox. 18. Maxwell CR, Spangenberg RJ, Hoek JB, Silberstein
Amsterdam: Rodopi; 2001:1-24. SD, Oshinsky ML. Acetate causes alcohol hangover
5. Christian Nordqvist. What are the benefits of wine? headache in rats. PLoS ONE. 2010;5:e15963.
2013. Available at http://www.medicalnewstoday 19. Wiese JG, Shlipak MG, Browner WS. The alcohol
.com/articles/265635.php. (Accessed December 1, hangover. Ann Intern Med. 2000;132:897-902.
2013). 20. Peatfield RC, Fletcher G, Rhodes K, Gardiner IM,
6. Frederick P. Why was Coca Cola invented? 2010. de Belleroche J. Pharmacological analysis of red
Available at http://www.viewamerica.net/art/en- wine-induced migrainous headaches. J Headache
coca2.html (Accessed November 27, 2013). Pain. 2003;4:18-23.
7. Panconesi A. Alcohol and migraine: Trigger factor, 21. Jansen SC, Van Dusseldorp M, Bottema KC, Dubois
consumption, mechanisms. A review. J Headache AEJ. Intolerance to dietary biogenic amines: A
Pain. 2008;9:19-27. review. Ann Allergy Asthma Immunol. 2003;91:233-
8. Turner DP, Smitherman TA, Martin VT, Penzien 241.
DB, Houle TT. Causality and headache triggers. 22. Jarish R, Wantke F. Wine and headache. Int Arch
Headache. 2013;53:628-635. Allergy Immunol. 1996;110:7-12.
9. Headache Classification Committee of the Interna- 23. Wantke F, Gotz M, Jarish R. The red wine provoca-
tional Headache Society. The international classifi- tion test: Intolerance to histamine as a model for
cation of headache disorders, 3rd edition (beta food intolerance. Allergy Proc. 1994;15:27-32.
version). Cephalalgia. 2013;33:728. 24. Maintz L, Novak N. Histamine and histamine intol-
10. Peatfield R, Hussain N, Glover VA, Sandler M. erance. Am J Clin Nutr. 2007;85:1185-1196.
Prostacyclin, tyramine and red wine. In: Olesen J, 25. Nicolodi M, Sicuteri F. Wine and migraine: Compat-
Moskowitz M, eds. Experimental Headache Models. ibility or incompatibility. Drugs Exp Clin Res. 1999;
Philadelphia, PA: Lippincott-Raven; 1995:267- XXV:147-153.
276. 26. Gorman-McAdams M. Sulfites in wine. The myths,
11. Peatfield RC, Glover V, Littlewood JT, Sandler M, the facts, and the truth. 2009.Available at http://www.
Clifford Rose F. The prevalence of diet-induced thekitchn.com/sulfites-in-wine-necessary-or-100878.
headache. Cephalalgia. 1984;4:179-183. (Accessed December 28, 2013).
12. Littlewood JT, Gibb C, Glover V, Sandler M, Davies 27. Kennedy JA, Matthews MA, Waterhouse AL. Effect
PTG, Clifford Rose F. Red wine as a cause of of maturity and vine water status on grape skin
migraine. Lancet. 1988;1:558-559. and wine flavonoids. Am J Enol Vitic. 2002;53:268-
13. Pradalier A, Weinman S, Launay JM, Baron JF, Dry 274.
J. Total IgE, specific IgE and prick-tests against 28. Cheynier V, Duenas-Paton M, Salas E, et al. Struc-
foods in common migraine – a prospective study. ture and properties of wine pigments and tannins.
Cephalalgia. 1983;3:231-234. Am J Enol Vitic. 2006;57:298-305.
14. Relja G, Nider G, Chiodo-Grandi F, Kosica N, 29. Fulcrand H, Duenas M, Salas E, Cheynier V. Phe-
Musco G, Negro C. Is red or white wine an impor- nolic reactions during winemaking and aging. Am J
tant inducing factor in migraine attacks? Cephalal- Enol Vitic. 2006;57:289-297.
gia. 1993;13(Suppl. 13):129. 30. He J, Santos-Buelga C, Mateus N, Freitas V. Isolation
15. Littlewood JT, Gibb C, Glover V, et al. Red wine as and quantification of oligomeric pyranoanthocyanin-
a migraine trigger. In: Clifford Rose F, ed. Advances flavanol pigments from red wines by combination of
in Headache Research. London: John Libbey & Co column chromatographic techniques. J Chromatogr
Ltd; 1987:123-127. A. 2006;1134:215-225.
Headache 975

31. Pattichis K, Louca LL, Jarman J, Sandler M, Glover 43. Kennedy JA, Hayasaka Y. Compositional investiga-
V. 5-Hydroxytriptamine release from platelets by tion of pigmented tannin. Am Chem Soc Symp Ser.
different red wines: Implications for migraine. Eur J 2004;886:247-264.
Pharmacol. 1995;292:173-177. 44. Luz Sanz M, Martinez-Castro I, Moreno-Arribas
32. Jarman J, Glover V, Sandler M. Release of (14C) MV. Identification of the origin of commercial
5-hydroxytryptamine from human platelets by red enological tannins by the analysis of monosaccha-
wine. Life Sci. 1991;48:2297-2300. rides and polyalcohols. Food Chem. 2008;111:778-
33. Pattichis K, Louca LL, Jarman J, Glover V. Red 783.
wine can cause a rise in human whole blood 5- 45. Salagoity-Auguste M, Tricard C, Marsal F, Sudraud
hydroxytriptamine levels. Med Sci Res. 1994;22: P. Preliminary investigation for the differentiation
381-382. of enological tannins according to botanical origin:
34. Kaufman HS. Headaches after red wine. Lancet. Determination of gallic acid and its derivatives. Am
1981;1:1263-1265. J Enol Vitic. 1986;37:301-303.
35. Kaufman HS, Starr D. Prevention of the red wine 46. Robinson J, ed. The Oxford Companion to Wine, 3rd
headache (RWH): A blind controlled study. In: edn. London: Oxford University Press; 2006:421-
Clifford Rose F, ed. New Advances in Headache 422.
Research. London: Smith Gordon; 1991:369-373. 47. Clarke O. Encyclopedia of Grapes. Orlando:
36. Goodman D, Gibb R, Reeve J, Adamson C. Harcourt Books; 2001:118-119.
Valpolicella Blend Wine. 2013. Available at http:// 48. Krymchantowski AV, Jevoux CC. Cabernet
www.wine-searcher.com/grape-1688-valpolicella- Sauvignons from France do trigger migraine more
blend. (Accessed October 10, 2013). often than those from South America: An open pro-
37. Robinson J ed. The Oxford Companion to Wine, 3rd spective study. Cephalalgia. 2013;33(Suppl. 8):90.
edn. London: Oxford University Press; 2006:162- Abstract.
163. 49. Castillo-Munoz N, Gomez-Alonso S, Garcia-
38. Wickins D. Top 5 characteristics of Sangiovese. 2011. Romero E, Hermosin-Gutierrez I. Flavonol profiles
Available at http://winelovewinelust.com/2011/04/ of Vitis vinifera red grapes and their single-cultivar
28/top-5-characteristics-of-sangiovese/. (Accessed wines. J Agric Food Chem. 2007;55:992-1002.
October 10). 50. Robinson J, ed. The Oxford Companion to Wine, 3rd
39. Krymchantowski AV, Jevoux CC. Red wine-type edn. London: Oxford University Press.; 2006:119-
and triggering of migraine: An open prospective 121.
study. Abstract. Headache. 2012;52:884. 51. Clarke O, Rand M, Rock M, Riches L. Encyclopedia
40. Headache Classification Subcommittee of the Inter- of Grapes. Orlando: Harcourt Books; 2001:47-56.
national Headache Society. The international classi- 52. Mattivi F, Guzzon R, Vrhovsek U, Stefanini M,
fication of headache disorders 2nd edition. Velasco R. Metabolite profiling of grape: Flavonols
Cephalalgia. 2004;24(Suppl. 1):24-137. and anthocyanins. J Agric Food Chem. 2006;54:7692-
41. Robinson J, ed. The Oxford Companion to Wine, 3rd 7702.
edn. London: Oxford University Press; 2006:442- 53. Garrido J, Borges F. Wine and grape polyphenols –
443. A chemical perspective. Food Res Int. 2011;44:3134.
42. Mattivi F, Vrhovsek U, Masuero D, Trainotti D. Dif- 54. Atanasova V, Fulcrand H, Cheynier V, Moutounet
ferences in the amount and structure of extractable M. Effect of oxygenation on polyphenol changes
skin and seed tannins amongst red grape cultivars. occurring in the course of wine-making. Anal Chim
Aust J Grape Wine Res. 2009;15:27-35. Acta. 2002;458:15-27.