Foods and supplements in the management of migraine headaches.
ABSTRACT Although a wide range of acute and preventative medications are now available for the treatment of migraine headaches, many patients will not have a significant improvement in the frequency and severity of their headaches unless lifestyle modifications are made. Also, given the myriad side effects of traditional prescription medications, there is an increasing demand for "natural" treatment like vitamins and supplements for common ailments such as headaches. Here, we discuss the role of food triggers in the management of migraines, and review the evidence for supplements in migraine treatment.
A review of the English language literature on preclinical and clinical studies of any type on food triggers, vitamins, supplements, and migraine headaches was conducted.
A detailed nutritional history is helpful in identifying food triggers. Although the data surrounding the role of certain foods and substances in triggering headaches is controversial, certain subsets of patients may be sensitive to phenylethylamine, tyramine, aspartame, monosodium glutamate, nitrates, nitrites, alcohol, and caffeine. The available evidence for the efficacy of certain vitamins and supplements in preventing migraines supports the use of these agents in the migraine treatment.
The identification of food triggers, with the help of food diaries, is an inexpensive way to reduce migraine headaches. We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Confusion in the nomenclature of Ménière's disease and lack of a standard definition of the disorder until 1995 has hampered accurate assessment of treatment efficacy since the presently defined disorder was first described in 1938. The lack of a widely accepted mechanism of the disease has also delayed the development of rational treatments. Past treatments have focused on relieving elevated pressures in the hydropic ear and more recently on treatment of underlying migraine. Present dietary methods of control include sodium restriction and migraine trigger elimination. Pharmacologic treatments include diuretics, migraine prophylactic medications, histamine analogs, and oral steroids. Surgical procedures include intratympanic steroid perfusion, shunts, and ablative procedures when conservative treatments fail. External pressure devices are also used. Evidence of efficacy is lacking for most interventions other than ablation. At our institution, Ménière's disease is treated as a cerebrovascular disorder. Control of risk factors for cerebrovascular ischemia is combined with treatment of pressure dysfunction in the hydropic ear. Screening for risk factors is performed at presentation. Migraine, dyslipidemia, obesity, diabetes, sleep apnea, hypertension, and atherosclerosis are among the major factors that often require medical management. Migraine prophylactic medications, magnesium supplementation, sodium restriction, migraine trigger elimination, diuretics, anticoagulants, and antihypertensives are among the treatments used initially. Steroids administered orally or intratympanically are used if control is not achieved medically, and ablation remains the definitive treatment in unilateral cases experiencing treatment failure.Therapeutics and Clinical Risk Management 01/2015; 11:301-7. · 1.34 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.The Journal of Headache and Pain 10/2014; 15(1):69. · 3.28 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The present cross-sectional study was designed to assess the frequency of 36 possible triggering factors precipitating a migraine crisis (hormonal, environmental, and dietary) in adult outpatients suffering from migraine attacks. A group of 123 migraine sufferers, aged 43.2 ± 13.9 (mean ± SD) years, including 114 (92.7%) women, 68.3% having migraine without aura, 68.3% reporting pain severe enough to require drug prophylaxis, and 29.3% presenting with hypertension, were evaluated. The most common triggers were stress and fasting, and environmental and hormonal factors were frequently found to precipitate a crisis. More than 90% of the patients reported susceptibility to 5 or more factors, and only 2.4% did not complain about any dietary factor. The large number of triggers detected in the present study emphasises the importance of awareness and avoidance of these factors in the management of patients with migraine.Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 04/2012; 27(2):483-489. · 1.25 Impact Factor
Foods and Supplements in the Management
of Migraine Headaches
Christina Sun-Edelstein, MD* and Alexander Mauskop, MD*w
Objective: Although a wide range of acute and preventative
medications are now available for the treatment of migraine
headaches, many patients will not have a significant improvement
in the frequency and severity of their headaches unless lifestyle
modifications are made. Also, given the myriad side effects of
traditional prescription medications, there is an increasing demand
for ‘‘natural’’ treatment like vitamins and supplements for common
ailments such as headaches. Here, we discuss the role of food
triggers in the management of migraines, and review the evidence
for supplements in migraine treatment.
Methods: A review of the English language literature on preclinical
and clinical studies of any type on food triggers, vitamins,
supplements, and migraine headaches was conducted.
Results: A detailed nutritional history is helpful in identifying food
triggers. Although the data surrounding the role of certain foods
and substances in triggering headaches is controversial, certain
subsets of patients may be sensitive to phenylethylamine, tyramine,
aspartame, monosodium glutamate, nitrates, nitrites, alcohol, and
caffeine. The available evidence for the efficacy of certain vitamins
and supplements in preventing migraines supports the use of these
agents in the migraine treatment.
Conclusions: The identification of food triggers, with the help of
food diaries, is an inexpensive way to reduce migraine headaches.
We also recommend the use of the following supplements in the
preventative treatment of migraines, in decreasing order of
preference: magnesium, Petasites hybridus, feverfew, coenzyme
Q10, riboflavin, and alpha lipoic acid.
Key Words: migraine, food triggers, magnesium, feverfew, butter-
bur, riboflavin, coenzyme Q10, alpha lipoic acid, alternative
(Clin J Pain 2009;25:446–452)
range of acute and preventative medications are now
available for the treatment of headaches, most patients will
not have a significant improvement in the frequency and
severity of their headaches unless lifestyle modifications are
made. These include sleep hygiene, stress management,
regular aerobic exercise, and dietary modification. Unfor-
tunately, these lifestyle recommendations are frequently
overlooked by physicians. In this review the role of food
igraine is a common and disabling disorder that
affects over 28 million Americans.1Although a wide
and nutrients in the treatment and prevention of migraine
headaches will be discussed.
SEARCH STRATEGY AND SELECTION CRITERIA
References for this review were identified by searches
of PubMed from 1966 to February 2008 with the terms
‘‘migraine,’’ ‘‘food trigger,’’ ‘‘alternative treatment,’’ ‘‘mag-
nesium,’’ ‘‘coenzyme Q10 (CoQ10),’’ ‘‘riboflavin,’’ ‘‘fever-
few,’’ ‘‘alpha lipoic acid,’’ and ‘‘butterbur.’’ Articles were
also identified through searches of the authors’ own files.
Only papers published in English were reviewed.
Migraine affects 18% of women and 6% of men in the
United States,2and has an estimated worldwide prevalence
of about 10%.3For both men and women, the prevalence
of migraine rises throughout early adult life and falls after
midlife. In girls and women, the rate almost triples between
age 10 and 30 years.
Population-based studies have reported that migraine
is inherited, with a relative risk of migraine headache in a
first-degree family member ranging from 1.4 to 1.9 when
the proband has migraine without aura.4,5In monozygotic
twins the concordance rates for migraine range from 37%
to 52%, and 15% to 21% for dizygotic twins.6,7These
figures indicate that both genetic and environmental factors
play a significant role in the migraine.
Although the understanding of migraine pathophy-
siology has increased dramatically in recent years, the exact
etiology remains to be defined. The current prevailing
theory is based on a hyperexcitable ‘‘trigeminovascular
complex’’ in patients who are genetically predisposed to
migraine. In these people, there is a lowered threshold for
migraine attacks and a vulnerability to environmental
triggers. In susceptible individuals, the trigeminovascular
neurons release neurotransmitters, such as calcitonin gene-
related peptide and substance P, when headache triggers are
encountered. This leads to vasodilation, mast cell degra-
nuation, increased vascular permeability and meningeal
edema, resulting in neurogenic inflammation. This noci-
ceptive information is transmitted from the trigeminal
nerve to brainstem nuclei, thalamic nuclei, and the cortex,
where migraine pain is ultimately perceived.8The locus
coeruleus, dorsal raphe, and the periaqueductal gray also
play modulatory roles in the transmission of pain.9
Mitochondrial dysfunction, which leads to impaired
oxygen metabolism, has been speculated to play a role in
migraine pathophysiology,10–12as migraineurs have been
shown to have a reduction in mitochondrial phosphoryla-
tion potential in between headaches.13,14This is the basis
Copyrightr2009 by Lippincott Williams & Wilkins
Received for publication September 8, 2008; revised October 27, 2008;
accepted November 1, 2008.
From the *The New York Headache Center; and wSUNY Downstate
Medical Center, New York, NY.
Reprints: Christina Sun-Edelstein, MD, The New York Headache
Center, New York, NY 10021 (e-mail: firstname.lastname@example.org).
Clin J Pain?Volume 25, Number 5, June 2009
for the use of supplements that enhance mitochondrial
function in the treatment of migraine, such as riboflavin,
CoQ10, and alpha lipoic acid.
THE ROLE OF FOODS AND SUPPLEMENTS
The importance of eating regularly cannot be over-
emphasized, as skipping meals can trigger headaches.15
Skipped meals and fasting were reported migraine triggers
in over 56% in a population-based study16and 40% to
57% in subspecialty clinic-based studies.17–19The mechan-
ism by which fasting and skipping meals triggers headaches
may be related to alterations in serotonin and norepinephr-
ine in brainstem pathways,20or the release of stress
hormones such as cortisol. Hypoglycemia could potentially
bring on a headache.9In one study213 quarters of
participants with migraine headaches demonstrated 5-hour
glucose tolerance tests consistent with reactive hypogly-
Although migraine triggers as a whole can act at
central or peripheral sites to precipitate an attack, most
food and beverage triggers likely act peripherally at the
level of the dural blood vessel or the peripheral trigeminal
nerve, as many dietary trigger components cannot cross an
intact blood-brain barrier.9Caffeine (see below) is one
notable exception. Furthermore, the vascular space is the
initial site of exposure for dietary triggers.
The recognition of dietary migraine triggers is
important because it helps not only in reducing the
frequency of migraine, but also in giving migraineurs a
sense of control over a condition that can render them
helpless and debilitated.9Two subspecialty clinic-based
studies,18,22in which participants were asked to report their
dietary triggers and rate their level of certainty that the food
was a migraine trigger, have shed some light on the
prevalence of dietary triggers. Reported dietary triggers
included alcohol (29% to 35%), chocolate (19% to 22%),
cheese (9% to 18%), caffeine (14%), and monosodium
glutamate (MSG) (12%).
Although the foods and substances discussed below
are often cited by patients as headache triggers, not all of
the foods will trigger a migraine in any one individual.
Therefore, migraineurs need not avoid all the potential
triggers described below if there is clearly no relationship
between their headaches and those substances. Headaches
are generally triggered by a combination of substances,
during a time of particular vulnerability (eg, menses, stress,
sleep deprivation). Food diaries can be helpful in sorting
out which ones are problematic for each patient, but this is
complicated by the fact that food triggers are not always
consistent. Furthermore, headaches triggered by certain
foods can occur 24 hours after trigger exposure, making it
difficult to pinpoint the offending substance.9Nonetheless,
keeping a detailed food and headache diary over the course
of several months may be useful in detecting relationships
between certain foods and headaches. Although the data
regarding the role of all the following substances in
triggering headaches is controversial (with the exception
of alcohol and caffeine), the evidence suggests that subsets
of migraineurs may be susceptible to these potential
Phenylethylamine is a substance found in cacao. In
migraineurs, especially those who have reduced monoamine
oxidase B activity, phenylethylamine causes the release of
vasoactive amines such as serotonin and catecholamine.23
Although migraine patients commonly cite chocolate as a
migraine trigger, the role of phenylethylamine remains
inconclusive. Furthermore, in patients with headaches
triggered by chocolate, caffeine (see below) may be the
Tyramine is an amine derived from the amino acid
tyrosine, and is found in aged cheese, cured meats, smoked
fish, beer, fermented food and yeast extract, among other
foods. Tyramine’s primary effect is the release of norepi-
nephrine from sympathetic nerve terminals and thus it may
trigger headaches by means of the release of norepinephrine
and its agonist effect on a-adrenergic receptors.9The
relationship between tyramine and headache was initially
observed when patients on monoamine oxidase inhibitors
developed headaches and hypertensive crises after eating
aged cheese, which has a high tyramine content.24
Aspartame is an artificial sweetener (NutraSweet) that
is 180 to 200 times sweeter than sugar.23Since its
introduction in 1981, there have been many reports of
neurologic or behavioral symptoms, especially headache,
attributed to its use.25Although some studies26,27found
that aspartame did not cause more headaches than placebo,
other evidence suggests that aspartame may be a headache
trigger in people who ingest moderate to high doses (900 to
3000mg/d) over a prolonged period of time.28,29
Sucralose is the active component of another common
artificial sweetener (Splenda). Although it was not initially
considered to be a migraine trigger, some case reports30–32
have suggested otherwise.
MSG is a flavor enhancer that is widely used in
Chinese food. It is also used in meat tenderizer (Accent)
and many canned, prepared, and packaged foods under the
guise of various descriptions including ‘‘hydrolyzed vege-
table protein,’’ ‘‘autolyzed yeast,’’ ‘‘sodium caseinate,’’
‘‘yeast extract,’’ ‘‘hydrolyzed oat flour,’’ ‘‘texturized pro-
tein,’’ or ‘‘calcium casinate.’’ The pathophysiologic me-
chanism by which MSG might trigger headaches may
involve a direct vasoconstrictor effect at high doses,33
activity as an agonist of stimulatory glutamate receptors9or
the activation of a neurotransmission pathway in which
nitric oxide is released in endothelial cells, ultimately
Nitrates and Nitrites
Sodium nitrite is a preservative that is used for food
coloring, prevention of botulism, and to add a cured or
smoked flavor. After eating foods with nitrites, such as
sausages or other cured meats and fish, some people
develop headaches within minutes to hours.35This effect is
probably due to the release of nitric oxide and subsequent
vasodilation,9,36though the interaction of nitrites with
blood pigment to produce methemoglobinemia may also
play a role.37Patients who seem to be sensitive to these
Clin J Pain?Volume 25, Number 5, June 2009Migraine Headaches
r2009 Lippincott Williams & Wilkinswww.clinicalpain.com|447
substances should avoid foods with sodium nitrite, sodium
nitrate, potassium nitrite, or potassium nitrate.
Alcohol, in particular red wine, is frequently cited as a
migraine trigger. It can have an immediate (within 3h) or
delayed (hangover) effect. Some patients even report that
alcohol can trigger a headache within minutes. Whether red
wine is more likely than white wine to trigger headaches is
controversial.38–40Wine contains tyramine, sulfites, hista-
mine, and the phenolic flavonoids, all of which can
theoretically precipitate migraines.9,41,42
Alcohol hangover headache (AHH) is a common
occurrence that generally occurs after the ingestion of large
amounts of alcohol. In addition to headache, AHH
comprises a constellation of symptoms including anorexia,
tremulousness, dizziness, nausea, tachycardia, irritability,
and depressed concentration.43The headache usually
occurs the morning after alcohol consumption, when the
blood alcohol concentration is falling44and can continue
for 24 hours after the blood alcohol concentration reaches
zero. AHH is not always dose-related and in fact occurs
more commonly in light or moderate drinkers than regular
Darker colored alcoholic beverages, such as red wine,
whiskey, and bourbon, contain congeners, which are the
natural byproducts of alcohol fermentation.47These drinks
are more likely to induce AHH as compared with clear
alcoholic beverages such as gin or vodka. The exact
mechanism by which AHH occurs is unknown, but may
involve a vasodilatory effect on the intracranial vasculature,
alteration of sleep patterns, or an inflammatory mechanism
through an alteration of cytokine pathways and prosta-
glandin release.48–50Magnesium depletion is known to be
caused by alcohol and is a possible cause of this headache.
Patients who are prone to AHH should drink in
moderation, and stay well hydrated. Anecdotal information
suggests that eating fatty food before alcohol consumption
may help to slow or delay alcohol absorption, and
consuming foods rich in fructose (ie, honey, tomato juice)
may allow for more effective alcohol metabolism. Certain
nonsteroidal anti-inflammatory drugs, in particular, the
anthranilic acids (such as mefenamic acid) may also be
effective in the treatment of AHH.43
Caffeine is a common dietary substance found in
coffee, tea, soda, and chocolate. It is also included in
various prescription (Fioricet, Fiorinal, Esgic) and over-
the-counter headache medications (Excedrin, Anacin).
Caffeine works by means of the blockade of inhibitory
and excitatory adenosine receptors in the brain and
vasculature, resulting in vasoconstriction and the release
of excitatory neurotransmitters. Some of the involved
pathways are important in the modulation of pain
Caffeine’s effect on the central nervous system varies
with the dose and frequency of use. In general, one serving
of brewed coffee has 115mg caffeine, whereas a serving of
Pepsi has 38mg. Excedrin contains 65mg caffeine per
tablet. At low-to-moderate doses (50 to 300mg), caffeine
causes increased alertness, concentration, and energy. At
doses greater than 300mg anxiety, restlessness, insomnia,
and irritability can occur.9,53
Caffeine’s effect on headaches is paradoxical in that it
can serve to either worsen or alleviate headaches, depending
on dosage and frequency. When used infrequently, caffeine
is effective in the treatment of headaches because it has a
mild analgesic effect and also assists in the absorption of
other analgesics. It also crosses the blood-brain barrier
quickly. These characteristics make caffeine a useful
(>300mg/d) consumed on a regular basis are associated
with headache. Regular use of caffeine-containing analge-
sics is associated with medication-overuse headaches
(formerly referred to as ‘‘rebound headaches’’).54–57
Headaches also occur with abrupt withdrawal of
caffeine, usually in people who regularly consume at least
200mg daily. The higher the level of baseline caffeine
ingestion, the greater the likelihood of caffeine withdrawal
headache, although headaches can occur even when
patients consuming 100mg caffeine daily stop abruptly.58
Caffeine withdrawal is also associated with depression,
drowsiness, and impaired concentration.
Patients with headaches who wish to continue drinking
caffeinated beverages should limit their daily intake to less
than 200mg. Patients who use caffeine-containing analge-
sics should limit intake to 2d/wk to avoid medication-
overuse headache. Those who wish to cease caffeine
consumption should gradually taper their intake over
analgesics. High doses
Vitamins and Other Supplements in
the Prevention of Migraine
Magnesium is an essential cation that plays a vital role
in multiple physiologic processes. Deficits in magnesium
can be seen in any chronic medical illness, including
cardiovascular disease, diabetes, preeclampsia, eclampsia,
sickle cell disease, and chronic alcoholism.59Symptoms of
magnesium deficiency include premenstrual syndrome, leg
muscle cramps, coldness of extremities, weakness, anorexia,
nausea, digestive disorders, lack of coordination, and
confusion. Magnesium may be involved in migraine
pathogenesis by counteracting vasospasm, inhibiting plate-
let aggregation, and the stabilization of cell membranes.60
Its concentration influences serotonin receptors, nitric oxide
synthesis and release, inflammatory mediators, and various
other migraine-related receptors and neurotransmitters.61
Magnesium also plays a role in the control of vascular tone
and reactivity to endogenous hormones and neurotrans-
mitters, through its relationship with the NMDA recep-
Studies have shown that migraineurs have low brain
magnesium during migraine attacks63and may also have
a systemic magnesium deficiency.64,65Furthermore, a
deficiency of magnesium may play a particularly important
role in menstrual migraine.66Two double-blind, placebo-
controlled trials have shown that oral magnesium supple-
mentation is effective in headache prevention.67,68A third
study69was negative, but this result has been attributed to
the use of a poorly absorbed magnesium salt, as diarrhea
occurred in almost half of patients in the treatment group.
Intravenous magnesium has been shown to be an effective
migraine abortive agent in patients with low ionized
magnesium levels, but not in those with normal levels.70
The most commonly reported adverse effect of magnesium
supplementation is diarrhea.
Sun-Edelstein and MauskopClin J Pain?Volume 25, Number 5, June 2009
r2009 Lippincott Williams & Wilkins
Riboflavin, also known as vitamin B2, is a precursor
for flavin mononucleotides that are cofactors in the Krebs
cycle. It is essential for membrane stability and the
maintenance of energy-related cellular functions.71There
has been one well-designed randomized controlled trials
evaluating the use of riboflavin as a migraine prophylactic
agent. Daily use of 400mg riboflavin for 3 months resulted
in a 50% reduction in attacks in 59% of patients, as
compared with 15% for placebo. Two minor adverse
reactions, diarrhea and polyuria, were reported in the
CoQ10 is an endogenous enzyme cofactor made by all
cells in the body, functioning to promote mitochondrial
proton-electron translocation. In an open label study73in
which 31 patients with migraine used 150mg daily of
CoQ10 for 3 months, 61% had at least a 50% reduction in
migraine days without significant adverse events. Supple-
mentation was effective within the first month of therapy.
Later, a small randomized controlled trial74was conducted
in which the treatment group received 100mg of CoQ10 3
times daily. Although a soluble form of CoQ10 that is not
currently available in the United States was used in the
study, results showed that CoQ10 significantly decreased
attack frequency, headache days, and days with nausea.
Gastrointestinal disturbances and ‘‘cutaneous allergy’’ were
reported, but at a low rate.
CoQ10 supplementation may be particularly effective
in the treatment of pediatric migraine. CoQ10 levels were
measured in a study75of 1550 patients (mean age
13.3±3.5y) with frequent headaches, and found to be
below the reference range in 32.9%. Supplementation with
1 to 3mg/kg/d of CoQ10 in liquid gel capsule formulation
resulted in an improvement in total CoQ10 levels, headache
frequency and degree of headache disability.
Alpha Lipoic Acid
Like riboflavin and CoQ10, alpha lipoic acid (also
known as thioctic acid) enhances mitochondrial oxygen
metabolism and ATP production.76Its use in migraine
prevention has been evaluated in one open pilot study
(unpublished data, discussed in Ref. 77) and one random-
ized placebo-controlled trial77to date. Fifty-four patients
were recruited into the randomized, placebo-controlled
study, in which participants received either 600mg alpha
lipoic acid or placebo daily for 3 months. Although there
was a clear trend for reduction of migraine frequency after
treatment with alpha lipoic acid, the result was not
significant. This result was attributed to the fact that the
study was underpowered. However, within-group analyses
did show a significant reduction in attack frequency,
headache days, and headache severity in the treatment
Feverfew (Tanacetum Pathenium)
Feverfew is an herbal preparation that is available as
the dried leaves of the weed plant tanacetum pathenium. It
was used to treat headache, inflammation, and fever several
centuries ago, and rediscovered in the late 20th century.
The mechanism by which it works in migraine prophylaxis
may be related to the parthenolides within the leaves. These
may inhibit serotonin release from platelets and white
blood cells, and inhibit platelet aggregation. Feverfew may
also have anti-inflammatory action through the inhibition
of prostaglandin synthesis and phospholipase A.78–81
Several randomized controlled studies have been
conducted over the past decades with conflicting re-
sults,82–87including a meta-analysis87that did not recom-
mend its use for headaches due to the paucity and low
average quality of the existing randomized controlled trials
on the subject. Inconsistencies in the results of those studies
were probably related to wide variations in the strength of
the active ingredient (parthenolide), and differences in the
stability of feverfew preparations. Taking these differences
into account, a new, more stable feverfew extract (MIG-99)
was evaluated in a placebo-controlled trial involving 147
patients.88Although none of the doses were significant for
the primary endpoint (number of migraine attacks in the
last month of the 3-month study compared with baseline)
relative to placebo, a subset of patients with high frequency
of migraine attacks did seem to benefit. In a follow-up
multicenter, double-blind, placebo-controlled study with
170 participants,89those investigators evaluated 6.25mg 3
times a day of MIG-99 versus placebo, and reported a
statistically significant and clinically relevant reduction in
migraine frequency in the MIG-99 group compared with
placebo. Side effects reported in clinical trials include
gastrointestinal disturbances, mouth ulcers, and a ‘‘post-
feverfew syndrome’’ of joint aches.
Butterbur (Petasites Hybridus)
In recent years, Petasites hybridus root extract, also
known as butterbur, has emerged as a potential new
treatment in the prevention of migraine. The butterbur
plant is a perennial shrub that was used in ancient times for
its medicinal properties. Petasites is thought to act through
calcium channel regulation and inhibition of peptide-
leukotriene biosynthesis. Leukotrienes and other inflam-
matory mediators may have a role in the inflammatory
cascade associated with migraine.90,91Although the butter-
bur plant itself contains pyrrolizidine alkaloids which are
hepatotoxic and carcinogenic, these compounds are re-
moved in the commercially available preparations.
A randomized, double-blind,
trial92using 50mg of butterbur twice daily, showed a
significantly reduced number of migraine attacks and
migraine days per month. Later, Lipton et al93compared
Petasites extract 75mg twice daily, Petasites extract 50mg
twice daily, and placebo twice daily in a 3-arm, parallel-
group, randomized trial of 245 patients and found that the
higher dose of Petasites extract was more effective than
placebo in decreasing the number of monthly migraine
attacks. A multicenter prospective open-label study94of
butterbur in 109 children and adolescents with migraine
resulted in 77% of all patients reporting a reduction in
migraine frequency of at least 50%. In all 3 studies,
butterbur was well tolerated and no serious adverse events
occurred. The most frequently reported adverse reactions
were mild gastrointestinal events, predominantly eructation
Ginger has been used for its medicinal qualities in
China for centuries, in the treatment of pain, inflammation,
and musculoskeletal symptoms. It has anti-inflammatory
qualities that could be related to the reduction of platelet
Clin J Pain?Volume 25, Number 5, June 2009Migraine Headaches
r2009 Lippincott Williams & Wilkinswww.clinicalpain.com|449
aggregation and the inhibition of prostaglandin and
leukotriene biosynthesis.95There are anecdotal and folklo-
ric descriptions of its efficacy in relieving headache and
Valerian root is a perennial herb that is used for its
sedative and hypnotic qualities, especially in insomniacs.
The effective dose for insomnia is 300 to 600mg, which is
equivalent to 2 to 3g of dried herbal valerian root soaked in
1 cup of hot water.96In migraine patients with anxiety, it
may be preferable to benzodiazepines as it is not associated
with sleepiness on awakening. At doses higher than
recommended, it is associated with headaches and muscle
Eicosapentaenoic acid (EPA), one of the body’s
natural omega-3 fatty acids, may also be useful in the
prevention of headaches. Small studies97have suggested
that headache severity and frequency can be reduced by
adding EPA to the diet, possibly by lowering prostaglandin
levels and serotonin activity. Omega-3 fatty acid supple-
mentation has also been associated with a positive outcome
in the treatment of mood disorders.98Although the FDA
has not established a recommended daily allowance for
EPA, a dose of 600mg/d in 3 divided doses has been
suggested for headache prevention.99Foods richest in EPA
are fish that inhabit cold deep water, such as salmon, tuna,
mackerel, and herring. EPA should not be taken in by
diabetic patients or people at risk of stroke, nosebleeds, or
Pregnancy and Lactation
Pregnancy and lactation are situations that also
warrant special consideration in the treatment of the
migraineur. Although migraines generally improve during
pregnancy, headaches may worsen or remain the same in
some women.2An increase in headaches during the first
trimester is not uncommon, due to wide fluctuations in
Women of reproductive age should be counseled about
the relevant teratogenic risks of acute and preventative
migraine medications. Owing to the limitations on phar-
macologic treatment of migraine during pregnancy and
lactation, nondrug approaches such as biofeedback, regular
exercise, and lifestyle modification are emphasized in this
population.100Food triggers should be identified through
the use of food diaries and elimination diets, preferably
before pregnancy. Maintaining hydration and electrolye
balance is also crucial, especially for those in whom nausea
and vomiting are prominent. These women should also
avoid herbal remedies, including feverfew and butterbur, as
they may be teratogenic.100
For patients who continue to have frequent headaches
during pregnancy and lactation, magnesium supplementa-
tion is an option for both acute and preventative treatment.
High-dose (4 to 6g) intravenous magnesium sulfate is used
for the prevention of recurrent seizures in eclamptic
women, and also for seizure prophylaxis in women with
hypertensive disorders of pregnancy.101For acute migraine
treatment, the dose is much lower. One gram of magnesium
sulfate in 10mL normal saline given by slow push or
dripped in slowly in a larger volume is used for both
pregnant and nonpregnant patients. For preventative
treatment, magnesium oxide, chelated magnesium, or slow
release magnesium is recommended. Supplementation is
unlikely to be associated with adverse effects,102and may
even be effective in the prevention of premature labor and
sudden infant death syndrome.103
Given the data discussed we recommend the following
oral supplements, in decreasing order of preference.
? Magnesium: Chelated magnesium, magnesium oxide,
and slow-release magnesium are likely to be the best
absorbed. The daily dose is 400mg. Diarrhea may be a
limiting adverse effect in some patients.
? Petasites hybridus (Petadolex): 75mg twice daily for 1
month, then 50mg twice daily.
? Feverfew: 100mg daily.
? CoQ10: 300mg daily.
? Riboflavin (vitamin B2): 400mg daily.
? Alpha lipoic acid: 600mg daily.
To our knowledge, there are no significant interactions
between these supplements and traditional pharmacologic
treatments. Intravenous magnesium given within 1 week of
menstruation, is an option for women with menstrual
migraines who do not respond to oral supplementation.
Patients with nonmenstrual migraines can also be given
magnesium infusions on an as needed basis if they do not
respond to oral magnesium or have gastrointestinal side
effects from oral dosing.
Although a wide range of acute and preventative
treatments for migraine are available, nutritional guidance
plays an integral role in the care of the migraineur. In the
evaluation of the migraine patient, a detailed nutritional
history should be taken, with special attention to skipped
meals, caffeine consumption, and the presence of perceived
food triggers. Food diaries are essential in determining the
relationship between certain foods and headaches. The
identification of food triggers and the use of supplements
are inexpensive ways in which the primary care physician or
neurologist can break a cycle of frequent migraines.
Although changing one’s diet may require a great deal of
motivation from the patient, the results are likely to be
lasting and rewarding.
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