BACKGROUND AND EDUCATIONAL DATA
Clinical Applications
of Natural Medicine
Migraine
Donald Brown, N.D.
Alan Gaby, M.D.
Ronald Reichert, N.D.
Published by Natural Product Research Consultants
Series Editor
Donald Brown, N.D.
Dr. Brown is the founder
and director of Natural Product Research Consultants and the editor
of the Quarterly Review of Natural Medicine. He is a faculty member
of Bastyr University in Seattle, Washington, where he teaches
herbal medicine and therapeutic nutrition. Dr. Brown's book, Herbal
Prescriptions for Better Health, was published in February 1996
by Prima Publishing.
CONTRIBUTORS
Alan Gaby, M.D.
Dr. Gaby is past-president of the American Holistic Medical Association
and medical editor of The Townsend Letter for Doctors. He served
on the Ad Hoc Advisory Panel of the National Institutes of Health
Office of Alternative Medicine. He is the author of Preventing
and Reversing Osteoporosis and B6: The Natural Healer.
Ronald Reichert, N.D.
An expert in European phytotherapy, Dr. Reichert resides in Vancouver,
B.C., where he has an active medical practice. Dr. Reichert contributes
regular articles to lay and professional publications in Canada.
In addition to his regular herbal research columns, Dr. Reichert
provides professional review of German translations for the Quarterly
Review of Natural Medicine.
Copyright (c) 1997
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No part of this publication may be reproduced
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ABOUT THIS PUBLICATION
The information
presented in this Condition-Specific Monograph is intended for
professional education and is obtained from published research,
articles and books. This update is not intended to replace the
care of a licensed health professional in the diagnosis and treatment
of illness.
CLINICAL APPLICATIONS
OF NATURAL MEDICINE MIGRAINE
Migraine
has been a well known medical problem for over 5,000 years and
represents one of the most investigated types of head pain. Research
on large groups of people has shown that in the U.S. 18% of women
and 6% of men suffer from migraine.1 This extrapolates to approximately
18 million females and 5.6 million males over the age of 12 with
this disorder.2 The prevalence of migraine, according to the Center
for Disease Control, has increased 60% from 1981 to 1989.3 4 The
economic impact of migraine is staggering, with annual cost of
the disease estimated at 18 billion dollars.5
CAUSES OF MIGRAINES
The basic
cause of migraine is still unknown. Although genetics may play
a role, with 50 to 70% of migraine sufferers reporting a familial
occurrence, no consistent biochemical or physiological characteristic
can be recognized in the relatives of those afflicted with the
condition.6
PHYSICAL AND
FUNCTIONAL CONCERNS
There are
several theories as to what causes a migraine and what happens
to us when they occur. One of these theories suggests that certain
arteries in our brain contract and cause a reduction blood flow
to the visual area of our brain. It is suggested that this reduction
of blood flow results in the visual and other symptoms that accompany
a migraine.
This theory further suggests that the
pain that often follows these symptoms was the result of dilation
(expansion) of the carotid artery and pressure on the nerves in
the artery wall. Yet another theory proposes that nerve cells
in the brain begin to lose function which causes a reduction blood
flow, which reduces levels of magnesium, which in turn adds to
decreasing nerve cell function and that this dysfunction spreads
in a wave like fashion to all effected areas.7 Many researchers
feel that serotonin, an important brain chemical may fuel migraines.8
9 10 11 12 13 Platelets (components of our blood) contain all
of the serotonin normally present in blood, and, after they aggregate,
(clump together) serotonin is released, resulting in a potent
constricting effect on the arteries.14 15 16 17
SIGNS AND SYMPTOMS
The two
most important categories are migraine without aura (common migraine)
and migraine with aura (classic migraine). A diagnosis of migraine
without aura is made if the patient fulfills specific criteria.
The patient must have a history of five previous similar episodes,
with pain lasting between 4 and 72 hours. Additionally, they must
meet two of the following four characteristic symptoms: (1) unilateral
head pain; (2) pain must be throbbing or pulsing; (3) an experience
of moderate to severe pain which inhibits or restricts the ability
to function;(4) pain is made worse by routine physical activity.
Furthermore, they must have one of the following two symptoms
present: (1) nausea and/or vomiting; (2) adverse reactions to
light or sound.18 In contrast, migraine with aura employs the
same diagnostic criteria as common migraine with the following
exceptions. Patients only need a history of two prior migraine
attacks and must fulfill three of the following four criteria:
(1) one or more aura symptoms; (2) aura symptoms that develop
over more than 4 minutes; (3) aura lasts less than 60 seconds;
(4) headache follows within 60 minutes of the aura ending. Auras
represent several forms of visual disturbances that are described
as dark or black point(s) that may or may not expand and obscure
the patient's vision. The black spot may be surrounded by lights
with zigzag lines. Patients with classic migraine symptoms may
exhibit stroke-like symptoms including symptoms affecting one
hand, arm, or side of the face.19 It is interesting to note that
migraine sufferers are more likely to experience specific headache
variants including intense throbbing head pain, brought on by
exertion (exertional headache); ice-pick-like pains or electrical
jabs, called stabbing headaches; and unilateral, intense eye pain.20
21
TREATMENT
For the
migraine sufferer, there is a wide variety of therapeutic approaches
both pharmacologic and non-pharmacologic. However, for practical
reasons the management of migraine can be divided into two categories;
abortive and preventative. As abortive treatment of migraine simply
address the symptoms,via the use of drugs. Initial therapy for
mild migraine headache is usually aspirin or other non-steroidal
anti-inflammatory agents (e.g. ibuprofen and naproxen sodium).
These pain relievers, along with sleep in a quiet, dark room,
an ice pack on the head and an anti nausea drug.22 23
Certain drugs that constrict arteries
are used with varying degrees of success and side effects. Your
pharmacist can discuss them with you. Some of these drugs, though
effective frequently result in rebound headache and other side
effects.24 25
Another drug, sumatriptan (Imitrex(r)),has
been shown to reduce the intensity of moderate to severe migraine
headaches.27 Side effects from this type of drug include, tingling,
heaviness, and a sensation of pressure. In contrast to abortive
therapy, preventative drug strategies can be employed if the frequency
of migraine attacks is sufficiently high. Propranolol is widely
prescribed in the United States as a treatment for migraine prevention.
Although it has proven to be effective in migraine prevention,
its side effects include fatigue, depression, impotence, insomnia,
dizziness, and cold extremities.28 Like drug intervention, non-pharmaceutical
preventive therapies may also be effective. These include behavioral
modification techniques such as stress management, biofeedback,
exercise, acupuncture, trigger point injections and numerous physical
therapy techniques (e.g. massage, manipulation and transcutaneous
nerve stimulation).29
PHYTOMEDICINE
CONSIDERATIONS
FEVERFEW
Feverfew (Tanacetum parthenium) is a member of the daisy family
(Asteraceae) and is a short, bushy perennial that grows along
fields and roadsides. Its yellow-green leaves and yellow flowers
resemble those of chamomile, for which it is sometimes confused.
The flowers bloom from July to October.
The leaves are used in medicinal preparations.30 The name "feverfew"
is derived from the Latin for "chase away fevers." It
is mentioned in the Greek literature asa remedy for inflammation
and swelling as well as menstrual cramps. Feverfew enjoyed wide
use by British herbalists as an analgesic in the treatment of
fevers and arthritis, but faded into obscurity.
Feverfew has enjoyed a revival over the
past two decades due to approval of its use for treatment of migraine
by both the Canadian and British governments.
ACTIVE CONSTITUENTS: The most important
of these compounds is parthenolide . First identified in 1960,
parthenolide is the portion of the leaf believed to be responsible
for feverfew's anti-migraine activity.31 A critical consideration
in commercial feverfew products has been the highly variable content
of parthenolide. An analysis of commercial feverfew products in
Canada found about half are virtually devoid of this compound.32
As a minimal standard, the Health Protection Branch of the Health
and Welfare Department of the Canadian Government has proposed
that feverfew preparations should contain at least 0.2% parthenolide
content.
Health care practitioners should also
be aware that parthenolide is highly unstable and seek feverfew
extracts that address this issue. Your pharmacist has identified
one of the few sources of feverfew where the parthenolide content
is assured.
MECHANISM OF ACTION: Feverfew,
and specifically parthenolide,inhibits platelet aggregation (which
if you remember can release serotonin which may fuel migraines)
and histamine release. It has also been shown to inhibit release
of serotonin from platelets 33,34 This is believed to reduce the
severity, duration and frequency of migraine headaches and lead
to an improvement in blood vessel tone.35,36 37
CLINICAL APPLICATIONS: Clinical
studies with feverfew have focused on the treatment and prevention
of migraine and have primarily taken place in Great Britain. These
studies indicate the efficacy of feverfew as a useful tool in
the long-term management of migraines.
The initial clinical study enrolled migraine
patients who had been using feverfew for several years.38 Seventeen
patients were enrolled and given either feverfew (50 mg daily)
or placebo. Eight patients, who remained on feverfew, experienced
continued relief of migraines over a six month period. The nine
receiving placebo had an almost three-fold increase in migraines.
Many of these headaches were incapacitating, and anxiety, insomnia
and muscle and joint soreness were also reported. This has prompted
some concern at the abrupt cessation of feverfew therapy. A second
study enrolled 72 migraine sufferers.39 They received either 82
mg of feverfew daily or placebo.
Treatment with feverfew for four months
led to a decreased incidence and severity of migraines. Feverfew
also led to less vomiting attacks and fewer visual disturbances
during migraine attacks. Adverse events were mild (primarily mild
gastrointestinal upset and nervousness) and did not result in
discontinuation of treatment.
RECOMMENDED DOSAGE: Appropriate
dosing of feverfew leaf for migraine prevention is based on parthenolide
content. The Canadian Health Protection Branch has granted a Drug
Identification Number (DIN) for feverfew.40 They recommend a daily
dosage of 125 mg of a dried feverfew leaf preparation from authentic
Tanacetum parthenium containing a minimum of 0.2% parthenolide
for migraine prevention. This translates to a daily parthenolide
dosage of at least 250 mcg. This should be considered a minimum
amount for efficacy. Results from studies that are not yet published
indicate that 100 mg. per day of feverfew extract at .7% parthenolide
content may be desirable. (Remember that over 50% of most feverfew
extracts have little or no parthenolide content regardless of
their label claims. Your pharmacist can help to avoid this problem.
Continuous use for at least four to six weeks is recommended.
SIDE EFFECTS/CONTRAINDICATIONS:
In addition to the adverse events listed in the clinical studies
above, the most common side effect reported with feverfew has
been mouth ulceration.41 This has predominantly been found in
individuals chewing the leaves not with higher quality standardized
extracts. Scattered reports of dermatitis have been reported with
use of feverfew. To date, no long-term toxicity studies have been
performed. Feverfew is contraindicated for pregnant or lactating
women and should not be used in children under the age of two
years.
OTHER HERBAL
CONSIDERATIONS
GINGER
Ginger (Zingiber officinale) contains constituents that inhibit
platelet aggregation.42,43 44,45 While all of these actions point
to the potential use of ginger with migraine, controlled clinical
trials are lacking. One case study published in the Journal of
Ethnopharmacology reported on a 42 year old female migraine sufferer
who found relief taking 500 to 600 mg of ginger powder mixed with
water every four hours for four days.46 The patient was instructed
to begin ginger at the onset of visual aura. The authors report
improvement within 30 minutes of beginning ginger. They also note
that continued use of ginger by the woman led to decreased frequency
and intensity of migraines.
GINKGO BILOBA EXTRACT
GBE has been shown to offer some promise for the management of
migraines in two small French clinical trials.47 48 49 The daily
dose ranged from 120 to 240 mg. Clearly, more research is needed
on the potential use of GBE for migraine.
NUTRITIONAL
SUPPLEMENT CONSIDERATIONS
MAGNESIUM
It has pointed out that various factors which are known to trigger
migraines (namely stress, pregnancy, menstruation, alcohol ingestion,
and some diuretics) also promote magnesium depletion.50 In addition,
magnesium exerts many of the same effects as drugs that are helpful
in the prevention or treatment of migraines.51 These effects include:
(1) inhibition of spasm; (2) inhibition of platelet aggregation;
(3) stabilization of cell membranes; (4) interference with the
synthesis, release or action of inflammatory compounds; and (5)
improvements in cerebral vascular tone. In addition, brain magnesium
concentrations were significantly lower by 19% in patients during
a migraine attack than in healthy controls. These observations
suggest that magnesium may play a role in the prevention and/or
treatment of migraine. Clinical trials have supported that possibility.
In an open trial, more than 3,000 patients with common or classical
migraine received magnesium (usually at a dose of 200 mg/day).52
Almost all of the patients were women and most were of childbearing
age. The "success rate" was reported to be 80%, but
the criteria for determining success were not specified.
CONDITION-SPECIFIC
MONOGRAPH SERIES
MIGRAINE
That uncontrolled study was followed by a double-blind trial in
which 20 patients with perimenstrual migraine received 360 mg/day
of magnesium or a placebo.53 The treatments were given for two
months, starting on the 15th day of each menstrual cycle and continuing
until menstruation. At the end of the treatment period, the "Pain
Total Index" (which measures duration and intensity of migraines)
was significantly lower in the magnesium group than in the placebo
group. The number of days with headaches was significantly reduced
in patients receiving magnesium, but not in those given placebo.
Prior to the start of treatment, white-blood-cell (WBC) magnesium
concentrations were lower in the migraine patients than in healthy
controls.
Magnesium treatment was followed by a
significant increase in WBC magnesium levels. These data suggest
that magnesium deficiency contributes to the dysfunction of perimenstrual
migraine. In another double-blind study, 81 patients aged 18 to
65 years with migraines (mean attack frequency, 3.6 per month)
were randomly assigned to receive magnesium (600 mg every morning)
or a placebo for 12 weeks. 54 The frequency of attacks was significantly
reduced in the magnesium group, compared with the placebo group
(by 41.6%vs. 15.8%; p < 0.05). The duration and intensity of
attacks also tended to decrease compared to placebo, but the difference
was not statistically significant. Diarrhea occurred in 18.6%
and gastric irritation in 4.7% of patients receiving magnesium.
One study failed to find a beneficial effect of magnesium for
migraine prevention. 55 In that study, 69 patients with migraines
were randomly assigned to receive magnesium (242 mg twice daily)
or a placebo, in double-blind fashion, for 12 weeks. Response
to therapy was assessed according to the criterion of the International
Headache Society; i.e. a reduction of at least 50% in the duration
or intensity of migraines. Using that criterion, approximately
30% of patients in each group were considered responders, with
no significant difference between groups. However, this negative
finding should be interpreted cautiously. Only a few studies have
measured improvement according to the protocol of the International
Headache Society and most of those studies showed no significant
benefit from the treatment being tested. Even beta-blockers (a
class of drugs known to prevent migraine recurrences) were ineffective
when tested by the International Headache Society criteria. It
is noteworthy that 33% of patients receiving magnesium (but only
11% of patients given placebo) felt that their treatment was superior
to previously used migraine medications. Thus, the results of
this study are not inconsistent with previous reports of a beneficial
effect of magnesium.
Magnesium has also been given intravenously
to treat acute episodes of migraine.56 Forty patients with an
acute migraine attack were given 1 g of magnesium sulfate (in
a 10% solution) over five minutes. Fifteen minutes after the infusion,
35 patients (87.5%) experienced at least a 50% reduction in pain.
Nine patients (22.5%) had complete relief of pain. In 21 of the
35 patients who improved, relief persisted for 24 hours or more.
The effectiveness of magnesium was related to the pre-treatment
serum concentration of magnesium. This study suggests that intravenous
administration of magnesium is an effective treatment for acute
migraine attacks, particularly in patients whose serum magnesium
concentrations are low. These studies provide a rationale for
oral magnesium supplementation for migraine prophylaxis.
A reasonable dosage is 200 to 600 mg/day
(the larger amounts should be taken in divided doses with meals
to reduce the risk of diarrhea). Intravenous administration of
magnesium may also be considered as a method of aborting acute
migraine attacks. While measurement of serum ionized magnesium
might be useful to predict which patients are most likely to respond
to intravenous magnesium, this test is not yet commercially available.
A therapeutic trial with intravenous magnesium
is usually acceptable, provided that the physician is trained
in proper administration of this compound. Dr. Alexander Mauskop
of the New York Headache clinic has lead the research in the use
of magnesium and has been issued a patent on the subject. Dr.
Mauskop is considered internationally to be one of the leading
experts on all types of headaches including migraines. His book
"The Headaches Alternative" is available from Dell Publishing,
N.Y, N.Y.
RIBOFLAVIN
49 patients with recurrent migraines were given riboflavin, 400
mg/day with breakfast, for at least three months.57 The mean number
of migraine attacks fell by 67% and mean migraine severity improved
by 68%. One patient stopped treatment because of gastric intolerance
(that person was also taking small amounts of aspirin), but no
other side effects were reported. This study suggests that riboflavin
supplementation may reduce the recurrence rate of migraines.
L-TRYPTOPHAN
It has been suggested that migraines are related to a deficiency
of serotonin in the brain.58 As the precursor to serotonin, L-tryptophan
might therefore play a role in migraine prevention.
To test that hypothesis, eight migraine
patients who had been resistant to therapy received 500 mg of
L-tryptophan every six hours or a placebo (L-leucine), each for
three months, in a double-blind, crossover trial.59 The mean headache
index(number of attacks multiplied by the intensity) was 32.8%
lower with L-tryptophan than with placebo. Although that difference
was not statistically significant, headache indices were markedly
lower in four of the eight patients during L-tryptophan treatment,
compared to placebo treatment. These results are consistent with
the possibility that L-tryptophan is of value for a subset of
migraine patients. In a double-blind study, migraine patients
received 3 g/day of L-tryptophan or a placebo for one month.
60 Patients receiving L-tryptophan had
significantly fewer migraines of significantly shorter duration
than did patients receiving placebo. These observations suggest
that L-tryptophan may have preventive value for a portion of migraine
patients. L-tryptophan has not been reported to cause any severe
side effects. However, in 1989 a contaminated batch of L-tryptophan
was implicated as the cause of a severe and sometimes fatal disorder
known as eosinophilia myalgia syndrome. Uncontaminated L-tryptophan,
on the other hand, has not been associated with this disorder.
Currently, uncontaminated L-tryptophan is available by prescription
from compounding pharmacists.
FISH OIL
Interest in the relationship between fish oil and migraines was
triggered by the observation that migraine patients had significantly
lower concentrations of omega-3 fatty acids in platelet and red
blood cell membranes, compared with healthy individuals.61 Omega-3
fatty acids (which are found primarily in fish oils, flaxseed
oil and some other vegetable and nut oils) are known to inhibit
platelet aggregation. This effect would presumably decrease platelet
serotonin release, with an accompanying reduction in cerebral
artery spasm and migraine attacks.
Fifteen patients with migraines that had
failed to respond to anti-migraine drugs received (in random order)
a fish-oil concentrate (vegetable oil) for six weeks, in a double-blind,
crossover trial.62 Compared with placebo, treatment with the oils
resulted in a significant reduction in mean headache intensity.
Fish-oil concentrates can cause gastrointestinal side effects,
but are otherwise usually well tolerated. Other sources of omega-3
fatty acids (such as flaxseed oil) might conceivably have a beneficial
effect, as well.
DIETARY CONSIDERATIONS
It is generally accepted that a small proportion of migraine patients
will react to tyramine, a chemical found in aged cheese, yogurt,
beer, wine, liver, yeast and certain other foods. In these patients,
avoidance of tyramine-containing foods will often prevent recurrences
of migraine. Abnormal glucose metabolism has been identified in
some patients with migraines. In one study, a five-hour glucose
tolerance test was performed on 74 patients who experienced migraines
in the mid-morning or mid-afternoon.63 Six patients (8%) were
classified as diabetic and 56 (76%) had a pattern consistent with
reactive hypoglycemia (a large drop in blood sugar after a meal).
Following dietary therapy with a low-sucrose, six-meal regimen,
all patients with a diabetic glucose curve and 56% of those with
reactive hypoglycemia (low blood sugar) had an improvement of
greater than 75% in the frequency and severity of migraines.
Food allergy has also been implicated
as an important factor in migraine. In one study, 60 patients
who had been suffering from frequent migraines for a mean duration
of about 20 years followed an exclusion diet for five days.64
During that time, only two low-risk foods (usually lamb and pears)
and spring water were consumed. Migraines disappeared in most
cases by the fifth day. Each patient then tested one to three
common foods per day, looking for reactions. The mean number of
foods causing symptoms was 10 per patient (range, 1 to 30). The
foods most frequently causing symptoms and/or pulse changes were
wheat (78%), orange (65%), egg (45%), tea and coffee (40% each),
chocolate and milk (37% each), beef (35%), corn, cane sugar and
yeast (33% each), mushrooms (30%), and peas (28%). When the offending
foods were avoided, all patients improved. The number of headaches
in the group fell from 402 to 6 per month, with 85% of the patients
becoming headache free. This study provides strong evidence that
identification and avoidance of allergy causing foods is an effective
procedure for a large proportion of patients with chronic recurrent
migraines. Patients with recurrent migraines should be evaluated
for possible blood-sugar abnormalities and food allergies. When
either of these abnormalities is found, appropriate dietary modifications
should be made. In addition, a trial of a low-tyramine diet should
be considered.
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