Migraine

Patients with migraine report an average of one to five attacks per

month of moderate to severe pain, usually unilateral and
accompanied by other symptoms, as gastrointestinal upset,
photophobia, and phonophobia. The natural products that are
efficacious in treating an acute attack are caffeine and magnesium
which is occasionally used in acute care setting. Triptan agents with
other classes of drugs, are used to resolve the acute attack.
Common natural products used for prophylaxis include feverfew,
butterbur, riboflavin, coenzyme Q 10 and Mg.
 Feverfew
• Feverfew (tanacetum parthenium) is a
perennial herb native to southeastern
Europe. The plant is also known as
midsummer daisy. The plant has flowers
with yellow center disks an white petals.
The aromatic leaves have been use
traditionally for inflammatory conditions
and headaches. Now the most common
use for feverfew is in migraine
prophylaxis.
• The mechanism of action of feverfew in migraine prophylaxis
remain unclear. Parthenolide, the principal sesquiterpene
lactone, has been studied as the active ingredient, but one study
found it has no benefit for prevention of migraine. It seems that
some combination of feverfew constituents is contributing to an
antimigraine effect. This effect may be due to inhibition of
serotonin release, prostaglandin synthesis and platelet
aggregation. Feverfew components might also prevent vascular
muscle contraction. Parthenolide may be useful as an anti-
inflammatory an chemotheraputic agent.
• Studies of feverfew in migraine prophylaxis offer conflicting
results. Two randomized, placebo- controlled trials that used
whole feverfew leaf found it effective as prophylactic agent. The
onset of benefit was observed in 4 – 8 weeks. Others found no
benefit. Patient should be consulted to chose whole- leaf,
encapsulated products, in dosage of 80- 100 mg per day.
 Safety consideration and drug interactions
• Feverfew is tolerated better than the available prescription
agents. There is a theoretical risk of additive antiplatelet or
anticoagulant effects when used with aspirin warfarin or
clopidogril. There are preliminary data indicating that feverfew
may inhibit hepatic enzymes, which will increase drug
concentration. Chewing feverfew leaves can cause oral ulcers.
When stop using feverfew, patient may experience a post
feverfew syndrome characterized by anxiety, insomnia, joint
stiffness, and rebound headaches. It should not be taken by
women who are pregnant or breast feeding. Feverfew is a
ragweed plant, patient allergic to this family avoid its use.
Choosing reputable product is essential because products quality
are variable.
 Butterbur
Butterbur grows in wet, marshy
areas along rivers in north America,
parts of Asia, and Europe. The
leaves, rhizomes and roots of
butterbur contain the
sesquiterpene compounds petasin
and isopetasin.
 Butterbur
• The sesquiterpene compounds petasin and isopetasin ( found in
leaves, rhizomes and roots of butterbur). These constituents
inhibit leukotriene synthesis (leukotriene are fatty signaling
molecules. One of their roles is to trigger contractions in the
smooth muscles lining the trachea; their overproduction is a
major cause of inflammation in asthma and allergic rhinitis) which
may also contribute to butterbur’s antispasmodic and anti-
inflammatory action. Butterbur extracts contain other
components that may contribute to efficacy including flavonoids,
tannins, and pyrrolizidine alkaloids.
• A standardized extract of butterbur has been used in
randomized, placebo- controlled, double- blind clinical trials. It
reduce the frequency of migraine by 48% to 60% along with the
reduction of the existing migraines. Butterbur also appears
effective for allergic rhinitis. The benefit from this product
increases with time. A typical dose is 75mg twice daily.
Safety consideration and drug interactions
• Butterbur leaf and rhizome contain pyrrolizidine alkaloids,
which are hepato-toxic and potentially cacinogenic.
Fortunately, these compounds can be safely removed.
Consumers need to choose pyrrolizidine- free extract. It is
prudent to avoid all butterbur products, including
pyrrolizidine- free extract in persons with liver disease. Side
effect of pyrrolizidine- free extracts are rare mainly mild GIT
complaints.
 Riboflavin
• Riboflavin (vit B2) is an essential nutrient critical to the body's
production of ATP, the main cellular energy source. Riboflavin is
precursor of flavin mononucleotide and flavin adenine
dinucleotide, which are required for the activity of flavoenzymes
involved in the electron transport chain. Riboflavin
supplementation is thought to remedy a type of mitochondrial
dysfunction which results in impaired oxygen metabolism. The
impaired oxygen metabolism may be contributing to an increase in
migraine frequency.
• Two studies indicate it is beneficial in reduction of migraine
frequency.
• The recommended dietary intake of riboflavin is 1.1mg/day for
women and 1.3mg/day for men. Riboflavin deficiency is rare
except in alcoholics. The dose used in migraine prophylaxis is 400
mg/day, for at least 4 weeks. This dose is high but safe.

Safety consideration and drug interactions

• No toxic effect of riboflavin at doses of 400 mg/day have been

reported. It is reasonable to recommend in pregnancy.
 Coenzyme Q10 (CoQ10)
• CoQ10 is also known as ubiquinone (means found
everywhere), is natural occurring antioxidant compound
found in every cell in the body. It plays a fundamental role in
mitochondria in energy production. Body normally produce
sufficient CoQ10. CoQ10 level decrease with age and certain
disease as heart disease. Some drugs as statin may interfere
with its production.
• Co Q10 is used most commonly for congestive heart failure,
however the data for heart failure is inconclusive. Data for
migraine prophylaxis appear better, but the two available
studies are small. In one trial reduction of migraine was 55% at
the end of 3 months. In the second it was 46%, the used dose
was 100mg 3 times daily and it is the recommended dose.
 Safety consideration and drug interactions
• Co Q10 does not cause significant adverse events. Concomitant
administration of CoQ10 and the chemotherapy drug doxorubicin
(adriamycin) should be avoided as CoQ10 can alter doxorubicin
metabolism and increase the concentration of a potentially toxic
metabolite. CoQ10 is used to help prevent cardiac toxicity of
doxorubicin, when used after cessation of chemotherapy.
Cholesterol lowering drugs as simvastatin, lorvastatin and
gemfibrozil may decrease plasma and tissue levels of CoQ10, and in
this case it is unclear whether normalization of CoQ10 via
supplementation is beneficial. Paravastatin and atrovastatin do not
lower CoQ10. the beta blockers propranolol and metoprolol may
also inhibit coenzyme Q10 dependent enzymes and ultimately
lower CoQ10 levels. CoQ10 is structurally similar to vitamin K,
therefore, a procoagulant effect when combined with warfarin has
been suggested but a small study showed no interaction between
them.
 Magnesium
• Magnesium is an essential nutrient found in significant quantities
throughout the body and used in numerous purposes, including
muscle relaxation, blood clotting, and manufacture of ATP. Mg is
most used as laxative and antacid, and as natural Ca channel
blocker for hypertension. Most people get adequate Mg through
the diet, the RDI is 420mg/day for male and 320mg/day for
females. In one double – blind study of 81 patient,
supplementation with Mg 600mg/day reduced migraine frequency
by 42% compared to 16% in placebo group, 20% reported diarrhea
and less often GIT upset. Two other studies show benefit . A
reasonable Mg dose is 600mg/day for at least 4 weeks trial. All Mg
salts are absorbed fairly well, MgO is thought to be less absorbed
than Mg citrate.
 Safety consideration and drug interactions
• Mg can cause diarrhea and to lesser extent GIT upset, particularly
in high dose. Large dose can cause hypermagnesemia, which can
produce fatal arrhythmias. In patients with reduced renal function
must be careful due to reduced elimination. Patients with heart
disease should not take excessive dose of Mg without consulting
their physician due to preexisting risk of arrhythmias. Quinolone
antibiotics, such as ciprofloxacin, and tetracycline antibiotics
should be taken 2 hours before or 4 hours after Mg supplements.
patients need to choose a formulation that has been tested for
lead content. Mg in the suggested dose is safe in pregnancy.