Melatonin and Other Hormones
Estrogen and progesterone are not the only hormones involved in
migraine headaches. Rather, it appears that in migraine sufferers, the
body's regulation of many hormones is abnormal, and each imbalance may
contribute to the pathology of migraines. For example, research has
shown that the pineal gland in migraine sufferers is depressed, which
leads to reduced levels of both serotonin and melatonin during migraine
headaches (Claustrat B et al 1997; Claustrat B et al 1989).
Subsequently, several studies have demonstrated that melatonin
effectively relieves migraine pain, decreases frequency of migraines,
reduces intensity of migraines, and shortens migraine duration (Gagnier
JJ 2001; Peres MF et al 2004).
One study, conducted with 23 volunteer participants (21 women and 2
men), found that administration of melatonin at bedtime was well
tolerated and resulted in a 100 percent success rate (i.e., none of the
patients suffered from migraine afterward). Melatonin was one part of a
program that included four components:
- Hormone restoration therapy with bioidentical hormones
- Simultaneous correction of the imbalance between sympathetic
and parasympathetic nervous systems and the ratio of calcium to
magnesium (Use of calcium in the daytime and magnesium at night
reinforces the balance.)
- “Resetting” of the pineal gland through melatonin
supplementation (which can be enhanced with the addition of L-theanine
if needed)
- Improvement of intestinal absorption by restoration of normal intestinal flora through the use of probiotics
In this study, all the patients had suffered from deficiencies in
steroid hormones, especially pregnenolone, before beginning the study.
During the course of the study, patients were given complete hormone
restoration therapy, including estrogen, progesterone, testosterone,
pregnenolone, and dehydroepiandrosterone (DHEA). The researchers
concluded that their clinical experience strongly supports the notion
that migraine can be managed only when levels of all the basic
hormones—pregnenolone, DHEA, testosterone, estrogen, and progesterone
(as well as melatonin)—are optimal (Dzugan SA et al 2003).
Nutrients That Target Migraine
Magnesium. Maintaining a healthy balance between
magnesium and calcium is central to Vitamin Depot Online.com's approach to
migraine. Studies have shown that up to 50 percent of migraine patients
suffer from magnesium deficiencies during an acute attack (Mauskop A et
al 1998). Magnesium infusions have led to fast and continuous relief of
migraine symptoms, possibly by reducing the brain's hyperexcitability
(Mauskop A et al 1995; Mauskop A et al 1998). Several double- blind
trials showed that oral magnesium supplementation may either reduce the
frequency of migraine attacks (Mauskop A et al 1998) or decrease the
number of headache days (Wang F et al 2003). These results may be due
to magnesium's ability to rebalance the calcium/magnesium ratio in the
brain, thus offsetting the excitability caused by excess calcium in the
intracellular space.
Butterbur root. Several studies found butterbur
root ( Petasites hybridus) is an effective prophylactic agent for
migraine (Diener HC et al 2004; Grossman W et al 2001; Lipton RB et al
2004). In one placebo-controlled study, 33 patients were given 25 mg of
butterbur root twice a day, and 27 patients were given placebo. After
three months, the patients taking butterbur experienced a reduction of
3.4 attacks per month to 1.8.
While the mechanism by which butterbur exerts its effect in migraine
prophylaxis is unknown, it may work through its anti-inflammatory
effects and its blockade of calcium channels in vascular smooth muscles
(Scheidegger C et al 1998; Thomet OA et al 2001; Brune K et al 1993;
Thomet OA et al 2001; Ko WC et al 2001; Wang GJ et al 2001).
A recent randomized, double-blind, placebo-controlled study
evaluated butterbur root extract (in doses of 50 mg or 75 mg twice
daily) compared with placebo. After 16 weeks of treatment, 68 percent
of patients on 75 mg twice daily had a 50 percent or greater reduction
in migraine attack frequency, which was significantly better than those
using placebo in this study (Lipton RB et al 2004).
Feverfew. Feverfew ( Tanacetum parthenium)
preparations have been studied for migraine prophylaxis in several
trials (de Weerdt GJ et al 1996; Johnson ES et al 1985; Murphy JJ et al
1988; Palevitch D et al 1997; Pfaffenrath V et al 2002; Pittler MH et
al 2004).
An active component of fevervew, chrysanthenyl acetate, is thought
to have pain-relieving properties and to inhibit prostaglandin
synthetase (Pittler MH et al 2004; Pugh WJ et al 1988). Melatonin is
also present in feverfew and may contribute to overall effectiveness of
this herb (Murch SJ et al 1997). Feverfew is also thought to have
anti-inflammatory effects (Williams CA et al 1995) and seems to inhibit
pain transmission and inflammation (Jain NK et al 1999).
Some trials have shown that use of feverfew results in decreased
frequency of migraine headaches and diminishes symptoms of nausea,
vomiting, and pain, as well as light and sound sensitivity (Johnson ES
et al 1985; Murphy JJ et al 1988; Palevitch D et al 1997; Pfaffenrath V
et al 2002).
One of these trials aimed to test a dose-response of a new
formulation of feverfew for migraine prophylaxis. A total of 147
patients participated in this randomized, double-blind,
placebo-controlled study, which compared the efficacy and safety of
three different doses of the new formulation and placebo. For the first
4 weeks, no treatment was given, and the participants' number of
migraine attacks was measured. The active treatment or placebo was then
given for 12 weeks. While overall, feverfew was not statistically more
effective than placebo, the highest dose of feverfew extract
administered significantly decreased the frequency of migraine episodes
in patients who had at least four attacks during the initial 4-week
phase (Pfaffenrath V et al 2002).
Riboflavin. Riboflavin (vitamin B 2) has been used
as a prophylactic measure for migraine. An open-label, pilot study of
49 participants (45 with common migraine and 4 with classic migraine)
was conducted in Liege, Belgium. Participants were given 400 mg of
riboflavin as a single oral dose dailyfor at least
three months. Treatment resulted in mean global improvement of 68.2
percent. It was concluded that high-dose riboflavin may have a role in
migraine prophylaxis due to its efficacy, short-term lack of side
effects, and relatively low cost (Schoenen J et al 1994).
A follow-up trial studied 55 migraine patients (Schoenen J et al
1998). Riboflavin at 400 mg daily or placebo was given for three
months. Statistically significant reductions in frequency of migraine
episodes and headache days were observed with riboflavin compared with
placebo. The authors concluded that riboflavin was an efficacious,
safe, and cost-effective option for migraine prophylaxis (Schoenen J et
al 1998).
Another recently conducted, open-label study in Germany found that
administration of 400 mg riboflavin daily significantly reduced
frequency of migraine headaches and the use of abortive medications
after three months and after six months of treatment (Boehnke C et al
2004). The authors concluded that their findings were similar to those
of other investigators and that riboflavin was a well-tolerated and
effective prophylactic agent for migraine.
Further studies performed in Liege, Belgium, reported that the
combination of beta-blockers and riboflavin may augment their clinical
efficacy without enhancing adverse events (Sandor PS et al 2000).
Coenzyme Q10. Several studies have demonstrated
effectiveness of coenzyme Q10 in reducing the frequency of migraine
headaches (Rozen TD et al 2002; Sandor PS et al 2005). A clinical trial
of 31 patients reported a significant reduction in the average number
of days with migraine after three months of treatment. Migraine
frequency also fell significantly, from 4.85 attacks to 2.81. The
administered dose was 150 mg daily.
A randomized, double-blind, placebo-controlled trial of 42 patients
compared coenzyme Q10 at 100 mg three times a day with placebo.
Participants were randomized to either placebo or coenzyme Q10 for
three months. Coenzyme Q10 significantly decreased migraine attack
frequency (=50 percent reduction) in 47.6 percent of patients, compared
with 14.4 percent of patients on placebo. In addition, coenzyme Q10
seemed to decrease headache days and days with nausea better than
placebo (Sandor PS et al 2005).
S-adenosyl-L-methionine (SAMe). Only one small,
open clinical trial (Gatto G et al 1986) of SAMe has been conducted to
date. It found that long-term administration of SAMe could result in
pain relief in migraine sufferers. The authors speculated that this
relief may be due to SAMe's effect on turnover of serotonin, a target
in conventional drug therapy.
Vitamin Depot Online.com Foundation Recommendations
To minimize the frequency of migraine attacks, migraine triggers
need to be identified and avoided (Silberstein SD et al 2003; Peatfield
RC et al 1993). It is recommended that migraine sufferers stop smoking,
get sufficient sleep (but not oversleep because oversleep may serve as
a migraine trigger), and minimize stress. Nutrients that may be
effective prophylactic agents for migraine include the following:
- Butterbur root extract
(Petadolex)—50 milligrams (mg) up to three times daily with meals. Dose
could be tapered after four to six months of oral administration, then
increased again when there is an elevation in migraine incidence.
- Feverfew extract—100 mg daily. Formulations of feverfew standardized to 0.2 to 0.35 percent of parthenolide have been used in most studies.
- Riboflavin (vitamin B 2)—100 to 200 mg daily with food.
- Melatonin—3 to 6 mg daily before bedtime. To maximize the effect and relieve anxiety, combine with 100 to 400 mg of L-theanine.
- SAMe—generally, between 400 mg and 1600 mg orally daily.
- Coenzyme Q10—100
mg up to three times daily. Avoid smoking, because smoking leads to
reduction in body stores of coenzyme Q10 ( Elsayed NM et al 2001).
- Magnesium—magnesium
citrate 160-mg capsules at night before bed. Use the maximum dose
tolerated without a laxative effect, usually 1 to 4 capsules. In
addition, magnesium may provide some relief if taken during the early,
vasoconstrictive stages of the headache.
- Probiotics—3.5 billion of Lactobacillus group, 1 billion of Bifidobacterium group, and 0.5 billion of Streptococcus thermophilus.
To balance the hormonal abnormalities present in most migraine
patients, a complete hormone profile is strongly recommended. This will
likely uncover abnormalities that can be corrected with hormone
restoration therapy using bioidentical hormones. For more information
on bioidentical hormones or hormone blood testing, call 1-800-544-5440,
or visit www.lef.org. A complete hormone profile will check levels of
major hormones, including pregnenolone, estrogen, progesterone, DHEA,
and testosterone. These hormones may then be supplemented as necessary
to restore youthful hormone levels and correct any imbalance that might
be contributing to migraine headaches. A suggested beginning dose of
DHEA is 15 to 75 mg daily. |
Migraine Safety Caveats
An aggressive program of dietary supplementation should not be
launched without the supervision of a qualified physician. Several of
the nutrients suggested in this protocol may have adverse effects.
These include:
Coenzyme Q10
- See your doctor and monitor your blood glucose level frequently if
you take CoQ10 and have diabetes. Several clinical reports suggest that
taking CoQ10 may improve glycemic control and the function of beta
cells in people who have type 2 diabetes.
- Statin drugs (such as lovastatin, simvastatin, and pravastatin) are known to decrease CoQ10 levels.
Feverfew
- Consult your doctor before taking feverfew if you take warfarin (Coumadin). Feverfew has blood-thinning properties.
Magnesium
- Do not take magnesium if you have kidney failure or myasthenia gravis.
Melatonin
- Do not take melatonin if you are depressed.
- Do not take high doses of melatonin if you are trying to
conceive. High doses of melatonin have been shown to inhibit ovulation.
- Melatonin can cause morning grogginess, a feeling of having a
hangover or a “heavy head,” or gastrointestinal symptoms such as nausea
and diarrhea.
SAMe
- Consult your doctor before taking SAMe if you have bipolar
disorder. See your doctor frequently if you take SAMe and you have
bipolar disorder.
- Consult your doctor before taking SAMe if you take
antidepressants. See your doctor frequently if you take SAMe in place
of or in addition to antidepressants.
- Consult your doctor before taking SAMe if you have cancer.
Nucleic acid methylation patterns may change in people who have cancer
and take SAMe.
- Do not take SAMe if you are undergoing gene therapy.
- SAMe can cause anxiety, hyperactive muscle movement, insomnia,
hypomania, and gastrointestinal symptoms such as nausea and diarrhea.
Vitamin B2 (riboflavin)
- High doses of vitamin B2 (riboflavin) may interfere with the Abbott TDx drugs-of-abuse assay.
- Riboflavin absorption is increased in hypothyroidism and decreased in hyperthyroidism.
- If you are taking nucleoside reverse-transcriptase inhibitors,
even a mild riboflavin deficiency can increase your risk of lactic
acidosis.
For more information see the Safety Appendix |
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