Feverfew, Butterbur, magnesium and riboflavin, as well as elimination of caffeine can make a world of difference for people with migraines and other chronic headache problems.
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Feverfew, Butterbur, magnesium and riboflavin, as well as elimination of caffeine can make a world of difference for people with migraines and other chronic headache problems.
NEW YORK—Botanical medicines like Butterbur extract and Feverfew, nutritional supplements including magnesium and riboflavin, and lifestyle changes particularly elimination of caffeine, can be effective in treating and preventing migraine headaches.
Often, natural medicines can alleviate the need for costly, side-effect laden pharmaceuticals, said Alexander Mauskop, MD, during the Integrative Pain Medicine course sponsored by Columbia University’s Rosenthal Center for Complementary and Alternative Medicine.
Dr. Mauskop, director of the New York Headache Center, and one of the nation’s leading researchers on migraines, reviewed the evidence on herbal and nutritional therapies, and outlined a comprehensive holistic approach to the management of patients with migraines and other chronic headache problems.
Over 25 million Americans suffer from migraines, which strike women three times more often than men. These often debilitating vascular headaches are most commonly experienced between the ages of 15 and 55, and 70%–80% of sufferers have a family history of migraine.
Migraine headaches can produce throbbing, pounding, smashing, grinding or piercing pain often compounded by nausea and vomiting, photophobia and phonophobia. Approximately 20% of migraine sufferers experience an “aura” prior to the onset of the pain. Visual disturbances such as wavy lines, dots, flashing lights and blind spots in addition to disruptions in smell, taste or touch begin from twenty minutes to one hour before the actual onset of migraine.
Many factors can trigger migraine episodes, including: alcohol, chocolate, caffeine, stress, specific foods and food additives. Lack of magnesium, serotonin imbalances, and electrical changes in the brain also contribute.
The etiology of migraines remains poorly understood, said Dr. Mauskop. However, most experts agree they originate in the brain and are related to inappropriate contraction and expansion of cerebral vasculature. Following initial expansion, arteries go in to spasm and blood flow slows. Once the constriction stops, vessels quickly dilate, thus stretching nerve fibers coiled around the vessels. Stretching of the nerves is thought to cause a release of neurotransmitters and other chemical mediators of pain, inflammation, and further vessel dilation.
Many migraine experts believe serotonin plays a role in migraines. Serotonin, which helps to control pain sensation, regulates sleep, mood and sexual behavior, is also involved in regulating cerebral vascular tone. Some researchers have posited a “neural” theory, holding that migraines begin in specific nerves or in the brain stem.
According to Dr. Mauskop, it is not an either-or question. He believes that both “vascular and neural influences play important roles in causing migraines.” Stress also plays a role. Intense stress can create changes in the brain and cause serotonin release, leading to vasoconstriction and rapid flooding of substance P along with other pain mediating chemicals.
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Whatever the pathogenic roots of migraine headaches may be, it is increasingly clear that dietary factors can trigger episodes and reinforce the chronic nature of the problem. Caffeine, alcohol and food additives are common provoking factors, and avoidance of these triggers is a key first step in helping migraine patients.
“I insist that all of my patients get off caffeine. I cannot help them if they do not,” stressed Dr. Mauskop. This may seem paradoxical, given that many widely used over-the-counter and prescription headache medications contain caffeine. These include Anacin, Excedrin, Fiorinal, Fioricet, Norgesic, and Synalgos DC. “These drugs are very popular, and the HMOs love them because they are 10 cents per pill or less, compared with $20 per pill for newer migraine drugs like Imitrex.”
From a chronic headache viewpoint, caffeine is a double-edged sword. At doses of 150–250 mg per day (the equivalent of 2 cups of coffee or 2 caffeine-rich soft drinks), caffeine will keep blood vessels from dilating, thus down-regulating one of the mechanisms driving migraines. Excessive doses, on the other hand, can trigger headaches. And there is the further problem of withdrawal.
Caffeine does induce dependence, and many people who routinely consume caffeine will experience splitting headaches if they stop. In a double-blind caffeine cessation study, 52% of subjects who previously consumed a mean of 2.5 cups of coffee daily, had moderate to severe headaches once they stopped (see chart). “If you are already prone to headaches, or you have a history of migraines, your odds are basically 100%,” Dr. Mauskop added.
Many patients who use caffeine-containing drugs over long periods find they must continually escalate the dose to stave off rebound headaches. “Some of these patients are taking 20 Fioricets per day—that’s bad news,” he said.
Given that abrupt cessation will almost inevitably trigger severe rebound headaches and other symptoms, Dr. Mauskop advises his patients to go through this process over a weekend. He provides patients with injectable imitrex, compazine suppositories (to reduce nausea), and a weekend supply of vicodin, percoset or valium. The approach is a bit drastic and drug-centered, but for patients who’ve been taking high caffeine doses for years on end, it may be the only way. “I tell them, basically, to knock themselves out and sleep through the withdrawal. They’ll be fine by Monday.”
Alcohol is a powerful short-term vasodilator. Blood vessels dilate, then quickly constrict, then widen again. Or they may just constrict for a period of time—the perfect set-up for a migraine. Alcoholic drinks, especially red wine, may also contain preservatives and additives such as sulfites that contribute to the change in blood vessels. In general, migraine patients should avoid consuming alcohol.
Some amine components of amino acids can act as triggers for the release of hormones that constrict blood vessels. The most common of these is tyramine, an important element of adrenaline. Chocolate contains a form of tyramine called phenylethylamine (PEA), and some people with histories of migraine recognize chocolate as a trigger. Fermented foods such as aged cheese, yogurt, pickled and marinated foods, and sauerkraut also contain tyramine.
Food additives that trigger migraines are MSG (monosodium glutamate) and nitrites. Both are used as preservatives and flavor enhancers. MSG is found in a lot of Asian take-out food, meat tenderizers, and pre-packaged foods. MSG has several aliases such as sodium caseinate, hydrolyzed oat flour, texturized protein, and calcium caseinate. An “MSG-free” product may not actually be so.
Nitrates used to cure meat can be found in hotdogs, bacon, ham, bologna and smoked meats. They can also be found in food colorings and brined vegetables. In general, migraine patients should avoid processed, chemically-laden foods.
Acupuncture can short-circuit migraine headaches, and regular acupuncture treatments can help prevent them (Melchart D, Linde K, Fischer P, et al. Cephalalgia 1999; 179–786). Acupuncture increases blood flow through a mechanism known as the “axon reflex”, which dilates the small vessels around the needle area. An increase in circulation where blood flow is poor is called removal or clearing up of “stagnation” in traditional Chinese medical terminology. It is viewed as a good approach for most chronic conditions including migraines.
However, since pain during a migraine is believed to be associated with dilation of blood vessels in the head, insertion of needles into the head and neck area is not desirable, and may even worsen the patient’s pain and accompanying symptoms. Acupuncturists who work with migraine patients, generally try to minimize activity of the blood vessels in the head and neck by limiting the acupuncture points to the arms and legs.
Regular exercise can play an important role in headache prevention. Daily exercise strengthens the circulatory system, which increases oxygen delivery to tissues. Aerobic exercise also stimulates endorphin release, and therefore contributes to endogenous analgesia. This is especially important for migraine patients, because the chronic use of pain relievers can reduce endogenous endorphin production, leading to an increased tendency to feel pain.
Magnesium has a pivotal role in preventing and treating migraine headaches, according to Dr. Mauskop. There is considerable evidence showing that migraine patients are chronically magnesium deficient (Ramadan NM, et al. Headache 1989; 29: 590–593), and that up to 50% of patients during an acute migraine have markedly low levels of ionized magnesium. There are also studies showing magnesium given orally or intravenously can avert or prevent migraines.
This essential mineral plays a role in many physiologic processes that may relate to headache: in itself it has vasodilatory effects, and it is a critical cofactor in the synthesis or metabolism of glutamate, angiotensin II, serotonin, acetylcholine, norepinephrine and a host of enzyme complexes. Without enough magnesium, serotonin flows unchecked in the brain, constricting blood vessels and releasing other pain-producing chemicals such as substance P (Mauskop A. What Your Doctor May Not Tell You About Migraines 2001; 42).
A clinical trial of 360 mg magnesium pyrrolidone carboxylic acid in women with menstrual migraines showed a substantial reduction in migraine frequency. The mean number of migraine days per month dropped from 4.7 to 2.4 among the treated women (Facchinetti F, et al. Cephalalgia 1996; 16: 257–263). These women also had significant reductions in menstrual symptom scores.
A multicenter placebo-controlled study of oral trimagnesium dicitrate, 600 mg per day, showed a 42% reduction in migraine attack frequency among the treated patients, compared with a reduction of only 16% on placebo. The patients taking the magnesium salt had a 52% reduction in headache days, compared with only 20% in the placebo group (Peikert A, et al. Cephalalgia 1996; 16: 257–263).
More recently, a trial of magnesium oxide, 9 mg per day, was shown to reduce headache frequency in a cohort of children with chronic migraine headaches (Wang F, et al. Headache 2003; 43: 601–610). There is only one placebo controlled study of magnesium showing no benefit (Pfaffenrath V, et al. Cephalalgia 1996; 16: 436–440). Dr. Mauskop pointed out, however, that this trial used magnesium-u-aspartate-hydrochloride-trihydrate, a poorly absorbed magnesium salt not available in the US, and rarely used elsewhere.
Based on his own experience, Dr. Mauskop recommends magnesium oxide as the preferred form of this element. “It costs very little but it is very well absorbed.” If patients have problems with diarrhea, he switches to a chelated magnesium salt or a slow-release form. In general, 300–400 mg of magnesium oxide per day is the appropriate dose. MagOX™ (Blair Pharmaceuticals), has 240 mg magnesium per pill and is an excellent supplement for migraine patients.
One way to determine if a patient will benefit from magnesium supplementation is to ask about muscle cramps. If a patient regularly experiences cramps, especially at night, and they often have cold hands and feet, they are very likely magnesium-deficient. “This is very common in migraine patients.”
Magnesium can also be given intravenously, as magnesium sulfate, with excellent results. “You can get dramatic relief with IV magnesium. It is much better than Imitrex,” he said. Patients typically feel pleasantly warm and more relaxed after a magnesium infusion, and the headache resolves quickly. In fact, an infusion is probably the best way to tell if a patient will benefit from oral supplementation. “If they respond, they’re deficient. If they don’t respond, you don’t have to bother with supplements because they won’t work.”
Potential causes of magnesium deficiency are: stress, alcohol use, genetics, low intake, gastrointestinal disorders, and chronic illness. The current recommended dietary allowance (RDA) for magnesium is 400 mg per day. Between15%–20% of the US population is frankly deficient.
When using magnesium in the headache context, be aware that from a vascular point of view, there’s something of a tug-o’-war that occurs between magnesium and calcium. Magnesium promotes relaxation of vascular smooth muscle, while calcium promotes vasoconstriction. Excessive magnesium can make it difficult for the body to absorb enough calcium. However, magnesium deficiency is a more common problem than excess.
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Riboflavin (Vitamin B2) is a water-soluble vitamin important for body growth, red blood cell production, and assists in releasing energy from carbohydrates, proteins and fats. Some migraine patients will be riboflavin-deficient, and there is a placebo-controlled trial showing that over 4 months, riboflavin reduced monthly migraine episodes from a mean of 4 to less than 2.
Riboflavin’s effect is not immediate, and requires daily ingestion for at least a few weeks. Consequently, it is not so much a rescue remedy as a component in a comprehensive prevention strategy. The therapeutic amount for migraine prevention is 400 mg per day. In general, supplementation with all B vitamins (thiamine, niacin, pridoxine, and cyanocobalamine) will help patients with migraines, as will folic acid. Coenzyme Q10, at a dose of 300 mg, is also effective in reducing migraine frequency.
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| Feverfew (Tanacetum parthenium) growing on Herb Pharm’s certified organic farm in Williams, OR. The leaves of this plant, along with the root of Butterbur (Petasites hybridus), contain compounds that can help reduce the frequency, duration and disability of migraine headaches. Photo courtesy of Herb Pharm. |
Feverfew (Tanacetum parthenium) is an anti-inflammatory herb with a long history of traditional use for headaches. It was something of a “forgotten” herb until 1978 when a British newspaper told of a woman who cured her migraines with Feverfew leaves. In 1988, Lancet published a well-designed study suggesting Feverfew can help prevent migraine headaches or lessen their severity (Murphy JJ, Heptinsall S, Mitchell JRA. Lancet 1988;189–192).
To date, there are five published double-blind placebo controlled studies of Feverfew in treatment of migraines, four of which showed a positive trend, and one of which showed clear therapeutic efficacy, Dr. Mauskop said. In one study, the mean number of attacks following treatment was 3.6 per month in the Feverfew group versus 4.7 in the placebo cohort. The herb can also reduce intensity of headache pain, as well as nausea and vomiting.
Parthenolide, one of the biochemical constituents of Feverfew, inhibits release of inflammatory mediators, as well as reducing secretion of serotonin and histamine, two neurotransmitters involved in migraine pathogenesis. Feverfew, by itself, is fairly slow-acting. Patients usually need to take the herb for 4–6 weeks before they notice significant improvements. According to Dr. Mauskop, this herb is best used in combination with other nutritional or botanical medicines.
However, it is important to bear in mind that compounds within the Feverfew plant can interfere with blood clotting. If a patient is taking anticoagulants they must be monitored carefully, or should avoid this herb.
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| Butterbur (Petasites hybridus). Photo courtesy of Herb Pharm. |
Extracts of the root of the Butterbur plant (Petasites hybridus) can be used as both acute therapy and ongoing preventive medicine. Butterbur root contains compounds called petasin and isopetasin that inhibit vascular smooth muscle constriction, and reduce leukotriene synthesis. Essentially, it is an antispasmodic, and appears to block the calcium channels in vascular smooth muscle.
However, this root in its natural state also contains pyrrolizidin alkaloids, which are hepatic toxins and potential carcinogens. Fortunately, there is a toxin-free formulation of this valuable herbal medicine. Weber and Weber, a German botanical medicine manufacturer, entered the US market several years ago with a proprietary Butterbur extract called Petadolex™. The company uses a patented process to remove these toxins, and Dr. Mauskop stressed that Petadolex is the only Butterbur preparation that should be used clinically.
The company has funded several clinical studies of Petadolex. The most recent was a large multicenter trial in which Dr. Mauskop participated. The study involved 245 migraine patients divided into three groups; placebo, Petadolex, 50 mg twice daily, and Petadolex, 75 mg three times daily. Over a four-month period, migraine attack frequency was reduced by a mean of 48% for the 75 mg group, 36% for the 50 mg group, and 26% for the placebo group.
Sixty-eight percent of those taking the higher dose of Petadolex had a 50% or greater reduction in headache frequency, compared with 49% in the placebo arm. As in earlier trials, there were no significant adverse effects associated with the Butterbur extract; the only treatment associated side effects were mild gastrointestinal disturbances such as burping (Lipton RB, et al. Neurology 2004: 63: 2240–2244). The authors concluded that Butterbur extract, 75 mg twice daily, is more effective than placebo and is well tolerated as a preventive therapy for migraine. However, lower doses do not appear to be as effective.
The main drawback to Petadolex is its cost. The product costs approximately $40 per month, which is comparable to the cost of prescription migraine medications.
In considering how to approach migraine patients, keep in mind that this is a complex, multifactorial condition with many triggers and mediating influences. No single treatment, whether pharmaceutical, botanical or nutritional has a greater than 60% efficacy, and this includes the most advanced medications like Imitrex. The key to preventing migraines is through comprehensive lifestyle changes and combination therapies.
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In an effort to bring together nutrients and botanicals with which he has had good clinical success, Dr. Mauskop recently helped to formulate a product called MigreLief (Akeso Health Sciences—www.migrelief.com), a fixed-dose combination therapy containing 360 mg magnesium, 400 mg riboflavin, and 100 mg of Puracol, a proprietary preparation of the Feverfew plant that is especially high in parthenolides. The dose ratio reflects the doses of each individual component that has been shown effective in clinical trials. This combination can dramatically reduce the frequency of migraine attacks, said Dr. Mauskop.
MigreLief is based on the clinical realization that individual patients will likely obtain greater or lesser benefit from each individual ingredient. By combining all three into a simple, low-cost product, patients are spared the need and the cost of three single-ingredient products. The fixed dose combination also means that patients need only take two tablets daily, rather than 6–8 tablets to obtain comparable levels from individual riboflavin, magnesium and feverfew products.
UPDATE, Fall 2005: MigreLief is no longer available under the MigraHealth label.
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