The Leaf that Relieves
A New Way to Deal with Migraine Headaches

The art of life is the art of avoiding pain; and he is the best pilot who steers clearest of the rocks and shoals with which it is beset.

- Thomas Jefferson

ho could argue with Jefferson's statement? Surely humans have always done their best to avoid pain - especially in the head. From the prehistoric caveman trying to avoid getting bashed with a club to the modern businessman struggling to fill out his tax returns without having his head explode, people hate heads that hurt. Since time immemorial, they have tried all kinds of remedies for the garden-variety headache and its sadistic cousin, the migraine.

 
Tanacetum parthenium

One remedy that has long been known to work for preventing migraines is feverfew (Tanacetum parthenium), a strongly aromatic perennial herb that grows throughout Europe, Australia, and North America. Also known by the names featherfew, featherfoil, febrifuge, and others, it is related to daisies and sunflowers. The leaves of this plant contain a potent mix of chemicals, called sesquiterpene lactones, whose physiological mechanisms of action are still far from clear to scientists. But to people with a propensity to migraines, that hardly matters, as long as those chemicals can hold the cranial demons at bay.

As is true of many herbal products that have stood the test of long use as folk remedies before gaining scientific vindication through advanced methods of laboratory and clinical evaluation, feverfew has been used medicinally for thousands of years but has only recently come under the microscope of modern medicine. After having been in use from ancient times through the Middle Ages, it seems to have fallen into relative obscurity for several centuries, until it was "rediscovered" in Great Britain in the 1970s. A resurgence of interest in feverfew occurred there when stories began circulating about its astonishing ability to ward off migraines. This led to a spate of scientific studies of its effects.1

The results, as we will see below, are encouraging, particularly as they are supported by the "gold standard" of clinical trials: the randomized, placebo-controlled, double-blind study. It is only by means of such studies that the bias inherent in any anecdotal evidence of the usefulness of a product can be eliminated and replaced by the impartiality of objective facts.

THE NATURE OF HEADACHES
Virtually everyone gets a headache now and then - we all know what they feel like. Most headaches are relatively benign and are gone within a few hours or overnight - they're aggravating and painful, but no big deal, really. One gets by with aspirin and some rest. Others, however, can last for days, months, or even years. They can be barely noticeable or fierce and incapacitating, and in some people they are chronic: they come and go more or less regularly - and often very frequently - over a lifetime.

Any unusually sudden or severe headache, or a headache that is accompanied by unaccustomed other symptoms that do not resemble a cold or the flu, for example, could be a sign of a serious disorder, such as stroke, meningitis, brain tumor, glaucoma, or severe dehydration. These require prompt or immediate medical attention.

About 90% of headaches are tension headaches, which affect both sexes equally. Perhaps they are the result of muscles getting tight because of psychological stress or poor posture - no one really knows. Headaches can also be caused, however, by other factors, such as exposure to loud noises or noxious chemicals (people vary greatly in what is noxious to them), or by something as simple as going too long without eating. And, of course, politicians.

A particularly brutal affliction is the cluster headache, a severe, recurring headache believed to be associated with the release of histamine and characterized by excruciating pain that begins around or behind one eye, with watering of the eye and a runny nose on that side of the head. These headaches, which afflict only one side of the head during any given episode, tend to occur in clusters of one to three a day over a period of weeks or months (usually all on the same side), followed by periods of remission. They occur most often in young men who smoke. There is no known cause or cure, but not smoking is a good start.


Migraines afflict about 18% of
women and 6% of men, and they
can strike children as well. 

WHAT IS A MIGRAINE?
Migraines are a different breed entirely (although the categories tend to overlap, and determination is sometimes difficult). Typically more painful than tension headaches, but usually not as painful as cluster headaches, they can present a uniquely awful spectrum of symptoms. Most people never get them, but those who do attest to their debilitating nature. The severe, throbbing pain usually starts on just one side of the head (the word migraine comes from the Greek hemikrania, meaning half the skull) and spreads to the other side, often punctuated by jabs of sharp, shooting pain. Migraines can be accompanied by nausea and vomiting and usually last for one day, although they can last for several days. If you've never had one, count your blessings.

In about 10% of migraines, the attack itself is preceded by the infamous "aura." For example, one may have a weird sensation of flashing lights, typically in a herringbone or some other geometric pattern. There can also be a heightened sensitivity to light or sound or touch, blurred vision, partial blindness, difficulty in speaking, vertigo, weakness on one side of the body, or numbness or tingling on one side. When the aura occurs, the victim is forewarned of the pain and suffering to come, usually within half an hour.

MIGRAINES AFFECT MORE WOMEN THAN MEN
Migraines afflict about 18% of women and 6% of men, and they can strike children as well. They tend to occur most often between the ages of 20 and 35, diminishing with age, and they tend to run in families, meaning that there can be a genetic predisposition. In those who get them, migraines can occur anywhere from a few in a lifetime to several per week. Remissions are common during pregnancy and menopause. They can be brought on by a wide variety of factors, among which, for women, are hormonal swings associated with the menstrual cycle or the use of birth-control pills. (PMS is bad enough without the added insult of migraine headaches.)

WHAT TRIGGERS MIGRAINES
Among the many factors that can trigger migraines in both men and women are stress, fatigue, excessive or insufficient sleep, certain foods, bright lights, loud noises, strong odors, cigarette smoke, changes in the weather, dental pain, liver problems, and fluctuations in blood-sugar levels.

The foods most commonly implicated are alcohol (especially in the form of red wine), peanuts, aged cheese, the artificial sweetener aspartame, caffeine (in excess), and fermented foods, but many others are also known to trigger migraines. Different people are sensitive to different foods. Chocolate has long been thought to be a trigger for most migraineurs, as the victims are sometimes called, but new studies have now cast doubt on this - some good news (perhaps), for a change.

What do all the factors listed above have in common? Nobody knows, and the cause of migraines is still largely a mystery. It was long thought that the pain was caused by a rapid dilation of the cranial arteries following their abnormal constriction for some reason, but this vascular mechanism is now in doubt. Newer evidence suggests a neurological mechanism, having to do with abnormalities of the neurotransmitter serotonin or with the serotonin receptors on brain cells, but there is conflicting evidence on that too, and there is no shortage of unproved theories. Suffice it to say that the cause or causes of migraines are unclear, controversial, and probably complex.

FEVERFEW WORKS FOR MIGRAINES
Although it is clearly important from a scientific viewpoint to understand the true nature of migraine, it is sufficient from a therapeutic viewpoint to be able to answer the question: What works in preventing migraines or relieving them? One answer is feverfew. Whether we ever understand why it works is not as important as that it works. We will get to the evidence for that shortly.

CONVENTIONAL TREATMENTS: EXCESSIVE SIDE EFFECTS
There is no cure for tension headaches, but the symptoms can usually be relieved with nonprescription drugs such as aspirin, acetaminophen, ibuprofen, or naproxen. These are all NSAIDs (nonsteroidal anti-inflammatory drugs), which are notorious for long-term side effects (they cause about 200,000 hospitalizations a year in the United States, often from stomach bleeding) but are relatively safe for short-term, episodic use. They are ineffective against cluster headaches, which can, however, be treated with various prescription drugs and sometimes with oxygen inhalation.

As for migraines, the best prevention is avoidance of your personal triggering factors, but there is also a wide variety of powerful prescription drugs that are effective for prevention or therapy, or both. Being prescription drugs, of course, they tend to be expensive and to be burdened with significant, often serious, side effects. Less expensive and typically less effective, but with fewer and less severe short-term side effects, are the NSAIDs and caffeine, which can also help. In the long term, however, NSAIDs can be quite a different story and far less benign.

FEVERFEW WORKS FOR MIGRAINES
Among the various natural alternatives to drugs that are used for tension headaches are white willow bark and meadowsweet, both of which contain salicin, a chemical precursor of aspirin that does not cause stomach problems, and peppermint oil, which is massaged into the forehead and temples. These and some other products can relieve the symptoms of headache. Unfortunately, much of the support for these alternatives is anecdotal and is not well documented in the scientific literature.

For migraines, natural alternatives to drugs are useful primarily in preventing the affliction, and secondarily in relieving its symptoms. Of course, prevention is preferable to therapy in any case. Among the remedies that have been widely used are feverfew, magnesium, 5-HTP, riboflavin (vitamin B2), pantothenic acid (formerly called vitamin B5), pyridoxine (vitamin B6), vitamin C, and omega-3 fatty acids. These alternatives have, for the most part, been the subjects of well-designed scientific studies.

The current role of natural alternatives in dealing with migraine is stated clearly in a book recently published by the very conservative and highly respected Reader's Digest Association:2 "For the estimated 10% of the population who suffer from migraines, there is good news. A growing body of research suggests that certain supplements may be as effective as - or even superior to - conventional medicine in the prevention and treatment of these debilitating headaches." The book goes on to discuss the role of feverfew and other supplements that can be used for migraine.

FEVERFEW FOR PREVENTION
For preventing migraines, feverfew is widely used in Europe and has been approved by health authorities in Canada. When taken for several months, it can reduce the frequency of migraines, and it can often reduce their severity when they do occur. Evidence for the effectiveness of feverfew has been accumulating since serious scientific studies on it began in the early 1980s.


The authors of the systematic review
stated that the clinical data they
evaluated favor the conclusion
that feverfew is effective in
preventing migraine.

In animal experiments, feverfew impedes platelet aggregation, the clumping together of the tiny, disklike components of blood plasma that promote clotting. It does the same for the synthesis of prostaglandins, hormonelike substances that mediate a wide variety of important physiological functions, such as metabolism, smooth muscle activity, and nerve transmission. And it does the same for the release of histamine, an amino acid that is released from cells of the immune system as part of an allergic reaction. Finally, it reduces the release of the neurotransmitter serotonin from platelets and polymorphonuclear leukocytes, a type of white blood cell.3

OTHER USES OF FEVERFEW
Feverfew is used primarily for migraine, arthritis, rheumatic diseases, and allergies. In folk medicine, it has long been used for cramps, as a tonic, a stimulant, a digestive aid, a blood purifier, and for gynecological disorders and intestinal parasites. Externally it has been used as a wash for inflammation and wounds.3 Conspicuous by its absence from this list is - fever. Many reference works do, however, also cite fever as one of the ailments for which feverfew is believed to be effective. Perhaps it is, but that is of no concern with regard to headaches, which are not accompanied by fever unless they are symptoms of some other illnesses, such as flu.

THE SCIENCE BEHIND FEVERFEW
The first systematic review of the scientific literature on the clinical effectiveness of feverfew for the prevention of migraine was published in 1998 in the journal Cephalalgia (Greek for "pain in the head"; no, we don't know what a certain other Greek term would be, so don't ask).4 The authors' main criteria for including published studies in the review were (1) that only randomized, placebo-controlled, double-blind clinical trials would be considered, and (2) that they must have been performed on feverfew alone, not in combination with any other substance. The first criterion tends to ensure objectivity; the second prevents ambiguity.

The authors of the review analyzed five studies, published between 1985 and 1997, that met their criteria. Although the results were mixed, probably owing in part to different experimental protocols in the studies in question, they were, overall, very encouraging. Of the five studies, three showed a positive effect of feverfew compared with placebo, and two did not. It was speculated that a possible reason for the lack of effect in at least one of these two was that the extract used had been weak owing to inadequate preparation or to inadvertent degradation during the preparation.

In one of the studies in question, 72 patients aged 24 to 72 received either feverfew or placebo for four months after a one-month placebo run-in period.5 Then all the patients were crossed over to the other group for the second four-month period, so that each patient became his or her own control, in effect (each feverfew receiver switched to placebo, and vice versa). Treatment with feverfew resulted in a 24% reduction in the number of migraine attacks, which tended to be less severe when they did occur. There was no significant reduction in their duration, but there was a significant reduction in nausea and vomiting.

All in all, 67% of the total of 216 patients included in the five studies clearly benefited from taking feverfew, in doses ranging from 50 to 143 mg per day, over periods of from one to six months.4 The benefits in most cases included reduced frequency and severity of migraine attacks, reduced visual disturbances, and reduced incidence of nausea and vomiting.

The authors of one of the five studies in question had not evaluated these factors, but had instead measured the effect of feverfew on serotonin uptake and platelet activity in 20 patients. Since no effect on either of these functions was observed, the authors concluded, without further data, that feverfew was ineffective against migraine. This presupposed that at least one of the two functions in question is related to the cause or symptoms of migraine, a supposition that is most probably true but that remains unproved.


Treatment with feverfew resulted
in a significant reduction in
the number and severity
of migraine attacks.

The authors of the systematic review stated that the clinical data they evaluated favor the conclusion that feverfew is effective in preventing migraine, but they also advocate further research to confirm this finding - always a good recommendation.

Since the compound in feverfew believed to be chiefly responsible for migraine relief is parthenolide, it is a good idea, to be compatible with the research, to consume an extract containing at least 600 mcg of this constituent per day (for example, 150 mg standardized to contain 0.4% of parthenolide, or 50 mg standardized to contain 1.2% of parthenolide). It should be noted that some feverfew preparations on the market have been found to contain virtually no parthenolide at all. On the other hand, there are other constituents of feverfew thought to be active, so it is wise as well to consume from 200 to 300 mg of the ground, capsulized, leaf per day. Some offerings on the market have a highly concentrated extract but no leaf. As always, it pays to buy only from reputable manufacturers and to read the product label carefully to make sure you know what you're getting. Caveat emptor.

OTHER BENEFICIAL NUTRIENTS FOR MIGRAINE
As noted above, other natural nutritional supplements have long been used for migraine, with varying modes and degrees of efficacy. Let us now look at some of these.

5-HTP
A characteristic of those who are prone to migraine is low levels of serotonin and of endorphins, the body's natural painkillers. The well-known link between low serotonin and headaches is the basis for many of the prescription drugs used for the prevention and treatment of migraine, which is sometimes called a "serotonin-deficiency syndrome." In addition to being expensive, these drugs tend to have severe side effects, so a natural alternative is highly preferable. That alternative is 5-HTP (5-hydroxytryptophan), a safe chemical precursor to serotonin that is known to be effective in combating migraine.

The effects of both 5-HTP and the prescription drugs are extremely complex because of the complexity of the serotonergic system itself. There are different kinds of serotonin receptors; some are involved in preventing migraines, whereas others are involved in triggering them. How it all works out depends on the interplay of many factors. Suffice it to say that 5-HTP stimulates the production of both serotonin and endorphins, and it works. In the words of two prominent experts in natural medicine, "5-HTP is at least as effective as other pharmacological agents used to prevent migraine headaches, and it is certainly much safer and better tolerated."6

Studies have shown that 200 mg of 5-HTP is effective for migraine.7 And according to researchers at the University of Milan's pain research and treatment unit, as many as 93.5% of people with chronic daily headaches gain relief from 5-HTP.8

VITAMIN B2 (Riboflavin)
Riboflavin, a B-complex vitamin discovered in 1879 but not identified until 1933, performs a host of vital and highly varied functions in the human body. Among these is the maintenance of adequate biochemical energy supplies in the mitochondria of brain cells. It is believed that migraine sufferers may have reduced energy reserves in the brain, so it is reasonable to suppose that supplementation with riboflavin may be helpful in preventing attacks.


According to researchers at the
University of Milan's pain research
and treatment unit, as many
as 93.5% of people with chronic
daily headaches gain relief
from 5-HTP.

Indeed, it has been found in one randomized, placebo-controlled trial that large doses of riboflavin (400 mg per day) are effective in reducing the frequency of migraines and the number of headache days.9 The authors of this study concluded that "Because of its high efficacy, excellent tolerability, and low cost, riboflavin is an interesting option for migraine prophylaxis . . . ."

VITAMIN B6 (Pyridoxine)
Pyridoxine, another B-complex vitamin, is probably involved in more bodily functions - over 100 - than any other vitamin or mineral. It is surely the champion workhorse of nutrients. In its primary role as a coenzyme (a substance that acts in concert with enzymes to catalyze cellular reactions), it helps the body to make red blood cells, proteins, and brain neurotransmitters such as serotonin (see 5-HTP section above), and to release stored energy from cells, among many other tasks. It is also believed to play a role in the prevention and amelioration of many diseases. One study showed that pyridoxine can help increase the efficiency of converting 5-HTP to serotonin in the brain by as much as 20%.10

MAGNESIUM
Yet another workhorse that performs many tasks in the human body is magnesium, a mineral in which many people are deficient, especially those whose diets are heavy on processed foods. Magnesium plays a vital role in cardiovascular function, among others, and even a moderate deficiency can significantly increase the risk of heart disease and diabetes. It is also known to affect certain processes that are believed to be important in the pathogenesis of migraine.

Interestingly, it is known that many migraine sufferers have low tissue levels of magnesium (even if their serum levels are normal), and it may be that this mineral plays a role in establishing a threshold for attacks. In a rigorously designed study on 81 migraine patients aged 18 to 65, it was found that magnesium (600 mg per day) reduced the frequency of attacks by 42% vs. 16% in the controls, but it did not significantly reduce the duration or severity of attacks when they did occur.11 A number of other studies also attest to the value of magnesium for migraine.12-15

GINGER ROOT
Since ancient times, ginger (Zingiber officinale) has been renowned for its stomach-settling properties, especially its remarkable ability to combat nausea and vomiting.16 It is helpful to pregnant women and postoperative patients in this regard, and it is even effective in combating seasickness, a malady in which feelings of nausea can take on supernatural dimensions. Although there are no clinical studies indicating its effectiveness against the nausea of migraine, it is reasonable to suppose that it may help there too. It has no known side effects.

GINKGO
The extract of ginkgo leaves (Ginkgo biloba) has been used for millennia to enhance circulatory and central nervous system functions. Ginkgo is widely used today to help with age-related memory loss and to relieve anxiety and depression, among other things. Two small clinical trials with ginkgo extract recently conducted in France suggest that this herb may also be beneficial in migraine patients.17

PUTTING IT ALL TOGETHER
The picture that emerges from all this is that migraine headaches can be prevented or alleviated to a significant degree through the use of one or more safe, natural, inexpensive nutritional supplements. Moreover, some of these supplements are at least as effective as prescription drugs, and they have almost no side effects.

Although the origins and mechanisms of migraine are not fully understood, there is no question that the scientific literature is telling us: it is possible to alleviate significantly many aspects of this painful scourge. Thomas Jefferson would be pleased.

References

  1. Groenewegen WA, Knight DW, Heptinstall S. Progress in the medicinal chemistry of the herb feverfew. Prog Med Chem 1992;29:217-38.
  2. Kalyn W, ed. The Healing Power of Vitamins, Minerals, and Herbs. Reader's Digest Association, Inc., Pleasantville, N Y, 1999, p. 170.
  3. Fleming T, ed. PDR for Herbal Medicines. Medical Economics Company, Montvale, NJ, 1998, pp. 1171-3.
  4. Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalalgia 1998;18:704-8.
  5. Murphy JJ, Heptinstall S, Mitchell JRA. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. The Lancet 1988 July 23;ii:189-92.
  6. Murray M, Pizzorno J. Encyclopedia of Natural Medicine, rev. 2nd ed. Prima Health, Rocklin, CA, 1998, p. 659.
  7. Sicuteri F. The ingestion of serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) improves migraine headache. Headache 1973 Apr;13(1):19-22.
  8. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985 Jul-Sep;29(3):239-48.
  9. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998 Feb;50(2):466-70.
  10. Hartvig P, Lindner KJ, Bjurling P, Laengstrom B, Tedroff J. Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography. J Neural Transm Gen Sect 1995;102(2):91-7.
  11. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996 Jun;16(4):257-63.
  12. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci 1998;5(1):24-7.
  13. Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, Taneri Z, Soyka D, Gobel H, Fischer M. Magnesium in the prophylaxis of migraine - a double-blind placebo-controlled study. Cephalalgia 1996 Oct;16(6):436-40.
  14. Taubert K. Magnesium in migraine. Results of a multicenter pilot study. Fortschr Med 1994 Aug 30;112(24):328-30.
  15. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991 May;31(5):298-301.
  16. Langner E, Greifenberg S, Gruenwald J. Ginger: history and use. Adv Ther 1998 Jan-Feb;15(1):25-44.
  17. DeFeudis FV. Ginkgo biloba Extract (EGb761): Pharmacological Activities and Clinical Applications. Elsevier, Paris, 1991, p. 142.

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