Evidence supports the use of dried feverfew leaf for migraine prophylaxis. It is benign, although some users experience mouth ulcers or gastrointestinal symptoms.
[LFODPKM ] Letter Key
Latin Name
Tanacetum parthenium (L.) Schulz Bip/formerly Chrysanthemum parthenium (L.) Bernh.
Family
Asteraceae/Compositae
Other Common Names
Altamisa, Santa Maria
Description
- A perennial herb, feverfew is a member of the chrysanthemum family and has small, daisy-like flowers.
Part Used
Leaf, aerial parts
Known Active Constituents
- Sesquiterpene lactones, especially germacranolides (including parthenolide and 3-beta hydroxyparthenolide), sesquiterpenes, monoterpenes, polyacetylene compounds, and flavonoids (1). Melatonin is also present (2.45 µg/g in fresh green leaf; 2.19 µg/g in freeze-dried green leaf) (2).
- Flowerheads contain as much as four times the parthenolide of leaves (3). Parthenolide levels in the leaf also increase up to fourfold after the plant flowers (1). Parthenolide in dried leaves may exceed 1% or may be entirely absent (4).
- Although parthenolide is commonly thought to be the most active compound, there is no evidence that parthenolide is active in preventing or treating migraine; other constituents are likely to be responsible for antimigraine activity (2).
Mechanism/Pharmacokinetics
- The mechanism of action is unknown, and no information on pharmacokinetics is available.
- Aqueous feverfew extracts inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen, or thrombin but not arachidonic acid. In platelets, phospholipase A2 is inhibited, but thromboxane B2 production is not affected. Most studies show no effect of feverfew extracts on cyclooxygenase production; effects on the arachidonic acid pathway are more likely (3).
[Outline]
[CAO ] Letter Key
Clinical Trials
- Migraine prophylaxis
- A systematic review of six randomized, double-blind, placebo-controlled trials (four crossover) of feverfew for migraine prophylaxis found that four of six trials showed a positive effect (5). These trials are summarized briefly.
- In a randomized, double-blind crossover trial, 72 migraine patients (59 completed) were given placebo or dried whole feverfew leaf (82 mg, containing 0.62% parthenolide) for 4 months and then were crossed over to the other group (6). While receiving feverfew, patients had fewer and less severe migraines, with less vomiting; the duration of individual attacks remained the same.
- In a crossover trial, 57 participants took feverfew (100 mg powdered leaf, containing 0.2% parthenolide) daily for 2 months, and then the participants were randomized to continued feverfew or placebo for 1 month, after which they were crossed over to the other group for one month (7). During the initial phase, feverfew decreased pain intensity compared with baseline. During the placebo-controlled crossover, pain intensity, severity of nausea and vomiting, and sensitivity to noise and light were significantly less during the feverfew phase compared with the placebo phase.
- A trial in 147 subjects, published only in abstract form, tested placebo against three daily doses of feverfew (6.25 mg, 18.75 mg, and 56.25 mg/day of a super-critical carbon dioxide feverfew leaf extract ×3 months) on frequency of migraine and found a significant reduction in attacks; the 18.75-mg dose appeared superior to the other two doses (8).
- Another trial tested the effects of feverfew withdrawal in regular users. In this study, 17 participants with migraine who had been using feverfew leaf daily for 2 to 4 years were randomized to capsules containing 50 mg of dried feverfew per day or placebo for 6 months (9). Patients receiving feverfew showed no change in migraine incidence; those receiving placebo had a significant increase in frequency and severity of migraines, nausea, and vomiting. Two patients whose migraines had been in complete remission while self-treated with feverfew suffered severe migraines while on placebo and withdrew from the study to resume feverfew treatment. "Post-feverfew syndrome" (rebound of migraine symptoms, anxiety, sleep difficulties, and muscle and joint stiffness) occurred in 10% of regular feverfew users who were switched to placebo.
- A crossover trial in 50 patients (44 completed) tested the effect of feverfew capsules (143 mg/day containing 0.35% parthenolide, in a 90% ethanol extract) for 4 months on severity of migraines and number of work days lost; no change was seen in either measure (10). (An alcohol extract may be less effective than dried leaves.)
- A crossover study tested the effect of 100 mg feverfew/day for 2 months in 20 participants on serotonin uptake and platelet activity, as well as migraines, and found no effect (11). This study is reported only as an abstract of a poster presentation, with no information as to the nature of the feverfew preparation or details about outcome measures (12).
- Rheumatoid arthritis
- In a double-blind placebo-controlled trial, 41 female patients with rheumatoid arthritis inadequately controlled with nonsteroidal antiinflammatory drugs (NSAIDs) were given either one capsule of feverfew (70 to 86 g) or placebo for 6 weeks (13). The addition of feverfew to NSAID treatment did not make a significant difference in functional capacity, stiffness, pain, grip strength, sedimentation rate, rheumatoid factor, or immunoglobulins.
- Platelet aggregation
- Platelets from 10 participants who had taken feverfew for 3.5 to 8 years were subjected to platelet aggregation studies and found to be normal (14). ADP and thrombin-induced aggregation was similar to four controls (former feverfew users who had discontinued the herb at least 6 months before the test); a few feverfew users (number not given) had attenuated response to serotonin and a prostaglandin (PG) endoperoxide.
Animal/In Vitro
- Feverfew extract and parthenolide inhibit mitogen-induced proliferation of human peripheral blood mononuclear cells in vitro; however, cytotoxicity occurs after incubation for 48 to 72 hours (3). Feverfew extract, administered intraperitoneally, inhibits collagen-induced bronchoconstriction in guinea pigs (possibly because of phospholipase A2 inhibition) (3).
- Antifungal and antimicrobial effects of parthenolide, essential oil, and eudesmanolides isolated from feverfew have been demonstrated in vitro (3).
Other Claimed Benefits/Actions
- Tinnitus
- Vertigo
- Arthritis
- Fever
- Menstrual disorders
- Labor difficulties
- Stomachache
- Toothache
- Insect bites
[Outline]
Q: Does feverfew work for treatment of acute migraine?
A: No studies have been done on this, but some migraine patients report that taking a dose of extract or eating a few leaves of feverfew during the prodromal phase of a migraine can avert a headache. Some migraineurs grow the plant on a windowsill to have ready access to the fresh leaves.
Q: How common are aphthous ulcers, and do they still occur if the herb is taken in capsules?
A: Even capsules of dried feverfew can cause aphthous ulcers, apparently through a systemic effect (2). In a survey of 300 feverfew users, aphthous ulcers from chewing fresh leaves were reported by 11.3% of users, and 6.5% reported digestive disturbances (9).
Q: Does it matter what kind of feverfew is used?
A: There are several controversies about feverfew quality. Sesquiterpene lactones are regarded as the active constituents in feverfew, and parthenolide is the main sesquiterpene lactone in European feverfew. North American feverfew (and feverfew grown in some parts of Europe) may not contain any parthenolide, although other sesquiterpene lactones are present (15). Even if parthenolide is only a marker compound, preparations standardized for parthenolide are available and I think preferable, if only because all successful studies on the herb so far have used parthenolide-containing European feverfew. Even if parthenolide is only a marker compound, its presence provides some assurance of similarity.
Another controversy centers around whether only strains of feverfew that have a single row of florets are effective; there is no evidence to support this claim (2). Some think fresh leaves are most effective; given the variation of (unknown active) compounds in variants, however, dried preparations are a reasonable choice. Another quality claim is that freeze-dried leaves are more effective than air-dried leaves, but there is no evidence for that. Prolonged storage of dried feverfew does decrease parthenolide content; at room temperature, parthenolide decreases 20% in 1 year and 50% in 2 years (2).