Feverfew is a member of the daisy family. It has been used in traditional medicine as far back as the first century for inflammatory conditions and to prevent the occurrence of migraine headaches. Traditionally consumed as whole fresh or dried leaves or as a tea, feverfew is available in supplemental form as an encapsulated powder standardized for the potential active ingredient known as par-thenolide. Although many feverfew extracts are standardized to parthenolide, the predominant sesquiterpene lactone, it is unknown whether parthenolide is necessary for the antimigraine effect for which feverfew supplements are so popular and effective, feverfew extracts standardized for parthenolide, as well as extracts not standardized, have been shown effective for reducing the occurrence of migraine headaches and for reducing the severity and range of side effects of migraine episodes thai do occur.

Migraines can cause excruciating pain and often completely incapacitate the sufferer, feverfew is relatively inexpensive and safe and has shown clear effects in reducing the number of migraine attacks in some people. Although some studies suggest that it is important to look for a supplement thai is standardized to at least 0.2% parthenolide (Knight, 1995), may be only one of several active constituents that deliver the ant migraine effects associated with feverfew.

Although feverfew’s mechanism of action is not yet fully understood, researchers have suggested several possibilities. Uiological and plant studies have revealed that the plant extracts of feverfew have been found to exhibit inhibitory effects on the release of 5-hydroxy-lryptamine (serotonin) from blood platelets and polymorphonuclear leukocytes; platelet aggregation and secretion; prostaglandin, thromboxane, and leukotriene production; antimicrobial activity; and an antithrombotic potential (Awang, 1997). The parthenolide in feverfew causes most of this activity. Specifically, parthenolide inhibits thromboxane B2 and leukotriene B4 in human leukocytes, producing an anti-inflammatory effect (Sumner et al., 1992). These properties also consist of inhibition of the enzyme phospholipase A2, which facilitates the release of arachidonic acid from the phospholipid cellular membrane (Heptinstall, 19SS). Parthenolide has also been shown to inhibit expression of inducible cyclo-oxygenase-2 and proinflammatory cytokines in macrophages and may interfere with contractile and relaxant mechanisms in blood vessels (Knight, 1995; Sumner et al., 1992).

Laboratory and clinical studies have shown an effect of feverfew leaves and extracts on inflammatory processes, including arachidonate metabolism and platelet function (Sumner et al., 1992). Feverfew extracts produce a clear inhibition of histarnine release and reduce production of prostaglandins, which may explain some of the antiinflammatory activities of feverfew (Knight, 1995). Parthenolide and related sesquiterp-enes may interfere with serotonin release from platelets (which has been suggested as a primary cause of migraines), suggesting a mechanism by which feverfew functions (o inhibit smooth muscle cell contraction and prevent migraines from occurring (Vogler et al., 199S).

Several clinical trials have assessed the use of feverfew preparations to prevent migraine headaches. A randomized, double-blind, placebo-controlled, crossover study evaluated the use of dried feverfew leaves in 72 patients who had experienced, over more than two years, classic or common migraine headaches, with at least one attack monthly (Murphy et al., 1988). After a 1-month, single-blind, placebo run-in phase, patients were randomized to placebo or feverfew groups. These patients received one capsule daily for 4 months and then were crossed over to the other treatment group. Results of the study illustrated that feverfew capsules (70-114 mg) decreased the number of attacks by 24% and decreased symptoms of nausea and vomiting compared with the placebo (Johnson et al., 1935).

A similar 4-month randomized, double-blind, placebo-controlled, crossover trial was conducted to assess the effectiveness of feverfew as a prophylactic therapy for migraines in 57 patients who had never taken feverfew before. Patients who attended an outpatient pain clinic were selected at random and divided into two groups that completed three phases of the study. Phase 1 was an open-label run-in phase in which both groups received 100 mg (two capsules) daily of encapsulated, dried, powdered feverfew leaves for 2 months. In phases 2 and 3, the study groups were randomized to receive 100 mg of feverfew/day or a matching placebo for 1 month and then cross over for another month. No washout period occurred between the crossover phases. Patients completed a questionnaire that included parameters such as the number of years suffering, frequency and duration of migraine attacks, pain intensity, and symptoms accompanying migraine attacks, such as nausea, vomiting, and sensitivity to light and noise. A numerical self-assessment pain scale was used, in which 0 represented no pain and 10 represented severe pain. The linked symptoms were estimated by the patients on a numerical analog scale in which 0 represented no pain and 4 represented severe

pain. The results demonstrated a significant reduction in pain intensity, nausea, vomiting, and sensitivity to light and noise compared with the placebo. These results provide convincing evidence that feverfew may be used prophylactkally for migraine attacks (Murphy et al., 1988, Pittler and Vogler, 2000).

Another randomized, double-blind, placebo-controlled trial evaluated 17 patients who chronically ate feverfew leaves for self-prophylaxis of migraines. Patients were randomized to receive either 50 mg/day of feverfew or a matching placebo. All patients were then instructed to take two capsules (25 nig each) ever)’ morning with food for six periods of 4 weeks. They were also instructed to treat acute migraine attacks with soluble aspirin. Patients recorded and graded various visual symptoms, nausea, vomiting, and headache on dietary cards pro-vided for them. The results showed that the placebo group experienced a significant increase in the frequency and severity of headaches, nausea, and vomiting. Patients given feverfew, however, showed no change in the frequency or severity of headaches, suggesting that feverfew may be taken prophylactic-ally to prevent attacks of migraines (Palevitch et al., 1997).

In subjects consuming SO mg/day of feverfew for ] month, 25% experienced a reduction in the number of migraine attacks and a clear reduction in the occurrence of the nausea and vomiting that often accompany migraine attacks (Palevitch etal., 1997). In another study, subjects consumed 100 mg/day of dried feverfew leaves (standardized to contain 0.2 mg of parthenolide) and showed reduced migraine intensity after 60 days (Prusinski et al., 1999).

Several side effects have been noted in clinical studies, including mouth ulcers (when the leaves are chewed), gastrointestinal discomfort, and dry mouth (Johnson et al., 19S5; Murphy et al., 1988). Women who are pregnant or lactating should avoid consuming feverfew, as should people with known sensitivities to other members of the same plant family, such as ragweed and chamomile. Long-term use may be associated with an anticoagulant effect, so feverfew should probably not be used in conjunction with other blood-thinning agents (Sriramarao and Rao, 1993).

Most studies have used dosages ranging from 25 mg to 125 mg of feverfew leaf per day, many with a parthenolide content of at least 0.2 mg (0.2-0.9%). Supplements should be taken prophylactlcally to prevent the occurrence of migraines, rather than in an attempt to relieve a migraine attack once it occurs. A period of 1-2 months of taking feverfew is recommended before achieving the therapeutic effect. Some alternative practitioners recommend an occasional break from treatment, but be aware that a “feverfew rebound” syndrome has been reported in which tension headaches follow the abrupt discontinuance of feverfew consumption (Vogler et al., 1998).

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