Research

Research has been conducted to elucidate the mechanisms of Feverfew actions. Parthenolide, and perhaps other sesquiterpene lactones, have been shown to reduce the secretory activity of blood platelets and white blood cells in laboratory studies, providing a possible basis for Feverfew's effectiveness in migraine, arthritis, and psoriasis. Abnormal platelet behavior has been implicated as a possible explanation for the development of migraines. Platelets release the hormone serotonin (also referred to as 5-Hydroxy Triptophan) during a migraine attack. Serotonin constricts blood vessels among other actions. Serotonin antagonists have been suggested for use in a supportive role in migraine prevention. Feverfew has been shown (in vitro) to inhibit serotonin release from platelets. While proposed as a possible mechanism of activity, the bearings of these laboratory observations on the efficacy of Feverfew is presently unclear (Murphy, Heptinstall and Mitchell 1988).

Headache / Migraine

In the past decade, interest in clinical studies on Feverfew began with the wife of the chief medical officer of Britain's National Coal Board who suffered chronic migraines. A miner heard about her problem and told her he had also been a longtime sufferer - until he started chewing a few feverfew leaves every day. The woman tried the herb, and noticed an immediate improvement, and after 14 months was free of her searing headaches. Her husband brought his wife's experience to the attention of Dr. E. Stewart Johnson of the City of London Migraine Clinic. Dr. Johnson gave feverfew leaves to ten of his patients. Three pronounced themselves cured, and the other seven reported significant improvement. Dr. Johnson then gave feverfew to 270 of his migraine patients, then surveyed their experiences. Seventy percent reported significant relief - and for many, standard medical treatment had provided no relief at all. A preliminary broad-based clinical study by E. Stewart Johnson in the UK was conducted to evaluate the effect of Feverfew on 300 migraine suffers who had been taking Feverfew for about 2.5 years. According to the report published in the British medical publication Mims Magazine, 70 percent of those migraine sufferers interviewed claimed to have experienced a reduction in frequency and/or pain from migraine since they had used the herb. Three small fresh leaves or one large fresh leaf were consumed each day. Many involved in the study had previously failed to respond to orthodox medical treatment (Johnson 1983, as reviewed by Warren 1986). This preliminary clinical trial stimulated additional studies. Soon after, the results of an even more rigorous experiment were published in the British medical journal Lancet. Seventy-two migraine sufferers were randomly assigned to receive either a look-alike placebo or a capsule a day of powered, freeze-dried feverfew (the equivalent of two medium-size leaves). The results were striking: Feverfew cut migraines 24 percent, and the headaches the herb-takers experienced were comparatively mild, with significantly less nausea and vomiting. A 1985 study by Johnson et al. on the efficacy of Feverfew for the prophylactic treatment of migraine was conducted at the City of London Migraine Clinic in collaboration with the Chelsea College of the University of London. The seventeen patients involved in the double-blind study had all eaten the leaves of Feverfew for at least three months before commencement of the study. Before the test, the average daily dose of fresh leaves ingested by the patients was sixty mg. per day. During the study, patients were given twenty-five mg. of freeze-dried leaf capsules. Nine of the patients received placebo, and experienced an increase in the frequency and severity of headache, nausea, and vomiting. Those who took the Feverfew experienced no change in the frequency or severity of migraine symptoms, prompting the researchers to conclude that Feverfew is efficacious in the preventative treatment of migraine (Johnson et al. 1985, Awang 1989a, Hobbs 1989). The study has been criticized on the basis of self selection, since patients had been self-medicating with Feverfew products prior to the trial. Murphy, Heptinstall and Mitchell (1988) reported on the results of a randomized, double-blind, placebo-controlled, cross-over trial of Feverfew in migraine prevention conducted at the University Hospital, Nottingham. Following a one-month single-blind run-in period, seventy-two volunteers were randomly selected to receive either one capsule of Feverfew daily or a matching placebo (dried cabbage leaves) for a four month period. One hard capsule of dried leaves, with weights ranging from 40-114 mg., was judged to correspond to two medium-sized leaves. At the completion of the study, full information was available for fifty-nine participants. According to the authors, the Feverfew treatment was clearly associated with a reduction in both frequency of migraine headaches and vomiting associated with the attacks. There was also a minor trend towards a reduction in the severity of migraines. However, there was no significant effect in limiting the duration of migraine attacks compared with the placebo. No adverse reactions were recorded in the study, though the authors note the need for longer term safety studies given the fact that lifelong treatment may be necessary for migraine sufferers. Furthermore, they note that more information on quality of commercial preparations is necessary given the varying amounts of parthenolide in commercial purported Feverfew products. In 1996, a double-blind, placebo-controlled study by a Dutch research group, tested an extract of Feverfew for the prevention of migraine headaches (de Weerdt, C J and co-workers: Phytomedicine 3, 225-230, 1996). In the crossover study, 50 patients who had never taken Feverfew before and experienced at least one migraine attack per months participated for four months of active treatment and four months of placebo. Active treatment consisted of 143 mg / day of a granulated extract of Feverfew containing 0.5 mg of parthenolide and corresponding to about 170 mg of original dried herb. The Feverfew preparation used in this study did not exert any significant preventative effect on the frequency of migraine attacks, although patients seemed to have a tendency to use fewer symptomatic drugs while they were using Feverfew. These results are not in accordance with the earlier studies cited above, and the authors suggest that this might be because the previous studies were conducted in patients who had already found Feverfew to be beneficial. Another reason provided by the authors could be due to the dried plant preparation used. or the fact that a "dried" extract was prescribed, rather than the crude leaf or a liquid extract. Despite the fact that the preparation contained a known dose of parthenolide, a suggested active component, perhaps other compounds are also important. This is often the case with herbs and is the reason that wholistic extracts often work while other preparations do not. Another point is that the dosage of 143 mg / day of crude drug is low by normal standards. Results with Feverfew would perhaps come with more certainty if a dose of 2 ml / day or more of a 1:4 wholistic extract were used. This would correspond to at least 400 mg / day of dried leaf and about 2 mg / day of parthenolide - which is four times the parthenolide intake used in the above trial. A new clinical trial (Palevitch, D. G. Earon, and R. Carasso. "Feverfew as a prophylactic treatment for migraine: Phytotherapy Research 1997, 11(7):506-511), published by an Israeli research group, provides data showing that preventive use of feverfew can profoundly reduce migraine pain and other symptoms, including vomiting, nausea, and sensitivity to noise and light. The four-month, three-phase study looked at the use of feverfew in fifty-seven patients, who were divided into two groups. This was the first clinical study in which all the participants had not previously tried feverfew, yet did exhibit symptom relief, which eliminated the possibility of bias about whether the herb works. Those who took Feverfew during the study experienced significant reduction of pain, compared to those taking a placebo. When the researchers swapped the groups' treatments, or performed a "crossover", the results also reversed, further supporting the trial's findings. While no long-term studies have been done on safety, minor ulceration of the oral mucosa was reported in twelve percent of the patients in the study by Johnson et al. (1985). A relatively small number (seven percent) of patients chewing the fresh leaves have experienced oral mucosa and tongue inflammation, accompanied by swelling of the lips, and occasional loss of taste which prevented continued use of the plant (Awang 1989a).

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Inflammatory Disease

Based on previous reports of anti-inflammatory activity of Feverfew, Pattrick, Heptinstall, and Doherty (1989) conducted a double-blind, placebo controlled, randomized study on the effect of the dried chopped leaves (70-86 mg.) in the treatment of rheumatoid arthritis. Over the six week trial, forty-one female patients with symptomatic rheumatoid arthritis received Feverfew or placebo. Over thirteen laboratory and/or clinical parameters were assessed. The authors concluded that there were no important differences between the control group and those receiving Feverfew. Therefore, oral dosage did not seem to be of any benefit in the treatment of rheumatoid arthritis. However, those patients participating in the study had "inadequately controlled inflammatory joint symptoms" from the outset, and were already being considered for a change of treatment. In other words, they were not responding well to the treatment they had previously received before the Feverfew study began. The authors not that the results do not preclude possible benefits for the use of Feverfew in osteoarthritis and soft tissue lesions "for which self treatment with feverfew is probably most common." Although this study demonstrated no apparent benefit from oral feverfew in rheumatoid arthritis, the dosage used was extremely small (76 mg dried, powdered feverfew leaf corresponding to two medium-sized leaves), the level of parthenolide was not determined in the product (parthenolide, believed to be the active constituent, is very variable from one species or crop to the next), and patients continued to take NSAIDs, a practice that has been suggested to reduce the efficacy of feverfew. Therefore, it is safe to conclude that the benefit of feverfew in rheumatoid arthritis has not yet been determined.

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