HerbalEGram:

Tanacetum parthenium
by Steven Foster

Feverfew (Tanacetum parthenium) has gained popularity in the past decade for a time-honored use-a pain-reliever for the treatment of migraine headache. Recent scientific research has resulted in new interest in the plant, given successful clinical trials in which the plant has been efficaciously used to provide symptomatic relief in migraine, a troubling condition that often does not respond to modern treatment methods.

Botany and Nomenclature

A member of the aster family (Asteraceaeor Compositae), Feverfew is a strongly aromatic perennial originatingfrom mountain scrub and rocky soil of the Balkan peninsula. Forcenturies it has been cultivated as a medicinal plant as well as anornamental in Europe, and is now naturalized in hedges and waste placesthroughout much of Europe. The plant is naturalized in both North andSouth America.

It appears to haveescaped from cultivation and become naturalized in the United States inthe mid-nineteenth century. It is absent from the first edition of AsaGray's Manual of Botany (1848), but by the time the 1870 editionof his Field Forest, and Garden Botany was published, Grayobserved that it is "cultivated in old gardens, and [is] runningwild."

Feverfew is naturalizedin waste places, roadsides, and borders of woods from Quebec south toMaryland, west to Missouri, and Ohio (Fernald, 1950).

Botanically, the plant isbest known in the modem literature as Tanacetum parthenium (L.)Schultz Bip. Other botanical names by which it has previously been knowninclude Chrysanthemum parthenium (L.) Bernh., Leucanthemumparthenium (L.) Gren. & Gordon, and Pyrethrum parthenium (L.)Sm. The Swedish botanist Linnaeus referred to it as Matricariaparthenium.

Unfortunately, the names Tanacetumparthenium and Chrysanthemum parthenium were both noted asvalid botanical names in seminal taxonomic reference works published in1976. The former appeared in Volume 4 of Flora Europaea (Heywood inTutin et al. eds., 1976) and the latter in Hortus Third(L.H. Bailey Hortorium, 1976). According to Tucker (1986), if the genus Chrysanthemumis defined sensu stricto (in the strictest or narrowestsense)-as is done by Heywood-then the genus includes only five annualspecies of the Mediterranean and Eurasia. If Chrysanthemum is interpretedsensu lato (in the broadest sense)-as is done in Hortus Third-thenit would include upwards of 200 species. It is the inclination of moderntaxonomists to separate the genus Chrysanthemum into severalgenera in the aster family. Here the "splitters" win over the"lumpers."

Consequently, most perennial speciesformerly included in the genus Chrysanthemum are now referred toseparate genera including Dendranthema (the"chrysanthemums" of horticulture), Balsamita, Leucanthemum andTanacetum (Mabberly, 1987).

Feverfew received thename Tanacetum parthenium from C.H. Schultz (Schultz Bipontinus,1805-1867) in an 1844 German monograph on the genus Tanacetum.

The generic name Tanacetum is derived from an altered form of athanasis (athanatos) meaning immortal, in allusion to the ever-lasting nature of the dried flowers. The specific name "parthenium" is derived from the Greek parthenos, virgin, which was originally applied to another plant by Hippocrates, referring to traditional use by women to help relieve menstrual cramps (Nicholson, 1886-87). This is an instance where botanical nomenclature has failed to provide a single unambiguous name for a well-defined species. However, most of us can at least agree on the English common name, Feverfew, deriving from the Latin febrifuga, a febrifuge, referring to the plant's traditional role in lowering fevers.

History

In 1655 when John Goodyer produced thefirst English translation of the materia medica of Dioscorides (thefirst century Greek physician), eleven different Latin names were givenfor feverfew. Dioscorides mentioned use, as Goodyer puts it, for "melancholicall,"which can be interpreted as used for headaches (Gunther, 1934). In the1633 edition of Gerard's Herbal, Thomas Johnson, notes that"feverfew dried and made into pouder, and two drams of it takenwith honie or sweet wine, purgeth by siege melancholy and flegme,whereforre it is very good for them that are giddie in the head, orwhich have the turning called Vertigo, this is a swimming andturning in the head. Also it is good for such as be melancholike, sad,pensive, and without speech" (Johnson, 1633, p. 653).

Culpepper (1787 ed.) alsoobserves efficacy for headache, "It is very effectual for all painsin the head coming of a cold cause, the herb being bruised and appliedto the crown of the head; as also for the Vertigo, that is a sunning orswimming of the head" (p. 150).

Throughout the eighteenth and nineteenthcenturies, references to the plant were only passing. William Cullenconsidered the plant more active than wormwood (Artemisia absinthium),but admits, "I have seldom had such opportunity of seeing itemployed as to enable me to determine precisely concerning itsvirtues" (Cullen, 1808, Vol 2, p. 209). It is absent from most ofthe major pharmacopoeias and only briefly mentioned in dispensatories.It was once the official "Herba Matricariae " of Germany,where it was commonly known as Mutterkraut. The 1849 Dispensatoryof the United States only affords it "useful tonicproperties," and admits it is little employed (Wood and Bache,1849).

Prior to the last decade, twentieth century use of the plant had been relegated to folk medicine and popular herbals. Joseph Meyer (1917) lists its properties as tonic, carminative, emmenagogue, vermifuge and stimulant. Primary uses have included fevers, menstrual regulation, or external application as an anodyne (pain-reliever). Naturalized in South and Central America, the Kallaway of the Andes, use feverfew or Santa Maria, as it is also known, to promote the functional activity of the stomach, for colic, stomachache, morning sickness and kidney pains. One twig of the plant is steeped in a cup of boiling water and drunk once a day (Bastien, 1987). In Costa Rica, a decoction has been used for cardioactive, digestive and emmenagogue properties, as well as an enema for worms. Mexicans have used it as a sitz bath to regulate menstruation as well as an antispasmodic and tonic. Venezuelans have used the plant decoction for the treatment of earache (Duke, 1985).

Modern Use

Modern interest has primarily focused onthe use of feverfew in the prophylaxis of migraine. Parthenolide isregarded as the primary chemical constituent responsible for theactivity of feverfew in the prevention of migraines. It was firstisolated by Sorm and coworkers (Soucek, Herout and Sorm, 1959) whoassigned the wrong structure to it. Govindachari (1964) isolated thesame compound and deduced the correct structure from the roots ofchampaca (Michelia champaca), an evergreen member of the magnoliafamily from the Himalayas. This chemical, a sesquiterpene lactone, isfound in at least thirty four plant species, including some forms ofcommon tansy (Tanacetum vulgare). Bohlmann and Zdero (1982)identified thirty-nine constituents of feverfew, including parthenolide(D. Awang, personal communication, 1991).

Correctly-identifiedwhole dried leaf, (with at least 0.2 percent parthenolide), has beenproposed by Canadian regulatory authorities as a minimum standard forreasonable certainty of claims in feverfew products. French authoritieshave proposed a level of 0.1 percent (of leaf and stem). The feverfewused in two published clinical trials on the effects of feverfew iscomparable to the Canadian standard. The parthenolide content of varioussources of feverfew has been found to be highly variable (Awang, 1987,1989a, 1989b, 1990, Awang, et al., 1991; Heptinstall, et al., 1992).While North American feverfew leaf products were found to contain lessthan 0.1% parthenolide, Awang et al. (1991) found that adouble-flowered form T. parthenium form flosculosum, contained1.27% parthenolide. Future product development, therefore, may focus onidentifying plant material with consistently high levels of parthenolide.

Health and Welfare Canadahas issued a DIN (Drug Identification Number) to a feverfew productmanufactured in England. This is an important regulatory development, asit is the first DIN issued to an herbal product which allows substantiveclaims for a relatively significant medical condition. While somevalerian products, for example, can claim they may help as asleep aid, the new feverfew product will be allowed to carry the claim"used as a prophylactic against migraines." The product willbe required to be standardized to contain 0.2% parthenolide (Awang,1994).

Research has beenconducted to elucidate the mechanisms of feverfew actions. Parthenolide,and perhaps other sesquiterpene lactones, have been shown to reduce thesecretory activity of blood platelets and white blood cells inlaboratory studies, providing a possible basis for feverfew'seffectiveness in migraine, arthritis, and psoriasis.

Abnormal plateletbehavior has been implicated as a possible explanation for thedevelopment of migraines. Platelets release the hormone serotonin (alsoreferred to as 5-HT) during a migraine attack. Serotonin constrictsblood vessels among other actions. Serotonin antagonists have beensuggested for use in a supportive role in migraine prevention. Feverfewhave has been shown (in vitro) to inhibit serotonin release fromplatelets (Murphy, Heptinstall and Mitchell, 1988). The effectiveness ofvarious feverfew preparations in inhibiting the release of serotoninfrom human blood platelets has been found to correlate well withparthenolide content in freeze-dried or air-dried whole feverfew leaf (Heptinstallet al., 1992).

In the past decade interest in clinicalstudies on feverfew resulted from a national newspaper article inEngland in which 25,000 replies were received in response to a requestfor personal experience on the benefit of feverfew in allaying thesymptoms of migraine (Anon., 1989). A preliminary broad-based clinicalstudy by E. Stewart Johnson in the UK was conducted to evaluate theeffect of feverfew on 300 migraine suffers who had been taking feverfewfor about 2.5 years. According to the report published in the Britishmedical publication Mims Magazine, 70 percent of those migrainesufferers interviewed claimed to have experienced a reduction infrequency and/or pain from migraine since they had used the herb. Threesmall fresh leaves or one large fresh leaf were consumed each day. Manyinvolved in the study had previously failed to respond to orthodoxmedical treatment (Johnson, 1983; as reviewed by Warren, 1986). Thispreliminary clinical trial stimulated additional studies.

A 1985 study by Johnson etal. on the efficacy of feverfew for the prophylactic treatment ofmigraine was conducted at the City of London Migraine Clinic incollaboration with the Chelsea College of the University of London. Theseventeen patients involved in the double-blind study had all eaten theleaves of feverfew for at least three months before commencement of thestudy. Before the test, the average daily dose of fresh leaves ingestedby the patients was sixty mg. per day. During the study, patients weregiven twenty-five mg. of freeze-dried leaf capsules. Nine of thepatients received placebo, and experienced an increase in the frequencyand severity of headache, nausea, and vomiting. Those who took thefeverfew experienced no change in the frequency or severity of migrainesymptoms, prompting the researchers to conclude that feverfew isefficacious in the preventative treatment of migraine (Johnson etal., 1985; Awang, 1989a, 1993; Hobbs, 1989). The study has beencriticized on the basis of self selection, since patients had beenself-medicating with feverfew products prior to the trial.

Murphy, Heptinstall andMitchell (1988) reported on the results of a randomized, double-blind,placebo-controlled, cross-over trial of feverfew in migraine preventionconducted at the University Hospital, Nottingham. Following a one-monthsingle-blind run-in period, seventy-two volunteers were randomlyselected to receive either one capsule of feverfew daily or a matchingplacebo (dried cabbage leaves) for a four month period. One hard capsuleof dried leaves, with weights ranging from 40-114 mg., was judged tocorrespond to two medium-sized leaves. At the completion of the studyfull information was available for fifty-nine participants. According tothe authors, the feverfew treatment was clearly associated with areduction in both frequency of migraine headaches and vomitingassociated with the attacks. There was also a minor trend towards areduction in the severity of migraines. However, there was nosignificant effect in limiting the duration of migraine attacks comparedwith the placebo. No adverse reactions were recorded in the study,though the authors note the need for longer term safety studies giventhe fact that lifelong treatment may be necessary for migrainesufferers.

While no long-termstudies have been done on safety, minor ulceration of the oral mucosawas reported in twelve percent of the patients in the study by Johnson etal. (1985). A relatively small number (seven percent) of patientschewing the fresh leaves have experienced oral mucosa and tongueinflammation, accompanied by swelling of the lips, and occasionalloss of taste which prevented continued use of the plant (Awang, 1989a).

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 note 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."

Feverfew (Tanacetum parthenium) has been recorded as a potential treatment for fevers and headaches for about 2000 years. Long grown in herb gardens of Europe, and naturalized in North and South America, the plant has had a long reputation of folk use for the treatment of headaches. Over the past 15 years pharmacological, chemical, and clinical studies have confirmed the value of the use of feverfew in the symptomatic relief of migraine symptoms. Further studies are necessary to determine long-term safety, and the optimum form, duration, composition, and quality control of feverfew products, along with possible utility in inflammatory joint diseases and psoriasis. Ironically, given the fact that the name feverfew derives from its historical use to lower fevers, it is surprising that the plant has not been studied for fever-reducing activity. For more detailed information on feverfew see the excellent review articles by Awang (1989a and 1993) and Hobbs (1989).

References

Anon. 1989. Feverfew and Migraines. MEDPLANT Abstracts I(l).

Awang, D. V. C. 1987. Feverfew (Tanacetum parthenium). The Pharmaceutical Journal 239:487.

.1989a. Feverfew. Canadian Pharmaceutical Journal 122(5):266-70.

.1989b. Chemotaxonomy and the Regulation of Commercial Plant Products - Identity and Standardization. Presentation to the 57 Congres de l'Association Canadienne Francaise pour l'Advancment des Sciences, Montreal, Quebec, 15-19 May 1989.

.1990. Feverfew Feedback (Letter). HerbalGram 22: 2, 34, 42.

.1993. Feverfew Fever: A Headache for the Consumer. HerbalGram 29: 34-36, 66.

.1994. Personal communication.

Awang, D. V. C., B. A. Dawson, D. G. Kindack, C. W. Crompton, and S. Heptinstall. 199 1. Parthenolide Content of Feverfew (Tanacetum parthenium) Assessed by HPLC and ¹H-NMR Spectroscopy. Jour. Nat. Prod. 54(6):1516-21.

Bastien, J. W. 1987. Healers of the Andes: Kallaway Herbalists and Their Medicinal Plants. Salt Lake City: University of Utah Press.

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Revised edition 1996 American Botanical Council
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