Herbal Remedies

FeverfewWhen the Head Hurts

Steven Foster

The use of feverfew for the treat-ment of headaches dates back atleast to the first century and is

recorded in the work of Dioscorides(the first-century Greek physician), whoalso mentioned its use for stomach ail-ments, fevers, and menstrual irregulari-ties. The 1633 edition of Gerarde'sHerball1 hints at the use of the plant forheadaches: "It is good for them that are

giddie in the head." The 1787 Dublinedition of Culpepper'sla famous herbalaffirms its traditional use forheadaches: "It is very effectual for allpain in the head coming of a cold cause,the herb being bruised and applied tothe crown of the head." Feverfew hastraditionally been considered a tonic,carminative, emmenagogue, vermifuge,and stimulant, used primarily for feversand menstrual regulation. In SouthAmerica, where feverfew is natural-ized, it has been used for colic, stom-achache, morning sickness, and kidneypains. In Costa Rica, feverfew has alsobeen used as a digestive aid and emme-

nagogue. Mexicans have used it as a

sitz bath to regulate menstruation as

well as an antispasmodic and tonic.2Although the herb has been used sincethe beginning of Western civilization,we have only begun to understand itsutility as a medicinal plant. Prior to thelast decade, twentieth-century use ofthe plant had been relegated to folkmedicine and popular herbáis.3

Chemical Compositionand Differences

Feverfew provides an excellent exam-

ple of the importance of calibratingcommercial products to known active

chemical constituents to produce pre-dictable clinical results. Parthenolide, a

sesquiterpene lactone, is regarded as

the chemical constituent responsible forthe activity of feverfew in the preven-tion of migraines. Because the com-

pound has been identified in at least 34other plant species in two plant fami-lies, it is not a reliable indicator of iden-tity of feverfew. Depending on chemo-type and geographic location of origi-nating material, the parthenolide con-

tent of feverfew has been found to behighly variable or altogether absent.4'5There are several different chemotypes.One type contains about 80 percentparthenolide as the total sesquiterpenefraction, with smaller amounts of othercomponents including germacrano-lides, guaianolides, and other com-

pounds. A second chemotype includesthe eudesmanolides, reynosin and san-

tamirin; the third type is a mixture ofendesmanolides and guaianolides. AMexican chemotype is dominated bythe eudesmanolides, reynosin and san-

tamarin, as well as the guaianolides,canin and artecanin. It contains no

parthenolide. Another chemotype(Yugoslavia) is also dominated byeudesmanolides and guaianolides, withparthenolide absent.5 A cultivar, T.parthenium f. flosculosum (DC) Beck, was

found to contain the highest knownlevel of parthenolide, up to 1.27 percentin the leaves.7

Recommending CommercialFeverfew Products to Your PatientsFeverfew, and its recent development as

an antimigraine agent, provides docu-mented evidence of the need for herbproducts to be properly identified (bothbotanically and chemically), with pre-dictable levels of active constituents, and

delivered in appropriate dosage formsand amounts, in order for herbalmedicines to take their rightful role inmodern health care. A study published in1992 by Heptinstall et al. assessed theparthenolide content in feverfew tabletsand capsules, tinctures, leaf, powderedleaf, or bulk herb.6 In a clinical studydemonstrating the efficacy of feverfew formigraine (Murphy et al., 1988), feverfewcapsules of known parthenolide contentwere used. The mean daily dose was 82mg of the leaves, containing an averagecontent of 0.66 percent parthenolide,delivering a mean daily dose of 543pg/day.8 In order to ensure uniformity ofdosage and predictable results, Healthand Welfare Canada proposed a mini-mum level of 0.2 percent parthenolide forfeverfew leaf products submitted for a

Drug Identification Number (DIN), alongwith certification of botanical identity. TheFrench government proposed a level of 0.1percent parthenolide, presumably in orderto accommodate the low parthenolidecontent in commercial herbage containinghigh levels of stem material. In the UnitedStates, all herbs sold in the form of dietarysupplements prior to the passage of theDietary Supplement Health and Educa-tion Act of 1994 are grandfathered in as

"dietary supplements." Therefore, the reg-ulatory status of feverfew in the UnitedStates is that of a dietary supplement. Atleast three adulterants, Matricariamarítima, Matricaria recutita (Germanchamomile), and Tanacetum vulgäre(Tansy) have been known to be suppliedto manufacturers as "feverfew." In the1992 study by Heptinstall et al., none ofthe North American products tested con-

tained as much as 0.1 percent partheno-lide, if it was detected at all.6 Followingpublication of this and other studies, man-

ufacturers sought sources for highparthenolide-level, properly identified

335

336 ALTERNATIVE & COMPLEMENTARY THERAPIES—SEPTEMBER/OCTOBER 1995

Where Does FeverfewCome From?3

Feverfew is derived from the leavesand/or leaves and flowering tops of Tanace-tum parthenium (L.) Schultz Bip. It is a mem-ber of the aster family (Asteraceae or

Compositae). Feverfew was formerlyknown as Chrysanthemum parthenium (L.)Bernh., a name that still appears in some

advocacy literature. The generic nameTanacetum is derived from an altered formof athanasis (othonatos) meaning "immor-tal," alluding to the everlasting nature ofthe dried flowers. The specific name

"parthenium" is derived from the Greekpartfienos, virgin, which was originallyapplied to another plant by Hippocrates,referring to traditional use by women tohelp relieve menstrual cramps.

The plant is native to the mountain scruband rocky soil of the Balkan peninsula. Ithas been grown as an ornamental flowerthroughout Europe for centuries, and iscommonly naturalized in hedges and wasteplaces in much of Europe. The plant hasalso escaped cultivation and establisheditself in North and South America.

aSource: foster, S. Feverfew—Tanacetiumparthenium. Botanical Series, No. 310. Austin,TX: American Botanical Council, 1991.

feverfew. Several commercial growersnow offer feverfew with 0.4 percentparthenolide content or greater. Therefore,when recommending feverfew productsto patients, it is essential that the healthcare practitioner recommend productsthat have assayed or standardized levelsof parthenolide from which a reasonablypredictable efficacy can be achieved.7

DosageAverage daily dosage is calculated as

125 mg of dried leaves per day, assuminga minimum parthenolide content of 0.2percent.

Migraine Clinical Studies

Long used as a folk remedy for thetreatment of fevers, menstrual disorders,arthritis, and migraine headaches, fever-few gained popularity, particularly in

When recommending feverfew products to

patients, it is essential that the health care

practitioner recommend products that have assayedor standardized levels of parthenolide.

Britain in the late 1970s, following a num-

ber of newspaper reports on feverfew'seffective treatment for prophylaxis ofmigraine symptoms after orthodox thera-pies failed. One brief newspaper articlegenerated more than 25,000 letters froman interested public. Based on knowledgethat a large number of migraine suffererswere self-medicating with feverfew, a

double-blind, placebo-controlled trial ofthe herb was carried out at the City ofLondon Migraine Clinic, with results pub-lished in 1985. After analysis of detailedquestionnaires completed by 300 feverfewusers, 17 volunteers completed the clinicalstudy. Most involved in the initial surveyself-medicated by eating the freshlypicked leaves of the plant. Depending onleaf size, two to three leaves were eaten as

a daily dosage. The authors of the study,E.S. Johnson, et al., judged that the aver-

age daily dose of 2.44 leaves was roughlyequivalent to 60 mg of the dried herb. Forpurposes of the study, a daily trial dose oftwo 25-mg capsules of freeze-dried pul-verized leaf was used. Eight patientsreceived feverfew, with nine others receiv-ing placebo. According to the authors,treatment patients experienced far fewersevere and incapacitating headaches thanthose receiving placebo. Treatment volun-teers suffered a far lower incidence of nau-sea and vomiting associated withmigraines than did placebo patients. Thiswas the first clinical evidence whichshowed that when taken prophylactically,feverfew prevented attacks of migrainesand associated symptoms.8

A 1988 study conducted at UniversityHospital, Nottingham,9 assessed the use

of feverfew in migraine prophylaxis in a

randomized double-blind, placebo-con-trolled crossover study. Sixty of 76

patients admitted to the trial completedthe study. Treatment or placebo was

given for four months, then the groupsgiven treatment or placebo were switchedfor an additional four months. Accordingto the authors, treatment with feverfewwas clearly associated with a reduction inthe frequency of migraines, associatedvomiting attacks, with a trend toward a

reduction in migraine severity.While the mechanism of action is not

fully understood, migraine prophylaxis isattributed to parthenolide inhibition ofthe release of 5-HT-serotonin (5-hydrox-ytryptamine) from platelets.

Arthritis and Feverfew's Anti-Inflammatory Properties

Feverfew has long been used for its per-ceived anti-inflammatory activity. In theUnited Kingdom, for example, the plant iswell known as a folk medicine for reduc-ing joint inflammation associated withrheumatism and arthritis. Use for this pur-pose may be more widespread than as a

preventative for migraine headaches.Based on previous reports of its anti-inflammatory activity, a 1989 double-blind, placebo-controlled, randomizedstudy evaluated the effect of dried leaves(70-86 mg) in the treatment of rheumatoidarthritis. Over the six-week trial, 41 femalepatients with symptomatic rheumatoidarthritis received feverfew or placebo.Over 13 laboratory and /or clinical param-eters were assessed. The authors conclud-ed that there were no important differ-ences between the control group andthose receiving feverfew. Participatingpatients, however, had not previouslyresponded to conventional therapies. Theresults do not preclude possible benefits

ALTERNATIVES COMPLEMENTARY THERAPIES—SEPTEMBER/OCTOBER 1995 337

In the London group's initial survey of 300patients, mouth ulcération was reported by I 1.3

percent of feverfew leaf users.

of feverfew in treating osteoarthritis andsoft tissue lesions.1,10

Advising Patients AboutSide Effects

In the Nottingham migraine clinicalstudy, although side effects includedmouth ulcération (10 treatment, 16 place-bo), indigestion (4 treatment, 2 placebo),heartburn (3 treatment, 3 placebo), dizzi-ness/lightheadedness (2 treatment, 2placebo), and other minor observations,no clear correlation attributable to fever-few was observed. No changes were

reported in hématologie and biochemicaltests, including urea, creatinine, elec-trolytes, blood sugar, and liver function.There was also no difference in urinalysisof the two groups. In the Londonmigraine study, there was a generalabsence of adverse events; however, theself-selected nature of the study groupwould itself predict an absence of side-effect reporting. In the London group'sinitial survey of 300 patients, mouthulcération (from chewing fresh leaves)was reported by 11.3 percent of feverfewleaf users. Digestive disturbances were

experienced by 6.5 percent of self-medi-cating feverfew users. Among those whochewed feverfew leaf for migraine treat-ment, it was also reported to sometimesproduce a more general inflammation ofthe oral mucosa and tongue, accompa-nied by swelling of the lips, and, on rare

occasions, loss of taste. Occasionally,mouth ulcération is serious enough to dis-continue treatment. Sesquiterpene lac-tones are known to cause contact dermati-tis, and it is postulated that these com-

pounds may cause inflammation of theoral mucosa when chewing the leaves. No

studies have been undertaken to deter-mine the safety of the long-term ingestionof feverfew leaf.

In clinical practice, the relatively minorside effects reported may be acceptable to

patients over the often incapacitatingexperience of migraine headaches.8'9 Iforal mucosa inflammation, mouth ulcéra-tion, or other side effects occur, the practi-tioner and patient must decide whetheror not to discontinue treatment. D

References1. Johnson, T. The Herball or Generall Historie ofPlantes, Reprinted. New York: Dover Publica-tions, Inc., 1975 (orginal ed. 1633), p.653la. Culpepper, N. The English PhysicianEnlarged. Dublin: H. Colbert, 1787, p.150.2. Duke, JA. CRC Handbook of Medicinal Herbs.Boca Raton, FL: CRC Press, 1985.3. Foster, S. Herbal Renaissance—Growing, Usingand Understanding Herbs in the Modern World.Layton, UT: Gibbs Smith Publisher, 1993.4. Awang, D.V.C. Feverfew. Can Pharm j122(5):266-270,1989.5. Awang, D.V.C. Chemotaxonomy and theregulation of commercial plant products—identity and standardization. Presentation tothe 57 Congrès de l'Association CanadienneFrançaise pour 1'Advancement des Sciences,Montréal, Québec, 15-19 May 1989.6. Heptinstall, S., Awang, D.V.C., Dawson,B.A., Kindack, D., Knight, D.W., May, J.Parthenolide content and bioactivity of fever-few (Tanacetum parthenium [L.] Schultz-Bip.).Estimation of commercial and authenticatedfeverfew products. / Pharm Pharmacol44:391-395,1991.7. Awang, D.V.C, Dawson, B.A., Kindack,D.G., Crompton, C.W., Heptinstall, S.Parthenolide content of feverfew (Tanacetumparthenium) assessed by HPLC and 'H-NMRspectroscopy. / Nat Prod 54(6):1516-1521,1991.8. Johnson, E.S., Kadam, N.P., Hylands, D.M.,

ResourcesHobbs, C. Feverfew Tanacetum parthenium:

A review. HerbalGram 20(Spring):26-36,1989.Available from:American Botanical CouncilP.O. Box 201660Austin, TX 78720-1660

Hancock, K. Feverfew—Your Headache MayBe Over. New Canaan, CT: KeatsPublishing, Inc., 1986.Available from:Keats Publishing, Inc.Box 876New Canaan, CT 06840ISBN 0-87983-392-0

Britt, J., Keen, K. Feverfew. London:Century Hutchinson, Ltd., 1987.Available from:Century Hutchinson, Ltd.Brookmount House62-65 Chandos PlaceConvent GardenLondon WC2N 4NW, UKISBN 0-7126-1548-2

Hylands, P.J. Efficacy of feverfew as a prophy-lactic treatment of migraine. Br Med j291:569-573,1985.9. Murphy, J., Heptinstall, S., Mitchell, J.R.A.Randomized, double-blind, placebo-controlledtrial of feverfew in migraine prevention. LancetJuly 23:189-192,1989.10. Pattrick, M., Heptinstall, S., Doherty, M.Feverfew in rheumatoid arthritis: A double-blind placebo-controlled study. Ann Rheum Dis48:547-549,1989.

To order reprints of this article, write to or call:Karen Ballen, ALTERNATIVE & COMPLE-MENTARY THERAPIES, Mary Ann Liebert,Inc., 2 Madison Avenue, Larchmont, NY 10538,(914) 834-3100.